Research ArticleQuantum Calculation for Musk Molecules Infrared Spectratowards the Understanding of Odor

Elaine Rose Maia1 Daniela Regina Bazuchi Magalhatildees1 Dan A Lerner2

Dorotheacutee Berthomieu2 and Jean-Marie Bernassau3

1 Laboratorio de Estudos Estruturais Moleculares (LEEM) Instituto de Quımica Universidade de Brasılia (UnB)CP 4478 70904-970 Brasilia DF Brazil

2 Institut Charles Gerhardt UMR 5253 CNRS-UM2-ENSCM-UM1 Materiaux Avances pour la Catalyse et la SanteENSCM 8 rue de lrsquoEcole Normale 34296 Montpellier Cedex 5 France

3 Sanofi Montpellier 264 rue du Professeur Blayac 34080 Montpellier France

Correspondence should be addressed to Daniela Regina Bazuchi Magalhaes danielabazuchigmailcom

Received 24 June 2014 Accepted 16 August 2014 Published 7 September 2014

Academic Editor Devis Di Tommaso

Copyright copy 2014 Elaine Rose Maia et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

It is not clear so far how humans can recognize odor One of the theories regarding structure-odor relationship is vibrationaltheory which claims that odors can be recognized by their modes of vibration In this sense this paper brings a novel comparisonmade between musky and nonmusky molecules as to check the existence of correlation between their modes on the infraredspectra and odor For this purpose sixteen musky odorants were chosen as well as seven other molecules that are structurallysimilar to them but with no musk odor All of them were submitted to solid theoretical methodology (using molecularmechanicsmolecular dynamics and Neglect of Diatomic Differential Overlap Austin Model 1 methods to optimize geometries)as to achieve density functional theory spectra information with both Gradient Corrected Functional Perdew-Wang generalized-gradient approximation (GGAPW91) and hybrid Becke three-parameter Lee-Yang-Parr (B3LYP) functional For a proper analysisover spectral data a mathematical method was designed generating weighted averages for theoretical frequencies and computingdeviations from these averages It was then devised thatmusky odorants satisfied demands of the vibrational theory while nonmuskcompounds belonging either to nitro group or to acyclic group failed to fulfill the same criteria

1 Introduction

11 Theories regarding Odor Prediction and RecognitionMusks are responsible for bringing sensuality and warmth toa fragrance [1] as well as adding their excellent fixative prop-erties [2 3] Presently natural products extraction involveshigh costs and generates small amounts of raw materialso synthetic odorants are greatly demanded To properlydesign a new odorant previous information on how odorsare read is necessary There are major recent advances onneurobiology biophysics biochemical fields [4ndash7] though itis still unclear how humans recognize odor At this scenarioquantitative structure-activity relationship models (QSARmodels) are valuable for the proposal of new potentialmusky smelling molecules [8ndash12] Such approach allows forthe reduction in the number of costly and unnecessary

chemical syntheses Theories regarding odor recognition atthe biological level have also been discussed in the literatureOne of them known as the odotope theory [13ndash15] statesthat noncovalent bonds (ie weak repulsive and attractiveinteractions) between themolecule and the olfactory receptor(OR) proteins (responsible for decoding the molecule andstarting transduction) would elicit a unique response in thecerebral cortex

A second theory regarding structure-odor relationshipis the vibrational theory which relates the moleculersquos vibra-tional modes to its odor It was firstly proposed by Dysonin 1938 followed by Wright in 1977 and refined by severalauthors [16] It claims that ORs would be able to recognizeodorant vibrational modes In 1996 [17] Turin suggestedthat such reading would occur at the protein-odorant levelthrough a mechanism close to inelastic electron tunneling

Hindawi Publishing CorporationAdvances in ChemistryVolume 2014 Article ID 398948 13 pageshttpdxdoiorg1011552014398948

2 Advances in Chemistry

spectroscopy (IETS) an inelastic nonoptical vibrational spec-troscopy [18] After building a specific algorithm to mimicvibrational modes at protein level the author could state thatmusksmdashfor instancemdashwill present four bands near 700 10001500 (or 1750 cmminus1 for nitromusks) and 2200 cmminus1 and thateach band will have 400 cmminus1 width [19] There is much tobe understood concerning odor recognition supported onvibrational theoryrsquos ideas as indicated by the variety of papersdealing with the subject [20ndash24]

12 Paperrsquos Aims In order to explore vibrational theorymusks and non-musks (see Figure 1) have been equallymodeled so to come to their theoretical IR spectra Firstlymolecules have been computationally analyzed by molecularmechanics and molecular dynamics (MMMD) in order toascertain the conformational space available to them Aftersemiempirical calculations employing Neglect of DiatomicDifferential Overlap Austin Model 1 (NDDO AM1) Hamil-tonian took place for geometry corrections Then final cal-culations for energy optimization and IR spectra collectionwere set with density functional theory (DFT) using bothGradient Corrected Functional Perdew-Wang generalized-gradient approximation (GGAPW91) and hybrid Beckethree-parameter Lee-Yang-Parr (B3LYP) functionals withthe double numerical basis set with polarization (DNP)for GGAPW91 and 6-311+G(dp) for B3LYP Methodologyadopted is up-to-date with the literature and was mainlybased on Lerner and coworkers paper [26] For a completediscussion on computed harmonic vibrational frequenciesand their scaling factors and accuracy see data obtained byScott and Radom [27]

GGAPW91 and B3LYP theoretical spectra were com-pared to the experimental data (when available in freedata banks as NIST and SDBS) and then were evaluatedconcerning the expression of the four characteristic muskbands (centered at 700 1000 1500 or 1750 and 2200 cmminus1)Now these four bands were properly indicated using aspecific algorithm built to reproduce IETS at biological levelhowever the vibrational modes primarily responsible forsuch bands were not nominated To clarify this questiona comparison was carried between IR theoretical data andIET data published previously since both spectra show thesame vibrational modes at the same frequencies and itis much simpler to estimate theoretical IR spectra Asidefrom the equivalence on estimating vibrational modes thereare no other comparisons that could fit in once modeintensities are differently calculated in one technique andanother generating bands that can be either more prominentor even absent when comparing spectra Besides using IRspectra to predict odor or olfactory receptor affinity hasfailed repeatedly [28] Finally vibrational modes responsiblefor ldquomusk bandsrdquo in the spectra are not to be taken assolely responsible for musk odor It is well known thatthere are several molecular descriptors involved at majorbiological phenomena such as carrying the odorant from theenvironment to anOR and docking odorant-OR and they areequally relevant when considering the vibrationally assistedodor recognition mechanism

The sixteen musks 1ndash16 are already in use in perfumesso to have their activity is certified The seven molecules 17ndash23 are structurally similar to the previous molecules but donot possess any musky odor besides nonmusks 17 and 18are woody Absence of odor is not to be taken as a differentodor character but (i) as a moleculersquos inability to bind itsOR due to particularities of its structure or (ii) as the lackof specific vibrational modes in their minimum quantityprecluding proper energy decrease on electron scattering andits subsequent tunneling [13 14 16] So regarding adoptedcriteria relying on the choice of such molecules it addressesthe main hypothesis here being tested only musk odorantsare supposed to express vibrational modes under mentionedranges and no other molecule is supposed to present thesame vibrational pattern All compounds have their IUPACname andChemical Abstracts Service (CAS) registry numberlisted in Table 1

2 Methods and Methodology

21 Computational Methods Calculation programs usedwere those available in the Materials Studio Package Pro-gram [29] and Gaussian 09 [30] for B3LYP calculationsMolecules had their conformational space studied undervac-uum environment through MMDM calculations using theCFF99COMPASS [31] force field implemented in the Dis-cover Simulation program [32 33] Main parameters chosenfor MM routine were Conjugate Gradient method [34] withthe Polak-Ribiere algorithm [35] running until it achievedconvergence at 10 times 10minus4 kcalsdotmolminus1 sdot gtminus1 MD trajectorieswere carried out at 650K during 10 ns with a time step of10 fs (therefore collecting 1000 frames) in the canonicalensemble After previous scanning in which temperature andtrajectory time were changed parameters chosen showed tobe effective on expressing molecules flexibility allowing thecollection of a representative subset of initial conformations

Selected conformers fromMMDM procedure were thenminimizedwith Vamp program [36] usingNDDOAM1 [37ndash39] as a previous optimization step towards DFT calculationSpin multiplicity was automatically determined and a con-vergence of 01 kcalsdotmolminus1 sdotgtminus1 for the heat of formation valuewas set Self-consistent field (SCF) cycles had a convergencetolerance of 50 times 10minus7 eVsdotatomminus1

Final geometries were minimized using the DMol3 pro-gram [40ndash42] forDFT calculations Basis set chosenwasDNP[43] with GGAPW91 [44] as exchange functional Totalenergy convergence of 10 times 10minus5Ha was required with a37 A global cutoff Final cutoff of the SCF cycles was 50 times10minus7 eVsdotatomminus1 and the orbital cutoff quality was kept equalto 01 eVsdotatomminus1 The same starting structure used in GGAPW91 calculation was employed for hybrid functional B3LYP[45] calculation with 6-311+G(dp) basis set now usingGaussian 09 Moldenrsquos processing program [46] was appliedalong with Xming emulator [47] to achieve IR continuumspectra

22 Development of a Frequency-Weighted Average and OtherUseful Tools A mathematical formula had to be developed

Advances in Chemistry 3

1 2 3 45

6 7 8 910

11 12 13

14 15 16

1718

19 20

21 22 23

O

OO

OO

O O O

O

OO

O

O

OO O

O

OO

O

OO

O

O O O

O

OH

SR

O

O

O

RR

R R

OO

O

OO

S

O

S

S

O

O

SS

S

OO

O O

S

R

N+

Ominus

+NminusO

N+

Ominus

+NminusO

N+

N+

Ominus

Ominus

N+

N+

O

O

O

O

O

O

OOO

minus

Ominus

minusO minusOOminus

N++N +N

O

O

Figure 1 Odorants under study macrocyclic musks (MCM) pentadecanolide (1) (R)-exaltolide (2) (S)-exaltolide (3) cis-globanone (4)and trans-globanone (5) polycyclic musks (PCM) (4S7S)-galaxolide (6) (4S7R)-galaxolide (7) indane (8) tetralin (9) and tonkene (10)nitromusks (NM) musk ketone (11) musk moskene (12) and musk ambrette (13) acyclic musks (ACM) romandolide (14) helvetolide (15)and cyclomusk (16) nonmusks macrocyclic analogs (MCa) (17) and (18) acyclic analogs (Aa) (19) and (20) and nitro analogs (Na) (21)(22) and (23)

4 Advances in Chemistry

Table 1 Molecules studied

Number IUPAC name CAS number1 Oxacyclohexadecan-2-one 106-02-52 16(R)-Methyl-oxacyclohexadecan-2-one 69297-56-93 16(S)-Methyl-oxacyclohexadecan-2-one 129214-00-24 (5Z)-Cyclohexadec-5-en-1-one 37609-25-95 (5E)-Cyclohexadec-5-en-1-one6 (4S7S)-Cyclopenta[g]-2-benzopyran 134678-hexahydro-466788-hexamethyl 172339-62-77 (4S7R)-Cyclopenta[g]-2-benzopyran 134678-hexahydro-466788-hexamethyl 252332-95-98 1-(23-Dihydro-11233-pentamethyl-1119867-inden-5-yl)-ethanone 4755-83-39 1-[(6119878)-5678-Tetrahydro-355688-hexamethyl-2-naphthalenyl]-ethanone 85549-79-710 2H-[1]-Benzothieno[32-b]pyran-2-one 5732-22-911 4-(11-Dimethylethyl)-26-dimethyl-35-dinitro-benzaldehyde 99758-50-612 4-(11-Dimethylethyl)-26-dimethyl-35-dinitro-benzaldehyde 116-66-513 none14 2-(1-Oxopropoxy)- 1-(33-dimethylcyclohexyl)ethyl ester 236391-76-715 1-Propanol 2-[1-(33-dimethylcyclohexyl)ethoxy]-2-methyl- 1-propanoate 141773-73-116 1-Cyclopentene-1-propanol 1205731205732-trimethyl-5-(1-methylethenyl)- 1-propanoate 84012-64-617 Oxacyclotetradecane-210-dione 38223-27-718 Cyclotetradecanone 3603-99-419 2-(1-Oxopropoxy)- 1-cyclohexyl-1-methylethyl ester 610770-00-820 none21 2-Methoxy-1-methyl-4-(2-methyl-2-propanyl)-35-dinitrobenzene 99758-79-922 2-Methoxy-4-methyl-1-(2-methylpropyl)-35-dinitro-benzene 99758-78-823 24-Bis(11-dimethylethyl)-5-methoxy-3-nitro-benzaldehyde 107342-73-4

in this paper in order to consider each and every modebelonging to the same 400 cm-1 range as well as theirintensities Therefore the use of weighted averages overtheoretical data was chosen its numerical result was calledcentral frequency (cf) With this central frequency it becamepossible to consider all theoretical peaks occurring in thevicinity of the diagnostic frequencies instead of just affirmingthe existence of the expected band only by naming the mostintense theoretical peak Central frequencies were estimatedas follows

Central frequency =sum119899

119894=1

]119894

times int119894

sum119899

119894=1

int119894

(1)

This mathematical approach (which simply generates afrequency-weighted average) was applied to theoretical fre-quencies found at plusmn200 cmminus1 around 700 1000 and 1500 (or1750) cmminus1 and resulted in central frequencies for compounds1ndash23 which were computed in Table 4 (for GGAPW91 data)and in Table 5 (for B3LYP data) The mentioned range hasbeen chosen so as to enable each band to complete its400 cmminus1 width as established in the vibrational theory

3 Results and Discussion

Data will be presented and discussed in three successivesections In the first section the collection of theoretical IRspectra will be presented In the second section they willbe compared to experimental IR spectra to discuss theirprecision and accuracy The third section will deal with therationalization betweenmusk spectra andmusk odor activityIn order to establish such relation best theoretical IR spectrawill be chosen from this paperrsquos second section

31 Part 1 Computation of IR Spectra Concerning ab ini-tio methods convolved GGAPW91 spectra are shown inFigure 2 while B3LYP spectra are gathered in Figure 3 ForGGAPW91 spectra carbon-oxygen single bond stretchesoccur on frequencies between 1018 cmminus1 (for nitro ana-log 21) and 1220 cmminus1 (for (4S7R)-galaxolide 7) carbon-nitrogen single bond stretches occur under the frequency of1200 cmminus1 for nitro compounds carbon-sulfur single bondstretches are observed at 1054 cmminus1 for tonkene 10 Carbon-carbon double bonds stretches happened at 1687 cmminus1 forcis-globanone 4 and at 1706 cmminus1 for trans-globanone 5while all other compounds expressing aromatic C=C bondshad their stretching modes between 1543 cmminus1 (as in musk

Advances in Chemistry 5

Frequency (cmminus1)

0100020003000

Rela

tive i

nten

sity

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

12345

678910

111213

141516

17181920

212223

Figure 2 Spectra obtained with GGAPW91 for MCM 1ndash5 PCM 6ndash10 NM 11ndash13 ACM 14ndash16 and nonmusks 17ndash23

ketone 11) and 1618 cmminus1 (for (4S7R)-galaxolide 7) Nitrogroups have presented their symmetric stretchingmodes near1310ndash1340 cmminus1 and their nonsymmetric stretching modes at1520ndash1560 cmminus1 For aldehydes ketones ethers and estersthe carbon-oxygen double bond stretching represents animportantmark for confirming spectra here the lowest valuefor such mode is found for tetralin 9 at 1680 cmminus1 whilethe highest value of 1777 cmminus1 belongs to acyclic analog 20Carbon-hydrogen bending modes start at very low frequen-cies and end at 1493 cmminus1 (for helvetolide 14) simultaneouslythe band of carbon-hydrogen stretching modes starts at2898 cmminus1 (for (4S7R)-galaxolide7) andfinishes at 3198 cmminus1(for nitro analog 22)

For B3LYP spectra the lowest frequency found for thecarbon-oxygen single bond stretching was 1006 cmminus1 (forromandolide 15) while its highest frequency was 1403 cmminus1(for tonkene 10) the frequency of the carbon-oxygen doublebond stretching was found between 1738 cmminus1 (for musk 8)and 1810 cmminus1 (formusk 14)The carbon-carbon double bondstretching occurred on the frequency of 1707 and 1718 cmminus1for compounds 4 and 5 and between 1699 and 1712 cmminus1for compound 16 finally the carbon-carbon double bondstretching for aromatic compounds occurred between 1531(for non-musk 21) and 1650 cmminus1 (for musk 7) The stretch-ing for nitrogen-oxygen in nitro groups was found at1250ndash1417 cmminus1 for symmetric modes and at 1531ndash1618 cmminus1

6 Advances in Chemistry

12345

678910

111213

141516

17181920

212223

Frequency (cmminus1)

01000200030004000

Rela

tive i

nten

sity

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Figure 3 Spectra obtained at B3LYP level for MCM 1ndash5 PCM 6ndash10 NM 11ndash13 ACM 14ndash16 and nonmusks 17ndash23

for asymmetric modes Finally carbon-hydrogen bendingmodes began at very low frequencies and went up to1540 cmminus1 at most (for musk 13) while carbon-hydrogenstretching occurred between 2953 cmminus1 (for compound 6)and 3229 cmminus1 (for nitromusk 13)

32 Part 2 Comparing GGAPW91 and B3LYP Spectrato Experimental Data For an overview over GGAPW91B3LYP and experimental [47] IR data Figure 4 and Table 2were built inwhich vibrationalmodes for themost importantfunctional groups are organized in accordance with theoreti-cal method adopted Each band expresses the range in whichlabeled vibrational mode occurs considering the maximumand theminimum found for all compoundsThus it becomespossible to state that B3LYP and GGAPW91 results for CndashH stretching modes start at 90 and 140 cmminus1 respectivelyvalues that are higher than the ones provided by experimentaldata simultaneously the same band ends at +50 cmminus1 forGGAPW91 and at +90 cmminus1 for B3LYP in comparison to theexperimental data CndashH bending modes finish at +30 cmminus1for GGAPW91 and at +80 cmminus1 for B3LYP when compared

to experimental values Aromatic C=C stretches occurredin an expected range for GGAPW91 with a +20 cmminus1 shiftfor alkene compounds B3LYP showed a continuous bandfor alkene and aromatic C=C stretches which started at+60 cmminus1 and ended at +30 cmminus1 over experimental dataCndashO stretching modes are found within an expected rangefor both GGAPW91 and B3LYP methods for tonkene 10GGAPW91 predicted CndashO mode at 1381 cmminus1 while thesame mode is found at 1403 cmminus1 in B3LYP data For C=Ostretchingmodes GGAPW91 showed a +20 cmminus1 incrementover lower and higher values found for experimental dataand B3LYP shifted over experimental range in +60 cmminus1Finally nitro N=O stretching modes have had both sym-metric and asymmetric modes accurately and precisely esti-mated for GGAPW91 for B3LYP symmetric nitro stretchingshowed a broader band than that of GGAPW91 and ofexperimental data starting at a +30 cmminus1 shift and finishingat a minus10 cmminus1 shift while their asymmetric modes werecorrectly predicted

Therefore while GGAPW91 final results were all fittedinto experimental reports considering the allowed plusmn30 cmminus1

Advances in Chemistry 7

Table 2 Collection of observed versus calculated IR mode frequencies for compounds 1ndash23

Vibrational modea Observed wavenumber (cmminus1) [25] Calculated wavenumber (cmminus1)GGAPW91 B3LYP

] CbndashH 3150ndash2850 3198ndash2898 3229ndash2953] CndashH (aldehyde) 2900ndash2800 2954ndash2892 2988ndash2939120575 CndashH up to 1465 up to 1493 up to 1540] C=C (alkene) 1680ndash1600 1706ndash1687 1718ndash1707] C=C (aromatic) 1600ndash1475 1618ndash1543 1650ndash1531] C=O (aldehyde) 1740ndash1720 1715ndash1693 1772ndash1749] C=O (ketone) 1725ndash1705 1733ndash1680 1784ndash1738] C=O (ester) 1750ndash1730 1777ndash1742 1810ndash1768120575 CndashO (alcohol ether and ester) 1300ndash1000 1381 1200ndash1018 1403 1312ndash1006]as nitro (RndashNO2) 1660ndash1500 1560ndash1520 1618ndash1531]119904 nitro (RndashNO2) 1390ndash1260 1340ndash1310 1417ndash1250a] stretching ]as asymmetric stretching ]119904 symmetric stretching 120575 bendingb] C(sp2)ndashH C(sp3)ndashH and C(aromatic)ndashH

shifts B3LYP results overestimated CndashH stretching andbending modes alkene C=C stretching modes and aldehydeand ketone C=O stretching modes

To quantify collected results experimental IR spectrumgiven for each particular molecule was compared to its theo-retical spectra as shown in Table 3 In the literaturemdashpublicand personal IR databasemdashonly spectra for compounds 1ndash5 8 10 and 12 were found The vibrational modes chosenas internal patterns of comparison were as follows whenoccurring (i) the two most intense peaks regarding theCndashO stretching mode (ii) the most intense peak for theC=O stretching mode (iii) the most intense peaks for thesymmetric and asymmetric CndashH stretching modes (iv) thehighest wavenumber found for the CndashH bending modes (v)the highest intensity for the C=C stretching mode and (vi)the most intense peaks for the symmetric and asymmetricN=O stretching modes They are altogether able to expressthe accuracy relying on theoretical data once all functionalgroups have had their modes listed within chosen criteriaand the whole spectrum has been covered

Extra information comes on the so-called DIFF columnsin Table 3 Consider

DIFF119894

= ExpWavenumber119894

minusTheoWavenumber119894

(2)

where the difference established between experimental andtheoretical values was plotted (for both GGAPW91 andB3LYP results) as shown in (2) In such equation for acertain mode 119894 the difference (DIFF) is obtained through thesubtraction of its theoretical value (TheoWavenumber) fromits experimental value (ExpWavenumber) The average of thecollected differences on Table 3 was estimated as the values ofabsolute difference were divided by the number of occurringmodes disregarding all CndashH stretch modes as follows

Deviation 1 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(3)

This choice was made due to the fact that all CndashHstretches were overestimated in more than 100 cmminus1 for both

theoretical methods as discussed before This last modetherefore had its deviation separately estimated as follows

Deviation 2 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(4)

in which the absolute DIFF119894

is collected is summed for all CndashH stretching modes within the same theoretical method andis divided by the number of occurring modes

So finally GGAPW91 IR results are found to be moreaccurate than B3LYP results with calculated deviations thatare equal to 13 cmminus1 and 43 cmminus1 respectively Neverthelessthey correspond to a 325 (DFT) and a 1075 (B3LYP)shift over the 4000ndash0 cmminus1 that represents the spectrumwhich ensures that both methods are powerfully predictiveSimultaneously both methods display great shift over CndashHstretching modes corresponding to an increase of 124 cmminus1and 145 cmminus1 respectively Considering that one of thispaperrsquos aims is to compare theoretical IR data with postulatesof the vibrational theory on musky odor the last mentionedmodes are irrelevant as they are not supposed to be respon-sible for muskiness

33 Part 3 IR Spectra and Musk Activity Herein bothGGAPW91 and B3LYP data will be taken into account so asto compare theoretical results with the bands described in thevibrational theory (700 1000 1500 or 1750 and 2200 cmminus1)which would assign as supposed by the previous theory amusky odor to these molecules

In Tables 5 and 6 the information was gathered so as todispose musks 1 to 23 in lines and their central frequencies(at 700 1000 and 1500 or 1750 cmminus1) in columns Besidesthe compounds were gathered in groups in accordance withtheir structural similarity (see first column on the left) MCMfor macrocyclic musks PCM for polycyclic musks NM fornitromusks and ACM for acyclic musks Nonmusks arecalled MCa for macrocyclic analogs Aa for acyclic analogsand Na for nitro analogs As no vibrational mode hasoccurred at 2200 plusmn 200 cmminus1 there is no such column

8 Advances in Chemistry

Table3Mostimpo

rtantw

avenum

bersforc

ompo

unds

1ndash5810and

12according

toDFT

B3LYP

and

experim

entald

ata

Highest

]Cndash

0DIFF

]C=

0DIFF

]Cndash

HDIFF

120575Cndash

HDIFF

]C=

CDIFF

]119904N=O

DIFF

]asN=O

DIFF

1GGAPW91

1207

1215

2833

1748

minus9

3017

3034minus160minus108

1479

minus18

B3LY

P118

11210

5438

1786minus47

3033

3069minus176minus143

1517minus56

Exp

1235

1248

1739

2857

2926

1461

2GGAPW91

1099

1231

107

1739

minus7

2999

3027minus153minus94

1474

minus14

B3LY

P1124

1240minus15minus2

1778minus46

3012

3058minus166minus125

1512minus52

Experim

entald

ata

1109

1238

1732

2846

2933

1460

3GGAPW91

1121

1220minus12

181738

minus6

2991

3037minus145minus104

1481minus21

B3LY

P119

41254minus85minus16

1774minus42

3029

3063minus183minus130

1510minus50

Exp

1109

1238

1732

2846

2933

1460

4GGAPW91

1726

minus11

2990

3051minus124minus123

1475

minus15

1687

B3LY

P1774minus59

3010

3051minus144minus123

1513minus53

1707

Exp

1715

2866

2928

1460

5GGAPW91

1733minus18

2994

3039minus128minus111

1473

minus13

1706

B3LY

P1773minus58

3031

3057minus165minus129

1511minus51

1718

Exp

1715

2866

2928

1460

8GGAPW91

1685

53005

3083minus115minus122

1483

minus13

1594

11B3

LYP

1738minus48

3033

3089minus143minus128

1518minus48

1639

minus34

Exp

1690

2890

2961

1470

1605

10GGAPW91

1759minus19

B3LY

P1807minus67

Exp

1740

12GGAPW91

3019

3086minus139minus105

1487

minus7

1598

71356

41547

3B3

LYP

3041

3090minus161minus109

1512minus32

1610

minus5

1373

minus13

1599

minus49

Exp

2880

2981

1480

1605

1360

1550

Advances in Chemistry 9

Table 4 Deviations estimated over differences between experimen-tal and theoretical wavenumbers forGGAPW91 andB3LYP IRdata

Method Deviation 1 (cmminus1) Deviation 2 (cmminus1)GGAPW91 13 124B3LYP 43 145

Experimentaldata

GGAPW91

B3LYP

3500 3000 2500 2000 1500 1000 500 0

Figure 4 Ranges for important vibrational modes collected forcompounds 1ndash23 through experimental data versus GGAPW91results versus B3LYP results Vibrational modes come in accordanceto bonding atoms and bond order in green CndashH modes in darkgreen C=C modes in light pink CndashO in burgundy C=O and inblue N=O modes

For each musk group the central frequencies averages(ave (5)) and their standard deviations (std (6)) wereestimated these values are plotted at the right side of thecentral frequency listThe next column on the right shows thedifferences between each central frequencies and the averageof central frequencies (diff (7)) Consider

avegroup =1

119899

119891

sum

119899=1

cf119899

(5)

where cf119899

represents the central frequencies found for eachgroup (MCM PCM etc) having herein been defined lowerand upper limits for 119899 so that 119899 = 1 5 for MCM 119899 = 6 10for PCM 119899 = 11 13 for NM and 119899 = 14 16 for ACMConsider

stdgroup = radic119891

sum

119899=1

[(cf119899

minus avegroup)2

] (6)

diff119899

= cf119899

minus avegroup (7)

The values found for the avegroup and stdgroup of theMCMgroup were the same as those found for theMCa group thosebelonging to NM were repeated for Na and data calculatedfor ACM were taken as parameters for Aa

Finally each diff119899

value was allowed to be lower or twotimes its stdgroup value as stated in

diff119899

le 2 times stdgroup (8)

If this happens it is possible to say that theoretical datafit vibrational theoryrsquos demands over study band if not theydo not agree When repeating this process for all three bandsunder the spectra values for the Total Deviations (TD) arecollected The zero input (0) means that all three bandsobeyed (8) Logically TD inputs between 1 and 3 indicate howmany of the bands presented a diff

119899

value that was higher thanthe stdgroup doubled value

34 Absence of the 2000ndash2400 cmminus1 Band None of the pre-vious tables bring a mode among the 2000ndash2400 cmminus1 rangeThe 2200 cmminus1 band was described by Turin as the carbonylstretching mode which only occurred at this range whenworking with NDDOAM1 Hamiltonian Through ab initiocalculation the mentioned mode was observed at the rangeof 1680ndash1810 cmminus1 and it was only taken into account forcfs estimates when dealing with the 1550ndash1950 cmminus1 band fornitro compounds Regarding structural features compounds6 7 12 and 13 do not possess the carbonyl group and arereal musks while compounds 17 18 19 20 and 23 containthe carbonyl group and are odorless Therefore carbonylstretches cannot be taken as criteria for IR data-muskybehavior profile

35 GGAPW91 cf rsquos Plots and Musk Activity Table 5 (withGGAPW91 results) presents only two molecules nonmusks20 and 23 which failed to express a complete match betweentheoretical data and the signed bands of the vibrational the-ory For nonmusk 20 the cf value estimated near 1000 cmminus1was higher than its avegroup value this compound had bothOndashCsp2 stretching modes occurring at high intensities andfrequencies below 1200 cmminus1 (which are precisely the 1090and 1144 cmminus1 wavenumbers) On the other hand musks 14ndash16 and nonmusk 19 have presented a stretch mode (or at leastone of them) outside the 1000 plusmn 200 cmminus1 range Concerningnonmusk 23 it can be said that it showed a lower cf valuewhich remained around the 700 cmminus1 band and a higher cfvalue near the 1000 cmminus1 band This can be explained by thefact that (i) referring to the 700 cmminus1 band 23 had an averagefor intensity modes that was lower than the average valuesfor the other Na and NM compounds and therefore lowerweight values (see (4)) and lower cf and (ii) referring to the1000 cmminus1 band the OndashCsp3 stretch mode at 1073 cmminus1 hadan intensity value that was 87 times higher than the secondmost intensemode generating the observed overestimated cfvalue

That being said and according to mathematical approachadopted in this paper no relationship was found betweenIR properties and the presence of musky odor throughGGAPW91 It does not mean that GGAPW91 calculationleads to affirm that musks and nonmusks have indistinguish-able spectra Itmeans that considering theweighted-averagesvalues resource in order to simplify the adoption of alltheoretical peaks under analysis resulting central frequenciesare similar among musks and nonmusks Such observationmay be due the fact that GGAPW91 spectra had narrowerbands for each vibrational mode rather than B3LYP spectraAs GGAPW91 proved to be a more accurate method itrequires a more accurate statistical tools so to properly dealwith all theoretical modes as to affirm (or deny) a possibledifference on musks and nonmusks IR spectra

36 B3LYP cf rsquos Plots and Musk Activity On the other handTable 6 (with B3LYP data) shows that all musks from 1 to16 have had theoretical central frequencies that fitted thefrequencies demanded at 700 1000 and 1500 (or 1750) cmminus1

10 Advances in Chemistry

Table 5 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for GGAPW91 collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd

Diff Around 1000 Avestd

Diff Around 1500 Avestd

Diff

MCM

1 742 743 minus1 1030 1049 minus19 1429 1411 18 02 761 12 18 1096 31 47 1404 11 minus7 03 748 5 1047 minus2 1417 6 04 734 minus9 1016 minus33 1405 minus6 05 730 minus13 1057 8 1402 minus9 0

PCM

6 751 733 18 1046 1020 26 1423 1480 minus57 07 769 34 36 1051 48 31 1424 54 minus56 08 678 minus55 977 minus43 1527 47 09 731 minus2 1066 46 1532 52 010 736 3 959 minus61 1495 15 0

NM11 735 755 minus20 1033 1019 14 1634 1589 45 012 763 17 8 1002 16 minus17 1567 39 minus22 013 766 11 1023 4 1567 minus22 0

ACM14 784 784 0 1084 1086 minus2 1402 1411 minus9 015 762 23 minus22 1079 9 minus7 1401 16 minus10 016 807 23 1096 10 1429 18 0

MCa 17 751 743 8 1067 1049 17 1405 1411 minus7 018 726 12 minus17 1049 31 0 1417 11 6 0

Aa 19 779 784 minus6 1073 1086 minus13 1411 1411 0 020 757 23 minus28 1105 9 19 1403 16 minus8 1

Na21 733 755 minus21 1033 1019 13 1557 1589 minus32 022 757 17 2 1006 16 minus13 1549 39 minus40 023 717 minus38 1060 41 1655 66 2

lowastTD total deviations

in the vibrational theory Simultaneously Aa and Na showedthat at least one of their cfs was too shifted from theiraverages Molecule 23 for instance is the only nonmusk pos-sessing an aldehyde functional group and its C=O stretchingmode is found at the 1550ndash1950 cmminus1 range under studyNevertheless nitromusk 11 also holds an aldehyde functionalgroup and though its cf at 1750 cmminus1 is indeed higher than theother cfs for the NM it is still 70 cmminus1 lower than 23rsquos cf Stillconcerning the analysis of Table 6 we can say that the acyclicanalogs 19 and 20 have had their central frequencies shiftedto lower values at the 1500 cmminus1 diagnostic band the onlyone in which there was no agreement between theoreticalresults and expectations deriving from the vibrational theoryAt the 1500 plusmn 200 cmminus1 range hydrocarbon scissoring modesand alkenearomatic C=C stretching modes are found and19 and 20 lack the gem-methyl at the cyclohexane that areobserved in 14 and 15 moreover although in 16 this gem-methyl is also absent it possesses two alkene groups forwhich its stretching modes are also found at this rangeFinally macrocyclic analogs showed the same spectra dataas macrocyclic musks as compounds 18 and 19 differ fromMCM in that they lack two methylene groups it is possibleto suggest that such loss leads the moleculersquos CndashH vibrational

mode sum to be too low to be detected by its OR as suggestedelsewhere [23] Besides both 18 and 19 present awoody smellby being smaller they may be able to bind to a variety ofdifferent ORs which do not reassemble the behavior of themusk detected by possibly only one OR or just a few more[48]

4 Conclusions

This paper worked on developing a method which couldstate the following (i) whether musky molecules had theirIR theoretical spectra fitted into the four bands assigned byvibrational theory in 2002 Turinrsquos paper and (ii) whethernonmuskymolecules did not have their IR theoretical spectrafitted into same criteria It was first concluded that only threebands were useful for discriminating musk from nonmuskodorants The fourth IR band refers to a carbonyl stretchingmode and data here presented showed that this mode cannotbe taken as criteria when building a muskiness profile

Present work was carried out with two different func-tionals applying DFT calculation level and both were ableto accurately predict IR spectra A mathematical strategyhas been adopted in order to summarize IR theoretical

Advances in Chemistry 11

Table 6 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for B3LYP collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd Diff Around 1000 Ave

std Diff Around 1500 Avestd Diff

MCM

1 754 748 6 1142 1093 48 1407 1423 minus16 02 768 16 20 1066 39 minus27 1428 10 5 03 749 1 1116 23 1421 minus2 04 744 minus3 1099 5 1430 6 05 723 minus25 1044 minus49 1429 6 0

PCM

6 749 722 28 1068 1019 49 1450 1476 minus26 07 752 51 31 1052 62 33 1450 32 minus27 08 692 minus30 971 minus48 1461 minus15 09 646 minus75 1069 50 1499 23 010 768 47 936 minus83 1520 44 0

NM11 754 766 minus12 952 977 minus26 1602 1597 5 012 771 10 5 993 22 16 1595 5 minus2 013 772 7 987 9 1593 minus3 0

ACM14 722 732 minus10 1101 1127 minus26 1424 1435 minus12 015 771 35 39 1130 24 3 1431 14 minus4 016 703 minus29 1149 22 1451 15 0

MCa 17 750 748 2 1067 1093 minus26 1418 1423 minus5 018 726 16 minus22 1072 39 minus21 1432 10 9 0

Aa 19 784 732 52 1097 1127 minus30 1357 1435 minus78 120 763 35 31 1087 24 minus40 1410 14 minus26 1

Na21 742 766 minus24 1015 977 38 1601 1597 4 122 767 10 1 1150 22 173 1600 5 3 123 702 minus64 1068 91 1675 78 3

lowastTD total deviations

data and properly compare musk to nonmusk moleculesUsing this approach GGAPW91 computed spectra showedno discriminating patterns between musks and nonmusksB3LYP data showed theoretical frequencies and the threediagnostic bands to bematching while nitro andmacrocyclicnonmusks failed in at least one of such comparisons

It was therefore possible to conclude that no specificmodealone is responsible for the discrimination of themusky odorInstead when a great amount of frequencies expressing weakor medium intensities were found along the 700ndash1700 cmminus1range musk odor occurs At this range observedmodes wereCH2

wag and scissor bending modes C=C stretches andsymmetric nitro stretching modes

This trial scanning over IR vibrational modes and theirrelation to musk odor perception brings new informationaltowards the understanding and application of vibrationaltheoryrsquos ideas and opens the possibility to a more extensivestudy in which a broader number of molecules may bemodeled so as to come to a quantitative proposal for amusky-like novel odorant regarding their IR vibrational modes

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The authors thank Professor Ines Sabioni Resck (fromInstituto de Quımica Brasılia Brazil) for initial ideas andreliance

References

[1] M Eh ldquoNew alicyclic musks the fourth generation of muskodorantsrdquoChemistryamp Biodiversity vol 1 no 12 pp 1975ndash19842004

[2] P Saiyasombati andG BKasting ldquoTwo-stage kinetic analysis offragrance evaporation and absorption from skinrdquo InternationalJournal of Cosmetic Science vol 25 no 5 pp 235ndash243 2003

[3] G B Kasting and P Saiyasombati ldquoA physico-chemical prop-erties based model for estimating evaporation and absorptionrates of perfumes from skinrdquo International Journal of CosmeticScience vol 23 no 1 pp 49ndash58 2001

[4] M Shirasu K Yoshikawa Y Takai et al ldquoOlfactory receptor andneural pathway responsible for highly selective sensing of muskodorsrdquo Neuron vol 81 no 1 pp 165ndash178 2014

[5] J Reisert and H Zhao ldquoResponse kinetics of olfactory receptorneurons and the implications in olfactory codingrdquo Journal ofGeneral Physiology vol 138 no 3 pp 303ndash310 2011

12 Advances in Chemistry

[6] J-P Rospars Y Gu A Gremiaux and P Lucas ldquoOdourtransduction in olfactory receptor neuronsrdquo Chinese Journal ofPhysiology vol 53 no 6 pp 364ndash372 2010

[7] B Malnic and A F Mercadante ldquoThe odorant signaling path-wayrdquo Annual Review of Biomedical Sciences vol 11 pp T86ndashT94 2009

[8] K Snitz A Yablonka T Weiss I Frumin R M Khan andN Sobel ldquoPredicting odor perceptual similarity from odorstructurerdquo PLoS Computational Biology vol 9 no 9 Article IDe1003184 2013

[9] B K Lavine CWhite NMirjankar CM Sundling and CMBreneman ldquoOdor-structure relationship studies of tetralin andindan musksrdquo Chemical Senses vol 37 no 8 pp 723ndash736 2012

[10] Y Zou H Mouhib W Stahl A Goeke Q Wang and PKraft ldquoEfficient macrocyclization by a novel oxy-oxonia-copereaction synthesis and olfactory properties of new macrocyclicmusksrdquo Chemistry vol 18 no 23 pp 7010ndash7015 2012

[11] S Liu ldquoStudy on the relationship between molecular odour ofpolycyclic musksrdquo Xiangliao Xiangjing Huazhuangpin vol 6pp 24ndash29 2004

[12] S-Y Takane and J B O Mitchell ldquoA structure-odor relation-ship study using EVA descriptors and hierarchical clusteringrdquoOrganicampBiomolecular Chemistry vol 2 no 22 pp 3250ndash32552004

[13] K J Rossiter ldquoStructure-odour relationshipsrdquo ChemicalReviews vol 96 no 8 pp 3201ndash3240 1996

[14] M Zarzo ldquoThe sense of smell molecular basis of odorantrecognitionrdquoBiological Reviews vol 82 no 3 pp 455ndash479 2007

[15] A Kato and K Touhara ldquoMammalian olfactory receptorspharmacologyGprotein coupling anddesensitizationrdquoCellularandMolecular Life Sciences vol 66 no 23 pp 3743ndash3753 2009

[16] L Turin and F Yoshii ldquoStructure-odor relations a modernperspectiverdquo in Handbook of Olfaction and Gustation R LDoty Ed pp 275ndash294 Marcel Dekker New York NY USA2003

[17] L Turin ldquoA spectroscopic mechanism for primary olfactoryreceptionrdquo Chemical Senses vol 21 no 6 pp 773ndash791 1996

[18] M A Reed ldquoInelastic electron tunneling spectroscopyrdquo Mate-rials Today vol 11 no 11 pp 46ndash50 2008

[19] L Turin ldquoA method for the calculation of odor character frommolecular structurerdquo Journal ofTheoretical Biology vol 216 no3 pp 367ndash385 2002

[20] L J W Haffenden V A Yaylayan and J Fortin ldquoInvestigationof vibrational theory of olfaction with variously labelled ben-zaldehydesrdquo Food Chemistry vol 73 no 1 pp 67ndash72 2001

[21] J C Brookes F Hartoutsiou A P Horsfield and A MStoneham ldquoCould humans recognize odor by phonon assistedtunnelingrdquo Physical Review Letters vol 98 no 3 Article ID038101 2007

[22] M I Franco L Turin A Mershin and E M C SkoulakisldquoMolecular vibration-sensing component in Drosophila mela-nogaster olfactionrdquo Proceedings of the National Academy ofSciences vol 108 no 9 pp 3797ndash3802 2011

[23] I A Solovrsquoyov P-Y Chang and K Schulten ldquoVibrationallyassisted electron transfer mechanism of olfaction myth orrealityrdquo Physical Chemistry Chemical Physics vol 14 no 40 pp13861ndash13871 2012

[24] S GaneDGeorganakis KManiati et al ldquoMolecular vibration-sensing component in human olfactionrdquo PLoS ONE vol 8 no1 Article ID e55780 2013

[25] D L Pavia G M Lampman G S Kriz and J R VyvyanIntroduction to Spectroscopy Cengage Learning Sao PauloBrazil 2010

[26] D A Lerner D Berthomieu and E R Maia ldquoModeling of theconformational flexibility and EZ isomerism of thiazoximicacid and cefotaximerdquo International Journal of Quantum Chem-istry vol 111 no 6 pp 1222ndash1238 2011

[27] A P Scott andL Radom ldquoHarmonic vibrational frequencies anevaluation of Hartree-Fock Moslashller-Plesset quadratic configu-ration interaction density functional theory and semiempiricalscale factorsrdquoThe Journal of Physical Chemistry vol 100 no 41pp 16502ndash16513 1996

[28] S Gabler J Soelter T Hussain S Sachse and M SchmukerldquoPhysicochemical vs vibrational descriptors for prediction ofodor receptor responsesrdquo Molecular Informatics vol 32 no 9-10 pp 855ndash865 2013

[29] Materials Studio SW and Insight II SW Acelrys San DiegoCalif USA

[30] M J Frisch G W Trucks H B Schlegel et al ldquoGaussian 09Revision A02rdquo Gaussian Inc Wallingford Conn USA 2009

[31] H Sun ldquoCompass an ab initio force-field optimized forcondensed-phase applicationsmdashoverview with details onalkane and benzene compoundsrdquo Journal of Physical ChemistryB vol 102 no 38 pp 7338ndash7364 1998

[32] P Dauber-Osguthorpe V A Roberts D J Osguthorpe J WolfM Genest and A T Hagler ldquoStructure and energetics of ligandbinding to proteins Escherichia coli dihydrofolate reductase-trimethoprim a drug-receptor systemrdquo Proteins StructureFunction and Genetics vol 4 no 1 pp 31ndash47 1988

[33] DH JMackay A J Cross andA THagler ldquoThe role of energyminimization in simulation strategies of biomolecular systemsrdquoin Prediction of Protein Structure and the Principles of ProteinConformation D G Fasman Ed pp 317ndash358 Plenum PressNew York NY USA 1990

[34] R Fletcher and C M Reeves ldquoFunction minimization byconjugate gradientsrdquo The Computer Journal vol 7 no 2 pp149ndash154 1964

[35] WH Press B P Flannery S A Teukolsky andW T VetterlingNumerical Recipes in C the Art of Scientific Computing Cam-bridge University Press London UK 1988

[36] J J P Stewart ldquoMopac a semiempirical molecular orbitalprogramrdquo Journal of Computer-Aided Molecular Design vol 4no 1 pp 101ndash105 1990

[37] J A Pople D P Santry and G A Segal ldquoApproximate self-consistent molecular orbital theory I Invariant proceduresrdquoThe Journal of Chemical Physics vol 43 no 10 pp S129ndashS1351965

[38] J A Pople and G A Segal ldquoApproximate self-consistentmolecular orbital theory III CNDO results for AB

2

and AB3

systemsrdquo The Journal of Chemical Physics vol 44 no 9 pp3289ndash3296 1966

[39] M J S Dewar E G Zoebisch E F Healy and J J P StewartldquoAM1 a new general purpose quantum mechanical molecularmodelrdquo Journal of the American Chemical Society vol 107 no13 pp 3902ndash3909 1985

[40] B Delley ldquoAn all-electron numerical method for solving thelocal density functional for polyatomic moleculesrdquoThe Journalof Chemical Physics vol 92 no 1 pp 508ndash517 1990

[41] B Delley ldquoFast calculation of electrostatics in crystals and largemoleculesrdquo Journal of Physical Chemistry vol 100 no 15 pp6107ndash6110 1996

Advances in Chemistry 13

[42] B Delley ldquoDMol methodology and applicationsrdquo in DensityFunctional Methods in Chemistry J W Andzelm and J KLabanowski Eds pp 101ndash108 Springer New York NY USA1991

[43] B Delley ldquoCalculated electron distribution for Tetrafluoroter-phthalonitrile (TFT)rdquo Chemical Physics vol 110 no 2-3 pp329ndash338 1986

[44] YWang and J P Perdew ldquoCorrelation hole of the spin-polarizedelectron gas with exact small-wave-vector and high-densityscalingrdquo Physical Review B vol 44 no 24 pp 13298ndash13307 1991

[45] P J Stephens F J Devlin C F Chabalowski and M J FrischldquoAb Initio calculation of vibrational absorption and circulardichroism spectra using density functional force fieldsrdquo Journalof Physical Chemistry vol 98 no 45 pp 11623ndash11627 1994

[46] G Schaftenaar and J H Noordik ldquoMolden a pre- and post-processing program for molecular and electronic structuresrdquoJournal of Computer-Aided Molecular Design vol 14 no 2 pp123ndash134 2000

[47] Xming ldquoXming X server for Windowsrdquo 2012 httpwwwstraightrunningcomXmingNotes

[48] K Nara L R Saraiva X Ye and L B Buck ldquoA large-scaleanalysis of odor coding in the olfactory epitheliumrdquo Journal ofNeuroscience vol 31 no 25 pp 9179ndash9191 2011

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

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Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

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Journal of

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Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

2 Advances in Chemistry

spectroscopy (IETS) an inelastic nonoptical vibrational spec-troscopy [18] After building a specific algorithm to mimicvibrational modes at protein level the author could state thatmusksmdashfor instancemdashwill present four bands near 700 10001500 (or 1750 cmminus1 for nitromusks) and 2200 cmminus1 and thateach band will have 400 cmminus1 width [19] There is much tobe understood concerning odor recognition supported onvibrational theoryrsquos ideas as indicated by the variety of papersdealing with the subject [20ndash24]

12 Paperrsquos Aims In order to explore vibrational theorymusks and non-musks (see Figure 1) have been equallymodeled so to come to their theoretical IR spectra Firstlymolecules have been computationally analyzed by molecularmechanics and molecular dynamics (MMMD) in order toascertain the conformational space available to them Aftersemiempirical calculations employing Neglect of DiatomicDifferential Overlap Austin Model 1 (NDDO AM1) Hamil-tonian took place for geometry corrections Then final cal-culations for energy optimization and IR spectra collectionwere set with density functional theory (DFT) using bothGradient Corrected Functional Perdew-Wang generalized-gradient approximation (GGAPW91) and hybrid Beckethree-parameter Lee-Yang-Parr (B3LYP) functionals withthe double numerical basis set with polarization (DNP)for GGAPW91 and 6-311+G(dp) for B3LYP Methodologyadopted is up-to-date with the literature and was mainlybased on Lerner and coworkers paper [26] For a completediscussion on computed harmonic vibrational frequenciesand their scaling factors and accuracy see data obtained byScott and Radom [27]

GGAPW91 and B3LYP theoretical spectra were com-pared to the experimental data (when available in freedata banks as NIST and SDBS) and then were evaluatedconcerning the expression of the four characteristic muskbands (centered at 700 1000 1500 or 1750 and 2200 cmminus1)Now these four bands were properly indicated using aspecific algorithm built to reproduce IETS at biological levelhowever the vibrational modes primarily responsible forsuch bands were not nominated To clarify this questiona comparison was carried between IR theoretical data andIET data published previously since both spectra show thesame vibrational modes at the same frequencies and itis much simpler to estimate theoretical IR spectra Asidefrom the equivalence on estimating vibrational modes thereare no other comparisons that could fit in once modeintensities are differently calculated in one technique andanother generating bands that can be either more prominentor even absent when comparing spectra Besides using IRspectra to predict odor or olfactory receptor affinity hasfailed repeatedly [28] Finally vibrational modes responsiblefor ldquomusk bandsrdquo in the spectra are not to be taken assolely responsible for musk odor It is well known thatthere are several molecular descriptors involved at majorbiological phenomena such as carrying the odorant from theenvironment to anOR and docking odorant-OR and they areequally relevant when considering the vibrationally assistedodor recognition mechanism

The sixteen musks 1ndash16 are already in use in perfumesso to have their activity is certified The seven molecules 17ndash23 are structurally similar to the previous molecules but donot possess any musky odor besides nonmusks 17 and 18are woody Absence of odor is not to be taken as a differentodor character but (i) as a moleculersquos inability to bind itsOR due to particularities of its structure or (ii) as the lackof specific vibrational modes in their minimum quantityprecluding proper energy decrease on electron scattering andits subsequent tunneling [13 14 16] So regarding adoptedcriteria relying on the choice of such molecules it addressesthe main hypothesis here being tested only musk odorantsare supposed to express vibrational modes under mentionedranges and no other molecule is supposed to present thesame vibrational pattern All compounds have their IUPACname andChemical Abstracts Service (CAS) registry numberlisted in Table 1

2 Methods and Methodology

21 Computational Methods Calculation programs usedwere those available in the Materials Studio Package Pro-gram [29] and Gaussian 09 [30] for B3LYP calculationsMolecules had their conformational space studied undervac-uum environment through MMDM calculations using theCFF99COMPASS [31] force field implemented in the Dis-cover Simulation program [32 33] Main parameters chosenfor MM routine were Conjugate Gradient method [34] withthe Polak-Ribiere algorithm [35] running until it achievedconvergence at 10 times 10minus4 kcalsdotmolminus1 sdot gtminus1 MD trajectorieswere carried out at 650K during 10 ns with a time step of10 fs (therefore collecting 1000 frames) in the canonicalensemble After previous scanning in which temperature andtrajectory time were changed parameters chosen showed tobe effective on expressing molecules flexibility allowing thecollection of a representative subset of initial conformations

Selected conformers fromMMDM procedure were thenminimizedwith Vamp program [36] usingNDDOAM1 [37ndash39] as a previous optimization step towards DFT calculationSpin multiplicity was automatically determined and a con-vergence of 01 kcalsdotmolminus1 sdotgtminus1 for the heat of formation valuewas set Self-consistent field (SCF) cycles had a convergencetolerance of 50 times 10minus7 eVsdotatomminus1

Final geometries were minimized using the DMol3 pro-gram [40ndash42] forDFT calculations Basis set chosenwasDNP[43] with GGAPW91 [44] as exchange functional Totalenergy convergence of 10 times 10minus5Ha was required with a37 A global cutoff Final cutoff of the SCF cycles was 50 times10minus7 eVsdotatomminus1 and the orbital cutoff quality was kept equalto 01 eVsdotatomminus1 The same starting structure used in GGAPW91 calculation was employed for hybrid functional B3LYP[45] calculation with 6-311+G(dp) basis set now usingGaussian 09 Moldenrsquos processing program [46] was appliedalong with Xming emulator [47] to achieve IR continuumspectra

22 Development of a Frequency-Weighted Average and OtherUseful Tools A mathematical formula had to be developed

Advances in Chemistry 3

1 2 3 45

6 7 8 910

11 12 13

14 15 16

1718

19 20

21 22 23

O

OO

OO

O O O

O

OO

O

O

OO O

O

OO

O

OO

O

O O O

O

OH

SR

O

O

O

RR

R R

OO

O

OO

S

O

S

S

O

O

SS

S

OO

O O

S

R

N+

Ominus

+NminusO

N+

Ominus

+NminusO

N+

N+

Ominus

Ominus

N+

N+

O

O

O

O

O

O

OOO

minus

Ominus

minusO minusOOminus

N++N +N

O

O

Figure 1 Odorants under study macrocyclic musks (MCM) pentadecanolide (1) (R)-exaltolide (2) (S)-exaltolide (3) cis-globanone (4)and trans-globanone (5) polycyclic musks (PCM) (4S7S)-galaxolide (6) (4S7R)-galaxolide (7) indane (8) tetralin (9) and tonkene (10)nitromusks (NM) musk ketone (11) musk moskene (12) and musk ambrette (13) acyclic musks (ACM) romandolide (14) helvetolide (15)and cyclomusk (16) nonmusks macrocyclic analogs (MCa) (17) and (18) acyclic analogs (Aa) (19) and (20) and nitro analogs (Na) (21)(22) and (23)

4 Advances in Chemistry

Table 1 Molecules studied

Number IUPAC name CAS number1 Oxacyclohexadecan-2-one 106-02-52 16(R)-Methyl-oxacyclohexadecan-2-one 69297-56-93 16(S)-Methyl-oxacyclohexadecan-2-one 129214-00-24 (5Z)-Cyclohexadec-5-en-1-one 37609-25-95 (5E)-Cyclohexadec-5-en-1-one6 (4S7S)-Cyclopenta[g]-2-benzopyran 134678-hexahydro-466788-hexamethyl 172339-62-77 (4S7R)-Cyclopenta[g]-2-benzopyran 134678-hexahydro-466788-hexamethyl 252332-95-98 1-(23-Dihydro-11233-pentamethyl-1119867-inden-5-yl)-ethanone 4755-83-39 1-[(6119878)-5678-Tetrahydro-355688-hexamethyl-2-naphthalenyl]-ethanone 85549-79-710 2H-[1]-Benzothieno[32-b]pyran-2-one 5732-22-911 4-(11-Dimethylethyl)-26-dimethyl-35-dinitro-benzaldehyde 99758-50-612 4-(11-Dimethylethyl)-26-dimethyl-35-dinitro-benzaldehyde 116-66-513 none14 2-(1-Oxopropoxy)- 1-(33-dimethylcyclohexyl)ethyl ester 236391-76-715 1-Propanol 2-[1-(33-dimethylcyclohexyl)ethoxy]-2-methyl- 1-propanoate 141773-73-116 1-Cyclopentene-1-propanol 1205731205732-trimethyl-5-(1-methylethenyl)- 1-propanoate 84012-64-617 Oxacyclotetradecane-210-dione 38223-27-718 Cyclotetradecanone 3603-99-419 2-(1-Oxopropoxy)- 1-cyclohexyl-1-methylethyl ester 610770-00-820 none21 2-Methoxy-1-methyl-4-(2-methyl-2-propanyl)-35-dinitrobenzene 99758-79-922 2-Methoxy-4-methyl-1-(2-methylpropyl)-35-dinitro-benzene 99758-78-823 24-Bis(11-dimethylethyl)-5-methoxy-3-nitro-benzaldehyde 107342-73-4

in this paper in order to consider each and every modebelonging to the same 400 cm-1 range as well as theirintensities Therefore the use of weighted averages overtheoretical data was chosen its numerical result was calledcentral frequency (cf) With this central frequency it becamepossible to consider all theoretical peaks occurring in thevicinity of the diagnostic frequencies instead of just affirmingthe existence of the expected band only by naming the mostintense theoretical peak Central frequencies were estimatedas follows

Central frequency =sum119899

119894=1

]119894

times int119894

sum119899

119894=1

int119894

(1)

This mathematical approach (which simply generates afrequency-weighted average) was applied to theoretical fre-quencies found at plusmn200 cmminus1 around 700 1000 and 1500 (or1750) cmminus1 and resulted in central frequencies for compounds1ndash23 which were computed in Table 4 (for GGAPW91 data)and in Table 5 (for B3LYP data) The mentioned range hasbeen chosen so as to enable each band to complete its400 cmminus1 width as established in the vibrational theory

3 Results and Discussion

Data will be presented and discussed in three successivesections In the first section the collection of theoretical IRspectra will be presented In the second section they willbe compared to experimental IR spectra to discuss theirprecision and accuracy The third section will deal with therationalization betweenmusk spectra andmusk odor activityIn order to establish such relation best theoretical IR spectrawill be chosen from this paperrsquos second section

31 Part 1 Computation of IR Spectra Concerning ab ini-tio methods convolved GGAPW91 spectra are shown inFigure 2 while B3LYP spectra are gathered in Figure 3 ForGGAPW91 spectra carbon-oxygen single bond stretchesoccur on frequencies between 1018 cmminus1 (for nitro ana-log 21) and 1220 cmminus1 (for (4S7R)-galaxolide 7) carbon-nitrogen single bond stretches occur under the frequency of1200 cmminus1 for nitro compounds carbon-sulfur single bondstretches are observed at 1054 cmminus1 for tonkene 10 Carbon-carbon double bonds stretches happened at 1687 cmminus1 forcis-globanone 4 and at 1706 cmminus1 for trans-globanone 5while all other compounds expressing aromatic C=C bondshad their stretching modes between 1543 cmminus1 (as in musk

Advances in Chemistry 5

Frequency (cmminus1)

0100020003000

Rela

tive i

nten

sity

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

12345

678910

111213

141516

17181920

212223

Figure 2 Spectra obtained with GGAPW91 for MCM 1ndash5 PCM 6ndash10 NM 11ndash13 ACM 14ndash16 and nonmusks 17ndash23

ketone 11) and 1618 cmminus1 (for (4S7R)-galaxolide 7) Nitrogroups have presented their symmetric stretchingmodes near1310ndash1340 cmminus1 and their nonsymmetric stretching modes at1520ndash1560 cmminus1 For aldehydes ketones ethers and estersthe carbon-oxygen double bond stretching represents animportantmark for confirming spectra here the lowest valuefor such mode is found for tetralin 9 at 1680 cmminus1 whilethe highest value of 1777 cmminus1 belongs to acyclic analog 20Carbon-hydrogen bending modes start at very low frequen-cies and end at 1493 cmminus1 (for helvetolide 14) simultaneouslythe band of carbon-hydrogen stretching modes starts at2898 cmminus1 (for (4S7R)-galaxolide7) andfinishes at 3198 cmminus1(for nitro analog 22)

For B3LYP spectra the lowest frequency found for thecarbon-oxygen single bond stretching was 1006 cmminus1 (forromandolide 15) while its highest frequency was 1403 cmminus1(for tonkene 10) the frequency of the carbon-oxygen doublebond stretching was found between 1738 cmminus1 (for musk 8)and 1810 cmminus1 (formusk 14)The carbon-carbon double bondstretching occurred on the frequency of 1707 and 1718 cmminus1for compounds 4 and 5 and between 1699 and 1712 cmminus1for compound 16 finally the carbon-carbon double bondstretching for aromatic compounds occurred between 1531(for non-musk 21) and 1650 cmminus1 (for musk 7) The stretch-ing for nitrogen-oxygen in nitro groups was found at1250ndash1417 cmminus1 for symmetric modes and at 1531ndash1618 cmminus1

6 Advances in Chemistry

12345

678910

111213

141516

17181920

212223

Frequency (cmminus1)

01000200030004000

Rela

tive i

nten

sity

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Figure 3 Spectra obtained at B3LYP level for MCM 1ndash5 PCM 6ndash10 NM 11ndash13 ACM 14ndash16 and nonmusks 17ndash23

for asymmetric modes Finally carbon-hydrogen bendingmodes began at very low frequencies and went up to1540 cmminus1 at most (for musk 13) while carbon-hydrogenstretching occurred between 2953 cmminus1 (for compound 6)and 3229 cmminus1 (for nitromusk 13)

32 Part 2 Comparing GGAPW91 and B3LYP Spectrato Experimental Data For an overview over GGAPW91B3LYP and experimental [47] IR data Figure 4 and Table 2were built inwhich vibrationalmodes for themost importantfunctional groups are organized in accordance with theoreti-cal method adopted Each band expresses the range in whichlabeled vibrational mode occurs considering the maximumand theminimum found for all compoundsThus it becomespossible to state that B3LYP and GGAPW91 results for CndashH stretching modes start at 90 and 140 cmminus1 respectivelyvalues that are higher than the ones provided by experimentaldata simultaneously the same band ends at +50 cmminus1 forGGAPW91 and at +90 cmminus1 for B3LYP in comparison to theexperimental data CndashH bending modes finish at +30 cmminus1for GGAPW91 and at +80 cmminus1 for B3LYP when compared

to experimental values Aromatic C=C stretches occurredin an expected range for GGAPW91 with a +20 cmminus1 shiftfor alkene compounds B3LYP showed a continuous bandfor alkene and aromatic C=C stretches which started at+60 cmminus1 and ended at +30 cmminus1 over experimental dataCndashO stretching modes are found within an expected rangefor both GGAPW91 and B3LYP methods for tonkene 10GGAPW91 predicted CndashO mode at 1381 cmminus1 while thesame mode is found at 1403 cmminus1 in B3LYP data For C=Ostretchingmodes GGAPW91 showed a +20 cmminus1 incrementover lower and higher values found for experimental dataand B3LYP shifted over experimental range in +60 cmminus1Finally nitro N=O stretching modes have had both sym-metric and asymmetric modes accurately and precisely esti-mated for GGAPW91 for B3LYP symmetric nitro stretchingshowed a broader band than that of GGAPW91 and ofexperimental data starting at a +30 cmminus1 shift and finishingat a minus10 cmminus1 shift while their asymmetric modes werecorrectly predicted

Therefore while GGAPW91 final results were all fittedinto experimental reports considering the allowed plusmn30 cmminus1

Advances in Chemistry 7

Table 2 Collection of observed versus calculated IR mode frequencies for compounds 1ndash23

Vibrational modea Observed wavenumber (cmminus1) [25] Calculated wavenumber (cmminus1)GGAPW91 B3LYP

] CbndashH 3150ndash2850 3198ndash2898 3229ndash2953] CndashH (aldehyde) 2900ndash2800 2954ndash2892 2988ndash2939120575 CndashH up to 1465 up to 1493 up to 1540] C=C (alkene) 1680ndash1600 1706ndash1687 1718ndash1707] C=C (aromatic) 1600ndash1475 1618ndash1543 1650ndash1531] C=O (aldehyde) 1740ndash1720 1715ndash1693 1772ndash1749] C=O (ketone) 1725ndash1705 1733ndash1680 1784ndash1738] C=O (ester) 1750ndash1730 1777ndash1742 1810ndash1768120575 CndashO (alcohol ether and ester) 1300ndash1000 1381 1200ndash1018 1403 1312ndash1006]as nitro (RndashNO2) 1660ndash1500 1560ndash1520 1618ndash1531]119904 nitro (RndashNO2) 1390ndash1260 1340ndash1310 1417ndash1250a] stretching ]as asymmetric stretching ]119904 symmetric stretching 120575 bendingb] C(sp2)ndashH C(sp3)ndashH and C(aromatic)ndashH

shifts B3LYP results overestimated CndashH stretching andbending modes alkene C=C stretching modes and aldehydeand ketone C=O stretching modes

To quantify collected results experimental IR spectrumgiven for each particular molecule was compared to its theo-retical spectra as shown in Table 3 In the literaturemdashpublicand personal IR databasemdashonly spectra for compounds 1ndash5 8 10 and 12 were found The vibrational modes chosenas internal patterns of comparison were as follows whenoccurring (i) the two most intense peaks regarding theCndashO stretching mode (ii) the most intense peak for theC=O stretching mode (iii) the most intense peaks for thesymmetric and asymmetric CndashH stretching modes (iv) thehighest wavenumber found for the CndashH bending modes (v)the highest intensity for the C=C stretching mode and (vi)the most intense peaks for the symmetric and asymmetricN=O stretching modes They are altogether able to expressthe accuracy relying on theoretical data once all functionalgroups have had their modes listed within chosen criteriaand the whole spectrum has been covered

Extra information comes on the so-called DIFF columnsin Table 3 Consider

DIFF119894

= ExpWavenumber119894

minusTheoWavenumber119894

(2)

where the difference established between experimental andtheoretical values was plotted (for both GGAPW91 andB3LYP results) as shown in (2) In such equation for acertain mode 119894 the difference (DIFF) is obtained through thesubtraction of its theoretical value (TheoWavenumber) fromits experimental value (ExpWavenumber) The average of thecollected differences on Table 3 was estimated as the values ofabsolute difference were divided by the number of occurringmodes disregarding all CndashH stretch modes as follows

Deviation 1 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(3)

This choice was made due to the fact that all CndashHstretches were overestimated in more than 100 cmminus1 for both

theoretical methods as discussed before This last modetherefore had its deviation separately estimated as follows

Deviation 2 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(4)

in which the absolute DIFF119894

is collected is summed for all CndashH stretching modes within the same theoretical method andis divided by the number of occurring modes

So finally GGAPW91 IR results are found to be moreaccurate than B3LYP results with calculated deviations thatare equal to 13 cmminus1 and 43 cmminus1 respectively Neverthelessthey correspond to a 325 (DFT) and a 1075 (B3LYP)shift over the 4000ndash0 cmminus1 that represents the spectrumwhich ensures that both methods are powerfully predictiveSimultaneously both methods display great shift over CndashHstretching modes corresponding to an increase of 124 cmminus1and 145 cmminus1 respectively Considering that one of thispaperrsquos aims is to compare theoretical IR data with postulatesof the vibrational theory on musky odor the last mentionedmodes are irrelevant as they are not supposed to be respon-sible for muskiness

33 Part 3 IR Spectra and Musk Activity Herein bothGGAPW91 and B3LYP data will be taken into account so asto compare theoretical results with the bands described in thevibrational theory (700 1000 1500 or 1750 and 2200 cmminus1)which would assign as supposed by the previous theory amusky odor to these molecules

In Tables 5 and 6 the information was gathered so as todispose musks 1 to 23 in lines and their central frequencies(at 700 1000 and 1500 or 1750 cmminus1) in columns Besidesthe compounds were gathered in groups in accordance withtheir structural similarity (see first column on the left) MCMfor macrocyclic musks PCM for polycyclic musks NM fornitromusks and ACM for acyclic musks Nonmusks arecalled MCa for macrocyclic analogs Aa for acyclic analogsand Na for nitro analogs As no vibrational mode hasoccurred at 2200 plusmn 200 cmminus1 there is no such column

8 Advances in Chemistry

Table3Mostimpo

rtantw

avenum

bersforc

ompo

unds

1ndash5810and

12according

toDFT

B3LYP

and

experim

entald

ata

Highest

]Cndash

0DIFF

]C=

0DIFF

]Cndash

HDIFF

120575Cndash

HDIFF

]C=

CDIFF

]119904N=O

DIFF

]asN=O

DIFF

1GGAPW91

1207

1215

2833

1748

minus9

3017

3034minus160minus108

1479

minus18

B3LY

P118

11210

5438

1786minus47

3033

3069minus176minus143

1517minus56

Exp

1235

1248

1739

2857

2926

1461

2GGAPW91

1099

1231

107

1739

minus7

2999

3027minus153minus94

1474

minus14

B3LY

P1124

1240minus15minus2

1778minus46

3012

3058minus166minus125

1512minus52

Experim

entald

ata

1109

1238

1732

2846

2933

1460

3GGAPW91

1121

1220minus12

181738

minus6

2991

3037minus145minus104

1481minus21

B3LY

P119

41254minus85minus16

1774minus42

3029

3063minus183minus130

1510minus50

Exp

1109

1238

1732

2846

2933

1460

4GGAPW91

1726

minus11

2990

3051minus124minus123

1475

minus15

1687

B3LY

P1774minus59

3010

3051minus144minus123

1513minus53

1707

Exp

1715

2866

2928

1460

5GGAPW91

1733minus18

2994

3039minus128minus111

1473

minus13

1706

B3LY

P1773minus58

3031

3057minus165minus129

1511minus51

1718

Exp

1715

2866

2928

1460

8GGAPW91

1685

53005

3083minus115minus122

1483

minus13

1594

11B3

LYP

1738minus48

3033

3089minus143minus128

1518minus48

1639

minus34

Exp

1690

2890

2961

1470

1605

10GGAPW91

1759minus19

B3LY

P1807minus67

Exp

1740

12GGAPW91

3019

3086minus139minus105

1487

minus7

1598

71356

41547

3B3

LYP

3041

3090minus161minus109

1512minus32

1610

minus5

1373

minus13

1599

minus49

Exp

2880

2981

1480

1605

1360

1550

Advances in Chemistry 9

Table 4 Deviations estimated over differences between experimen-tal and theoretical wavenumbers forGGAPW91 andB3LYP IRdata

Method Deviation 1 (cmminus1) Deviation 2 (cmminus1)GGAPW91 13 124B3LYP 43 145

Experimentaldata

GGAPW91

B3LYP

3500 3000 2500 2000 1500 1000 500 0

Figure 4 Ranges for important vibrational modes collected forcompounds 1ndash23 through experimental data versus GGAPW91results versus B3LYP results Vibrational modes come in accordanceto bonding atoms and bond order in green CndashH modes in darkgreen C=C modes in light pink CndashO in burgundy C=O and inblue N=O modes

For each musk group the central frequencies averages(ave (5)) and their standard deviations (std (6)) wereestimated these values are plotted at the right side of thecentral frequency listThe next column on the right shows thedifferences between each central frequencies and the averageof central frequencies (diff (7)) Consider

avegroup =1

119899

119891

sum

119899=1

cf119899

(5)

where cf119899

represents the central frequencies found for eachgroup (MCM PCM etc) having herein been defined lowerand upper limits for 119899 so that 119899 = 1 5 for MCM 119899 = 6 10for PCM 119899 = 11 13 for NM and 119899 = 14 16 for ACMConsider

stdgroup = radic119891

sum

119899=1

[(cf119899

minus avegroup)2

] (6)

diff119899

= cf119899

minus avegroup (7)

The values found for the avegroup and stdgroup of theMCMgroup were the same as those found for theMCa group thosebelonging to NM were repeated for Na and data calculatedfor ACM were taken as parameters for Aa

Finally each diff119899

value was allowed to be lower or twotimes its stdgroup value as stated in

diff119899

le 2 times stdgroup (8)

If this happens it is possible to say that theoretical datafit vibrational theoryrsquos demands over study band if not theydo not agree When repeating this process for all three bandsunder the spectra values for the Total Deviations (TD) arecollected The zero input (0) means that all three bandsobeyed (8) Logically TD inputs between 1 and 3 indicate howmany of the bands presented a diff

119899

value that was higher thanthe stdgroup doubled value

34 Absence of the 2000ndash2400 cmminus1 Band None of the pre-vious tables bring a mode among the 2000ndash2400 cmminus1 rangeThe 2200 cmminus1 band was described by Turin as the carbonylstretching mode which only occurred at this range whenworking with NDDOAM1 Hamiltonian Through ab initiocalculation the mentioned mode was observed at the rangeof 1680ndash1810 cmminus1 and it was only taken into account forcfs estimates when dealing with the 1550ndash1950 cmminus1 band fornitro compounds Regarding structural features compounds6 7 12 and 13 do not possess the carbonyl group and arereal musks while compounds 17 18 19 20 and 23 containthe carbonyl group and are odorless Therefore carbonylstretches cannot be taken as criteria for IR data-muskybehavior profile

35 GGAPW91 cf rsquos Plots and Musk Activity Table 5 (withGGAPW91 results) presents only two molecules nonmusks20 and 23 which failed to express a complete match betweentheoretical data and the signed bands of the vibrational the-ory For nonmusk 20 the cf value estimated near 1000 cmminus1was higher than its avegroup value this compound had bothOndashCsp2 stretching modes occurring at high intensities andfrequencies below 1200 cmminus1 (which are precisely the 1090and 1144 cmminus1 wavenumbers) On the other hand musks 14ndash16 and nonmusk 19 have presented a stretch mode (or at leastone of them) outside the 1000 plusmn 200 cmminus1 range Concerningnonmusk 23 it can be said that it showed a lower cf valuewhich remained around the 700 cmminus1 band and a higher cfvalue near the 1000 cmminus1 band This can be explained by thefact that (i) referring to the 700 cmminus1 band 23 had an averagefor intensity modes that was lower than the average valuesfor the other Na and NM compounds and therefore lowerweight values (see (4)) and lower cf and (ii) referring to the1000 cmminus1 band the OndashCsp3 stretch mode at 1073 cmminus1 hadan intensity value that was 87 times higher than the secondmost intensemode generating the observed overestimated cfvalue

That being said and according to mathematical approachadopted in this paper no relationship was found betweenIR properties and the presence of musky odor throughGGAPW91 It does not mean that GGAPW91 calculationleads to affirm that musks and nonmusks have indistinguish-able spectra Itmeans that considering theweighted-averagesvalues resource in order to simplify the adoption of alltheoretical peaks under analysis resulting central frequenciesare similar among musks and nonmusks Such observationmay be due the fact that GGAPW91 spectra had narrowerbands for each vibrational mode rather than B3LYP spectraAs GGAPW91 proved to be a more accurate method itrequires a more accurate statistical tools so to properly dealwith all theoretical modes as to affirm (or deny) a possibledifference on musks and nonmusks IR spectra

36 B3LYP cf rsquos Plots and Musk Activity On the other handTable 6 (with B3LYP data) shows that all musks from 1 to16 have had theoretical central frequencies that fitted thefrequencies demanded at 700 1000 and 1500 (or 1750) cmminus1

10 Advances in Chemistry

Table 5 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for GGAPW91 collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd

Diff Around 1000 Avestd

Diff Around 1500 Avestd

Diff

MCM

1 742 743 minus1 1030 1049 minus19 1429 1411 18 02 761 12 18 1096 31 47 1404 11 minus7 03 748 5 1047 minus2 1417 6 04 734 minus9 1016 minus33 1405 minus6 05 730 minus13 1057 8 1402 minus9 0

PCM

6 751 733 18 1046 1020 26 1423 1480 minus57 07 769 34 36 1051 48 31 1424 54 minus56 08 678 minus55 977 minus43 1527 47 09 731 minus2 1066 46 1532 52 010 736 3 959 minus61 1495 15 0

NM11 735 755 minus20 1033 1019 14 1634 1589 45 012 763 17 8 1002 16 minus17 1567 39 minus22 013 766 11 1023 4 1567 minus22 0

ACM14 784 784 0 1084 1086 minus2 1402 1411 minus9 015 762 23 minus22 1079 9 minus7 1401 16 minus10 016 807 23 1096 10 1429 18 0

MCa 17 751 743 8 1067 1049 17 1405 1411 minus7 018 726 12 minus17 1049 31 0 1417 11 6 0

Aa 19 779 784 minus6 1073 1086 minus13 1411 1411 0 020 757 23 minus28 1105 9 19 1403 16 minus8 1

Na21 733 755 minus21 1033 1019 13 1557 1589 minus32 022 757 17 2 1006 16 minus13 1549 39 minus40 023 717 minus38 1060 41 1655 66 2

lowastTD total deviations

in the vibrational theory Simultaneously Aa and Na showedthat at least one of their cfs was too shifted from theiraverages Molecule 23 for instance is the only nonmusk pos-sessing an aldehyde functional group and its C=O stretchingmode is found at the 1550ndash1950 cmminus1 range under studyNevertheless nitromusk 11 also holds an aldehyde functionalgroup and though its cf at 1750 cmminus1 is indeed higher than theother cfs for the NM it is still 70 cmminus1 lower than 23rsquos cf Stillconcerning the analysis of Table 6 we can say that the acyclicanalogs 19 and 20 have had their central frequencies shiftedto lower values at the 1500 cmminus1 diagnostic band the onlyone in which there was no agreement between theoreticalresults and expectations deriving from the vibrational theoryAt the 1500 plusmn 200 cmminus1 range hydrocarbon scissoring modesand alkenearomatic C=C stretching modes are found and19 and 20 lack the gem-methyl at the cyclohexane that areobserved in 14 and 15 moreover although in 16 this gem-methyl is also absent it possesses two alkene groups forwhich its stretching modes are also found at this rangeFinally macrocyclic analogs showed the same spectra dataas macrocyclic musks as compounds 18 and 19 differ fromMCM in that they lack two methylene groups it is possibleto suggest that such loss leads the moleculersquos CndashH vibrational

mode sum to be too low to be detected by its OR as suggestedelsewhere [23] Besides both 18 and 19 present awoody smellby being smaller they may be able to bind to a variety ofdifferent ORs which do not reassemble the behavior of themusk detected by possibly only one OR or just a few more[48]

4 Conclusions

This paper worked on developing a method which couldstate the following (i) whether musky molecules had theirIR theoretical spectra fitted into the four bands assigned byvibrational theory in 2002 Turinrsquos paper and (ii) whethernonmuskymolecules did not have their IR theoretical spectrafitted into same criteria It was first concluded that only threebands were useful for discriminating musk from nonmuskodorants The fourth IR band refers to a carbonyl stretchingmode and data here presented showed that this mode cannotbe taken as criteria when building a muskiness profile

Present work was carried out with two different func-tionals applying DFT calculation level and both were ableto accurately predict IR spectra A mathematical strategyhas been adopted in order to summarize IR theoretical

Advances in Chemistry 11

Table 6 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for B3LYP collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd Diff Around 1000 Ave

std Diff Around 1500 Avestd Diff

MCM

1 754 748 6 1142 1093 48 1407 1423 minus16 02 768 16 20 1066 39 minus27 1428 10 5 03 749 1 1116 23 1421 minus2 04 744 minus3 1099 5 1430 6 05 723 minus25 1044 minus49 1429 6 0

PCM

6 749 722 28 1068 1019 49 1450 1476 minus26 07 752 51 31 1052 62 33 1450 32 minus27 08 692 minus30 971 minus48 1461 minus15 09 646 minus75 1069 50 1499 23 010 768 47 936 minus83 1520 44 0

NM11 754 766 minus12 952 977 minus26 1602 1597 5 012 771 10 5 993 22 16 1595 5 minus2 013 772 7 987 9 1593 minus3 0

ACM14 722 732 minus10 1101 1127 minus26 1424 1435 minus12 015 771 35 39 1130 24 3 1431 14 minus4 016 703 minus29 1149 22 1451 15 0

MCa 17 750 748 2 1067 1093 minus26 1418 1423 minus5 018 726 16 minus22 1072 39 minus21 1432 10 9 0

Aa 19 784 732 52 1097 1127 minus30 1357 1435 minus78 120 763 35 31 1087 24 minus40 1410 14 minus26 1

Na21 742 766 minus24 1015 977 38 1601 1597 4 122 767 10 1 1150 22 173 1600 5 3 123 702 minus64 1068 91 1675 78 3

lowastTD total deviations

data and properly compare musk to nonmusk moleculesUsing this approach GGAPW91 computed spectra showedno discriminating patterns between musks and nonmusksB3LYP data showed theoretical frequencies and the threediagnostic bands to bematching while nitro andmacrocyclicnonmusks failed in at least one of such comparisons

It was therefore possible to conclude that no specificmodealone is responsible for the discrimination of themusky odorInstead when a great amount of frequencies expressing weakor medium intensities were found along the 700ndash1700 cmminus1range musk odor occurs At this range observedmodes wereCH2

wag and scissor bending modes C=C stretches andsymmetric nitro stretching modes

This trial scanning over IR vibrational modes and theirrelation to musk odor perception brings new informationaltowards the understanding and application of vibrationaltheoryrsquos ideas and opens the possibility to a more extensivestudy in which a broader number of molecules may bemodeled so as to come to a quantitative proposal for amusky-like novel odorant regarding their IR vibrational modes

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The authors thank Professor Ines Sabioni Resck (fromInstituto de Quımica Brasılia Brazil) for initial ideas andreliance

References

[1] M Eh ldquoNew alicyclic musks the fourth generation of muskodorantsrdquoChemistryamp Biodiversity vol 1 no 12 pp 1975ndash19842004

[2] P Saiyasombati andG BKasting ldquoTwo-stage kinetic analysis offragrance evaporation and absorption from skinrdquo InternationalJournal of Cosmetic Science vol 25 no 5 pp 235ndash243 2003

[3] G B Kasting and P Saiyasombati ldquoA physico-chemical prop-erties based model for estimating evaporation and absorptionrates of perfumes from skinrdquo International Journal of CosmeticScience vol 23 no 1 pp 49ndash58 2001

[4] M Shirasu K Yoshikawa Y Takai et al ldquoOlfactory receptor andneural pathway responsible for highly selective sensing of muskodorsrdquo Neuron vol 81 no 1 pp 165ndash178 2014

[5] J Reisert and H Zhao ldquoResponse kinetics of olfactory receptorneurons and the implications in olfactory codingrdquo Journal ofGeneral Physiology vol 138 no 3 pp 303ndash310 2011

12 Advances in Chemistry

[6] J-P Rospars Y Gu A Gremiaux and P Lucas ldquoOdourtransduction in olfactory receptor neuronsrdquo Chinese Journal ofPhysiology vol 53 no 6 pp 364ndash372 2010

[7] B Malnic and A F Mercadante ldquoThe odorant signaling path-wayrdquo Annual Review of Biomedical Sciences vol 11 pp T86ndashT94 2009

[8] K Snitz A Yablonka T Weiss I Frumin R M Khan andN Sobel ldquoPredicting odor perceptual similarity from odorstructurerdquo PLoS Computational Biology vol 9 no 9 Article IDe1003184 2013

[9] B K Lavine CWhite NMirjankar CM Sundling and CMBreneman ldquoOdor-structure relationship studies of tetralin andindan musksrdquo Chemical Senses vol 37 no 8 pp 723ndash736 2012

[10] Y Zou H Mouhib W Stahl A Goeke Q Wang and PKraft ldquoEfficient macrocyclization by a novel oxy-oxonia-copereaction synthesis and olfactory properties of new macrocyclicmusksrdquo Chemistry vol 18 no 23 pp 7010ndash7015 2012

[11] S Liu ldquoStudy on the relationship between molecular odour ofpolycyclic musksrdquo Xiangliao Xiangjing Huazhuangpin vol 6pp 24ndash29 2004

[12] S-Y Takane and J B O Mitchell ldquoA structure-odor relation-ship study using EVA descriptors and hierarchical clusteringrdquoOrganicampBiomolecular Chemistry vol 2 no 22 pp 3250ndash32552004

[13] K J Rossiter ldquoStructure-odour relationshipsrdquo ChemicalReviews vol 96 no 8 pp 3201ndash3240 1996

[14] M Zarzo ldquoThe sense of smell molecular basis of odorantrecognitionrdquoBiological Reviews vol 82 no 3 pp 455ndash479 2007

[15] A Kato and K Touhara ldquoMammalian olfactory receptorspharmacologyGprotein coupling anddesensitizationrdquoCellularandMolecular Life Sciences vol 66 no 23 pp 3743ndash3753 2009

[16] L Turin and F Yoshii ldquoStructure-odor relations a modernperspectiverdquo in Handbook of Olfaction and Gustation R LDoty Ed pp 275ndash294 Marcel Dekker New York NY USA2003

[17] L Turin ldquoA spectroscopic mechanism for primary olfactoryreceptionrdquo Chemical Senses vol 21 no 6 pp 773ndash791 1996

[18] M A Reed ldquoInelastic electron tunneling spectroscopyrdquo Mate-rials Today vol 11 no 11 pp 46ndash50 2008

[19] L Turin ldquoA method for the calculation of odor character frommolecular structurerdquo Journal ofTheoretical Biology vol 216 no3 pp 367ndash385 2002

[20] L J W Haffenden V A Yaylayan and J Fortin ldquoInvestigationof vibrational theory of olfaction with variously labelled ben-zaldehydesrdquo Food Chemistry vol 73 no 1 pp 67ndash72 2001

[21] J C Brookes F Hartoutsiou A P Horsfield and A MStoneham ldquoCould humans recognize odor by phonon assistedtunnelingrdquo Physical Review Letters vol 98 no 3 Article ID038101 2007

[22] M I Franco L Turin A Mershin and E M C SkoulakisldquoMolecular vibration-sensing component in Drosophila mela-nogaster olfactionrdquo Proceedings of the National Academy ofSciences vol 108 no 9 pp 3797ndash3802 2011

[23] I A Solovrsquoyov P-Y Chang and K Schulten ldquoVibrationallyassisted electron transfer mechanism of olfaction myth orrealityrdquo Physical Chemistry Chemical Physics vol 14 no 40 pp13861ndash13871 2012

[24] S GaneDGeorganakis KManiati et al ldquoMolecular vibration-sensing component in human olfactionrdquo PLoS ONE vol 8 no1 Article ID e55780 2013

[25] D L Pavia G M Lampman G S Kriz and J R VyvyanIntroduction to Spectroscopy Cengage Learning Sao PauloBrazil 2010

[26] D A Lerner D Berthomieu and E R Maia ldquoModeling of theconformational flexibility and EZ isomerism of thiazoximicacid and cefotaximerdquo International Journal of Quantum Chem-istry vol 111 no 6 pp 1222ndash1238 2011

[27] A P Scott andL Radom ldquoHarmonic vibrational frequencies anevaluation of Hartree-Fock Moslashller-Plesset quadratic configu-ration interaction density functional theory and semiempiricalscale factorsrdquoThe Journal of Physical Chemistry vol 100 no 41pp 16502ndash16513 1996

[28] S Gabler J Soelter T Hussain S Sachse and M SchmukerldquoPhysicochemical vs vibrational descriptors for prediction ofodor receptor responsesrdquo Molecular Informatics vol 32 no 9-10 pp 855ndash865 2013

[29] Materials Studio SW and Insight II SW Acelrys San DiegoCalif USA

[30] M J Frisch G W Trucks H B Schlegel et al ldquoGaussian 09Revision A02rdquo Gaussian Inc Wallingford Conn USA 2009

[31] H Sun ldquoCompass an ab initio force-field optimized forcondensed-phase applicationsmdashoverview with details onalkane and benzene compoundsrdquo Journal of Physical ChemistryB vol 102 no 38 pp 7338ndash7364 1998

[32] P Dauber-Osguthorpe V A Roberts D J Osguthorpe J WolfM Genest and A T Hagler ldquoStructure and energetics of ligandbinding to proteins Escherichia coli dihydrofolate reductase-trimethoprim a drug-receptor systemrdquo Proteins StructureFunction and Genetics vol 4 no 1 pp 31ndash47 1988

[33] DH JMackay A J Cross andA THagler ldquoThe role of energyminimization in simulation strategies of biomolecular systemsrdquoin Prediction of Protein Structure and the Principles of ProteinConformation D G Fasman Ed pp 317ndash358 Plenum PressNew York NY USA 1990

[34] R Fletcher and C M Reeves ldquoFunction minimization byconjugate gradientsrdquo The Computer Journal vol 7 no 2 pp149ndash154 1964

[35] WH Press B P Flannery S A Teukolsky andW T VetterlingNumerical Recipes in C the Art of Scientific Computing Cam-bridge University Press London UK 1988

[36] J J P Stewart ldquoMopac a semiempirical molecular orbitalprogramrdquo Journal of Computer-Aided Molecular Design vol 4no 1 pp 101ndash105 1990

[37] J A Pople D P Santry and G A Segal ldquoApproximate self-consistent molecular orbital theory I Invariant proceduresrdquoThe Journal of Chemical Physics vol 43 no 10 pp S129ndashS1351965

[38] J A Pople and G A Segal ldquoApproximate self-consistentmolecular orbital theory III CNDO results for AB

2

and AB3

systemsrdquo The Journal of Chemical Physics vol 44 no 9 pp3289ndash3296 1966

[39] M J S Dewar E G Zoebisch E F Healy and J J P StewartldquoAM1 a new general purpose quantum mechanical molecularmodelrdquo Journal of the American Chemical Society vol 107 no13 pp 3902ndash3909 1985

[40] B Delley ldquoAn all-electron numerical method for solving thelocal density functional for polyatomic moleculesrdquoThe Journalof Chemical Physics vol 92 no 1 pp 508ndash517 1990

[41] B Delley ldquoFast calculation of electrostatics in crystals and largemoleculesrdquo Journal of Physical Chemistry vol 100 no 15 pp6107ndash6110 1996

Advances in Chemistry 13

[42] B Delley ldquoDMol methodology and applicationsrdquo in DensityFunctional Methods in Chemistry J W Andzelm and J KLabanowski Eds pp 101ndash108 Springer New York NY USA1991

[43] B Delley ldquoCalculated electron distribution for Tetrafluoroter-phthalonitrile (TFT)rdquo Chemical Physics vol 110 no 2-3 pp329ndash338 1986

[44] YWang and J P Perdew ldquoCorrelation hole of the spin-polarizedelectron gas with exact small-wave-vector and high-densityscalingrdquo Physical Review B vol 44 no 24 pp 13298ndash13307 1991

[45] P J Stephens F J Devlin C F Chabalowski and M J FrischldquoAb Initio calculation of vibrational absorption and circulardichroism spectra using density functional force fieldsrdquo Journalof Physical Chemistry vol 98 no 45 pp 11623ndash11627 1994

[46] G Schaftenaar and J H Noordik ldquoMolden a pre- and post-processing program for molecular and electronic structuresrdquoJournal of Computer-Aided Molecular Design vol 14 no 2 pp123ndash134 2000

[47] Xming ldquoXming X server for Windowsrdquo 2012 httpwwwstraightrunningcomXmingNotes

[48] K Nara L R Saraiva X Ye and L B Buck ldquoA large-scaleanalysis of odor coding in the olfactory epitheliumrdquo Journal ofNeuroscience vol 31 no 25 pp 9179ndash9191 2011

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

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Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

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Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Advances in Chemistry 3

1 2 3 45

6 7 8 910

11 12 13

14 15 16

1718

19 20

21 22 23

O

OO

OO

O O O

O

OO

O

O

OO O

O

OO

O

OO

O

O O O

O

OH

SR

O

O

O

RR

R R

OO

O

OO

S

O

S

S

O

O

SS

S

OO

O O

S

R

N+

Ominus

+NminusO

N+

Ominus

+NminusO

N+

N+

Ominus

Ominus

N+

N+

O

O

O

O

O

O

OOO

minus

Ominus

minusO minusOOminus

N++N +N

O

O

Figure 1 Odorants under study macrocyclic musks (MCM) pentadecanolide (1) (R)-exaltolide (2) (S)-exaltolide (3) cis-globanone (4)and trans-globanone (5) polycyclic musks (PCM) (4S7S)-galaxolide (6) (4S7R)-galaxolide (7) indane (8) tetralin (9) and tonkene (10)nitromusks (NM) musk ketone (11) musk moskene (12) and musk ambrette (13) acyclic musks (ACM) romandolide (14) helvetolide (15)and cyclomusk (16) nonmusks macrocyclic analogs (MCa) (17) and (18) acyclic analogs (Aa) (19) and (20) and nitro analogs (Na) (21)(22) and (23)

4 Advances in Chemistry

Table 1 Molecules studied

Number IUPAC name CAS number1 Oxacyclohexadecan-2-one 106-02-52 16(R)-Methyl-oxacyclohexadecan-2-one 69297-56-93 16(S)-Methyl-oxacyclohexadecan-2-one 129214-00-24 (5Z)-Cyclohexadec-5-en-1-one 37609-25-95 (5E)-Cyclohexadec-5-en-1-one6 (4S7S)-Cyclopenta[g]-2-benzopyran 134678-hexahydro-466788-hexamethyl 172339-62-77 (4S7R)-Cyclopenta[g]-2-benzopyran 134678-hexahydro-466788-hexamethyl 252332-95-98 1-(23-Dihydro-11233-pentamethyl-1119867-inden-5-yl)-ethanone 4755-83-39 1-[(6119878)-5678-Tetrahydro-355688-hexamethyl-2-naphthalenyl]-ethanone 85549-79-710 2H-[1]-Benzothieno[32-b]pyran-2-one 5732-22-911 4-(11-Dimethylethyl)-26-dimethyl-35-dinitro-benzaldehyde 99758-50-612 4-(11-Dimethylethyl)-26-dimethyl-35-dinitro-benzaldehyde 116-66-513 none14 2-(1-Oxopropoxy)- 1-(33-dimethylcyclohexyl)ethyl ester 236391-76-715 1-Propanol 2-[1-(33-dimethylcyclohexyl)ethoxy]-2-methyl- 1-propanoate 141773-73-116 1-Cyclopentene-1-propanol 1205731205732-trimethyl-5-(1-methylethenyl)- 1-propanoate 84012-64-617 Oxacyclotetradecane-210-dione 38223-27-718 Cyclotetradecanone 3603-99-419 2-(1-Oxopropoxy)- 1-cyclohexyl-1-methylethyl ester 610770-00-820 none21 2-Methoxy-1-methyl-4-(2-methyl-2-propanyl)-35-dinitrobenzene 99758-79-922 2-Methoxy-4-methyl-1-(2-methylpropyl)-35-dinitro-benzene 99758-78-823 24-Bis(11-dimethylethyl)-5-methoxy-3-nitro-benzaldehyde 107342-73-4

in this paper in order to consider each and every modebelonging to the same 400 cm-1 range as well as theirintensities Therefore the use of weighted averages overtheoretical data was chosen its numerical result was calledcentral frequency (cf) With this central frequency it becamepossible to consider all theoretical peaks occurring in thevicinity of the diagnostic frequencies instead of just affirmingthe existence of the expected band only by naming the mostintense theoretical peak Central frequencies were estimatedas follows

Central frequency =sum119899

119894=1

]119894

times int119894

sum119899

119894=1

int119894

(1)

This mathematical approach (which simply generates afrequency-weighted average) was applied to theoretical fre-quencies found at plusmn200 cmminus1 around 700 1000 and 1500 (or1750) cmminus1 and resulted in central frequencies for compounds1ndash23 which were computed in Table 4 (for GGAPW91 data)and in Table 5 (for B3LYP data) The mentioned range hasbeen chosen so as to enable each band to complete its400 cmminus1 width as established in the vibrational theory

3 Results and Discussion

Data will be presented and discussed in three successivesections In the first section the collection of theoretical IRspectra will be presented In the second section they willbe compared to experimental IR spectra to discuss theirprecision and accuracy The third section will deal with therationalization betweenmusk spectra andmusk odor activityIn order to establish such relation best theoretical IR spectrawill be chosen from this paperrsquos second section

31 Part 1 Computation of IR Spectra Concerning ab ini-tio methods convolved GGAPW91 spectra are shown inFigure 2 while B3LYP spectra are gathered in Figure 3 ForGGAPW91 spectra carbon-oxygen single bond stretchesoccur on frequencies between 1018 cmminus1 (for nitro ana-log 21) and 1220 cmminus1 (for (4S7R)-galaxolide 7) carbon-nitrogen single bond stretches occur under the frequency of1200 cmminus1 for nitro compounds carbon-sulfur single bondstretches are observed at 1054 cmminus1 for tonkene 10 Carbon-carbon double bonds stretches happened at 1687 cmminus1 forcis-globanone 4 and at 1706 cmminus1 for trans-globanone 5while all other compounds expressing aromatic C=C bondshad their stretching modes between 1543 cmminus1 (as in musk

Advances in Chemistry 5

Frequency (cmminus1)

0100020003000

Rela

tive i

nten

sity

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

12345

678910

111213

141516

17181920

212223

Figure 2 Spectra obtained with GGAPW91 for MCM 1ndash5 PCM 6ndash10 NM 11ndash13 ACM 14ndash16 and nonmusks 17ndash23

ketone 11) and 1618 cmminus1 (for (4S7R)-galaxolide 7) Nitrogroups have presented their symmetric stretchingmodes near1310ndash1340 cmminus1 and their nonsymmetric stretching modes at1520ndash1560 cmminus1 For aldehydes ketones ethers and estersthe carbon-oxygen double bond stretching represents animportantmark for confirming spectra here the lowest valuefor such mode is found for tetralin 9 at 1680 cmminus1 whilethe highest value of 1777 cmminus1 belongs to acyclic analog 20Carbon-hydrogen bending modes start at very low frequen-cies and end at 1493 cmminus1 (for helvetolide 14) simultaneouslythe band of carbon-hydrogen stretching modes starts at2898 cmminus1 (for (4S7R)-galaxolide7) andfinishes at 3198 cmminus1(for nitro analog 22)

For B3LYP spectra the lowest frequency found for thecarbon-oxygen single bond stretching was 1006 cmminus1 (forromandolide 15) while its highest frequency was 1403 cmminus1(for tonkene 10) the frequency of the carbon-oxygen doublebond stretching was found between 1738 cmminus1 (for musk 8)and 1810 cmminus1 (formusk 14)The carbon-carbon double bondstretching occurred on the frequency of 1707 and 1718 cmminus1for compounds 4 and 5 and between 1699 and 1712 cmminus1for compound 16 finally the carbon-carbon double bondstretching for aromatic compounds occurred between 1531(for non-musk 21) and 1650 cmminus1 (for musk 7) The stretch-ing for nitrogen-oxygen in nitro groups was found at1250ndash1417 cmminus1 for symmetric modes and at 1531ndash1618 cmminus1

6 Advances in Chemistry

12345

678910

111213

141516

17181920

212223

Frequency (cmminus1)

01000200030004000

Rela

tive i

nten

sity

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Figure 3 Spectra obtained at B3LYP level for MCM 1ndash5 PCM 6ndash10 NM 11ndash13 ACM 14ndash16 and nonmusks 17ndash23

for asymmetric modes Finally carbon-hydrogen bendingmodes began at very low frequencies and went up to1540 cmminus1 at most (for musk 13) while carbon-hydrogenstretching occurred between 2953 cmminus1 (for compound 6)and 3229 cmminus1 (for nitromusk 13)

32 Part 2 Comparing GGAPW91 and B3LYP Spectrato Experimental Data For an overview over GGAPW91B3LYP and experimental [47] IR data Figure 4 and Table 2were built inwhich vibrationalmodes for themost importantfunctional groups are organized in accordance with theoreti-cal method adopted Each band expresses the range in whichlabeled vibrational mode occurs considering the maximumand theminimum found for all compoundsThus it becomespossible to state that B3LYP and GGAPW91 results for CndashH stretching modes start at 90 and 140 cmminus1 respectivelyvalues that are higher than the ones provided by experimentaldata simultaneously the same band ends at +50 cmminus1 forGGAPW91 and at +90 cmminus1 for B3LYP in comparison to theexperimental data CndashH bending modes finish at +30 cmminus1for GGAPW91 and at +80 cmminus1 for B3LYP when compared

to experimental values Aromatic C=C stretches occurredin an expected range for GGAPW91 with a +20 cmminus1 shiftfor alkene compounds B3LYP showed a continuous bandfor alkene and aromatic C=C stretches which started at+60 cmminus1 and ended at +30 cmminus1 over experimental dataCndashO stretching modes are found within an expected rangefor both GGAPW91 and B3LYP methods for tonkene 10GGAPW91 predicted CndashO mode at 1381 cmminus1 while thesame mode is found at 1403 cmminus1 in B3LYP data For C=Ostretchingmodes GGAPW91 showed a +20 cmminus1 incrementover lower and higher values found for experimental dataand B3LYP shifted over experimental range in +60 cmminus1Finally nitro N=O stretching modes have had both sym-metric and asymmetric modes accurately and precisely esti-mated for GGAPW91 for B3LYP symmetric nitro stretchingshowed a broader band than that of GGAPW91 and ofexperimental data starting at a +30 cmminus1 shift and finishingat a minus10 cmminus1 shift while their asymmetric modes werecorrectly predicted

Therefore while GGAPW91 final results were all fittedinto experimental reports considering the allowed plusmn30 cmminus1

Advances in Chemistry 7

Table 2 Collection of observed versus calculated IR mode frequencies for compounds 1ndash23

Vibrational modea Observed wavenumber (cmminus1) [25] Calculated wavenumber (cmminus1)GGAPW91 B3LYP

] CbndashH 3150ndash2850 3198ndash2898 3229ndash2953] CndashH (aldehyde) 2900ndash2800 2954ndash2892 2988ndash2939120575 CndashH up to 1465 up to 1493 up to 1540] C=C (alkene) 1680ndash1600 1706ndash1687 1718ndash1707] C=C (aromatic) 1600ndash1475 1618ndash1543 1650ndash1531] C=O (aldehyde) 1740ndash1720 1715ndash1693 1772ndash1749] C=O (ketone) 1725ndash1705 1733ndash1680 1784ndash1738] C=O (ester) 1750ndash1730 1777ndash1742 1810ndash1768120575 CndashO (alcohol ether and ester) 1300ndash1000 1381 1200ndash1018 1403 1312ndash1006]as nitro (RndashNO2) 1660ndash1500 1560ndash1520 1618ndash1531]119904 nitro (RndashNO2) 1390ndash1260 1340ndash1310 1417ndash1250a] stretching ]as asymmetric stretching ]119904 symmetric stretching 120575 bendingb] C(sp2)ndashH C(sp3)ndashH and C(aromatic)ndashH

shifts B3LYP results overestimated CndashH stretching andbending modes alkene C=C stretching modes and aldehydeand ketone C=O stretching modes

To quantify collected results experimental IR spectrumgiven for each particular molecule was compared to its theo-retical spectra as shown in Table 3 In the literaturemdashpublicand personal IR databasemdashonly spectra for compounds 1ndash5 8 10 and 12 were found The vibrational modes chosenas internal patterns of comparison were as follows whenoccurring (i) the two most intense peaks regarding theCndashO stretching mode (ii) the most intense peak for theC=O stretching mode (iii) the most intense peaks for thesymmetric and asymmetric CndashH stretching modes (iv) thehighest wavenumber found for the CndashH bending modes (v)the highest intensity for the C=C stretching mode and (vi)the most intense peaks for the symmetric and asymmetricN=O stretching modes They are altogether able to expressthe accuracy relying on theoretical data once all functionalgroups have had their modes listed within chosen criteriaand the whole spectrum has been covered

Extra information comes on the so-called DIFF columnsin Table 3 Consider

DIFF119894

= ExpWavenumber119894

minusTheoWavenumber119894

(2)

where the difference established between experimental andtheoretical values was plotted (for both GGAPW91 andB3LYP results) as shown in (2) In such equation for acertain mode 119894 the difference (DIFF) is obtained through thesubtraction of its theoretical value (TheoWavenumber) fromits experimental value (ExpWavenumber) The average of thecollected differences on Table 3 was estimated as the values ofabsolute difference were divided by the number of occurringmodes disregarding all CndashH stretch modes as follows

Deviation 1 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(3)

This choice was made due to the fact that all CndashHstretches were overestimated in more than 100 cmminus1 for both

theoretical methods as discussed before This last modetherefore had its deviation separately estimated as follows

Deviation 2 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(4)

in which the absolute DIFF119894

is collected is summed for all CndashH stretching modes within the same theoretical method andis divided by the number of occurring modes

So finally GGAPW91 IR results are found to be moreaccurate than B3LYP results with calculated deviations thatare equal to 13 cmminus1 and 43 cmminus1 respectively Neverthelessthey correspond to a 325 (DFT) and a 1075 (B3LYP)shift over the 4000ndash0 cmminus1 that represents the spectrumwhich ensures that both methods are powerfully predictiveSimultaneously both methods display great shift over CndashHstretching modes corresponding to an increase of 124 cmminus1and 145 cmminus1 respectively Considering that one of thispaperrsquos aims is to compare theoretical IR data with postulatesof the vibrational theory on musky odor the last mentionedmodes are irrelevant as they are not supposed to be respon-sible for muskiness

33 Part 3 IR Spectra and Musk Activity Herein bothGGAPW91 and B3LYP data will be taken into account so asto compare theoretical results with the bands described in thevibrational theory (700 1000 1500 or 1750 and 2200 cmminus1)which would assign as supposed by the previous theory amusky odor to these molecules

In Tables 5 and 6 the information was gathered so as todispose musks 1 to 23 in lines and their central frequencies(at 700 1000 and 1500 or 1750 cmminus1) in columns Besidesthe compounds were gathered in groups in accordance withtheir structural similarity (see first column on the left) MCMfor macrocyclic musks PCM for polycyclic musks NM fornitromusks and ACM for acyclic musks Nonmusks arecalled MCa for macrocyclic analogs Aa for acyclic analogsand Na for nitro analogs As no vibrational mode hasoccurred at 2200 plusmn 200 cmminus1 there is no such column

8 Advances in Chemistry

Table3Mostimpo

rtantw

avenum

bersforc

ompo

unds

1ndash5810and

12according

toDFT

B3LYP

and

experim

entald

ata

Highest

]Cndash

0DIFF

]C=

0DIFF

]Cndash

HDIFF

120575Cndash

HDIFF

]C=

CDIFF

]119904N=O

DIFF

]asN=O

DIFF

1GGAPW91

1207

1215

2833

1748

minus9

3017

3034minus160minus108

1479

minus18

B3LY

P118

11210

5438

1786minus47

3033

3069minus176minus143

1517minus56

Exp

1235

1248

1739

2857

2926

1461

2GGAPW91

1099

1231

107

1739

minus7

2999

3027minus153minus94

1474

minus14

B3LY

P1124

1240minus15minus2

1778minus46

3012

3058minus166minus125

1512minus52

Experim

entald

ata

1109

1238

1732

2846

2933

1460

3GGAPW91

1121

1220minus12

181738

minus6

2991

3037minus145minus104

1481minus21

B3LY

P119

41254minus85minus16

1774minus42

3029

3063minus183minus130

1510minus50

Exp

1109

1238

1732

2846

2933

1460

4GGAPW91

1726

minus11

2990

3051minus124minus123

1475

minus15

1687

B3LY

P1774minus59

3010

3051minus144minus123

1513minus53

1707

Exp

1715

2866

2928

1460

5GGAPW91

1733minus18

2994

3039minus128minus111

1473

minus13

1706

B3LY

P1773minus58

3031

3057minus165minus129

1511minus51

1718

Exp

1715

2866

2928

1460

8GGAPW91

1685

53005

3083minus115minus122

1483

minus13

1594

11B3

LYP

1738minus48

3033

3089minus143minus128

1518minus48

1639

minus34

Exp

1690

2890

2961

1470

1605

10GGAPW91

1759minus19

B3LY

P1807minus67

Exp

1740

12GGAPW91

3019

3086minus139minus105

1487

minus7

1598

71356

41547

3B3

LYP

3041

3090minus161minus109

1512minus32

1610

minus5

1373

minus13

1599

minus49

Exp

2880

2981

1480

1605

1360

1550

Advances in Chemistry 9

Table 4 Deviations estimated over differences between experimen-tal and theoretical wavenumbers forGGAPW91 andB3LYP IRdata

Method Deviation 1 (cmminus1) Deviation 2 (cmminus1)GGAPW91 13 124B3LYP 43 145

Experimentaldata

GGAPW91

B3LYP

3500 3000 2500 2000 1500 1000 500 0

Figure 4 Ranges for important vibrational modes collected forcompounds 1ndash23 through experimental data versus GGAPW91results versus B3LYP results Vibrational modes come in accordanceto bonding atoms and bond order in green CndashH modes in darkgreen C=C modes in light pink CndashO in burgundy C=O and inblue N=O modes

For each musk group the central frequencies averages(ave (5)) and their standard deviations (std (6)) wereestimated these values are plotted at the right side of thecentral frequency listThe next column on the right shows thedifferences between each central frequencies and the averageof central frequencies (diff (7)) Consider

avegroup =1

119899

119891

sum

119899=1

cf119899

(5)

where cf119899

represents the central frequencies found for eachgroup (MCM PCM etc) having herein been defined lowerand upper limits for 119899 so that 119899 = 1 5 for MCM 119899 = 6 10for PCM 119899 = 11 13 for NM and 119899 = 14 16 for ACMConsider

stdgroup = radic119891

sum

119899=1

[(cf119899

minus avegroup)2

] (6)

diff119899

= cf119899

minus avegroup (7)

The values found for the avegroup and stdgroup of theMCMgroup were the same as those found for theMCa group thosebelonging to NM were repeated for Na and data calculatedfor ACM were taken as parameters for Aa

Finally each diff119899

value was allowed to be lower or twotimes its stdgroup value as stated in

diff119899

le 2 times stdgroup (8)

If this happens it is possible to say that theoretical datafit vibrational theoryrsquos demands over study band if not theydo not agree When repeating this process for all three bandsunder the spectra values for the Total Deviations (TD) arecollected The zero input (0) means that all three bandsobeyed (8) Logically TD inputs between 1 and 3 indicate howmany of the bands presented a diff

119899

value that was higher thanthe stdgroup doubled value

34 Absence of the 2000ndash2400 cmminus1 Band None of the pre-vious tables bring a mode among the 2000ndash2400 cmminus1 rangeThe 2200 cmminus1 band was described by Turin as the carbonylstretching mode which only occurred at this range whenworking with NDDOAM1 Hamiltonian Through ab initiocalculation the mentioned mode was observed at the rangeof 1680ndash1810 cmminus1 and it was only taken into account forcfs estimates when dealing with the 1550ndash1950 cmminus1 band fornitro compounds Regarding structural features compounds6 7 12 and 13 do not possess the carbonyl group and arereal musks while compounds 17 18 19 20 and 23 containthe carbonyl group and are odorless Therefore carbonylstretches cannot be taken as criteria for IR data-muskybehavior profile

35 GGAPW91 cf rsquos Plots and Musk Activity Table 5 (withGGAPW91 results) presents only two molecules nonmusks20 and 23 which failed to express a complete match betweentheoretical data and the signed bands of the vibrational the-ory For nonmusk 20 the cf value estimated near 1000 cmminus1was higher than its avegroup value this compound had bothOndashCsp2 stretching modes occurring at high intensities andfrequencies below 1200 cmminus1 (which are precisely the 1090and 1144 cmminus1 wavenumbers) On the other hand musks 14ndash16 and nonmusk 19 have presented a stretch mode (or at leastone of them) outside the 1000 plusmn 200 cmminus1 range Concerningnonmusk 23 it can be said that it showed a lower cf valuewhich remained around the 700 cmminus1 band and a higher cfvalue near the 1000 cmminus1 band This can be explained by thefact that (i) referring to the 700 cmminus1 band 23 had an averagefor intensity modes that was lower than the average valuesfor the other Na and NM compounds and therefore lowerweight values (see (4)) and lower cf and (ii) referring to the1000 cmminus1 band the OndashCsp3 stretch mode at 1073 cmminus1 hadan intensity value that was 87 times higher than the secondmost intensemode generating the observed overestimated cfvalue

That being said and according to mathematical approachadopted in this paper no relationship was found betweenIR properties and the presence of musky odor throughGGAPW91 It does not mean that GGAPW91 calculationleads to affirm that musks and nonmusks have indistinguish-able spectra Itmeans that considering theweighted-averagesvalues resource in order to simplify the adoption of alltheoretical peaks under analysis resulting central frequenciesare similar among musks and nonmusks Such observationmay be due the fact that GGAPW91 spectra had narrowerbands for each vibrational mode rather than B3LYP spectraAs GGAPW91 proved to be a more accurate method itrequires a more accurate statistical tools so to properly dealwith all theoretical modes as to affirm (or deny) a possibledifference on musks and nonmusks IR spectra

36 B3LYP cf rsquos Plots and Musk Activity On the other handTable 6 (with B3LYP data) shows that all musks from 1 to16 have had theoretical central frequencies that fitted thefrequencies demanded at 700 1000 and 1500 (or 1750) cmminus1

10 Advances in Chemistry

Table 5 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for GGAPW91 collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd

Diff Around 1000 Avestd

Diff Around 1500 Avestd

Diff

MCM

1 742 743 minus1 1030 1049 minus19 1429 1411 18 02 761 12 18 1096 31 47 1404 11 minus7 03 748 5 1047 minus2 1417 6 04 734 minus9 1016 minus33 1405 minus6 05 730 minus13 1057 8 1402 minus9 0

PCM

6 751 733 18 1046 1020 26 1423 1480 minus57 07 769 34 36 1051 48 31 1424 54 minus56 08 678 minus55 977 minus43 1527 47 09 731 minus2 1066 46 1532 52 010 736 3 959 minus61 1495 15 0

NM11 735 755 minus20 1033 1019 14 1634 1589 45 012 763 17 8 1002 16 minus17 1567 39 minus22 013 766 11 1023 4 1567 minus22 0

ACM14 784 784 0 1084 1086 minus2 1402 1411 minus9 015 762 23 minus22 1079 9 minus7 1401 16 minus10 016 807 23 1096 10 1429 18 0

MCa 17 751 743 8 1067 1049 17 1405 1411 minus7 018 726 12 minus17 1049 31 0 1417 11 6 0

Aa 19 779 784 minus6 1073 1086 minus13 1411 1411 0 020 757 23 minus28 1105 9 19 1403 16 minus8 1

Na21 733 755 minus21 1033 1019 13 1557 1589 minus32 022 757 17 2 1006 16 minus13 1549 39 minus40 023 717 minus38 1060 41 1655 66 2

lowastTD total deviations

in the vibrational theory Simultaneously Aa and Na showedthat at least one of their cfs was too shifted from theiraverages Molecule 23 for instance is the only nonmusk pos-sessing an aldehyde functional group and its C=O stretchingmode is found at the 1550ndash1950 cmminus1 range under studyNevertheless nitromusk 11 also holds an aldehyde functionalgroup and though its cf at 1750 cmminus1 is indeed higher than theother cfs for the NM it is still 70 cmminus1 lower than 23rsquos cf Stillconcerning the analysis of Table 6 we can say that the acyclicanalogs 19 and 20 have had their central frequencies shiftedto lower values at the 1500 cmminus1 diagnostic band the onlyone in which there was no agreement between theoreticalresults and expectations deriving from the vibrational theoryAt the 1500 plusmn 200 cmminus1 range hydrocarbon scissoring modesand alkenearomatic C=C stretching modes are found and19 and 20 lack the gem-methyl at the cyclohexane that areobserved in 14 and 15 moreover although in 16 this gem-methyl is also absent it possesses two alkene groups forwhich its stretching modes are also found at this rangeFinally macrocyclic analogs showed the same spectra dataas macrocyclic musks as compounds 18 and 19 differ fromMCM in that they lack two methylene groups it is possibleto suggest that such loss leads the moleculersquos CndashH vibrational

mode sum to be too low to be detected by its OR as suggestedelsewhere [23] Besides both 18 and 19 present awoody smellby being smaller they may be able to bind to a variety ofdifferent ORs which do not reassemble the behavior of themusk detected by possibly only one OR or just a few more[48]

4 Conclusions

This paper worked on developing a method which couldstate the following (i) whether musky molecules had theirIR theoretical spectra fitted into the four bands assigned byvibrational theory in 2002 Turinrsquos paper and (ii) whethernonmuskymolecules did not have their IR theoretical spectrafitted into same criteria It was first concluded that only threebands were useful for discriminating musk from nonmuskodorants The fourth IR band refers to a carbonyl stretchingmode and data here presented showed that this mode cannotbe taken as criteria when building a muskiness profile

Present work was carried out with two different func-tionals applying DFT calculation level and both were ableto accurately predict IR spectra A mathematical strategyhas been adopted in order to summarize IR theoretical

Advances in Chemistry 11

Table 6 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for B3LYP collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd Diff Around 1000 Ave

std Diff Around 1500 Avestd Diff

MCM

1 754 748 6 1142 1093 48 1407 1423 minus16 02 768 16 20 1066 39 minus27 1428 10 5 03 749 1 1116 23 1421 minus2 04 744 minus3 1099 5 1430 6 05 723 minus25 1044 minus49 1429 6 0

PCM

6 749 722 28 1068 1019 49 1450 1476 minus26 07 752 51 31 1052 62 33 1450 32 minus27 08 692 minus30 971 minus48 1461 minus15 09 646 minus75 1069 50 1499 23 010 768 47 936 minus83 1520 44 0

NM11 754 766 minus12 952 977 minus26 1602 1597 5 012 771 10 5 993 22 16 1595 5 minus2 013 772 7 987 9 1593 minus3 0

ACM14 722 732 minus10 1101 1127 minus26 1424 1435 minus12 015 771 35 39 1130 24 3 1431 14 minus4 016 703 minus29 1149 22 1451 15 0

MCa 17 750 748 2 1067 1093 minus26 1418 1423 minus5 018 726 16 minus22 1072 39 minus21 1432 10 9 0

Aa 19 784 732 52 1097 1127 minus30 1357 1435 minus78 120 763 35 31 1087 24 minus40 1410 14 minus26 1

Na21 742 766 minus24 1015 977 38 1601 1597 4 122 767 10 1 1150 22 173 1600 5 3 123 702 minus64 1068 91 1675 78 3

lowastTD total deviations

data and properly compare musk to nonmusk moleculesUsing this approach GGAPW91 computed spectra showedno discriminating patterns between musks and nonmusksB3LYP data showed theoretical frequencies and the threediagnostic bands to bematching while nitro andmacrocyclicnonmusks failed in at least one of such comparisons

It was therefore possible to conclude that no specificmodealone is responsible for the discrimination of themusky odorInstead when a great amount of frequencies expressing weakor medium intensities were found along the 700ndash1700 cmminus1range musk odor occurs At this range observedmodes wereCH2

wag and scissor bending modes C=C stretches andsymmetric nitro stretching modes

This trial scanning over IR vibrational modes and theirrelation to musk odor perception brings new informationaltowards the understanding and application of vibrationaltheoryrsquos ideas and opens the possibility to a more extensivestudy in which a broader number of molecules may bemodeled so as to come to a quantitative proposal for amusky-like novel odorant regarding their IR vibrational modes

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The authors thank Professor Ines Sabioni Resck (fromInstituto de Quımica Brasılia Brazil) for initial ideas andreliance

References

[1] M Eh ldquoNew alicyclic musks the fourth generation of muskodorantsrdquoChemistryamp Biodiversity vol 1 no 12 pp 1975ndash19842004

[2] P Saiyasombati andG BKasting ldquoTwo-stage kinetic analysis offragrance evaporation and absorption from skinrdquo InternationalJournal of Cosmetic Science vol 25 no 5 pp 235ndash243 2003

[3] G B Kasting and P Saiyasombati ldquoA physico-chemical prop-erties based model for estimating evaporation and absorptionrates of perfumes from skinrdquo International Journal of CosmeticScience vol 23 no 1 pp 49ndash58 2001

[4] M Shirasu K Yoshikawa Y Takai et al ldquoOlfactory receptor andneural pathway responsible for highly selective sensing of muskodorsrdquo Neuron vol 81 no 1 pp 165ndash178 2014

[5] J Reisert and H Zhao ldquoResponse kinetics of olfactory receptorneurons and the implications in olfactory codingrdquo Journal ofGeneral Physiology vol 138 no 3 pp 303ndash310 2011

12 Advances in Chemistry

[6] J-P Rospars Y Gu A Gremiaux and P Lucas ldquoOdourtransduction in olfactory receptor neuronsrdquo Chinese Journal ofPhysiology vol 53 no 6 pp 364ndash372 2010

[7] B Malnic and A F Mercadante ldquoThe odorant signaling path-wayrdquo Annual Review of Biomedical Sciences vol 11 pp T86ndashT94 2009

[8] K Snitz A Yablonka T Weiss I Frumin R M Khan andN Sobel ldquoPredicting odor perceptual similarity from odorstructurerdquo PLoS Computational Biology vol 9 no 9 Article IDe1003184 2013

[9] B K Lavine CWhite NMirjankar CM Sundling and CMBreneman ldquoOdor-structure relationship studies of tetralin andindan musksrdquo Chemical Senses vol 37 no 8 pp 723ndash736 2012

[10] Y Zou H Mouhib W Stahl A Goeke Q Wang and PKraft ldquoEfficient macrocyclization by a novel oxy-oxonia-copereaction synthesis and olfactory properties of new macrocyclicmusksrdquo Chemistry vol 18 no 23 pp 7010ndash7015 2012

[11] S Liu ldquoStudy on the relationship between molecular odour ofpolycyclic musksrdquo Xiangliao Xiangjing Huazhuangpin vol 6pp 24ndash29 2004

[12] S-Y Takane and J B O Mitchell ldquoA structure-odor relation-ship study using EVA descriptors and hierarchical clusteringrdquoOrganicampBiomolecular Chemistry vol 2 no 22 pp 3250ndash32552004

[13] K J Rossiter ldquoStructure-odour relationshipsrdquo ChemicalReviews vol 96 no 8 pp 3201ndash3240 1996

[14] M Zarzo ldquoThe sense of smell molecular basis of odorantrecognitionrdquoBiological Reviews vol 82 no 3 pp 455ndash479 2007

[15] A Kato and K Touhara ldquoMammalian olfactory receptorspharmacologyGprotein coupling anddesensitizationrdquoCellularandMolecular Life Sciences vol 66 no 23 pp 3743ndash3753 2009

[16] L Turin and F Yoshii ldquoStructure-odor relations a modernperspectiverdquo in Handbook of Olfaction and Gustation R LDoty Ed pp 275ndash294 Marcel Dekker New York NY USA2003

[17] L Turin ldquoA spectroscopic mechanism for primary olfactoryreceptionrdquo Chemical Senses vol 21 no 6 pp 773ndash791 1996

[18] M A Reed ldquoInelastic electron tunneling spectroscopyrdquo Mate-rials Today vol 11 no 11 pp 46ndash50 2008

[19] L Turin ldquoA method for the calculation of odor character frommolecular structurerdquo Journal ofTheoretical Biology vol 216 no3 pp 367ndash385 2002

[20] L J W Haffenden V A Yaylayan and J Fortin ldquoInvestigationof vibrational theory of olfaction with variously labelled ben-zaldehydesrdquo Food Chemistry vol 73 no 1 pp 67ndash72 2001

[21] J C Brookes F Hartoutsiou A P Horsfield and A MStoneham ldquoCould humans recognize odor by phonon assistedtunnelingrdquo Physical Review Letters vol 98 no 3 Article ID038101 2007

[22] M I Franco L Turin A Mershin and E M C SkoulakisldquoMolecular vibration-sensing component in Drosophila mela-nogaster olfactionrdquo Proceedings of the National Academy ofSciences vol 108 no 9 pp 3797ndash3802 2011

[23] I A Solovrsquoyov P-Y Chang and K Schulten ldquoVibrationallyassisted electron transfer mechanism of olfaction myth orrealityrdquo Physical Chemistry Chemical Physics vol 14 no 40 pp13861ndash13871 2012

[24] S GaneDGeorganakis KManiati et al ldquoMolecular vibration-sensing component in human olfactionrdquo PLoS ONE vol 8 no1 Article ID e55780 2013

[25] D L Pavia G M Lampman G S Kriz and J R VyvyanIntroduction to Spectroscopy Cengage Learning Sao PauloBrazil 2010

[26] D A Lerner D Berthomieu and E R Maia ldquoModeling of theconformational flexibility and EZ isomerism of thiazoximicacid and cefotaximerdquo International Journal of Quantum Chem-istry vol 111 no 6 pp 1222ndash1238 2011

[27] A P Scott andL Radom ldquoHarmonic vibrational frequencies anevaluation of Hartree-Fock Moslashller-Plesset quadratic configu-ration interaction density functional theory and semiempiricalscale factorsrdquoThe Journal of Physical Chemistry vol 100 no 41pp 16502ndash16513 1996

[28] S Gabler J Soelter T Hussain S Sachse and M SchmukerldquoPhysicochemical vs vibrational descriptors for prediction ofodor receptor responsesrdquo Molecular Informatics vol 32 no 9-10 pp 855ndash865 2013

[29] Materials Studio SW and Insight II SW Acelrys San DiegoCalif USA

[30] M J Frisch G W Trucks H B Schlegel et al ldquoGaussian 09Revision A02rdquo Gaussian Inc Wallingford Conn USA 2009

[31] H Sun ldquoCompass an ab initio force-field optimized forcondensed-phase applicationsmdashoverview with details onalkane and benzene compoundsrdquo Journal of Physical ChemistryB vol 102 no 38 pp 7338ndash7364 1998

[32] P Dauber-Osguthorpe V A Roberts D J Osguthorpe J WolfM Genest and A T Hagler ldquoStructure and energetics of ligandbinding to proteins Escherichia coli dihydrofolate reductase-trimethoprim a drug-receptor systemrdquo Proteins StructureFunction and Genetics vol 4 no 1 pp 31ndash47 1988

[33] DH JMackay A J Cross andA THagler ldquoThe role of energyminimization in simulation strategies of biomolecular systemsrdquoin Prediction of Protein Structure and the Principles of ProteinConformation D G Fasman Ed pp 317ndash358 Plenum PressNew York NY USA 1990

[34] R Fletcher and C M Reeves ldquoFunction minimization byconjugate gradientsrdquo The Computer Journal vol 7 no 2 pp149ndash154 1964

[35] WH Press B P Flannery S A Teukolsky andW T VetterlingNumerical Recipes in C the Art of Scientific Computing Cam-bridge University Press London UK 1988

[36] J J P Stewart ldquoMopac a semiempirical molecular orbitalprogramrdquo Journal of Computer-Aided Molecular Design vol 4no 1 pp 101ndash105 1990

[37] J A Pople D P Santry and G A Segal ldquoApproximate self-consistent molecular orbital theory I Invariant proceduresrdquoThe Journal of Chemical Physics vol 43 no 10 pp S129ndashS1351965

[38] J A Pople and G A Segal ldquoApproximate self-consistentmolecular orbital theory III CNDO results for AB

2

and AB3

systemsrdquo The Journal of Chemical Physics vol 44 no 9 pp3289ndash3296 1966

[39] M J S Dewar E G Zoebisch E F Healy and J J P StewartldquoAM1 a new general purpose quantum mechanical molecularmodelrdquo Journal of the American Chemical Society vol 107 no13 pp 3902ndash3909 1985

[40] B Delley ldquoAn all-electron numerical method for solving thelocal density functional for polyatomic moleculesrdquoThe Journalof Chemical Physics vol 92 no 1 pp 508ndash517 1990

[41] B Delley ldquoFast calculation of electrostatics in crystals and largemoleculesrdquo Journal of Physical Chemistry vol 100 no 15 pp6107ndash6110 1996

Advances in Chemistry 13

[42] B Delley ldquoDMol methodology and applicationsrdquo in DensityFunctional Methods in Chemistry J W Andzelm and J KLabanowski Eds pp 101ndash108 Springer New York NY USA1991

[43] B Delley ldquoCalculated electron distribution for Tetrafluoroter-phthalonitrile (TFT)rdquo Chemical Physics vol 110 no 2-3 pp329ndash338 1986

[44] YWang and J P Perdew ldquoCorrelation hole of the spin-polarizedelectron gas with exact small-wave-vector and high-densityscalingrdquo Physical Review B vol 44 no 24 pp 13298ndash13307 1991

[45] P J Stephens F J Devlin C F Chabalowski and M J FrischldquoAb Initio calculation of vibrational absorption and circulardichroism spectra using density functional force fieldsrdquo Journalof Physical Chemistry vol 98 no 45 pp 11623ndash11627 1994

[46] G Schaftenaar and J H Noordik ldquoMolden a pre- and post-processing program for molecular and electronic structuresrdquoJournal of Computer-Aided Molecular Design vol 14 no 2 pp123ndash134 2000

[47] Xming ldquoXming X server for Windowsrdquo 2012 httpwwwstraightrunningcomXmingNotes

[48] K Nara L R Saraiva X Ye and L B Buck ldquoA large-scaleanalysis of odor coding in the olfactory epitheliumrdquo Journal ofNeuroscience vol 31 no 25 pp 9179ndash9191 2011

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

4 Advances in Chemistry

Table 1 Molecules studied

Number IUPAC name CAS number1 Oxacyclohexadecan-2-one 106-02-52 16(R)-Methyl-oxacyclohexadecan-2-one 69297-56-93 16(S)-Methyl-oxacyclohexadecan-2-one 129214-00-24 (5Z)-Cyclohexadec-5-en-1-one 37609-25-95 (5E)-Cyclohexadec-5-en-1-one6 (4S7S)-Cyclopenta[g]-2-benzopyran 134678-hexahydro-466788-hexamethyl 172339-62-77 (4S7R)-Cyclopenta[g]-2-benzopyran 134678-hexahydro-466788-hexamethyl 252332-95-98 1-(23-Dihydro-11233-pentamethyl-1119867-inden-5-yl)-ethanone 4755-83-39 1-[(6119878)-5678-Tetrahydro-355688-hexamethyl-2-naphthalenyl]-ethanone 85549-79-710 2H-[1]-Benzothieno[32-b]pyran-2-one 5732-22-911 4-(11-Dimethylethyl)-26-dimethyl-35-dinitro-benzaldehyde 99758-50-612 4-(11-Dimethylethyl)-26-dimethyl-35-dinitro-benzaldehyde 116-66-513 none14 2-(1-Oxopropoxy)- 1-(33-dimethylcyclohexyl)ethyl ester 236391-76-715 1-Propanol 2-[1-(33-dimethylcyclohexyl)ethoxy]-2-methyl- 1-propanoate 141773-73-116 1-Cyclopentene-1-propanol 1205731205732-trimethyl-5-(1-methylethenyl)- 1-propanoate 84012-64-617 Oxacyclotetradecane-210-dione 38223-27-718 Cyclotetradecanone 3603-99-419 2-(1-Oxopropoxy)- 1-cyclohexyl-1-methylethyl ester 610770-00-820 none21 2-Methoxy-1-methyl-4-(2-methyl-2-propanyl)-35-dinitrobenzene 99758-79-922 2-Methoxy-4-methyl-1-(2-methylpropyl)-35-dinitro-benzene 99758-78-823 24-Bis(11-dimethylethyl)-5-methoxy-3-nitro-benzaldehyde 107342-73-4

in this paper in order to consider each and every modebelonging to the same 400 cm-1 range as well as theirintensities Therefore the use of weighted averages overtheoretical data was chosen its numerical result was calledcentral frequency (cf) With this central frequency it becamepossible to consider all theoretical peaks occurring in thevicinity of the diagnostic frequencies instead of just affirmingthe existence of the expected band only by naming the mostintense theoretical peak Central frequencies were estimatedas follows

Central frequency =sum119899

119894=1

]119894

times int119894

sum119899

119894=1

int119894

(1)

This mathematical approach (which simply generates afrequency-weighted average) was applied to theoretical fre-quencies found at plusmn200 cmminus1 around 700 1000 and 1500 (or1750) cmminus1 and resulted in central frequencies for compounds1ndash23 which were computed in Table 4 (for GGAPW91 data)and in Table 5 (for B3LYP data) The mentioned range hasbeen chosen so as to enable each band to complete its400 cmminus1 width as established in the vibrational theory

3 Results and Discussion

Data will be presented and discussed in three successivesections In the first section the collection of theoretical IRspectra will be presented In the second section they willbe compared to experimental IR spectra to discuss theirprecision and accuracy The third section will deal with therationalization betweenmusk spectra andmusk odor activityIn order to establish such relation best theoretical IR spectrawill be chosen from this paperrsquos second section

31 Part 1 Computation of IR Spectra Concerning ab ini-tio methods convolved GGAPW91 spectra are shown inFigure 2 while B3LYP spectra are gathered in Figure 3 ForGGAPW91 spectra carbon-oxygen single bond stretchesoccur on frequencies between 1018 cmminus1 (for nitro ana-log 21) and 1220 cmminus1 (for (4S7R)-galaxolide 7) carbon-nitrogen single bond stretches occur under the frequency of1200 cmminus1 for nitro compounds carbon-sulfur single bondstretches are observed at 1054 cmminus1 for tonkene 10 Carbon-carbon double bonds stretches happened at 1687 cmminus1 forcis-globanone 4 and at 1706 cmminus1 for trans-globanone 5while all other compounds expressing aromatic C=C bondshad their stretching modes between 1543 cmminus1 (as in musk

Advances in Chemistry 5

Frequency (cmminus1)

0100020003000

Rela

tive i

nten

sity

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

12345

678910

111213

141516

17181920

212223

Figure 2 Spectra obtained with GGAPW91 for MCM 1ndash5 PCM 6ndash10 NM 11ndash13 ACM 14ndash16 and nonmusks 17ndash23

ketone 11) and 1618 cmminus1 (for (4S7R)-galaxolide 7) Nitrogroups have presented their symmetric stretchingmodes near1310ndash1340 cmminus1 and their nonsymmetric stretching modes at1520ndash1560 cmminus1 For aldehydes ketones ethers and estersthe carbon-oxygen double bond stretching represents animportantmark for confirming spectra here the lowest valuefor such mode is found for tetralin 9 at 1680 cmminus1 whilethe highest value of 1777 cmminus1 belongs to acyclic analog 20Carbon-hydrogen bending modes start at very low frequen-cies and end at 1493 cmminus1 (for helvetolide 14) simultaneouslythe band of carbon-hydrogen stretching modes starts at2898 cmminus1 (for (4S7R)-galaxolide7) andfinishes at 3198 cmminus1(for nitro analog 22)

For B3LYP spectra the lowest frequency found for thecarbon-oxygen single bond stretching was 1006 cmminus1 (forromandolide 15) while its highest frequency was 1403 cmminus1(for tonkene 10) the frequency of the carbon-oxygen doublebond stretching was found between 1738 cmminus1 (for musk 8)and 1810 cmminus1 (formusk 14)The carbon-carbon double bondstretching occurred on the frequency of 1707 and 1718 cmminus1for compounds 4 and 5 and between 1699 and 1712 cmminus1for compound 16 finally the carbon-carbon double bondstretching for aromatic compounds occurred between 1531(for non-musk 21) and 1650 cmminus1 (for musk 7) The stretch-ing for nitrogen-oxygen in nitro groups was found at1250ndash1417 cmminus1 for symmetric modes and at 1531ndash1618 cmminus1

6 Advances in Chemistry

12345

678910

111213

141516

17181920

212223

Frequency (cmminus1)

01000200030004000

Rela

tive i

nten

sity

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Figure 3 Spectra obtained at B3LYP level for MCM 1ndash5 PCM 6ndash10 NM 11ndash13 ACM 14ndash16 and nonmusks 17ndash23

for asymmetric modes Finally carbon-hydrogen bendingmodes began at very low frequencies and went up to1540 cmminus1 at most (for musk 13) while carbon-hydrogenstretching occurred between 2953 cmminus1 (for compound 6)and 3229 cmminus1 (for nitromusk 13)

32 Part 2 Comparing GGAPW91 and B3LYP Spectrato Experimental Data For an overview over GGAPW91B3LYP and experimental [47] IR data Figure 4 and Table 2were built inwhich vibrationalmodes for themost importantfunctional groups are organized in accordance with theoreti-cal method adopted Each band expresses the range in whichlabeled vibrational mode occurs considering the maximumand theminimum found for all compoundsThus it becomespossible to state that B3LYP and GGAPW91 results for CndashH stretching modes start at 90 and 140 cmminus1 respectivelyvalues that are higher than the ones provided by experimentaldata simultaneously the same band ends at +50 cmminus1 forGGAPW91 and at +90 cmminus1 for B3LYP in comparison to theexperimental data CndashH bending modes finish at +30 cmminus1for GGAPW91 and at +80 cmminus1 for B3LYP when compared

to experimental values Aromatic C=C stretches occurredin an expected range for GGAPW91 with a +20 cmminus1 shiftfor alkene compounds B3LYP showed a continuous bandfor alkene and aromatic C=C stretches which started at+60 cmminus1 and ended at +30 cmminus1 over experimental dataCndashO stretching modes are found within an expected rangefor both GGAPW91 and B3LYP methods for tonkene 10GGAPW91 predicted CndashO mode at 1381 cmminus1 while thesame mode is found at 1403 cmminus1 in B3LYP data For C=Ostretchingmodes GGAPW91 showed a +20 cmminus1 incrementover lower and higher values found for experimental dataand B3LYP shifted over experimental range in +60 cmminus1Finally nitro N=O stretching modes have had both sym-metric and asymmetric modes accurately and precisely esti-mated for GGAPW91 for B3LYP symmetric nitro stretchingshowed a broader band than that of GGAPW91 and ofexperimental data starting at a +30 cmminus1 shift and finishingat a minus10 cmminus1 shift while their asymmetric modes werecorrectly predicted

Therefore while GGAPW91 final results were all fittedinto experimental reports considering the allowed plusmn30 cmminus1

Advances in Chemistry 7

Table 2 Collection of observed versus calculated IR mode frequencies for compounds 1ndash23

Vibrational modea Observed wavenumber (cmminus1) [25] Calculated wavenumber (cmminus1)GGAPW91 B3LYP

] CbndashH 3150ndash2850 3198ndash2898 3229ndash2953] CndashH (aldehyde) 2900ndash2800 2954ndash2892 2988ndash2939120575 CndashH up to 1465 up to 1493 up to 1540] C=C (alkene) 1680ndash1600 1706ndash1687 1718ndash1707] C=C (aromatic) 1600ndash1475 1618ndash1543 1650ndash1531] C=O (aldehyde) 1740ndash1720 1715ndash1693 1772ndash1749] C=O (ketone) 1725ndash1705 1733ndash1680 1784ndash1738] C=O (ester) 1750ndash1730 1777ndash1742 1810ndash1768120575 CndashO (alcohol ether and ester) 1300ndash1000 1381 1200ndash1018 1403 1312ndash1006]as nitro (RndashNO2) 1660ndash1500 1560ndash1520 1618ndash1531]119904 nitro (RndashNO2) 1390ndash1260 1340ndash1310 1417ndash1250a] stretching ]as asymmetric stretching ]119904 symmetric stretching 120575 bendingb] C(sp2)ndashH C(sp3)ndashH and C(aromatic)ndashH

shifts B3LYP results overestimated CndashH stretching andbending modes alkene C=C stretching modes and aldehydeand ketone C=O stretching modes

To quantify collected results experimental IR spectrumgiven for each particular molecule was compared to its theo-retical spectra as shown in Table 3 In the literaturemdashpublicand personal IR databasemdashonly spectra for compounds 1ndash5 8 10 and 12 were found The vibrational modes chosenas internal patterns of comparison were as follows whenoccurring (i) the two most intense peaks regarding theCndashO stretching mode (ii) the most intense peak for theC=O stretching mode (iii) the most intense peaks for thesymmetric and asymmetric CndashH stretching modes (iv) thehighest wavenumber found for the CndashH bending modes (v)the highest intensity for the C=C stretching mode and (vi)the most intense peaks for the symmetric and asymmetricN=O stretching modes They are altogether able to expressthe accuracy relying on theoretical data once all functionalgroups have had their modes listed within chosen criteriaand the whole spectrum has been covered

Extra information comes on the so-called DIFF columnsin Table 3 Consider

DIFF119894

= ExpWavenumber119894

minusTheoWavenumber119894

(2)

where the difference established between experimental andtheoretical values was plotted (for both GGAPW91 andB3LYP results) as shown in (2) In such equation for acertain mode 119894 the difference (DIFF) is obtained through thesubtraction of its theoretical value (TheoWavenumber) fromits experimental value (ExpWavenumber) The average of thecollected differences on Table 3 was estimated as the values ofabsolute difference were divided by the number of occurringmodes disregarding all CndashH stretch modes as follows

Deviation 1 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(3)

This choice was made due to the fact that all CndashHstretches were overestimated in more than 100 cmminus1 for both

theoretical methods as discussed before This last modetherefore had its deviation separately estimated as follows

Deviation 2 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(4)

in which the absolute DIFF119894

is collected is summed for all CndashH stretching modes within the same theoretical method andis divided by the number of occurring modes

So finally GGAPW91 IR results are found to be moreaccurate than B3LYP results with calculated deviations thatare equal to 13 cmminus1 and 43 cmminus1 respectively Neverthelessthey correspond to a 325 (DFT) and a 1075 (B3LYP)shift over the 4000ndash0 cmminus1 that represents the spectrumwhich ensures that both methods are powerfully predictiveSimultaneously both methods display great shift over CndashHstretching modes corresponding to an increase of 124 cmminus1and 145 cmminus1 respectively Considering that one of thispaperrsquos aims is to compare theoretical IR data with postulatesof the vibrational theory on musky odor the last mentionedmodes are irrelevant as they are not supposed to be respon-sible for muskiness

33 Part 3 IR Spectra and Musk Activity Herein bothGGAPW91 and B3LYP data will be taken into account so asto compare theoretical results with the bands described in thevibrational theory (700 1000 1500 or 1750 and 2200 cmminus1)which would assign as supposed by the previous theory amusky odor to these molecules

In Tables 5 and 6 the information was gathered so as todispose musks 1 to 23 in lines and their central frequencies(at 700 1000 and 1500 or 1750 cmminus1) in columns Besidesthe compounds were gathered in groups in accordance withtheir structural similarity (see first column on the left) MCMfor macrocyclic musks PCM for polycyclic musks NM fornitromusks and ACM for acyclic musks Nonmusks arecalled MCa for macrocyclic analogs Aa for acyclic analogsand Na for nitro analogs As no vibrational mode hasoccurred at 2200 plusmn 200 cmminus1 there is no such column

8 Advances in Chemistry

Table3Mostimpo

rtantw

avenum

bersforc

ompo

unds

1ndash5810and

12according

toDFT

B3LYP

and

experim

entald

ata

Highest

]Cndash

0DIFF

]C=

0DIFF

]Cndash

HDIFF

120575Cndash

HDIFF

]C=

CDIFF

]119904N=O

DIFF

]asN=O

DIFF

1GGAPW91

1207

1215

2833

1748

minus9

3017

3034minus160minus108

1479

minus18

B3LY

P118

11210

5438

1786minus47

3033

3069minus176minus143

1517minus56

Exp

1235

1248

1739

2857

2926

1461

2GGAPW91

1099

1231

107

1739

minus7

2999

3027minus153minus94

1474

minus14

B3LY

P1124

1240minus15minus2

1778minus46

3012

3058minus166minus125

1512minus52

Experim

entald

ata

1109

1238

1732

2846

2933

1460

3GGAPW91

1121

1220minus12

181738

minus6

2991

3037minus145minus104

1481minus21

B3LY

P119

41254minus85minus16

1774minus42

3029

3063minus183minus130

1510minus50

Exp

1109

1238

1732

2846

2933

1460

4GGAPW91

1726

minus11

2990

3051minus124minus123

1475

minus15

1687

B3LY

P1774minus59

3010

3051minus144minus123

1513minus53

1707

Exp

1715

2866

2928

1460

5GGAPW91

1733minus18

2994

3039minus128minus111

1473

minus13

1706

B3LY

P1773minus58

3031

3057minus165minus129

1511minus51

1718

Exp

1715

2866

2928

1460

8GGAPW91

1685

53005

3083minus115minus122

1483

minus13

1594

11B3

LYP

1738minus48

3033

3089minus143minus128

1518minus48

1639

minus34

Exp

1690

2890

2961

1470

1605

10GGAPW91

1759minus19

B3LY

P1807minus67

Exp

1740

12GGAPW91

3019

3086minus139minus105

1487

minus7

1598

71356

41547

3B3

LYP

3041

3090minus161minus109

1512minus32

1610

minus5

1373

minus13

1599

minus49

Exp

2880

2981

1480

1605

1360

1550

Advances in Chemistry 9

Table 4 Deviations estimated over differences between experimen-tal and theoretical wavenumbers forGGAPW91 andB3LYP IRdata

Method Deviation 1 (cmminus1) Deviation 2 (cmminus1)GGAPW91 13 124B3LYP 43 145

Experimentaldata

GGAPW91

B3LYP

3500 3000 2500 2000 1500 1000 500 0

Figure 4 Ranges for important vibrational modes collected forcompounds 1ndash23 through experimental data versus GGAPW91results versus B3LYP results Vibrational modes come in accordanceto bonding atoms and bond order in green CndashH modes in darkgreen C=C modes in light pink CndashO in burgundy C=O and inblue N=O modes

For each musk group the central frequencies averages(ave (5)) and their standard deviations (std (6)) wereestimated these values are plotted at the right side of thecentral frequency listThe next column on the right shows thedifferences between each central frequencies and the averageof central frequencies (diff (7)) Consider

avegroup =1

119899

119891

sum

119899=1

cf119899

(5)

where cf119899

represents the central frequencies found for eachgroup (MCM PCM etc) having herein been defined lowerand upper limits for 119899 so that 119899 = 1 5 for MCM 119899 = 6 10for PCM 119899 = 11 13 for NM and 119899 = 14 16 for ACMConsider

stdgroup = radic119891

sum

119899=1

[(cf119899

minus avegroup)2

] (6)

diff119899

= cf119899

minus avegroup (7)

The values found for the avegroup and stdgroup of theMCMgroup were the same as those found for theMCa group thosebelonging to NM were repeated for Na and data calculatedfor ACM were taken as parameters for Aa

Finally each diff119899

value was allowed to be lower or twotimes its stdgroup value as stated in

diff119899

le 2 times stdgroup (8)

If this happens it is possible to say that theoretical datafit vibrational theoryrsquos demands over study band if not theydo not agree When repeating this process for all three bandsunder the spectra values for the Total Deviations (TD) arecollected The zero input (0) means that all three bandsobeyed (8) Logically TD inputs between 1 and 3 indicate howmany of the bands presented a diff

119899

value that was higher thanthe stdgroup doubled value

34 Absence of the 2000ndash2400 cmminus1 Band None of the pre-vious tables bring a mode among the 2000ndash2400 cmminus1 rangeThe 2200 cmminus1 band was described by Turin as the carbonylstretching mode which only occurred at this range whenworking with NDDOAM1 Hamiltonian Through ab initiocalculation the mentioned mode was observed at the rangeof 1680ndash1810 cmminus1 and it was only taken into account forcfs estimates when dealing with the 1550ndash1950 cmminus1 band fornitro compounds Regarding structural features compounds6 7 12 and 13 do not possess the carbonyl group and arereal musks while compounds 17 18 19 20 and 23 containthe carbonyl group and are odorless Therefore carbonylstretches cannot be taken as criteria for IR data-muskybehavior profile

35 GGAPW91 cf rsquos Plots and Musk Activity Table 5 (withGGAPW91 results) presents only two molecules nonmusks20 and 23 which failed to express a complete match betweentheoretical data and the signed bands of the vibrational the-ory For nonmusk 20 the cf value estimated near 1000 cmminus1was higher than its avegroup value this compound had bothOndashCsp2 stretching modes occurring at high intensities andfrequencies below 1200 cmminus1 (which are precisely the 1090and 1144 cmminus1 wavenumbers) On the other hand musks 14ndash16 and nonmusk 19 have presented a stretch mode (or at leastone of them) outside the 1000 plusmn 200 cmminus1 range Concerningnonmusk 23 it can be said that it showed a lower cf valuewhich remained around the 700 cmminus1 band and a higher cfvalue near the 1000 cmminus1 band This can be explained by thefact that (i) referring to the 700 cmminus1 band 23 had an averagefor intensity modes that was lower than the average valuesfor the other Na and NM compounds and therefore lowerweight values (see (4)) and lower cf and (ii) referring to the1000 cmminus1 band the OndashCsp3 stretch mode at 1073 cmminus1 hadan intensity value that was 87 times higher than the secondmost intensemode generating the observed overestimated cfvalue

That being said and according to mathematical approachadopted in this paper no relationship was found betweenIR properties and the presence of musky odor throughGGAPW91 It does not mean that GGAPW91 calculationleads to affirm that musks and nonmusks have indistinguish-able spectra Itmeans that considering theweighted-averagesvalues resource in order to simplify the adoption of alltheoretical peaks under analysis resulting central frequenciesare similar among musks and nonmusks Such observationmay be due the fact that GGAPW91 spectra had narrowerbands for each vibrational mode rather than B3LYP spectraAs GGAPW91 proved to be a more accurate method itrequires a more accurate statistical tools so to properly dealwith all theoretical modes as to affirm (or deny) a possibledifference on musks and nonmusks IR spectra

36 B3LYP cf rsquos Plots and Musk Activity On the other handTable 6 (with B3LYP data) shows that all musks from 1 to16 have had theoretical central frequencies that fitted thefrequencies demanded at 700 1000 and 1500 (or 1750) cmminus1

10 Advances in Chemistry

Table 5 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for GGAPW91 collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd

Diff Around 1000 Avestd

Diff Around 1500 Avestd

Diff

MCM

1 742 743 minus1 1030 1049 minus19 1429 1411 18 02 761 12 18 1096 31 47 1404 11 minus7 03 748 5 1047 minus2 1417 6 04 734 minus9 1016 minus33 1405 minus6 05 730 minus13 1057 8 1402 minus9 0

PCM

6 751 733 18 1046 1020 26 1423 1480 minus57 07 769 34 36 1051 48 31 1424 54 minus56 08 678 minus55 977 minus43 1527 47 09 731 minus2 1066 46 1532 52 010 736 3 959 minus61 1495 15 0

NM11 735 755 minus20 1033 1019 14 1634 1589 45 012 763 17 8 1002 16 minus17 1567 39 minus22 013 766 11 1023 4 1567 minus22 0

ACM14 784 784 0 1084 1086 minus2 1402 1411 minus9 015 762 23 minus22 1079 9 minus7 1401 16 minus10 016 807 23 1096 10 1429 18 0

MCa 17 751 743 8 1067 1049 17 1405 1411 minus7 018 726 12 minus17 1049 31 0 1417 11 6 0

Aa 19 779 784 minus6 1073 1086 minus13 1411 1411 0 020 757 23 minus28 1105 9 19 1403 16 minus8 1

Na21 733 755 minus21 1033 1019 13 1557 1589 minus32 022 757 17 2 1006 16 minus13 1549 39 minus40 023 717 minus38 1060 41 1655 66 2

lowastTD total deviations

in the vibrational theory Simultaneously Aa and Na showedthat at least one of their cfs was too shifted from theiraverages Molecule 23 for instance is the only nonmusk pos-sessing an aldehyde functional group and its C=O stretchingmode is found at the 1550ndash1950 cmminus1 range under studyNevertheless nitromusk 11 also holds an aldehyde functionalgroup and though its cf at 1750 cmminus1 is indeed higher than theother cfs for the NM it is still 70 cmminus1 lower than 23rsquos cf Stillconcerning the analysis of Table 6 we can say that the acyclicanalogs 19 and 20 have had their central frequencies shiftedto lower values at the 1500 cmminus1 diagnostic band the onlyone in which there was no agreement between theoreticalresults and expectations deriving from the vibrational theoryAt the 1500 plusmn 200 cmminus1 range hydrocarbon scissoring modesand alkenearomatic C=C stretching modes are found and19 and 20 lack the gem-methyl at the cyclohexane that areobserved in 14 and 15 moreover although in 16 this gem-methyl is also absent it possesses two alkene groups forwhich its stretching modes are also found at this rangeFinally macrocyclic analogs showed the same spectra dataas macrocyclic musks as compounds 18 and 19 differ fromMCM in that they lack two methylene groups it is possibleto suggest that such loss leads the moleculersquos CndashH vibrational

mode sum to be too low to be detected by its OR as suggestedelsewhere [23] Besides both 18 and 19 present awoody smellby being smaller they may be able to bind to a variety ofdifferent ORs which do not reassemble the behavior of themusk detected by possibly only one OR or just a few more[48]

4 Conclusions

This paper worked on developing a method which couldstate the following (i) whether musky molecules had theirIR theoretical spectra fitted into the four bands assigned byvibrational theory in 2002 Turinrsquos paper and (ii) whethernonmuskymolecules did not have their IR theoretical spectrafitted into same criteria It was first concluded that only threebands were useful for discriminating musk from nonmuskodorants The fourth IR band refers to a carbonyl stretchingmode and data here presented showed that this mode cannotbe taken as criteria when building a muskiness profile

Present work was carried out with two different func-tionals applying DFT calculation level and both were ableto accurately predict IR spectra A mathematical strategyhas been adopted in order to summarize IR theoretical

Advances in Chemistry 11

Table 6 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for B3LYP collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd Diff Around 1000 Ave

std Diff Around 1500 Avestd Diff

MCM

1 754 748 6 1142 1093 48 1407 1423 minus16 02 768 16 20 1066 39 minus27 1428 10 5 03 749 1 1116 23 1421 minus2 04 744 minus3 1099 5 1430 6 05 723 minus25 1044 minus49 1429 6 0

PCM

6 749 722 28 1068 1019 49 1450 1476 minus26 07 752 51 31 1052 62 33 1450 32 minus27 08 692 minus30 971 minus48 1461 minus15 09 646 minus75 1069 50 1499 23 010 768 47 936 minus83 1520 44 0

NM11 754 766 minus12 952 977 minus26 1602 1597 5 012 771 10 5 993 22 16 1595 5 minus2 013 772 7 987 9 1593 minus3 0

ACM14 722 732 minus10 1101 1127 minus26 1424 1435 minus12 015 771 35 39 1130 24 3 1431 14 minus4 016 703 minus29 1149 22 1451 15 0

MCa 17 750 748 2 1067 1093 minus26 1418 1423 minus5 018 726 16 minus22 1072 39 minus21 1432 10 9 0

Aa 19 784 732 52 1097 1127 minus30 1357 1435 minus78 120 763 35 31 1087 24 minus40 1410 14 minus26 1

Na21 742 766 minus24 1015 977 38 1601 1597 4 122 767 10 1 1150 22 173 1600 5 3 123 702 minus64 1068 91 1675 78 3

lowastTD total deviations

data and properly compare musk to nonmusk moleculesUsing this approach GGAPW91 computed spectra showedno discriminating patterns between musks and nonmusksB3LYP data showed theoretical frequencies and the threediagnostic bands to bematching while nitro andmacrocyclicnonmusks failed in at least one of such comparisons

It was therefore possible to conclude that no specificmodealone is responsible for the discrimination of themusky odorInstead when a great amount of frequencies expressing weakor medium intensities were found along the 700ndash1700 cmminus1range musk odor occurs At this range observedmodes wereCH2

wag and scissor bending modes C=C stretches andsymmetric nitro stretching modes

This trial scanning over IR vibrational modes and theirrelation to musk odor perception brings new informationaltowards the understanding and application of vibrationaltheoryrsquos ideas and opens the possibility to a more extensivestudy in which a broader number of molecules may bemodeled so as to come to a quantitative proposal for amusky-like novel odorant regarding their IR vibrational modes

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The authors thank Professor Ines Sabioni Resck (fromInstituto de Quımica Brasılia Brazil) for initial ideas andreliance

References

[1] M Eh ldquoNew alicyclic musks the fourth generation of muskodorantsrdquoChemistryamp Biodiversity vol 1 no 12 pp 1975ndash19842004

[2] P Saiyasombati andG BKasting ldquoTwo-stage kinetic analysis offragrance evaporation and absorption from skinrdquo InternationalJournal of Cosmetic Science vol 25 no 5 pp 235ndash243 2003

[3] G B Kasting and P Saiyasombati ldquoA physico-chemical prop-erties based model for estimating evaporation and absorptionrates of perfumes from skinrdquo International Journal of CosmeticScience vol 23 no 1 pp 49ndash58 2001

[4] M Shirasu K Yoshikawa Y Takai et al ldquoOlfactory receptor andneural pathway responsible for highly selective sensing of muskodorsrdquo Neuron vol 81 no 1 pp 165ndash178 2014

[5] J Reisert and H Zhao ldquoResponse kinetics of olfactory receptorneurons and the implications in olfactory codingrdquo Journal ofGeneral Physiology vol 138 no 3 pp 303ndash310 2011

12 Advances in Chemistry

[6] J-P Rospars Y Gu A Gremiaux and P Lucas ldquoOdourtransduction in olfactory receptor neuronsrdquo Chinese Journal ofPhysiology vol 53 no 6 pp 364ndash372 2010

[7] B Malnic and A F Mercadante ldquoThe odorant signaling path-wayrdquo Annual Review of Biomedical Sciences vol 11 pp T86ndashT94 2009

[8] K Snitz A Yablonka T Weiss I Frumin R M Khan andN Sobel ldquoPredicting odor perceptual similarity from odorstructurerdquo PLoS Computational Biology vol 9 no 9 Article IDe1003184 2013

[9] B K Lavine CWhite NMirjankar CM Sundling and CMBreneman ldquoOdor-structure relationship studies of tetralin andindan musksrdquo Chemical Senses vol 37 no 8 pp 723ndash736 2012

[10] Y Zou H Mouhib W Stahl A Goeke Q Wang and PKraft ldquoEfficient macrocyclization by a novel oxy-oxonia-copereaction synthesis and olfactory properties of new macrocyclicmusksrdquo Chemistry vol 18 no 23 pp 7010ndash7015 2012

[11] S Liu ldquoStudy on the relationship between molecular odour ofpolycyclic musksrdquo Xiangliao Xiangjing Huazhuangpin vol 6pp 24ndash29 2004

[12] S-Y Takane and J B O Mitchell ldquoA structure-odor relation-ship study using EVA descriptors and hierarchical clusteringrdquoOrganicampBiomolecular Chemistry vol 2 no 22 pp 3250ndash32552004

[13] K J Rossiter ldquoStructure-odour relationshipsrdquo ChemicalReviews vol 96 no 8 pp 3201ndash3240 1996

[14] M Zarzo ldquoThe sense of smell molecular basis of odorantrecognitionrdquoBiological Reviews vol 82 no 3 pp 455ndash479 2007

[15] A Kato and K Touhara ldquoMammalian olfactory receptorspharmacologyGprotein coupling anddesensitizationrdquoCellularandMolecular Life Sciences vol 66 no 23 pp 3743ndash3753 2009

[16] L Turin and F Yoshii ldquoStructure-odor relations a modernperspectiverdquo in Handbook of Olfaction and Gustation R LDoty Ed pp 275ndash294 Marcel Dekker New York NY USA2003

[17] L Turin ldquoA spectroscopic mechanism for primary olfactoryreceptionrdquo Chemical Senses vol 21 no 6 pp 773ndash791 1996

[18] M A Reed ldquoInelastic electron tunneling spectroscopyrdquo Mate-rials Today vol 11 no 11 pp 46ndash50 2008

[19] L Turin ldquoA method for the calculation of odor character frommolecular structurerdquo Journal ofTheoretical Biology vol 216 no3 pp 367ndash385 2002

[20] L J W Haffenden V A Yaylayan and J Fortin ldquoInvestigationof vibrational theory of olfaction with variously labelled ben-zaldehydesrdquo Food Chemistry vol 73 no 1 pp 67ndash72 2001

[21] J C Brookes F Hartoutsiou A P Horsfield and A MStoneham ldquoCould humans recognize odor by phonon assistedtunnelingrdquo Physical Review Letters vol 98 no 3 Article ID038101 2007

[22] M I Franco L Turin A Mershin and E M C SkoulakisldquoMolecular vibration-sensing component in Drosophila mela-nogaster olfactionrdquo Proceedings of the National Academy ofSciences vol 108 no 9 pp 3797ndash3802 2011

[23] I A Solovrsquoyov P-Y Chang and K Schulten ldquoVibrationallyassisted electron transfer mechanism of olfaction myth orrealityrdquo Physical Chemistry Chemical Physics vol 14 no 40 pp13861ndash13871 2012

[24] S GaneDGeorganakis KManiati et al ldquoMolecular vibration-sensing component in human olfactionrdquo PLoS ONE vol 8 no1 Article ID e55780 2013

[25] D L Pavia G M Lampman G S Kriz and J R VyvyanIntroduction to Spectroscopy Cengage Learning Sao PauloBrazil 2010

[26] D A Lerner D Berthomieu and E R Maia ldquoModeling of theconformational flexibility and EZ isomerism of thiazoximicacid and cefotaximerdquo International Journal of Quantum Chem-istry vol 111 no 6 pp 1222ndash1238 2011

[27] A P Scott andL Radom ldquoHarmonic vibrational frequencies anevaluation of Hartree-Fock Moslashller-Plesset quadratic configu-ration interaction density functional theory and semiempiricalscale factorsrdquoThe Journal of Physical Chemistry vol 100 no 41pp 16502ndash16513 1996

[28] S Gabler J Soelter T Hussain S Sachse and M SchmukerldquoPhysicochemical vs vibrational descriptors for prediction ofodor receptor responsesrdquo Molecular Informatics vol 32 no 9-10 pp 855ndash865 2013

[29] Materials Studio SW and Insight II SW Acelrys San DiegoCalif USA

[30] M J Frisch G W Trucks H B Schlegel et al ldquoGaussian 09Revision A02rdquo Gaussian Inc Wallingford Conn USA 2009

[31] H Sun ldquoCompass an ab initio force-field optimized forcondensed-phase applicationsmdashoverview with details onalkane and benzene compoundsrdquo Journal of Physical ChemistryB vol 102 no 38 pp 7338ndash7364 1998

[32] P Dauber-Osguthorpe V A Roberts D J Osguthorpe J WolfM Genest and A T Hagler ldquoStructure and energetics of ligandbinding to proteins Escherichia coli dihydrofolate reductase-trimethoprim a drug-receptor systemrdquo Proteins StructureFunction and Genetics vol 4 no 1 pp 31ndash47 1988

[33] DH JMackay A J Cross andA THagler ldquoThe role of energyminimization in simulation strategies of biomolecular systemsrdquoin Prediction of Protein Structure and the Principles of ProteinConformation D G Fasman Ed pp 317ndash358 Plenum PressNew York NY USA 1990

[34] R Fletcher and C M Reeves ldquoFunction minimization byconjugate gradientsrdquo The Computer Journal vol 7 no 2 pp149ndash154 1964

[35] WH Press B P Flannery S A Teukolsky andW T VetterlingNumerical Recipes in C the Art of Scientific Computing Cam-bridge University Press London UK 1988

[36] J J P Stewart ldquoMopac a semiempirical molecular orbitalprogramrdquo Journal of Computer-Aided Molecular Design vol 4no 1 pp 101ndash105 1990

[37] J A Pople D P Santry and G A Segal ldquoApproximate self-consistent molecular orbital theory I Invariant proceduresrdquoThe Journal of Chemical Physics vol 43 no 10 pp S129ndashS1351965

[38] J A Pople and G A Segal ldquoApproximate self-consistentmolecular orbital theory III CNDO results for AB

2

and AB3

systemsrdquo The Journal of Chemical Physics vol 44 no 9 pp3289ndash3296 1966

[39] M J S Dewar E G Zoebisch E F Healy and J J P StewartldquoAM1 a new general purpose quantum mechanical molecularmodelrdquo Journal of the American Chemical Society vol 107 no13 pp 3902ndash3909 1985

[40] B Delley ldquoAn all-electron numerical method for solving thelocal density functional for polyatomic moleculesrdquoThe Journalof Chemical Physics vol 92 no 1 pp 508ndash517 1990

[41] B Delley ldquoFast calculation of electrostatics in crystals and largemoleculesrdquo Journal of Physical Chemistry vol 100 no 15 pp6107ndash6110 1996

Advances in Chemistry 13

[42] B Delley ldquoDMol methodology and applicationsrdquo in DensityFunctional Methods in Chemistry J W Andzelm and J KLabanowski Eds pp 101ndash108 Springer New York NY USA1991

[43] B Delley ldquoCalculated electron distribution for Tetrafluoroter-phthalonitrile (TFT)rdquo Chemical Physics vol 110 no 2-3 pp329ndash338 1986

[44] YWang and J P Perdew ldquoCorrelation hole of the spin-polarizedelectron gas with exact small-wave-vector and high-densityscalingrdquo Physical Review B vol 44 no 24 pp 13298ndash13307 1991

[45] P J Stephens F J Devlin C F Chabalowski and M J FrischldquoAb Initio calculation of vibrational absorption and circulardichroism spectra using density functional force fieldsrdquo Journalof Physical Chemistry vol 98 no 45 pp 11623ndash11627 1994

[46] G Schaftenaar and J H Noordik ldquoMolden a pre- and post-processing program for molecular and electronic structuresrdquoJournal of Computer-Aided Molecular Design vol 14 no 2 pp123ndash134 2000

[47] Xming ldquoXming X server for Windowsrdquo 2012 httpwwwstraightrunningcomXmingNotes

[48] K Nara L R Saraiva X Ye and L B Buck ldquoA large-scaleanalysis of odor coding in the olfactory epitheliumrdquo Journal ofNeuroscience vol 31 no 25 pp 9179ndash9191 2011

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

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ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Advances in Chemistry 5

Frequency (cmminus1)

0100020003000

Rela

tive i

nten

sity

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Frequency (cmminus1)

0100020003000

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

12345

678910

111213

141516

17181920

212223

Figure 2 Spectra obtained with GGAPW91 for MCM 1ndash5 PCM 6ndash10 NM 11ndash13 ACM 14ndash16 and nonmusks 17ndash23

ketone 11) and 1618 cmminus1 (for (4S7R)-galaxolide 7) Nitrogroups have presented their symmetric stretchingmodes near1310ndash1340 cmminus1 and their nonsymmetric stretching modes at1520ndash1560 cmminus1 For aldehydes ketones ethers and estersthe carbon-oxygen double bond stretching represents animportantmark for confirming spectra here the lowest valuefor such mode is found for tetralin 9 at 1680 cmminus1 whilethe highest value of 1777 cmminus1 belongs to acyclic analog 20Carbon-hydrogen bending modes start at very low frequen-cies and end at 1493 cmminus1 (for helvetolide 14) simultaneouslythe band of carbon-hydrogen stretching modes starts at2898 cmminus1 (for (4S7R)-galaxolide7) andfinishes at 3198 cmminus1(for nitro analog 22)

For B3LYP spectra the lowest frequency found for thecarbon-oxygen single bond stretching was 1006 cmminus1 (forromandolide 15) while its highest frequency was 1403 cmminus1(for tonkene 10) the frequency of the carbon-oxygen doublebond stretching was found between 1738 cmminus1 (for musk 8)and 1810 cmminus1 (formusk 14)The carbon-carbon double bondstretching occurred on the frequency of 1707 and 1718 cmminus1for compounds 4 and 5 and between 1699 and 1712 cmminus1for compound 16 finally the carbon-carbon double bondstretching for aromatic compounds occurred between 1531(for non-musk 21) and 1650 cmminus1 (for musk 7) The stretch-ing for nitrogen-oxygen in nitro groups was found at1250ndash1417 cmminus1 for symmetric modes and at 1531ndash1618 cmminus1

6 Advances in Chemistry

12345

678910

111213

141516

17181920

212223

Frequency (cmminus1)

01000200030004000

Rela

tive i

nten

sity

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Figure 3 Spectra obtained at B3LYP level for MCM 1ndash5 PCM 6ndash10 NM 11ndash13 ACM 14ndash16 and nonmusks 17ndash23

for asymmetric modes Finally carbon-hydrogen bendingmodes began at very low frequencies and went up to1540 cmminus1 at most (for musk 13) while carbon-hydrogenstretching occurred between 2953 cmminus1 (for compound 6)and 3229 cmminus1 (for nitromusk 13)

32 Part 2 Comparing GGAPW91 and B3LYP Spectrato Experimental Data For an overview over GGAPW91B3LYP and experimental [47] IR data Figure 4 and Table 2were built inwhich vibrationalmodes for themost importantfunctional groups are organized in accordance with theoreti-cal method adopted Each band expresses the range in whichlabeled vibrational mode occurs considering the maximumand theminimum found for all compoundsThus it becomespossible to state that B3LYP and GGAPW91 results for CndashH stretching modes start at 90 and 140 cmminus1 respectivelyvalues that are higher than the ones provided by experimentaldata simultaneously the same band ends at +50 cmminus1 forGGAPW91 and at +90 cmminus1 for B3LYP in comparison to theexperimental data CndashH bending modes finish at +30 cmminus1for GGAPW91 and at +80 cmminus1 for B3LYP when compared

to experimental values Aromatic C=C stretches occurredin an expected range for GGAPW91 with a +20 cmminus1 shiftfor alkene compounds B3LYP showed a continuous bandfor alkene and aromatic C=C stretches which started at+60 cmminus1 and ended at +30 cmminus1 over experimental dataCndashO stretching modes are found within an expected rangefor both GGAPW91 and B3LYP methods for tonkene 10GGAPW91 predicted CndashO mode at 1381 cmminus1 while thesame mode is found at 1403 cmminus1 in B3LYP data For C=Ostretchingmodes GGAPW91 showed a +20 cmminus1 incrementover lower and higher values found for experimental dataand B3LYP shifted over experimental range in +60 cmminus1Finally nitro N=O stretching modes have had both sym-metric and asymmetric modes accurately and precisely esti-mated for GGAPW91 for B3LYP symmetric nitro stretchingshowed a broader band than that of GGAPW91 and ofexperimental data starting at a +30 cmminus1 shift and finishingat a minus10 cmminus1 shift while their asymmetric modes werecorrectly predicted

Therefore while GGAPW91 final results were all fittedinto experimental reports considering the allowed plusmn30 cmminus1

Advances in Chemistry 7

Table 2 Collection of observed versus calculated IR mode frequencies for compounds 1ndash23

Vibrational modea Observed wavenumber (cmminus1) [25] Calculated wavenumber (cmminus1)GGAPW91 B3LYP

] CbndashH 3150ndash2850 3198ndash2898 3229ndash2953] CndashH (aldehyde) 2900ndash2800 2954ndash2892 2988ndash2939120575 CndashH up to 1465 up to 1493 up to 1540] C=C (alkene) 1680ndash1600 1706ndash1687 1718ndash1707] C=C (aromatic) 1600ndash1475 1618ndash1543 1650ndash1531] C=O (aldehyde) 1740ndash1720 1715ndash1693 1772ndash1749] C=O (ketone) 1725ndash1705 1733ndash1680 1784ndash1738] C=O (ester) 1750ndash1730 1777ndash1742 1810ndash1768120575 CndashO (alcohol ether and ester) 1300ndash1000 1381 1200ndash1018 1403 1312ndash1006]as nitro (RndashNO2) 1660ndash1500 1560ndash1520 1618ndash1531]119904 nitro (RndashNO2) 1390ndash1260 1340ndash1310 1417ndash1250a] stretching ]as asymmetric stretching ]119904 symmetric stretching 120575 bendingb] C(sp2)ndashH C(sp3)ndashH and C(aromatic)ndashH

shifts B3LYP results overestimated CndashH stretching andbending modes alkene C=C stretching modes and aldehydeand ketone C=O stretching modes

To quantify collected results experimental IR spectrumgiven for each particular molecule was compared to its theo-retical spectra as shown in Table 3 In the literaturemdashpublicand personal IR databasemdashonly spectra for compounds 1ndash5 8 10 and 12 were found The vibrational modes chosenas internal patterns of comparison were as follows whenoccurring (i) the two most intense peaks regarding theCndashO stretching mode (ii) the most intense peak for theC=O stretching mode (iii) the most intense peaks for thesymmetric and asymmetric CndashH stretching modes (iv) thehighest wavenumber found for the CndashH bending modes (v)the highest intensity for the C=C stretching mode and (vi)the most intense peaks for the symmetric and asymmetricN=O stretching modes They are altogether able to expressthe accuracy relying on theoretical data once all functionalgroups have had their modes listed within chosen criteriaand the whole spectrum has been covered

Extra information comes on the so-called DIFF columnsin Table 3 Consider

DIFF119894

= ExpWavenumber119894

minusTheoWavenumber119894

(2)

where the difference established between experimental andtheoretical values was plotted (for both GGAPW91 andB3LYP results) as shown in (2) In such equation for acertain mode 119894 the difference (DIFF) is obtained through thesubtraction of its theoretical value (TheoWavenumber) fromits experimental value (ExpWavenumber) The average of thecollected differences on Table 3 was estimated as the values ofabsolute difference were divided by the number of occurringmodes disregarding all CndashH stretch modes as follows

Deviation 1 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(3)

This choice was made due to the fact that all CndashHstretches were overestimated in more than 100 cmminus1 for both

theoretical methods as discussed before This last modetherefore had its deviation separately estimated as follows

Deviation 2 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(4)

in which the absolute DIFF119894

is collected is summed for all CndashH stretching modes within the same theoretical method andis divided by the number of occurring modes

So finally GGAPW91 IR results are found to be moreaccurate than B3LYP results with calculated deviations thatare equal to 13 cmminus1 and 43 cmminus1 respectively Neverthelessthey correspond to a 325 (DFT) and a 1075 (B3LYP)shift over the 4000ndash0 cmminus1 that represents the spectrumwhich ensures that both methods are powerfully predictiveSimultaneously both methods display great shift over CndashHstretching modes corresponding to an increase of 124 cmminus1and 145 cmminus1 respectively Considering that one of thispaperrsquos aims is to compare theoretical IR data with postulatesof the vibrational theory on musky odor the last mentionedmodes are irrelevant as they are not supposed to be respon-sible for muskiness

33 Part 3 IR Spectra and Musk Activity Herein bothGGAPW91 and B3LYP data will be taken into account so asto compare theoretical results with the bands described in thevibrational theory (700 1000 1500 or 1750 and 2200 cmminus1)which would assign as supposed by the previous theory amusky odor to these molecules

In Tables 5 and 6 the information was gathered so as todispose musks 1 to 23 in lines and their central frequencies(at 700 1000 and 1500 or 1750 cmminus1) in columns Besidesthe compounds were gathered in groups in accordance withtheir structural similarity (see first column on the left) MCMfor macrocyclic musks PCM for polycyclic musks NM fornitromusks and ACM for acyclic musks Nonmusks arecalled MCa for macrocyclic analogs Aa for acyclic analogsand Na for nitro analogs As no vibrational mode hasoccurred at 2200 plusmn 200 cmminus1 there is no such column

8 Advances in Chemistry

Table3Mostimpo

rtantw

avenum

bersforc

ompo

unds

1ndash5810and

12according

toDFT

B3LYP

and

experim

entald

ata

Highest

]Cndash

0DIFF

]C=

0DIFF

]Cndash

HDIFF

120575Cndash

HDIFF

]C=

CDIFF

]119904N=O

DIFF

]asN=O

DIFF

1GGAPW91

1207

1215

2833

1748

minus9

3017

3034minus160minus108

1479

minus18

B3LY

P118

11210

5438

1786minus47

3033

3069minus176minus143

1517minus56

Exp

1235

1248

1739

2857

2926

1461

2GGAPW91

1099

1231

107

1739

minus7

2999

3027minus153minus94

1474

minus14

B3LY

P1124

1240minus15minus2

1778minus46

3012

3058minus166minus125

1512minus52

Experim

entald

ata

1109

1238

1732

2846

2933

1460

3GGAPW91

1121

1220minus12

181738

minus6

2991

3037minus145minus104

1481minus21

B3LY

P119

41254minus85minus16

1774minus42

3029

3063minus183minus130

1510minus50

Exp

1109

1238

1732

2846

2933

1460

4GGAPW91

1726

minus11

2990

3051minus124minus123

1475

minus15

1687

B3LY

P1774minus59

3010

3051minus144minus123

1513minus53

1707

Exp

1715

2866

2928

1460

5GGAPW91

1733minus18

2994

3039minus128minus111

1473

minus13

1706

B3LY

P1773minus58

3031

3057minus165minus129

1511minus51

1718

Exp

1715

2866

2928

1460

8GGAPW91

1685

53005

3083minus115minus122

1483

minus13

1594

11B3

LYP

1738minus48

3033

3089minus143minus128

1518minus48

1639

minus34

Exp

1690

2890

2961

1470

1605

10GGAPW91

1759minus19

B3LY

P1807minus67

Exp

1740

12GGAPW91

3019

3086minus139minus105

1487

minus7

1598

71356

41547

3B3

LYP

3041

3090minus161minus109

1512minus32

1610

minus5

1373

minus13

1599

minus49

Exp

2880

2981

1480

1605

1360

1550

Advances in Chemistry 9

Table 4 Deviations estimated over differences between experimen-tal and theoretical wavenumbers forGGAPW91 andB3LYP IRdata

Method Deviation 1 (cmminus1) Deviation 2 (cmminus1)GGAPW91 13 124B3LYP 43 145

Experimentaldata

GGAPW91

B3LYP

3500 3000 2500 2000 1500 1000 500 0

Figure 4 Ranges for important vibrational modes collected forcompounds 1ndash23 through experimental data versus GGAPW91results versus B3LYP results Vibrational modes come in accordanceto bonding atoms and bond order in green CndashH modes in darkgreen C=C modes in light pink CndashO in burgundy C=O and inblue N=O modes

For each musk group the central frequencies averages(ave (5)) and their standard deviations (std (6)) wereestimated these values are plotted at the right side of thecentral frequency listThe next column on the right shows thedifferences between each central frequencies and the averageof central frequencies (diff (7)) Consider

avegroup =1

119899

119891

sum

119899=1

cf119899

(5)

where cf119899

represents the central frequencies found for eachgroup (MCM PCM etc) having herein been defined lowerand upper limits for 119899 so that 119899 = 1 5 for MCM 119899 = 6 10for PCM 119899 = 11 13 for NM and 119899 = 14 16 for ACMConsider

stdgroup = radic119891

sum

119899=1

[(cf119899

minus avegroup)2

] (6)

diff119899

= cf119899

minus avegroup (7)

The values found for the avegroup and stdgroup of theMCMgroup were the same as those found for theMCa group thosebelonging to NM were repeated for Na and data calculatedfor ACM were taken as parameters for Aa

Finally each diff119899

value was allowed to be lower or twotimes its stdgroup value as stated in

diff119899

le 2 times stdgroup (8)

If this happens it is possible to say that theoretical datafit vibrational theoryrsquos demands over study band if not theydo not agree When repeating this process for all three bandsunder the spectra values for the Total Deviations (TD) arecollected The zero input (0) means that all three bandsobeyed (8) Logically TD inputs between 1 and 3 indicate howmany of the bands presented a diff

119899

value that was higher thanthe stdgroup doubled value

34 Absence of the 2000ndash2400 cmminus1 Band None of the pre-vious tables bring a mode among the 2000ndash2400 cmminus1 rangeThe 2200 cmminus1 band was described by Turin as the carbonylstretching mode which only occurred at this range whenworking with NDDOAM1 Hamiltonian Through ab initiocalculation the mentioned mode was observed at the rangeof 1680ndash1810 cmminus1 and it was only taken into account forcfs estimates when dealing with the 1550ndash1950 cmminus1 band fornitro compounds Regarding structural features compounds6 7 12 and 13 do not possess the carbonyl group and arereal musks while compounds 17 18 19 20 and 23 containthe carbonyl group and are odorless Therefore carbonylstretches cannot be taken as criteria for IR data-muskybehavior profile

35 GGAPW91 cf rsquos Plots and Musk Activity Table 5 (withGGAPW91 results) presents only two molecules nonmusks20 and 23 which failed to express a complete match betweentheoretical data and the signed bands of the vibrational the-ory For nonmusk 20 the cf value estimated near 1000 cmminus1was higher than its avegroup value this compound had bothOndashCsp2 stretching modes occurring at high intensities andfrequencies below 1200 cmminus1 (which are precisely the 1090and 1144 cmminus1 wavenumbers) On the other hand musks 14ndash16 and nonmusk 19 have presented a stretch mode (or at leastone of them) outside the 1000 plusmn 200 cmminus1 range Concerningnonmusk 23 it can be said that it showed a lower cf valuewhich remained around the 700 cmminus1 band and a higher cfvalue near the 1000 cmminus1 band This can be explained by thefact that (i) referring to the 700 cmminus1 band 23 had an averagefor intensity modes that was lower than the average valuesfor the other Na and NM compounds and therefore lowerweight values (see (4)) and lower cf and (ii) referring to the1000 cmminus1 band the OndashCsp3 stretch mode at 1073 cmminus1 hadan intensity value that was 87 times higher than the secondmost intensemode generating the observed overestimated cfvalue

That being said and according to mathematical approachadopted in this paper no relationship was found betweenIR properties and the presence of musky odor throughGGAPW91 It does not mean that GGAPW91 calculationleads to affirm that musks and nonmusks have indistinguish-able spectra Itmeans that considering theweighted-averagesvalues resource in order to simplify the adoption of alltheoretical peaks under analysis resulting central frequenciesare similar among musks and nonmusks Such observationmay be due the fact that GGAPW91 spectra had narrowerbands for each vibrational mode rather than B3LYP spectraAs GGAPW91 proved to be a more accurate method itrequires a more accurate statistical tools so to properly dealwith all theoretical modes as to affirm (or deny) a possibledifference on musks and nonmusks IR spectra

36 B3LYP cf rsquos Plots and Musk Activity On the other handTable 6 (with B3LYP data) shows that all musks from 1 to16 have had theoretical central frequencies that fitted thefrequencies demanded at 700 1000 and 1500 (or 1750) cmminus1

10 Advances in Chemistry

Table 5 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for GGAPW91 collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd

Diff Around 1000 Avestd

Diff Around 1500 Avestd

Diff

MCM

1 742 743 minus1 1030 1049 minus19 1429 1411 18 02 761 12 18 1096 31 47 1404 11 minus7 03 748 5 1047 minus2 1417 6 04 734 minus9 1016 minus33 1405 minus6 05 730 minus13 1057 8 1402 minus9 0

PCM

6 751 733 18 1046 1020 26 1423 1480 minus57 07 769 34 36 1051 48 31 1424 54 minus56 08 678 minus55 977 minus43 1527 47 09 731 minus2 1066 46 1532 52 010 736 3 959 minus61 1495 15 0

NM11 735 755 minus20 1033 1019 14 1634 1589 45 012 763 17 8 1002 16 minus17 1567 39 minus22 013 766 11 1023 4 1567 minus22 0

ACM14 784 784 0 1084 1086 minus2 1402 1411 minus9 015 762 23 minus22 1079 9 minus7 1401 16 minus10 016 807 23 1096 10 1429 18 0

MCa 17 751 743 8 1067 1049 17 1405 1411 minus7 018 726 12 minus17 1049 31 0 1417 11 6 0

Aa 19 779 784 minus6 1073 1086 minus13 1411 1411 0 020 757 23 minus28 1105 9 19 1403 16 minus8 1

Na21 733 755 minus21 1033 1019 13 1557 1589 minus32 022 757 17 2 1006 16 minus13 1549 39 minus40 023 717 minus38 1060 41 1655 66 2

lowastTD total deviations

in the vibrational theory Simultaneously Aa and Na showedthat at least one of their cfs was too shifted from theiraverages Molecule 23 for instance is the only nonmusk pos-sessing an aldehyde functional group and its C=O stretchingmode is found at the 1550ndash1950 cmminus1 range under studyNevertheless nitromusk 11 also holds an aldehyde functionalgroup and though its cf at 1750 cmminus1 is indeed higher than theother cfs for the NM it is still 70 cmminus1 lower than 23rsquos cf Stillconcerning the analysis of Table 6 we can say that the acyclicanalogs 19 and 20 have had their central frequencies shiftedto lower values at the 1500 cmminus1 diagnostic band the onlyone in which there was no agreement between theoreticalresults and expectations deriving from the vibrational theoryAt the 1500 plusmn 200 cmminus1 range hydrocarbon scissoring modesand alkenearomatic C=C stretching modes are found and19 and 20 lack the gem-methyl at the cyclohexane that areobserved in 14 and 15 moreover although in 16 this gem-methyl is also absent it possesses two alkene groups forwhich its stretching modes are also found at this rangeFinally macrocyclic analogs showed the same spectra dataas macrocyclic musks as compounds 18 and 19 differ fromMCM in that they lack two methylene groups it is possibleto suggest that such loss leads the moleculersquos CndashH vibrational

mode sum to be too low to be detected by its OR as suggestedelsewhere [23] Besides both 18 and 19 present awoody smellby being smaller they may be able to bind to a variety ofdifferent ORs which do not reassemble the behavior of themusk detected by possibly only one OR or just a few more[48]

4 Conclusions

This paper worked on developing a method which couldstate the following (i) whether musky molecules had theirIR theoretical spectra fitted into the four bands assigned byvibrational theory in 2002 Turinrsquos paper and (ii) whethernonmuskymolecules did not have their IR theoretical spectrafitted into same criteria It was first concluded that only threebands were useful for discriminating musk from nonmuskodorants The fourth IR band refers to a carbonyl stretchingmode and data here presented showed that this mode cannotbe taken as criteria when building a muskiness profile

Present work was carried out with two different func-tionals applying DFT calculation level and both were ableto accurately predict IR spectra A mathematical strategyhas been adopted in order to summarize IR theoretical

Advances in Chemistry 11

Table 6 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for B3LYP collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd Diff Around 1000 Ave

std Diff Around 1500 Avestd Diff

MCM

1 754 748 6 1142 1093 48 1407 1423 minus16 02 768 16 20 1066 39 minus27 1428 10 5 03 749 1 1116 23 1421 minus2 04 744 minus3 1099 5 1430 6 05 723 minus25 1044 minus49 1429 6 0

PCM

6 749 722 28 1068 1019 49 1450 1476 minus26 07 752 51 31 1052 62 33 1450 32 minus27 08 692 minus30 971 minus48 1461 minus15 09 646 minus75 1069 50 1499 23 010 768 47 936 minus83 1520 44 0

NM11 754 766 minus12 952 977 minus26 1602 1597 5 012 771 10 5 993 22 16 1595 5 minus2 013 772 7 987 9 1593 minus3 0

ACM14 722 732 minus10 1101 1127 minus26 1424 1435 minus12 015 771 35 39 1130 24 3 1431 14 minus4 016 703 minus29 1149 22 1451 15 0

MCa 17 750 748 2 1067 1093 minus26 1418 1423 minus5 018 726 16 minus22 1072 39 minus21 1432 10 9 0

Aa 19 784 732 52 1097 1127 minus30 1357 1435 minus78 120 763 35 31 1087 24 minus40 1410 14 minus26 1

Na21 742 766 minus24 1015 977 38 1601 1597 4 122 767 10 1 1150 22 173 1600 5 3 123 702 minus64 1068 91 1675 78 3

lowastTD total deviations

data and properly compare musk to nonmusk moleculesUsing this approach GGAPW91 computed spectra showedno discriminating patterns between musks and nonmusksB3LYP data showed theoretical frequencies and the threediagnostic bands to bematching while nitro andmacrocyclicnonmusks failed in at least one of such comparisons

It was therefore possible to conclude that no specificmodealone is responsible for the discrimination of themusky odorInstead when a great amount of frequencies expressing weakor medium intensities were found along the 700ndash1700 cmminus1range musk odor occurs At this range observedmodes wereCH2

wag and scissor bending modes C=C stretches andsymmetric nitro stretching modes

This trial scanning over IR vibrational modes and theirrelation to musk odor perception brings new informationaltowards the understanding and application of vibrationaltheoryrsquos ideas and opens the possibility to a more extensivestudy in which a broader number of molecules may bemodeled so as to come to a quantitative proposal for amusky-like novel odorant regarding their IR vibrational modes

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The authors thank Professor Ines Sabioni Resck (fromInstituto de Quımica Brasılia Brazil) for initial ideas andreliance

References

[1] M Eh ldquoNew alicyclic musks the fourth generation of muskodorantsrdquoChemistryamp Biodiversity vol 1 no 12 pp 1975ndash19842004

[2] P Saiyasombati andG BKasting ldquoTwo-stage kinetic analysis offragrance evaporation and absorption from skinrdquo InternationalJournal of Cosmetic Science vol 25 no 5 pp 235ndash243 2003

[3] G B Kasting and P Saiyasombati ldquoA physico-chemical prop-erties based model for estimating evaporation and absorptionrates of perfumes from skinrdquo International Journal of CosmeticScience vol 23 no 1 pp 49ndash58 2001

[4] M Shirasu K Yoshikawa Y Takai et al ldquoOlfactory receptor andneural pathway responsible for highly selective sensing of muskodorsrdquo Neuron vol 81 no 1 pp 165ndash178 2014

[5] J Reisert and H Zhao ldquoResponse kinetics of olfactory receptorneurons and the implications in olfactory codingrdquo Journal ofGeneral Physiology vol 138 no 3 pp 303ndash310 2011

12 Advances in Chemistry

[6] J-P Rospars Y Gu A Gremiaux and P Lucas ldquoOdourtransduction in olfactory receptor neuronsrdquo Chinese Journal ofPhysiology vol 53 no 6 pp 364ndash372 2010

[7] B Malnic and A F Mercadante ldquoThe odorant signaling path-wayrdquo Annual Review of Biomedical Sciences vol 11 pp T86ndashT94 2009

[8] K Snitz A Yablonka T Weiss I Frumin R M Khan andN Sobel ldquoPredicting odor perceptual similarity from odorstructurerdquo PLoS Computational Biology vol 9 no 9 Article IDe1003184 2013

[9] B K Lavine CWhite NMirjankar CM Sundling and CMBreneman ldquoOdor-structure relationship studies of tetralin andindan musksrdquo Chemical Senses vol 37 no 8 pp 723ndash736 2012

[10] Y Zou H Mouhib W Stahl A Goeke Q Wang and PKraft ldquoEfficient macrocyclization by a novel oxy-oxonia-copereaction synthesis and olfactory properties of new macrocyclicmusksrdquo Chemistry vol 18 no 23 pp 7010ndash7015 2012

[11] S Liu ldquoStudy on the relationship between molecular odour ofpolycyclic musksrdquo Xiangliao Xiangjing Huazhuangpin vol 6pp 24ndash29 2004

[12] S-Y Takane and J B O Mitchell ldquoA structure-odor relation-ship study using EVA descriptors and hierarchical clusteringrdquoOrganicampBiomolecular Chemistry vol 2 no 22 pp 3250ndash32552004

[13] K J Rossiter ldquoStructure-odour relationshipsrdquo ChemicalReviews vol 96 no 8 pp 3201ndash3240 1996

[14] M Zarzo ldquoThe sense of smell molecular basis of odorantrecognitionrdquoBiological Reviews vol 82 no 3 pp 455ndash479 2007

[15] A Kato and K Touhara ldquoMammalian olfactory receptorspharmacologyGprotein coupling anddesensitizationrdquoCellularandMolecular Life Sciences vol 66 no 23 pp 3743ndash3753 2009

[16] L Turin and F Yoshii ldquoStructure-odor relations a modernperspectiverdquo in Handbook of Olfaction and Gustation R LDoty Ed pp 275ndash294 Marcel Dekker New York NY USA2003

[17] L Turin ldquoA spectroscopic mechanism for primary olfactoryreceptionrdquo Chemical Senses vol 21 no 6 pp 773ndash791 1996

[18] M A Reed ldquoInelastic electron tunneling spectroscopyrdquo Mate-rials Today vol 11 no 11 pp 46ndash50 2008

[19] L Turin ldquoA method for the calculation of odor character frommolecular structurerdquo Journal ofTheoretical Biology vol 216 no3 pp 367ndash385 2002

[20] L J W Haffenden V A Yaylayan and J Fortin ldquoInvestigationof vibrational theory of olfaction with variously labelled ben-zaldehydesrdquo Food Chemistry vol 73 no 1 pp 67ndash72 2001

[21] J C Brookes F Hartoutsiou A P Horsfield and A MStoneham ldquoCould humans recognize odor by phonon assistedtunnelingrdquo Physical Review Letters vol 98 no 3 Article ID038101 2007

[22] M I Franco L Turin A Mershin and E M C SkoulakisldquoMolecular vibration-sensing component in Drosophila mela-nogaster olfactionrdquo Proceedings of the National Academy ofSciences vol 108 no 9 pp 3797ndash3802 2011

[23] I A Solovrsquoyov P-Y Chang and K Schulten ldquoVibrationallyassisted electron transfer mechanism of olfaction myth orrealityrdquo Physical Chemistry Chemical Physics vol 14 no 40 pp13861ndash13871 2012

[24] S GaneDGeorganakis KManiati et al ldquoMolecular vibration-sensing component in human olfactionrdquo PLoS ONE vol 8 no1 Article ID e55780 2013

[25] D L Pavia G M Lampman G S Kriz and J R VyvyanIntroduction to Spectroscopy Cengage Learning Sao PauloBrazil 2010

[26] D A Lerner D Berthomieu and E R Maia ldquoModeling of theconformational flexibility and EZ isomerism of thiazoximicacid and cefotaximerdquo International Journal of Quantum Chem-istry vol 111 no 6 pp 1222ndash1238 2011

[27] A P Scott andL Radom ldquoHarmonic vibrational frequencies anevaluation of Hartree-Fock Moslashller-Plesset quadratic configu-ration interaction density functional theory and semiempiricalscale factorsrdquoThe Journal of Physical Chemistry vol 100 no 41pp 16502ndash16513 1996

[28] S Gabler J Soelter T Hussain S Sachse and M SchmukerldquoPhysicochemical vs vibrational descriptors for prediction ofodor receptor responsesrdquo Molecular Informatics vol 32 no 9-10 pp 855ndash865 2013

[29] Materials Studio SW and Insight II SW Acelrys San DiegoCalif USA

[30] M J Frisch G W Trucks H B Schlegel et al ldquoGaussian 09Revision A02rdquo Gaussian Inc Wallingford Conn USA 2009

[31] H Sun ldquoCompass an ab initio force-field optimized forcondensed-phase applicationsmdashoverview with details onalkane and benzene compoundsrdquo Journal of Physical ChemistryB vol 102 no 38 pp 7338ndash7364 1998

[32] P Dauber-Osguthorpe V A Roberts D J Osguthorpe J WolfM Genest and A T Hagler ldquoStructure and energetics of ligandbinding to proteins Escherichia coli dihydrofolate reductase-trimethoprim a drug-receptor systemrdquo Proteins StructureFunction and Genetics vol 4 no 1 pp 31ndash47 1988

[33] DH JMackay A J Cross andA THagler ldquoThe role of energyminimization in simulation strategies of biomolecular systemsrdquoin Prediction of Protein Structure and the Principles of ProteinConformation D G Fasman Ed pp 317ndash358 Plenum PressNew York NY USA 1990

[34] R Fletcher and C M Reeves ldquoFunction minimization byconjugate gradientsrdquo The Computer Journal vol 7 no 2 pp149ndash154 1964

[35] WH Press B P Flannery S A Teukolsky andW T VetterlingNumerical Recipes in C the Art of Scientific Computing Cam-bridge University Press London UK 1988

[36] J J P Stewart ldquoMopac a semiempirical molecular orbitalprogramrdquo Journal of Computer-Aided Molecular Design vol 4no 1 pp 101ndash105 1990

[37] J A Pople D P Santry and G A Segal ldquoApproximate self-consistent molecular orbital theory I Invariant proceduresrdquoThe Journal of Chemical Physics vol 43 no 10 pp S129ndashS1351965

[38] J A Pople and G A Segal ldquoApproximate self-consistentmolecular orbital theory III CNDO results for AB

2

and AB3

systemsrdquo The Journal of Chemical Physics vol 44 no 9 pp3289ndash3296 1966

[39] M J S Dewar E G Zoebisch E F Healy and J J P StewartldquoAM1 a new general purpose quantum mechanical molecularmodelrdquo Journal of the American Chemical Society vol 107 no13 pp 3902ndash3909 1985

[40] B Delley ldquoAn all-electron numerical method for solving thelocal density functional for polyatomic moleculesrdquoThe Journalof Chemical Physics vol 92 no 1 pp 508ndash517 1990

[41] B Delley ldquoFast calculation of electrostatics in crystals and largemoleculesrdquo Journal of Physical Chemistry vol 100 no 15 pp6107ndash6110 1996

Advances in Chemistry 13

[42] B Delley ldquoDMol methodology and applicationsrdquo in DensityFunctional Methods in Chemistry J W Andzelm and J KLabanowski Eds pp 101ndash108 Springer New York NY USA1991

[43] B Delley ldquoCalculated electron distribution for Tetrafluoroter-phthalonitrile (TFT)rdquo Chemical Physics vol 110 no 2-3 pp329ndash338 1986

[44] YWang and J P Perdew ldquoCorrelation hole of the spin-polarizedelectron gas with exact small-wave-vector and high-densityscalingrdquo Physical Review B vol 44 no 24 pp 13298ndash13307 1991

[45] P J Stephens F J Devlin C F Chabalowski and M J FrischldquoAb Initio calculation of vibrational absorption and circulardichroism spectra using density functional force fieldsrdquo Journalof Physical Chemistry vol 98 no 45 pp 11623ndash11627 1994

[46] G Schaftenaar and J H Noordik ldquoMolden a pre- and post-processing program for molecular and electronic structuresrdquoJournal of Computer-Aided Molecular Design vol 14 no 2 pp123ndash134 2000

[47] Xming ldquoXming X server for Windowsrdquo 2012 httpwwwstraightrunningcomXmingNotes

[48] K Nara L R Saraiva X Ye and L B Buck ldquoA large-scaleanalysis of odor coding in the olfactory epitheliumrdquo Journal ofNeuroscience vol 31 no 25 pp 9179ndash9191 2011

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

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Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

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Theoretical ChemistryJournal of

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Journal of

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Analytical ChemistryInternational Journal of

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Quantum Chemistry

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Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

6 Advances in Chemistry

12345

678910

111213

141516

17181920

212223

Frequency (cmminus1)

01000200030004000

Rela

tive i

nten

sity

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Frequency (cmminus1)

01000200030004000

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Rela

tive i

nten

sity

Figure 3 Spectra obtained at B3LYP level for MCM 1ndash5 PCM 6ndash10 NM 11ndash13 ACM 14ndash16 and nonmusks 17ndash23

for asymmetric modes Finally carbon-hydrogen bendingmodes began at very low frequencies and went up to1540 cmminus1 at most (for musk 13) while carbon-hydrogenstretching occurred between 2953 cmminus1 (for compound 6)and 3229 cmminus1 (for nitromusk 13)

32 Part 2 Comparing GGAPW91 and B3LYP Spectrato Experimental Data For an overview over GGAPW91B3LYP and experimental [47] IR data Figure 4 and Table 2were built inwhich vibrationalmodes for themost importantfunctional groups are organized in accordance with theoreti-cal method adopted Each band expresses the range in whichlabeled vibrational mode occurs considering the maximumand theminimum found for all compoundsThus it becomespossible to state that B3LYP and GGAPW91 results for CndashH stretching modes start at 90 and 140 cmminus1 respectivelyvalues that are higher than the ones provided by experimentaldata simultaneously the same band ends at +50 cmminus1 forGGAPW91 and at +90 cmminus1 for B3LYP in comparison to theexperimental data CndashH bending modes finish at +30 cmminus1for GGAPW91 and at +80 cmminus1 for B3LYP when compared

to experimental values Aromatic C=C stretches occurredin an expected range for GGAPW91 with a +20 cmminus1 shiftfor alkene compounds B3LYP showed a continuous bandfor alkene and aromatic C=C stretches which started at+60 cmminus1 and ended at +30 cmminus1 over experimental dataCndashO stretching modes are found within an expected rangefor both GGAPW91 and B3LYP methods for tonkene 10GGAPW91 predicted CndashO mode at 1381 cmminus1 while thesame mode is found at 1403 cmminus1 in B3LYP data For C=Ostretchingmodes GGAPW91 showed a +20 cmminus1 incrementover lower and higher values found for experimental dataand B3LYP shifted over experimental range in +60 cmminus1Finally nitro N=O stretching modes have had both sym-metric and asymmetric modes accurately and precisely esti-mated for GGAPW91 for B3LYP symmetric nitro stretchingshowed a broader band than that of GGAPW91 and ofexperimental data starting at a +30 cmminus1 shift and finishingat a minus10 cmminus1 shift while their asymmetric modes werecorrectly predicted

Therefore while GGAPW91 final results were all fittedinto experimental reports considering the allowed plusmn30 cmminus1

Advances in Chemistry 7

Table 2 Collection of observed versus calculated IR mode frequencies for compounds 1ndash23

Vibrational modea Observed wavenumber (cmminus1) [25] Calculated wavenumber (cmminus1)GGAPW91 B3LYP

] CbndashH 3150ndash2850 3198ndash2898 3229ndash2953] CndashH (aldehyde) 2900ndash2800 2954ndash2892 2988ndash2939120575 CndashH up to 1465 up to 1493 up to 1540] C=C (alkene) 1680ndash1600 1706ndash1687 1718ndash1707] C=C (aromatic) 1600ndash1475 1618ndash1543 1650ndash1531] C=O (aldehyde) 1740ndash1720 1715ndash1693 1772ndash1749] C=O (ketone) 1725ndash1705 1733ndash1680 1784ndash1738] C=O (ester) 1750ndash1730 1777ndash1742 1810ndash1768120575 CndashO (alcohol ether and ester) 1300ndash1000 1381 1200ndash1018 1403 1312ndash1006]as nitro (RndashNO2) 1660ndash1500 1560ndash1520 1618ndash1531]119904 nitro (RndashNO2) 1390ndash1260 1340ndash1310 1417ndash1250a] stretching ]as asymmetric stretching ]119904 symmetric stretching 120575 bendingb] C(sp2)ndashH C(sp3)ndashH and C(aromatic)ndashH

shifts B3LYP results overestimated CndashH stretching andbending modes alkene C=C stretching modes and aldehydeand ketone C=O stretching modes

To quantify collected results experimental IR spectrumgiven for each particular molecule was compared to its theo-retical spectra as shown in Table 3 In the literaturemdashpublicand personal IR databasemdashonly spectra for compounds 1ndash5 8 10 and 12 were found The vibrational modes chosenas internal patterns of comparison were as follows whenoccurring (i) the two most intense peaks regarding theCndashO stretching mode (ii) the most intense peak for theC=O stretching mode (iii) the most intense peaks for thesymmetric and asymmetric CndashH stretching modes (iv) thehighest wavenumber found for the CndashH bending modes (v)the highest intensity for the C=C stretching mode and (vi)the most intense peaks for the symmetric and asymmetricN=O stretching modes They are altogether able to expressthe accuracy relying on theoretical data once all functionalgroups have had their modes listed within chosen criteriaand the whole spectrum has been covered

Extra information comes on the so-called DIFF columnsin Table 3 Consider

DIFF119894

= ExpWavenumber119894

minusTheoWavenumber119894

(2)

where the difference established between experimental andtheoretical values was plotted (for both GGAPW91 andB3LYP results) as shown in (2) In such equation for acertain mode 119894 the difference (DIFF) is obtained through thesubtraction of its theoretical value (TheoWavenumber) fromits experimental value (ExpWavenumber) The average of thecollected differences on Table 3 was estimated as the values ofabsolute difference were divided by the number of occurringmodes disregarding all CndashH stretch modes as follows

Deviation 1 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(3)

This choice was made due to the fact that all CndashHstretches were overestimated in more than 100 cmminus1 for both

theoretical methods as discussed before This last modetherefore had its deviation separately estimated as follows

Deviation 2 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(4)

in which the absolute DIFF119894

is collected is summed for all CndashH stretching modes within the same theoretical method andis divided by the number of occurring modes

So finally GGAPW91 IR results are found to be moreaccurate than B3LYP results with calculated deviations thatare equal to 13 cmminus1 and 43 cmminus1 respectively Neverthelessthey correspond to a 325 (DFT) and a 1075 (B3LYP)shift over the 4000ndash0 cmminus1 that represents the spectrumwhich ensures that both methods are powerfully predictiveSimultaneously both methods display great shift over CndashHstretching modes corresponding to an increase of 124 cmminus1and 145 cmminus1 respectively Considering that one of thispaperrsquos aims is to compare theoretical IR data with postulatesof the vibrational theory on musky odor the last mentionedmodes are irrelevant as they are not supposed to be respon-sible for muskiness

33 Part 3 IR Spectra and Musk Activity Herein bothGGAPW91 and B3LYP data will be taken into account so asto compare theoretical results with the bands described in thevibrational theory (700 1000 1500 or 1750 and 2200 cmminus1)which would assign as supposed by the previous theory amusky odor to these molecules

In Tables 5 and 6 the information was gathered so as todispose musks 1 to 23 in lines and their central frequencies(at 700 1000 and 1500 or 1750 cmminus1) in columns Besidesthe compounds were gathered in groups in accordance withtheir structural similarity (see first column on the left) MCMfor macrocyclic musks PCM for polycyclic musks NM fornitromusks and ACM for acyclic musks Nonmusks arecalled MCa for macrocyclic analogs Aa for acyclic analogsand Na for nitro analogs As no vibrational mode hasoccurred at 2200 plusmn 200 cmminus1 there is no such column

8 Advances in Chemistry

Table3Mostimpo

rtantw

avenum

bersforc

ompo

unds

1ndash5810and

12according

toDFT

B3LYP

and

experim

entald

ata

Highest

]Cndash

0DIFF

]C=

0DIFF

]Cndash

HDIFF

120575Cndash

HDIFF

]C=

CDIFF

]119904N=O

DIFF

]asN=O

DIFF

1GGAPW91

1207

1215

2833

1748

minus9

3017

3034minus160minus108

1479

minus18

B3LY

P118

11210

5438

1786minus47

3033

3069minus176minus143

1517minus56

Exp

1235

1248

1739

2857

2926

1461

2GGAPW91

1099

1231

107

1739

minus7

2999

3027minus153minus94

1474

minus14

B3LY

P1124

1240minus15minus2

1778minus46

3012

3058minus166minus125

1512minus52

Experim

entald

ata

1109

1238

1732

2846

2933

1460

3GGAPW91

1121

1220minus12

181738

minus6

2991

3037minus145minus104

1481minus21

B3LY

P119

41254minus85minus16

1774minus42

3029

3063minus183minus130

1510minus50

Exp

1109

1238

1732

2846

2933

1460

4GGAPW91

1726

minus11

2990

3051minus124minus123

1475

minus15

1687

B3LY

P1774minus59

3010

3051minus144minus123

1513minus53

1707

Exp

1715

2866

2928

1460

5GGAPW91

1733minus18

2994

3039minus128minus111

1473

minus13

1706

B3LY

P1773minus58

3031

3057minus165minus129

1511minus51

1718

Exp

1715

2866

2928

1460

8GGAPW91

1685

53005

3083minus115minus122

1483

minus13

1594

11B3

LYP

1738minus48

3033

3089minus143minus128

1518minus48

1639

minus34

Exp

1690

2890

2961

1470

1605

10GGAPW91

1759minus19

B3LY

P1807minus67

Exp

1740

12GGAPW91

3019

3086minus139minus105

1487

minus7

1598

71356

41547

3B3

LYP

3041

3090minus161minus109

1512minus32

1610

minus5

1373

minus13

1599

minus49

Exp

2880

2981

1480

1605

1360

1550

Advances in Chemistry 9

Table 4 Deviations estimated over differences between experimen-tal and theoretical wavenumbers forGGAPW91 andB3LYP IRdata

Method Deviation 1 (cmminus1) Deviation 2 (cmminus1)GGAPW91 13 124B3LYP 43 145

Experimentaldata

GGAPW91

B3LYP

3500 3000 2500 2000 1500 1000 500 0

Figure 4 Ranges for important vibrational modes collected forcompounds 1ndash23 through experimental data versus GGAPW91results versus B3LYP results Vibrational modes come in accordanceto bonding atoms and bond order in green CndashH modes in darkgreen C=C modes in light pink CndashO in burgundy C=O and inblue N=O modes

For each musk group the central frequencies averages(ave (5)) and their standard deviations (std (6)) wereestimated these values are plotted at the right side of thecentral frequency listThe next column on the right shows thedifferences between each central frequencies and the averageof central frequencies (diff (7)) Consider

avegroup =1

119899

119891

sum

119899=1

cf119899

(5)

where cf119899

represents the central frequencies found for eachgroup (MCM PCM etc) having herein been defined lowerand upper limits for 119899 so that 119899 = 1 5 for MCM 119899 = 6 10for PCM 119899 = 11 13 for NM and 119899 = 14 16 for ACMConsider

stdgroup = radic119891

sum

119899=1

[(cf119899

minus avegroup)2

] (6)

diff119899

= cf119899

minus avegroup (7)

The values found for the avegroup and stdgroup of theMCMgroup were the same as those found for theMCa group thosebelonging to NM were repeated for Na and data calculatedfor ACM were taken as parameters for Aa

Finally each diff119899

value was allowed to be lower or twotimes its stdgroup value as stated in

diff119899

le 2 times stdgroup (8)

If this happens it is possible to say that theoretical datafit vibrational theoryrsquos demands over study band if not theydo not agree When repeating this process for all three bandsunder the spectra values for the Total Deviations (TD) arecollected The zero input (0) means that all three bandsobeyed (8) Logically TD inputs between 1 and 3 indicate howmany of the bands presented a diff

119899

value that was higher thanthe stdgroup doubled value

34 Absence of the 2000ndash2400 cmminus1 Band None of the pre-vious tables bring a mode among the 2000ndash2400 cmminus1 rangeThe 2200 cmminus1 band was described by Turin as the carbonylstretching mode which only occurred at this range whenworking with NDDOAM1 Hamiltonian Through ab initiocalculation the mentioned mode was observed at the rangeof 1680ndash1810 cmminus1 and it was only taken into account forcfs estimates when dealing with the 1550ndash1950 cmminus1 band fornitro compounds Regarding structural features compounds6 7 12 and 13 do not possess the carbonyl group and arereal musks while compounds 17 18 19 20 and 23 containthe carbonyl group and are odorless Therefore carbonylstretches cannot be taken as criteria for IR data-muskybehavior profile

35 GGAPW91 cf rsquos Plots and Musk Activity Table 5 (withGGAPW91 results) presents only two molecules nonmusks20 and 23 which failed to express a complete match betweentheoretical data and the signed bands of the vibrational the-ory For nonmusk 20 the cf value estimated near 1000 cmminus1was higher than its avegroup value this compound had bothOndashCsp2 stretching modes occurring at high intensities andfrequencies below 1200 cmminus1 (which are precisely the 1090and 1144 cmminus1 wavenumbers) On the other hand musks 14ndash16 and nonmusk 19 have presented a stretch mode (or at leastone of them) outside the 1000 plusmn 200 cmminus1 range Concerningnonmusk 23 it can be said that it showed a lower cf valuewhich remained around the 700 cmminus1 band and a higher cfvalue near the 1000 cmminus1 band This can be explained by thefact that (i) referring to the 700 cmminus1 band 23 had an averagefor intensity modes that was lower than the average valuesfor the other Na and NM compounds and therefore lowerweight values (see (4)) and lower cf and (ii) referring to the1000 cmminus1 band the OndashCsp3 stretch mode at 1073 cmminus1 hadan intensity value that was 87 times higher than the secondmost intensemode generating the observed overestimated cfvalue

That being said and according to mathematical approachadopted in this paper no relationship was found betweenIR properties and the presence of musky odor throughGGAPW91 It does not mean that GGAPW91 calculationleads to affirm that musks and nonmusks have indistinguish-able spectra Itmeans that considering theweighted-averagesvalues resource in order to simplify the adoption of alltheoretical peaks under analysis resulting central frequenciesare similar among musks and nonmusks Such observationmay be due the fact that GGAPW91 spectra had narrowerbands for each vibrational mode rather than B3LYP spectraAs GGAPW91 proved to be a more accurate method itrequires a more accurate statistical tools so to properly dealwith all theoretical modes as to affirm (or deny) a possibledifference on musks and nonmusks IR spectra

36 B3LYP cf rsquos Plots and Musk Activity On the other handTable 6 (with B3LYP data) shows that all musks from 1 to16 have had theoretical central frequencies that fitted thefrequencies demanded at 700 1000 and 1500 (or 1750) cmminus1

10 Advances in Chemistry

Table 5 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for GGAPW91 collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd

Diff Around 1000 Avestd

Diff Around 1500 Avestd

Diff

MCM

1 742 743 minus1 1030 1049 minus19 1429 1411 18 02 761 12 18 1096 31 47 1404 11 minus7 03 748 5 1047 minus2 1417 6 04 734 minus9 1016 minus33 1405 minus6 05 730 minus13 1057 8 1402 minus9 0

PCM

6 751 733 18 1046 1020 26 1423 1480 minus57 07 769 34 36 1051 48 31 1424 54 minus56 08 678 minus55 977 minus43 1527 47 09 731 minus2 1066 46 1532 52 010 736 3 959 minus61 1495 15 0

NM11 735 755 minus20 1033 1019 14 1634 1589 45 012 763 17 8 1002 16 minus17 1567 39 minus22 013 766 11 1023 4 1567 minus22 0

ACM14 784 784 0 1084 1086 minus2 1402 1411 minus9 015 762 23 minus22 1079 9 minus7 1401 16 minus10 016 807 23 1096 10 1429 18 0

MCa 17 751 743 8 1067 1049 17 1405 1411 minus7 018 726 12 minus17 1049 31 0 1417 11 6 0

Aa 19 779 784 minus6 1073 1086 minus13 1411 1411 0 020 757 23 minus28 1105 9 19 1403 16 minus8 1

Na21 733 755 minus21 1033 1019 13 1557 1589 minus32 022 757 17 2 1006 16 minus13 1549 39 minus40 023 717 minus38 1060 41 1655 66 2

lowastTD total deviations

in the vibrational theory Simultaneously Aa and Na showedthat at least one of their cfs was too shifted from theiraverages Molecule 23 for instance is the only nonmusk pos-sessing an aldehyde functional group and its C=O stretchingmode is found at the 1550ndash1950 cmminus1 range under studyNevertheless nitromusk 11 also holds an aldehyde functionalgroup and though its cf at 1750 cmminus1 is indeed higher than theother cfs for the NM it is still 70 cmminus1 lower than 23rsquos cf Stillconcerning the analysis of Table 6 we can say that the acyclicanalogs 19 and 20 have had their central frequencies shiftedto lower values at the 1500 cmminus1 diagnostic band the onlyone in which there was no agreement between theoreticalresults and expectations deriving from the vibrational theoryAt the 1500 plusmn 200 cmminus1 range hydrocarbon scissoring modesand alkenearomatic C=C stretching modes are found and19 and 20 lack the gem-methyl at the cyclohexane that areobserved in 14 and 15 moreover although in 16 this gem-methyl is also absent it possesses two alkene groups forwhich its stretching modes are also found at this rangeFinally macrocyclic analogs showed the same spectra dataas macrocyclic musks as compounds 18 and 19 differ fromMCM in that they lack two methylene groups it is possibleto suggest that such loss leads the moleculersquos CndashH vibrational

mode sum to be too low to be detected by its OR as suggestedelsewhere [23] Besides both 18 and 19 present awoody smellby being smaller they may be able to bind to a variety ofdifferent ORs which do not reassemble the behavior of themusk detected by possibly only one OR or just a few more[48]

4 Conclusions

This paper worked on developing a method which couldstate the following (i) whether musky molecules had theirIR theoretical spectra fitted into the four bands assigned byvibrational theory in 2002 Turinrsquos paper and (ii) whethernonmuskymolecules did not have their IR theoretical spectrafitted into same criteria It was first concluded that only threebands were useful for discriminating musk from nonmuskodorants The fourth IR band refers to a carbonyl stretchingmode and data here presented showed that this mode cannotbe taken as criteria when building a muskiness profile

Present work was carried out with two different func-tionals applying DFT calculation level and both were ableto accurately predict IR spectra A mathematical strategyhas been adopted in order to summarize IR theoretical

Advances in Chemistry 11

Table 6 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for B3LYP collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd Diff Around 1000 Ave

std Diff Around 1500 Avestd Diff

MCM

1 754 748 6 1142 1093 48 1407 1423 minus16 02 768 16 20 1066 39 minus27 1428 10 5 03 749 1 1116 23 1421 minus2 04 744 minus3 1099 5 1430 6 05 723 minus25 1044 minus49 1429 6 0

PCM

6 749 722 28 1068 1019 49 1450 1476 minus26 07 752 51 31 1052 62 33 1450 32 minus27 08 692 minus30 971 minus48 1461 minus15 09 646 minus75 1069 50 1499 23 010 768 47 936 minus83 1520 44 0

NM11 754 766 minus12 952 977 minus26 1602 1597 5 012 771 10 5 993 22 16 1595 5 minus2 013 772 7 987 9 1593 minus3 0

ACM14 722 732 minus10 1101 1127 minus26 1424 1435 minus12 015 771 35 39 1130 24 3 1431 14 minus4 016 703 minus29 1149 22 1451 15 0

MCa 17 750 748 2 1067 1093 minus26 1418 1423 minus5 018 726 16 minus22 1072 39 minus21 1432 10 9 0

Aa 19 784 732 52 1097 1127 minus30 1357 1435 minus78 120 763 35 31 1087 24 minus40 1410 14 minus26 1

Na21 742 766 minus24 1015 977 38 1601 1597 4 122 767 10 1 1150 22 173 1600 5 3 123 702 minus64 1068 91 1675 78 3

lowastTD total deviations

data and properly compare musk to nonmusk moleculesUsing this approach GGAPW91 computed spectra showedno discriminating patterns between musks and nonmusksB3LYP data showed theoretical frequencies and the threediagnostic bands to bematching while nitro andmacrocyclicnonmusks failed in at least one of such comparisons

It was therefore possible to conclude that no specificmodealone is responsible for the discrimination of themusky odorInstead when a great amount of frequencies expressing weakor medium intensities were found along the 700ndash1700 cmminus1range musk odor occurs At this range observedmodes wereCH2

wag and scissor bending modes C=C stretches andsymmetric nitro stretching modes

This trial scanning over IR vibrational modes and theirrelation to musk odor perception brings new informationaltowards the understanding and application of vibrationaltheoryrsquos ideas and opens the possibility to a more extensivestudy in which a broader number of molecules may bemodeled so as to come to a quantitative proposal for amusky-like novel odorant regarding their IR vibrational modes

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The authors thank Professor Ines Sabioni Resck (fromInstituto de Quımica Brasılia Brazil) for initial ideas andreliance

References

[1] M Eh ldquoNew alicyclic musks the fourth generation of muskodorantsrdquoChemistryamp Biodiversity vol 1 no 12 pp 1975ndash19842004

[2] P Saiyasombati andG BKasting ldquoTwo-stage kinetic analysis offragrance evaporation and absorption from skinrdquo InternationalJournal of Cosmetic Science vol 25 no 5 pp 235ndash243 2003

[3] G B Kasting and P Saiyasombati ldquoA physico-chemical prop-erties based model for estimating evaporation and absorptionrates of perfumes from skinrdquo International Journal of CosmeticScience vol 23 no 1 pp 49ndash58 2001

[4] M Shirasu K Yoshikawa Y Takai et al ldquoOlfactory receptor andneural pathway responsible for highly selective sensing of muskodorsrdquo Neuron vol 81 no 1 pp 165ndash178 2014

[5] J Reisert and H Zhao ldquoResponse kinetics of olfactory receptorneurons and the implications in olfactory codingrdquo Journal ofGeneral Physiology vol 138 no 3 pp 303ndash310 2011

12 Advances in Chemistry

[6] J-P Rospars Y Gu A Gremiaux and P Lucas ldquoOdourtransduction in olfactory receptor neuronsrdquo Chinese Journal ofPhysiology vol 53 no 6 pp 364ndash372 2010

[7] B Malnic and A F Mercadante ldquoThe odorant signaling path-wayrdquo Annual Review of Biomedical Sciences vol 11 pp T86ndashT94 2009

[8] K Snitz A Yablonka T Weiss I Frumin R M Khan andN Sobel ldquoPredicting odor perceptual similarity from odorstructurerdquo PLoS Computational Biology vol 9 no 9 Article IDe1003184 2013

[9] B K Lavine CWhite NMirjankar CM Sundling and CMBreneman ldquoOdor-structure relationship studies of tetralin andindan musksrdquo Chemical Senses vol 37 no 8 pp 723ndash736 2012

[10] Y Zou H Mouhib W Stahl A Goeke Q Wang and PKraft ldquoEfficient macrocyclization by a novel oxy-oxonia-copereaction synthesis and olfactory properties of new macrocyclicmusksrdquo Chemistry vol 18 no 23 pp 7010ndash7015 2012

[11] S Liu ldquoStudy on the relationship between molecular odour ofpolycyclic musksrdquo Xiangliao Xiangjing Huazhuangpin vol 6pp 24ndash29 2004

[12] S-Y Takane and J B O Mitchell ldquoA structure-odor relation-ship study using EVA descriptors and hierarchical clusteringrdquoOrganicampBiomolecular Chemistry vol 2 no 22 pp 3250ndash32552004

[13] K J Rossiter ldquoStructure-odour relationshipsrdquo ChemicalReviews vol 96 no 8 pp 3201ndash3240 1996

[14] M Zarzo ldquoThe sense of smell molecular basis of odorantrecognitionrdquoBiological Reviews vol 82 no 3 pp 455ndash479 2007

[15] A Kato and K Touhara ldquoMammalian olfactory receptorspharmacologyGprotein coupling anddesensitizationrdquoCellularandMolecular Life Sciences vol 66 no 23 pp 3743ndash3753 2009

[16] L Turin and F Yoshii ldquoStructure-odor relations a modernperspectiverdquo in Handbook of Olfaction and Gustation R LDoty Ed pp 275ndash294 Marcel Dekker New York NY USA2003

[17] L Turin ldquoA spectroscopic mechanism for primary olfactoryreceptionrdquo Chemical Senses vol 21 no 6 pp 773ndash791 1996

[18] M A Reed ldquoInelastic electron tunneling spectroscopyrdquo Mate-rials Today vol 11 no 11 pp 46ndash50 2008

[19] L Turin ldquoA method for the calculation of odor character frommolecular structurerdquo Journal ofTheoretical Biology vol 216 no3 pp 367ndash385 2002

[20] L J W Haffenden V A Yaylayan and J Fortin ldquoInvestigationof vibrational theory of olfaction with variously labelled ben-zaldehydesrdquo Food Chemistry vol 73 no 1 pp 67ndash72 2001

[21] J C Brookes F Hartoutsiou A P Horsfield and A MStoneham ldquoCould humans recognize odor by phonon assistedtunnelingrdquo Physical Review Letters vol 98 no 3 Article ID038101 2007

[22] M I Franco L Turin A Mershin and E M C SkoulakisldquoMolecular vibration-sensing component in Drosophila mela-nogaster olfactionrdquo Proceedings of the National Academy ofSciences vol 108 no 9 pp 3797ndash3802 2011

[23] I A Solovrsquoyov P-Y Chang and K Schulten ldquoVibrationallyassisted electron transfer mechanism of olfaction myth orrealityrdquo Physical Chemistry Chemical Physics vol 14 no 40 pp13861ndash13871 2012

[24] S GaneDGeorganakis KManiati et al ldquoMolecular vibration-sensing component in human olfactionrdquo PLoS ONE vol 8 no1 Article ID e55780 2013

[25] D L Pavia G M Lampman G S Kriz and J R VyvyanIntroduction to Spectroscopy Cengage Learning Sao PauloBrazil 2010

[26] D A Lerner D Berthomieu and E R Maia ldquoModeling of theconformational flexibility and EZ isomerism of thiazoximicacid and cefotaximerdquo International Journal of Quantum Chem-istry vol 111 no 6 pp 1222ndash1238 2011

[27] A P Scott andL Radom ldquoHarmonic vibrational frequencies anevaluation of Hartree-Fock Moslashller-Plesset quadratic configu-ration interaction density functional theory and semiempiricalscale factorsrdquoThe Journal of Physical Chemistry vol 100 no 41pp 16502ndash16513 1996

[28] S Gabler J Soelter T Hussain S Sachse and M SchmukerldquoPhysicochemical vs vibrational descriptors for prediction ofodor receptor responsesrdquo Molecular Informatics vol 32 no 9-10 pp 855ndash865 2013

[29] Materials Studio SW and Insight II SW Acelrys San DiegoCalif USA

[30] M J Frisch G W Trucks H B Schlegel et al ldquoGaussian 09Revision A02rdquo Gaussian Inc Wallingford Conn USA 2009

[31] H Sun ldquoCompass an ab initio force-field optimized forcondensed-phase applicationsmdashoverview with details onalkane and benzene compoundsrdquo Journal of Physical ChemistryB vol 102 no 38 pp 7338ndash7364 1998

[32] P Dauber-Osguthorpe V A Roberts D J Osguthorpe J WolfM Genest and A T Hagler ldquoStructure and energetics of ligandbinding to proteins Escherichia coli dihydrofolate reductase-trimethoprim a drug-receptor systemrdquo Proteins StructureFunction and Genetics vol 4 no 1 pp 31ndash47 1988

[33] DH JMackay A J Cross andA THagler ldquoThe role of energyminimization in simulation strategies of biomolecular systemsrdquoin Prediction of Protein Structure and the Principles of ProteinConformation D G Fasman Ed pp 317ndash358 Plenum PressNew York NY USA 1990

[34] R Fletcher and C M Reeves ldquoFunction minimization byconjugate gradientsrdquo The Computer Journal vol 7 no 2 pp149ndash154 1964

[35] WH Press B P Flannery S A Teukolsky andW T VetterlingNumerical Recipes in C the Art of Scientific Computing Cam-bridge University Press London UK 1988

[36] J J P Stewart ldquoMopac a semiempirical molecular orbitalprogramrdquo Journal of Computer-Aided Molecular Design vol 4no 1 pp 101ndash105 1990

[37] J A Pople D P Santry and G A Segal ldquoApproximate self-consistent molecular orbital theory I Invariant proceduresrdquoThe Journal of Chemical Physics vol 43 no 10 pp S129ndashS1351965

[38] J A Pople and G A Segal ldquoApproximate self-consistentmolecular orbital theory III CNDO results for AB

2

and AB3

systemsrdquo The Journal of Chemical Physics vol 44 no 9 pp3289ndash3296 1966

[39] M J S Dewar E G Zoebisch E F Healy and J J P StewartldquoAM1 a new general purpose quantum mechanical molecularmodelrdquo Journal of the American Chemical Society vol 107 no13 pp 3902ndash3909 1985

[40] B Delley ldquoAn all-electron numerical method for solving thelocal density functional for polyatomic moleculesrdquoThe Journalof Chemical Physics vol 92 no 1 pp 508ndash517 1990

[41] B Delley ldquoFast calculation of electrostatics in crystals and largemoleculesrdquo Journal of Physical Chemistry vol 100 no 15 pp6107ndash6110 1996

Advances in Chemistry 13

[42] B Delley ldquoDMol methodology and applicationsrdquo in DensityFunctional Methods in Chemistry J W Andzelm and J KLabanowski Eds pp 101ndash108 Springer New York NY USA1991

[43] B Delley ldquoCalculated electron distribution for Tetrafluoroter-phthalonitrile (TFT)rdquo Chemical Physics vol 110 no 2-3 pp329ndash338 1986

[44] YWang and J P Perdew ldquoCorrelation hole of the spin-polarizedelectron gas with exact small-wave-vector and high-densityscalingrdquo Physical Review B vol 44 no 24 pp 13298ndash13307 1991

[45] P J Stephens F J Devlin C F Chabalowski and M J FrischldquoAb Initio calculation of vibrational absorption and circulardichroism spectra using density functional force fieldsrdquo Journalof Physical Chemistry vol 98 no 45 pp 11623ndash11627 1994

[46] G Schaftenaar and J H Noordik ldquoMolden a pre- and post-processing program for molecular and electronic structuresrdquoJournal of Computer-Aided Molecular Design vol 14 no 2 pp123ndash134 2000

[47] Xming ldquoXming X server for Windowsrdquo 2012 httpwwwstraightrunningcomXmingNotes

[48] K Nara L R Saraiva X Ye and L B Buck ldquoA large-scaleanalysis of odor coding in the olfactory epitheliumrdquo Journal ofNeuroscience vol 31 no 25 pp 9179ndash9191 2011

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

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Analytical Methods in Chemistry

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Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Theoretical ChemistryJournal of

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Analytical ChemistryInternational Journal of

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Quantum Chemistry

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Organic Chemistry International

ElectrochemistryInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Advances in Chemistry 7

Table 2 Collection of observed versus calculated IR mode frequencies for compounds 1ndash23

Vibrational modea Observed wavenumber (cmminus1) [25] Calculated wavenumber (cmminus1)GGAPW91 B3LYP

] CbndashH 3150ndash2850 3198ndash2898 3229ndash2953] CndashH (aldehyde) 2900ndash2800 2954ndash2892 2988ndash2939120575 CndashH up to 1465 up to 1493 up to 1540] C=C (alkene) 1680ndash1600 1706ndash1687 1718ndash1707] C=C (aromatic) 1600ndash1475 1618ndash1543 1650ndash1531] C=O (aldehyde) 1740ndash1720 1715ndash1693 1772ndash1749] C=O (ketone) 1725ndash1705 1733ndash1680 1784ndash1738] C=O (ester) 1750ndash1730 1777ndash1742 1810ndash1768120575 CndashO (alcohol ether and ester) 1300ndash1000 1381 1200ndash1018 1403 1312ndash1006]as nitro (RndashNO2) 1660ndash1500 1560ndash1520 1618ndash1531]119904 nitro (RndashNO2) 1390ndash1260 1340ndash1310 1417ndash1250a] stretching ]as asymmetric stretching ]119904 symmetric stretching 120575 bendingb] C(sp2)ndashH C(sp3)ndashH and C(aromatic)ndashH

shifts B3LYP results overestimated CndashH stretching andbending modes alkene C=C stretching modes and aldehydeand ketone C=O stretching modes

To quantify collected results experimental IR spectrumgiven for each particular molecule was compared to its theo-retical spectra as shown in Table 3 In the literaturemdashpublicand personal IR databasemdashonly spectra for compounds 1ndash5 8 10 and 12 were found The vibrational modes chosenas internal patterns of comparison were as follows whenoccurring (i) the two most intense peaks regarding theCndashO stretching mode (ii) the most intense peak for theC=O stretching mode (iii) the most intense peaks for thesymmetric and asymmetric CndashH stretching modes (iv) thehighest wavenumber found for the CndashH bending modes (v)the highest intensity for the C=C stretching mode and (vi)the most intense peaks for the symmetric and asymmetricN=O stretching modes They are altogether able to expressthe accuracy relying on theoretical data once all functionalgroups have had their modes listed within chosen criteriaand the whole spectrum has been covered

Extra information comes on the so-called DIFF columnsin Table 3 Consider

DIFF119894

= ExpWavenumber119894

minusTheoWavenumber119894

(2)

where the difference established between experimental andtheoretical values was plotted (for both GGAPW91 andB3LYP results) as shown in (2) In such equation for acertain mode 119894 the difference (DIFF) is obtained through thesubtraction of its theoretical value (TheoWavenumber) fromits experimental value (ExpWavenumber) The average of thecollected differences on Table 3 was estimated as the values ofabsolute difference were divided by the number of occurringmodes disregarding all CndashH stretch modes as follows

Deviation 1 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(3)

This choice was made due to the fact that all CndashHstretches were overestimated in more than 100 cmminus1 for both

theoretical methods as discussed before This last modetherefore had its deviation separately estimated as follows

Deviation 2 =sum119899

119894=1

1003816100381610038161003816DIFF119894

1003816100381610038161003816

119899

(4)

in which the absolute DIFF119894

is collected is summed for all CndashH stretching modes within the same theoretical method andis divided by the number of occurring modes

So finally GGAPW91 IR results are found to be moreaccurate than B3LYP results with calculated deviations thatare equal to 13 cmminus1 and 43 cmminus1 respectively Neverthelessthey correspond to a 325 (DFT) and a 1075 (B3LYP)shift over the 4000ndash0 cmminus1 that represents the spectrumwhich ensures that both methods are powerfully predictiveSimultaneously both methods display great shift over CndashHstretching modes corresponding to an increase of 124 cmminus1and 145 cmminus1 respectively Considering that one of thispaperrsquos aims is to compare theoretical IR data with postulatesof the vibrational theory on musky odor the last mentionedmodes are irrelevant as they are not supposed to be respon-sible for muskiness

33 Part 3 IR Spectra and Musk Activity Herein bothGGAPW91 and B3LYP data will be taken into account so asto compare theoretical results with the bands described in thevibrational theory (700 1000 1500 or 1750 and 2200 cmminus1)which would assign as supposed by the previous theory amusky odor to these molecules

In Tables 5 and 6 the information was gathered so as todispose musks 1 to 23 in lines and their central frequencies(at 700 1000 and 1500 or 1750 cmminus1) in columns Besidesthe compounds were gathered in groups in accordance withtheir structural similarity (see first column on the left) MCMfor macrocyclic musks PCM for polycyclic musks NM fornitromusks and ACM for acyclic musks Nonmusks arecalled MCa for macrocyclic analogs Aa for acyclic analogsand Na for nitro analogs As no vibrational mode hasoccurred at 2200 plusmn 200 cmminus1 there is no such column

8 Advances in Chemistry

Table3Mostimpo

rtantw

avenum

bersforc

ompo

unds

1ndash5810and

12according

toDFT

B3LYP

and

experim

entald

ata

Highest

]Cndash

0DIFF

]C=

0DIFF

]Cndash

HDIFF

120575Cndash

HDIFF

]C=

CDIFF

]119904N=O

DIFF

]asN=O

DIFF

1GGAPW91

1207

1215

2833

1748

minus9

3017

3034minus160minus108

1479

minus18

B3LY

P118

11210

5438

1786minus47

3033

3069minus176minus143

1517minus56

Exp

1235

1248

1739

2857

2926

1461

2GGAPW91

1099

1231

107

1739

minus7

2999

3027minus153minus94

1474

minus14

B3LY

P1124

1240minus15minus2

1778minus46

3012

3058minus166minus125

1512minus52

Experim

entald

ata

1109

1238

1732

2846

2933

1460

3GGAPW91

1121

1220minus12

181738

minus6

2991

3037minus145minus104

1481minus21

B3LY

P119

41254minus85minus16

1774minus42

3029

3063minus183minus130

1510minus50

Exp

1109

1238

1732

2846

2933

1460

4GGAPW91

1726

minus11

2990

3051minus124minus123

1475

minus15

1687

B3LY

P1774minus59

3010

3051minus144minus123

1513minus53

1707

Exp

1715

2866

2928

1460

5GGAPW91

1733minus18

2994

3039minus128minus111

1473

minus13

1706

B3LY

P1773minus58

3031

3057minus165minus129

1511minus51

1718

Exp

1715

2866

2928

1460

8GGAPW91

1685

53005

3083minus115minus122

1483

minus13

1594

11B3

LYP

1738minus48

3033

3089minus143minus128

1518minus48

1639

minus34

Exp

1690

2890

2961

1470

1605

10GGAPW91

1759minus19

B3LY

P1807minus67

Exp

1740

12GGAPW91

3019

3086minus139minus105

1487

minus7

1598

71356

41547

3B3

LYP

3041

3090minus161minus109

1512minus32

1610

minus5

1373

minus13

1599

minus49

Exp

2880

2981

1480

1605

1360

1550

Advances in Chemistry 9

Table 4 Deviations estimated over differences between experimen-tal and theoretical wavenumbers forGGAPW91 andB3LYP IRdata

Method Deviation 1 (cmminus1) Deviation 2 (cmminus1)GGAPW91 13 124B3LYP 43 145

Experimentaldata

GGAPW91

B3LYP

3500 3000 2500 2000 1500 1000 500 0

Figure 4 Ranges for important vibrational modes collected forcompounds 1ndash23 through experimental data versus GGAPW91results versus B3LYP results Vibrational modes come in accordanceto bonding atoms and bond order in green CndashH modes in darkgreen C=C modes in light pink CndashO in burgundy C=O and inblue N=O modes

For each musk group the central frequencies averages(ave (5)) and their standard deviations (std (6)) wereestimated these values are plotted at the right side of thecentral frequency listThe next column on the right shows thedifferences between each central frequencies and the averageof central frequencies (diff (7)) Consider

avegroup =1

119899

119891

sum

119899=1

cf119899

(5)

where cf119899

represents the central frequencies found for eachgroup (MCM PCM etc) having herein been defined lowerand upper limits for 119899 so that 119899 = 1 5 for MCM 119899 = 6 10for PCM 119899 = 11 13 for NM and 119899 = 14 16 for ACMConsider

stdgroup = radic119891

sum

119899=1

[(cf119899

minus avegroup)2

] (6)

diff119899

= cf119899

minus avegroup (7)

The values found for the avegroup and stdgroup of theMCMgroup were the same as those found for theMCa group thosebelonging to NM were repeated for Na and data calculatedfor ACM were taken as parameters for Aa

Finally each diff119899

value was allowed to be lower or twotimes its stdgroup value as stated in

diff119899

le 2 times stdgroup (8)

If this happens it is possible to say that theoretical datafit vibrational theoryrsquos demands over study band if not theydo not agree When repeating this process for all three bandsunder the spectra values for the Total Deviations (TD) arecollected The zero input (0) means that all three bandsobeyed (8) Logically TD inputs between 1 and 3 indicate howmany of the bands presented a diff

119899

value that was higher thanthe stdgroup doubled value

34 Absence of the 2000ndash2400 cmminus1 Band None of the pre-vious tables bring a mode among the 2000ndash2400 cmminus1 rangeThe 2200 cmminus1 band was described by Turin as the carbonylstretching mode which only occurred at this range whenworking with NDDOAM1 Hamiltonian Through ab initiocalculation the mentioned mode was observed at the rangeof 1680ndash1810 cmminus1 and it was only taken into account forcfs estimates when dealing with the 1550ndash1950 cmminus1 band fornitro compounds Regarding structural features compounds6 7 12 and 13 do not possess the carbonyl group and arereal musks while compounds 17 18 19 20 and 23 containthe carbonyl group and are odorless Therefore carbonylstretches cannot be taken as criteria for IR data-muskybehavior profile

35 GGAPW91 cf rsquos Plots and Musk Activity Table 5 (withGGAPW91 results) presents only two molecules nonmusks20 and 23 which failed to express a complete match betweentheoretical data and the signed bands of the vibrational the-ory For nonmusk 20 the cf value estimated near 1000 cmminus1was higher than its avegroup value this compound had bothOndashCsp2 stretching modes occurring at high intensities andfrequencies below 1200 cmminus1 (which are precisely the 1090and 1144 cmminus1 wavenumbers) On the other hand musks 14ndash16 and nonmusk 19 have presented a stretch mode (or at leastone of them) outside the 1000 plusmn 200 cmminus1 range Concerningnonmusk 23 it can be said that it showed a lower cf valuewhich remained around the 700 cmminus1 band and a higher cfvalue near the 1000 cmminus1 band This can be explained by thefact that (i) referring to the 700 cmminus1 band 23 had an averagefor intensity modes that was lower than the average valuesfor the other Na and NM compounds and therefore lowerweight values (see (4)) and lower cf and (ii) referring to the1000 cmminus1 band the OndashCsp3 stretch mode at 1073 cmminus1 hadan intensity value that was 87 times higher than the secondmost intensemode generating the observed overestimated cfvalue

That being said and according to mathematical approachadopted in this paper no relationship was found betweenIR properties and the presence of musky odor throughGGAPW91 It does not mean that GGAPW91 calculationleads to affirm that musks and nonmusks have indistinguish-able spectra Itmeans that considering theweighted-averagesvalues resource in order to simplify the adoption of alltheoretical peaks under analysis resulting central frequenciesare similar among musks and nonmusks Such observationmay be due the fact that GGAPW91 spectra had narrowerbands for each vibrational mode rather than B3LYP spectraAs GGAPW91 proved to be a more accurate method itrequires a more accurate statistical tools so to properly dealwith all theoretical modes as to affirm (or deny) a possibledifference on musks and nonmusks IR spectra

36 B3LYP cf rsquos Plots and Musk Activity On the other handTable 6 (with B3LYP data) shows that all musks from 1 to16 have had theoretical central frequencies that fitted thefrequencies demanded at 700 1000 and 1500 (or 1750) cmminus1

10 Advances in Chemistry

Table 5 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for GGAPW91 collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd

Diff Around 1000 Avestd

Diff Around 1500 Avestd

Diff

MCM

1 742 743 minus1 1030 1049 minus19 1429 1411 18 02 761 12 18 1096 31 47 1404 11 minus7 03 748 5 1047 minus2 1417 6 04 734 minus9 1016 minus33 1405 minus6 05 730 minus13 1057 8 1402 minus9 0

PCM

6 751 733 18 1046 1020 26 1423 1480 minus57 07 769 34 36 1051 48 31 1424 54 minus56 08 678 minus55 977 minus43 1527 47 09 731 minus2 1066 46 1532 52 010 736 3 959 minus61 1495 15 0

NM11 735 755 minus20 1033 1019 14 1634 1589 45 012 763 17 8 1002 16 minus17 1567 39 minus22 013 766 11 1023 4 1567 minus22 0

ACM14 784 784 0 1084 1086 minus2 1402 1411 minus9 015 762 23 minus22 1079 9 minus7 1401 16 minus10 016 807 23 1096 10 1429 18 0

MCa 17 751 743 8 1067 1049 17 1405 1411 minus7 018 726 12 minus17 1049 31 0 1417 11 6 0

Aa 19 779 784 minus6 1073 1086 minus13 1411 1411 0 020 757 23 minus28 1105 9 19 1403 16 minus8 1

Na21 733 755 minus21 1033 1019 13 1557 1589 minus32 022 757 17 2 1006 16 minus13 1549 39 minus40 023 717 minus38 1060 41 1655 66 2

lowastTD total deviations

in the vibrational theory Simultaneously Aa and Na showedthat at least one of their cfs was too shifted from theiraverages Molecule 23 for instance is the only nonmusk pos-sessing an aldehyde functional group and its C=O stretchingmode is found at the 1550ndash1950 cmminus1 range under studyNevertheless nitromusk 11 also holds an aldehyde functionalgroup and though its cf at 1750 cmminus1 is indeed higher than theother cfs for the NM it is still 70 cmminus1 lower than 23rsquos cf Stillconcerning the analysis of Table 6 we can say that the acyclicanalogs 19 and 20 have had their central frequencies shiftedto lower values at the 1500 cmminus1 diagnostic band the onlyone in which there was no agreement between theoreticalresults and expectations deriving from the vibrational theoryAt the 1500 plusmn 200 cmminus1 range hydrocarbon scissoring modesand alkenearomatic C=C stretching modes are found and19 and 20 lack the gem-methyl at the cyclohexane that areobserved in 14 and 15 moreover although in 16 this gem-methyl is also absent it possesses two alkene groups forwhich its stretching modes are also found at this rangeFinally macrocyclic analogs showed the same spectra dataas macrocyclic musks as compounds 18 and 19 differ fromMCM in that they lack two methylene groups it is possibleto suggest that such loss leads the moleculersquos CndashH vibrational

mode sum to be too low to be detected by its OR as suggestedelsewhere [23] Besides both 18 and 19 present awoody smellby being smaller they may be able to bind to a variety ofdifferent ORs which do not reassemble the behavior of themusk detected by possibly only one OR or just a few more[48]

4 Conclusions

This paper worked on developing a method which couldstate the following (i) whether musky molecules had theirIR theoretical spectra fitted into the four bands assigned byvibrational theory in 2002 Turinrsquos paper and (ii) whethernonmuskymolecules did not have their IR theoretical spectrafitted into same criteria It was first concluded that only threebands were useful for discriminating musk from nonmuskodorants The fourth IR band refers to a carbonyl stretchingmode and data here presented showed that this mode cannotbe taken as criteria when building a muskiness profile

Present work was carried out with two different func-tionals applying DFT calculation level and both were ableto accurately predict IR spectra A mathematical strategyhas been adopted in order to summarize IR theoretical

Advances in Chemistry 11

Table 6 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for B3LYP collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd Diff Around 1000 Ave

std Diff Around 1500 Avestd Diff

MCM

1 754 748 6 1142 1093 48 1407 1423 minus16 02 768 16 20 1066 39 minus27 1428 10 5 03 749 1 1116 23 1421 minus2 04 744 minus3 1099 5 1430 6 05 723 minus25 1044 minus49 1429 6 0

PCM

6 749 722 28 1068 1019 49 1450 1476 minus26 07 752 51 31 1052 62 33 1450 32 minus27 08 692 minus30 971 minus48 1461 minus15 09 646 minus75 1069 50 1499 23 010 768 47 936 minus83 1520 44 0

NM11 754 766 minus12 952 977 minus26 1602 1597 5 012 771 10 5 993 22 16 1595 5 minus2 013 772 7 987 9 1593 minus3 0

ACM14 722 732 minus10 1101 1127 minus26 1424 1435 minus12 015 771 35 39 1130 24 3 1431 14 minus4 016 703 minus29 1149 22 1451 15 0

MCa 17 750 748 2 1067 1093 minus26 1418 1423 minus5 018 726 16 minus22 1072 39 minus21 1432 10 9 0

Aa 19 784 732 52 1097 1127 minus30 1357 1435 minus78 120 763 35 31 1087 24 minus40 1410 14 minus26 1

Na21 742 766 minus24 1015 977 38 1601 1597 4 122 767 10 1 1150 22 173 1600 5 3 123 702 minus64 1068 91 1675 78 3

lowastTD total deviations

data and properly compare musk to nonmusk moleculesUsing this approach GGAPW91 computed spectra showedno discriminating patterns between musks and nonmusksB3LYP data showed theoretical frequencies and the threediagnostic bands to bematching while nitro andmacrocyclicnonmusks failed in at least one of such comparisons

It was therefore possible to conclude that no specificmodealone is responsible for the discrimination of themusky odorInstead when a great amount of frequencies expressing weakor medium intensities were found along the 700ndash1700 cmminus1range musk odor occurs At this range observedmodes wereCH2

wag and scissor bending modes C=C stretches andsymmetric nitro stretching modes

This trial scanning over IR vibrational modes and theirrelation to musk odor perception brings new informationaltowards the understanding and application of vibrationaltheoryrsquos ideas and opens the possibility to a more extensivestudy in which a broader number of molecules may bemodeled so as to come to a quantitative proposal for amusky-like novel odorant regarding their IR vibrational modes

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The authors thank Professor Ines Sabioni Resck (fromInstituto de Quımica Brasılia Brazil) for initial ideas andreliance

References

[1] M Eh ldquoNew alicyclic musks the fourth generation of muskodorantsrdquoChemistryamp Biodiversity vol 1 no 12 pp 1975ndash19842004

[2] P Saiyasombati andG BKasting ldquoTwo-stage kinetic analysis offragrance evaporation and absorption from skinrdquo InternationalJournal of Cosmetic Science vol 25 no 5 pp 235ndash243 2003

[3] G B Kasting and P Saiyasombati ldquoA physico-chemical prop-erties based model for estimating evaporation and absorptionrates of perfumes from skinrdquo International Journal of CosmeticScience vol 23 no 1 pp 49ndash58 2001

[4] M Shirasu K Yoshikawa Y Takai et al ldquoOlfactory receptor andneural pathway responsible for highly selective sensing of muskodorsrdquo Neuron vol 81 no 1 pp 165ndash178 2014

[5] J Reisert and H Zhao ldquoResponse kinetics of olfactory receptorneurons and the implications in olfactory codingrdquo Journal ofGeneral Physiology vol 138 no 3 pp 303ndash310 2011

12 Advances in Chemistry

[6] J-P Rospars Y Gu A Gremiaux and P Lucas ldquoOdourtransduction in olfactory receptor neuronsrdquo Chinese Journal ofPhysiology vol 53 no 6 pp 364ndash372 2010

[7] B Malnic and A F Mercadante ldquoThe odorant signaling path-wayrdquo Annual Review of Biomedical Sciences vol 11 pp T86ndashT94 2009

[8] K Snitz A Yablonka T Weiss I Frumin R M Khan andN Sobel ldquoPredicting odor perceptual similarity from odorstructurerdquo PLoS Computational Biology vol 9 no 9 Article IDe1003184 2013

[9] B K Lavine CWhite NMirjankar CM Sundling and CMBreneman ldquoOdor-structure relationship studies of tetralin andindan musksrdquo Chemical Senses vol 37 no 8 pp 723ndash736 2012

[10] Y Zou H Mouhib W Stahl A Goeke Q Wang and PKraft ldquoEfficient macrocyclization by a novel oxy-oxonia-copereaction synthesis and olfactory properties of new macrocyclicmusksrdquo Chemistry vol 18 no 23 pp 7010ndash7015 2012

[11] S Liu ldquoStudy on the relationship between molecular odour ofpolycyclic musksrdquo Xiangliao Xiangjing Huazhuangpin vol 6pp 24ndash29 2004

[12] S-Y Takane and J B O Mitchell ldquoA structure-odor relation-ship study using EVA descriptors and hierarchical clusteringrdquoOrganicampBiomolecular Chemistry vol 2 no 22 pp 3250ndash32552004

[13] K J Rossiter ldquoStructure-odour relationshipsrdquo ChemicalReviews vol 96 no 8 pp 3201ndash3240 1996

[14] M Zarzo ldquoThe sense of smell molecular basis of odorantrecognitionrdquoBiological Reviews vol 82 no 3 pp 455ndash479 2007

[15] A Kato and K Touhara ldquoMammalian olfactory receptorspharmacologyGprotein coupling anddesensitizationrdquoCellularandMolecular Life Sciences vol 66 no 23 pp 3743ndash3753 2009

[16] L Turin and F Yoshii ldquoStructure-odor relations a modernperspectiverdquo in Handbook of Olfaction and Gustation R LDoty Ed pp 275ndash294 Marcel Dekker New York NY USA2003

[17] L Turin ldquoA spectroscopic mechanism for primary olfactoryreceptionrdquo Chemical Senses vol 21 no 6 pp 773ndash791 1996

[18] M A Reed ldquoInelastic electron tunneling spectroscopyrdquo Mate-rials Today vol 11 no 11 pp 46ndash50 2008

[19] L Turin ldquoA method for the calculation of odor character frommolecular structurerdquo Journal ofTheoretical Biology vol 216 no3 pp 367ndash385 2002

[20] L J W Haffenden V A Yaylayan and J Fortin ldquoInvestigationof vibrational theory of olfaction with variously labelled ben-zaldehydesrdquo Food Chemistry vol 73 no 1 pp 67ndash72 2001

[21] J C Brookes F Hartoutsiou A P Horsfield and A MStoneham ldquoCould humans recognize odor by phonon assistedtunnelingrdquo Physical Review Letters vol 98 no 3 Article ID038101 2007

[22] M I Franco L Turin A Mershin and E M C SkoulakisldquoMolecular vibration-sensing component in Drosophila mela-nogaster olfactionrdquo Proceedings of the National Academy ofSciences vol 108 no 9 pp 3797ndash3802 2011

[23] I A Solovrsquoyov P-Y Chang and K Schulten ldquoVibrationallyassisted electron transfer mechanism of olfaction myth orrealityrdquo Physical Chemistry Chemical Physics vol 14 no 40 pp13861ndash13871 2012

[24] S GaneDGeorganakis KManiati et al ldquoMolecular vibration-sensing component in human olfactionrdquo PLoS ONE vol 8 no1 Article ID e55780 2013

[25] D L Pavia G M Lampman G S Kriz and J R VyvyanIntroduction to Spectroscopy Cengage Learning Sao PauloBrazil 2010

[26] D A Lerner D Berthomieu and E R Maia ldquoModeling of theconformational flexibility and EZ isomerism of thiazoximicacid and cefotaximerdquo International Journal of Quantum Chem-istry vol 111 no 6 pp 1222ndash1238 2011

[27] A P Scott andL Radom ldquoHarmonic vibrational frequencies anevaluation of Hartree-Fock Moslashller-Plesset quadratic configu-ration interaction density functional theory and semiempiricalscale factorsrdquoThe Journal of Physical Chemistry vol 100 no 41pp 16502ndash16513 1996

[28] S Gabler J Soelter T Hussain S Sachse and M SchmukerldquoPhysicochemical vs vibrational descriptors for prediction ofodor receptor responsesrdquo Molecular Informatics vol 32 no 9-10 pp 855ndash865 2013

[29] Materials Studio SW and Insight II SW Acelrys San DiegoCalif USA

[30] M J Frisch G W Trucks H B Schlegel et al ldquoGaussian 09Revision A02rdquo Gaussian Inc Wallingford Conn USA 2009

[31] H Sun ldquoCompass an ab initio force-field optimized forcondensed-phase applicationsmdashoverview with details onalkane and benzene compoundsrdquo Journal of Physical ChemistryB vol 102 no 38 pp 7338ndash7364 1998

[32] P Dauber-Osguthorpe V A Roberts D J Osguthorpe J WolfM Genest and A T Hagler ldquoStructure and energetics of ligandbinding to proteins Escherichia coli dihydrofolate reductase-trimethoprim a drug-receptor systemrdquo Proteins StructureFunction and Genetics vol 4 no 1 pp 31ndash47 1988

[33] DH JMackay A J Cross andA THagler ldquoThe role of energyminimization in simulation strategies of biomolecular systemsrdquoin Prediction of Protein Structure and the Principles of ProteinConformation D G Fasman Ed pp 317ndash358 Plenum PressNew York NY USA 1990

[34] R Fletcher and C M Reeves ldquoFunction minimization byconjugate gradientsrdquo The Computer Journal vol 7 no 2 pp149ndash154 1964

[35] WH Press B P Flannery S A Teukolsky andW T VetterlingNumerical Recipes in C the Art of Scientific Computing Cam-bridge University Press London UK 1988

[36] J J P Stewart ldquoMopac a semiempirical molecular orbitalprogramrdquo Journal of Computer-Aided Molecular Design vol 4no 1 pp 101ndash105 1990

[37] J A Pople D P Santry and G A Segal ldquoApproximate self-consistent molecular orbital theory I Invariant proceduresrdquoThe Journal of Chemical Physics vol 43 no 10 pp S129ndashS1351965

[38] J A Pople and G A Segal ldquoApproximate self-consistentmolecular orbital theory III CNDO results for AB

2

and AB3

systemsrdquo The Journal of Chemical Physics vol 44 no 9 pp3289ndash3296 1966

[39] M J S Dewar E G Zoebisch E F Healy and J J P StewartldquoAM1 a new general purpose quantum mechanical molecularmodelrdquo Journal of the American Chemical Society vol 107 no13 pp 3902ndash3909 1985

[40] B Delley ldquoAn all-electron numerical method for solving thelocal density functional for polyatomic moleculesrdquoThe Journalof Chemical Physics vol 92 no 1 pp 508ndash517 1990

[41] B Delley ldquoFast calculation of electrostatics in crystals and largemoleculesrdquo Journal of Physical Chemistry vol 100 no 15 pp6107ndash6110 1996

Advances in Chemistry 13

[42] B Delley ldquoDMol methodology and applicationsrdquo in DensityFunctional Methods in Chemistry J W Andzelm and J KLabanowski Eds pp 101ndash108 Springer New York NY USA1991

[43] B Delley ldquoCalculated electron distribution for Tetrafluoroter-phthalonitrile (TFT)rdquo Chemical Physics vol 110 no 2-3 pp329ndash338 1986

[44] YWang and J P Perdew ldquoCorrelation hole of the spin-polarizedelectron gas with exact small-wave-vector and high-densityscalingrdquo Physical Review B vol 44 no 24 pp 13298ndash13307 1991

[45] P J Stephens F J Devlin C F Chabalowski and M J FrischldquoAb Initio calculation of vibrational absorption and circulardichroism spectra using density functional force fieldsrdquo Journalof Physical Chemistry vol 98 no 45 pp 11623ndash11627 1994

[46] G Schaftenaar and J H Noordik ldquoMolden a pre- and post-processing program for molecular and electronic structuresrdquoJournal of Computer-Aided Molecular Design vol 14 no 2 pp123ndash134 2000

[47] Xming ldquoXming X server for Windowsrdquo 2012 httpwwwstraightrunningcomXmingNotes

[48] K Nara L R Saraiva X Ye and L B Buck ldquoA large-scaleanalysis of odor coding in the olfactory epitheliumrdquo Journal ofNeuroscience vol 31 no 25 pp 9179ndash9191 2011

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

8 Advances in Chemistry

Table3Mostimpo

rtantw

avenum

bersforc

ompo

unds

1ndash5810and

12according

toDFT

B3LYP

and

experim

entald

ata

Highest

]Cndash

0DIFF

]C=

0DIFF

]Cndash

HDIFF

120575Cndash

HDIFF

]C=

CDIFF

]119904N=O

DIFF

]asN=O

DIFF

1GGAPW91

1207

1215

2833

1748

minus9

3017

3034minus160minus108

1479

minus18

B3LY

P118

11210

5438

1786minus47

3033

3069minus176minus143

1517minus56

Exp

1235

1248

1739

2857

2926

1461

2GGAPW91

1099

1231

107

1739

minus7

2999

3027minus153minus94

1474

minus14

B3LY

P1124

1240minus15minus2

1778minus46

3012

3058minus166minus125

1512minus52

Experim

entald

ata

1109

1238

1732

2846

2933

1460

3GGAPW91

1121

1220minus12

181738

minus6

2991

3037minus145minus104

1481minus21

B3LY

P119

41254minus85minus16

1774minus42

3029

3063minus183minus130

1510minus50

Exp

1109

1238

1732

2846

2933

1460

4GGAPW91

1726

minus11

2990

3051minus124minus123

1475

minus15

1687

B3LY

P1774minus59

3010

3051minus144minus123

1513minus53

1707

Exp

1715

2866

2928

1460

5GGAPW91

1733minus18

2994

3039minus128minus111

1473

minus13

1706

B3LY

P1773minus58

3031

3057minus165minus129

1511minus51

1718

Exp

1715

2866

2928

1460

8GGAPW91

1685

53005

3083minus115minus122

1483

minus13

1594

11B3

LYP

1738minus48

3033

3089minus143minus128

1518minus48

1639

minus34

Exp

1690

2890

2961

1470

1605

10GGAPW91

1759minus19

B3LY

P1807minus67

Exp

1740

12GGAPW91

3019

3086minus139minus105

1487

minus7

1598

71356

41547

3B3

LYP

3041

3090minus161minus109

1512minus32

1610

minus5

1373

minus13

1599

minus49

Exp

2880

2981

1480

1605

1360

1550

Advances in Chemistry 9

Table 4 Deviations estimated over differences between experimen-tal and theoretical wavenumbers forGGAPW91 andB3LYP IRdata

Method Deviation 1 (cmminus1) Deviation 2 (cmminus1)GGAPW91 13 124B3LYP 43 145

Experimentaldata

GGAPW91

B3LYP

3500 3000 2500 2000 1500 1000 500 0

Figure 4 Ranges for important vibrational modes collected forcompounds 1ndash23 through experimental data versus GGAPW91results versus B3LYP results Vibrational modes come in accordanceto bonding atoms and bond order in green CndashH modes in darkgreen C=C modes in light pink CndashO in burgundy C=O and inblue N=O modes

For each musk group the central frequencies averages(ave (5)) and their standard deviations (std (6)) wereestimated these values are plotted at the right side of thecentral frequency listThe next column on the right shows thedifferences between each central frequencies and the averageof central frequencies (diff (7)) Consider

avegroup =1

119899

119891

sum

119899=1

cf119899

(5)

where cf119899

represents the central frequencies found for eachgroup (MCM PCM etc) having herein been defined lowerand upper limits for 119899 so that 119899 = 1 5 for MCM 119899 = 6 10for PCM 119899 = 11 13 for NM and 119899 = 14 16 for ACMConsider

stdgroup = radic119891

sum

119899=1

[(cf119899

minus avegroup)2

] (6)

diff119899

= cf119899

minus avegroup (7)

The values found for the avegroup and stdgroup of theMCMgroup were the same as those found for theMCa group thosebelonging to NM were repeated for Na and data calculatedfor ACM were taken as parameters for Aa

Finally each diff119899

value was allowed to be lower or twotimes its stdgroup value as stated in

diff119899

le 2 times stdgroup (8)

If this happens it is possible to say that theoretical datafit vibrational theoryrsquos demands over study band if not theydo not agree When repeating this process for all three bandsunder the spectra values for the Total Deviations (TD) arecollected The zero input (0) means that all three bandsobeyed (8) Logically TD inputs between 1 and 3 indicate howmany of the bands presented a diff

119899

value that was higher thanthe stdgroup doubled value

34 Absence of the 2000ndash2400 cmminus1 Band None of the pre-vious tables bring a mode among the 2000ndash2400 cmminus1 rangeThe 2200 cmminus1 band was described by Turin as the carbonylstretching mode which only occurred at this range whenworking with NDDOAM1 Hamiltonian Through ab initiocalculation the mentioned mode was observed at the rangeof 1680ndash1810 cmminus1 and it was only taken into account forcfs estimates when dealing with the 1550ndash1950 cmminus1 band fornitro compounds Regarding structural features compounds6 7 12 and 13 do not possess the carbonyl group and arereal musks while compounds 17 18 19 20 and 23 containthe carbonyl group and are odorless Therefore carbonylstretches cannot be taken as criteria for IR data-muskybehavior profile

35 GGAPW91 cf rsquos Plots and Musk Activity Table 5 (withGGAPW91 results) presents only two molecules nonmusks20 and 23 which failed to express a complete match betweentheoretical data and the signed bands of the vibrational the-ory For nonmusk 20 the cf value estimated near 1000 cmminus1was higher than its avegroup value this compound had bothOndashCsp2 stretching modes occurring at high intensities andfrequencies below 1200 cmminus1 (which are precisely the 1090and 1144 cmminus1 wavenumbers) On the other hand musks 14ndash16 and nonmusk 19 have presented a stretch mode (or at leastone of them) outside the 1000 plusmn 200 cmminus1 range Concerningnonmusk 23 it can be said that it showed a lower cf valuewhich remained around the 700 cmminus1 band and a higher cfvalue near the 1000 cmminus1 band This can be explained by thefact that (i) referring to the 700 cmminus1 band 23 had an averagefor intensity modes that was lower than the average valuesfor the other Na and NM compounds and therefore lowerweight values (see (4)) and lower cf and (ii) referring to the1000 cmminus1 band the OndashCsp3 stretch mode at 1073 cmminus1 hadan intensity value that was 87 times higher than the secondmost intensemode generating the observed overestimated cfvalue

That being said and according to mathematical approachadopted in this paper no relationship was found betweenIR properties and the presence of musky odor throughGGAPW91 It does not mean that GGAPW91 calculationleads to affirm that musks and nonmusks have indistinguish-able spectra Itmeans that considering theweighted-averagesvalues resource in order to simplify the adoption of alltheoretical peaks under analysis resulting central frequenciesare similar among musks and nonmusks Such observationmay be due the fact that GGAPW91 spectra had narrowerbands for each vibrational mode rather than B3LYP spectraAs GGAPW91 proved to be a more accurate method itrequires a more accurate statistical tools so to properly dealwith all theoretical modes as to affirm (or deny) a possibledifference on musks and nonmusks IR spectra

36 B3LYP cf rsquos Plots and Musk Activity On the other handTable 6 (with B3LYP data) shows that all musks from 1 to16 have had theoretical central frequencies that fitted thefrequencies demanded at 700 1000 and 1500 (or 1750) cmminus1

10 Advances in Chemistry

Table 5 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for GGAPW91 collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd

Diff Around 1000 Avestd

Diff Around 1500 Avestd

Diff

MCM

1 742 743 minus1 1030 1049 minus19 1429 1411 18 02 761 12 18 1096 31 47 1404 11 minus7 03 748 5 1047 minus2 1417 6 04 734 minus9 1016 minus33 1405 minus6 05 730 minus13 1057 8 1402 minus9 0

PCM

6 751 733 18 1046 1020 26 1423 1480 minus57 07 769 34 36 1051 48 31 1424 54 minus56 08 678 minus55 977 minus43 1527 47 09 731 minus2 1066 46 1532 52 010 736 3 959 minus61 1495 15 0

NM11 735 755 minus20 1033 1019 14 1634 1589 45 012 763 17 8 1002 16 minus17 1567 39 minus22 013 766 11 1023 4 1567 minus22 0

ACM14 784 784 0 1084 1086 minus2 1402 1411 minus9 015 762 23 minus22 1079 9 minus7 1401 16 minus10 016 807 23 1096 10 1429 18 0

MCa 17 751 743 8 1067 1049 17 1405 1411 minus7 018 726 12 minus17 1049 31 0 1417 11 6 0

Aa 19 779 784 minus6 1073 1086 minus13 1411 1411 0 020 757 23 minus28 1105 9 19 1403 16 minus8 1

Na21 733 755 minus21 1033 1019 13 1557 1589 minus32 022 757 17 2 1006 16 minus13 1549 39 minus40 023 717 minus38 1060 41 1655 66 2

lowastTD total deviations

in the vibrational theory Simultaneously Aa and Na showedthat at least one of their cfs was too shifted from theiraverages Molecule 23 for instance is the only nonmusk pos-sessing an aldehyde functional group and its C=O stretchingmode is found at the 1550ndash1950 cmminus1 range under studyNevertheless nitromusk 11 also holds an aldehyde functionalgroup and though its cf at 1750 cmminus1 is indeed higher than theother cfs for the NM it is still 70 cmminus1 lower than 23rsquos cf Stillconcerning the analysis of Table 6 we can say that the acyclicanalogs 19 and 20 have had their central frequencies shiftedto lower values at the 1500 cmminus1 diagnostic band the onlyone in which there was no agreement between theoreticalresults and expectations deriving from the vibrational theoryAt the 1500 plusmn 200 cmminus1 range hydrocarbon scissoring modesand alkenearomatic C=C stretching modes are found and19 and 20 lack the gem-methyl at the cyclohexane that areobserved in 14 and 15 moreover although in 16 this gem-methyl is also absent it possesses two alkene groups forwhich its stretching modes are also found at this rangeFinally macrocyclic analogs showed the same spectra dataas macrocyclic musks as compounds 18 and 19 differ fromMCM in that they lack two methylene groups it is possibleto suggest that such loss leads the moleculersquos CndashH vibrational

mode sum to be too low to be detected by its OR as suggestedelsewhere [23] Besides both 18 and 19 present awoody smellby being smaller they may be able to bind to a variety ofdifferent ORs which do not reassemble the behavior of themusk detected by possibly only one OR or just a few more[48]

4 Conclusions

This paper worked on developing a method which couldstate the following (i) whether musky molecules had theirIR theoretical spectra fitted into the four bands assigned byvibrational theory in 2002 Turinrsquos paper and (ii) whethernonmuskymolecules did not have their IR theoretical spectrafitted into same criteria It was first concluded that only threebands were useful for discriminating musk from nonmuskodorants The fourth IR band refers to a carbonyl stretchingmode and data here presented showed that this mode cannotbe taken as criteria when building a muskiness profile

Present work was carried out with two different func-tionals applying DFT calculation level and both were ableto accurately predict IR spectra A mathematical strategyhas been adopted in order to summarize IR theoretical

Advances in Chemistry 11

Table 6 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for B3LYP collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd Diff Around 1000 Ave

std Diff Around 1500 Avestd Diff

MCM

1 754 748 6 1142 1093 48 1407 1423 minus16 02 768 16 20 1066 39 minus27 1428 10 5 03 749 1 1116 23 1421 minus2 04 744 minus3 1099 5 1430 6 05 723 minus25 1044 minus49 1429 6 0

PCM

6 749 722 28 1068 1019 49 1450 1476 minus26 07 752 51 31 1052 62 33 1450 32 minus27 08 692 minus30 971 minus48 1461 minus15 09 646 minus75 1069 50 1499 23 010 768 47 936 minus83 1520 44 0

NM11 754 766 minus12 952 977 minus26 1602 1597 5 012 771 10 5 993 22 16 1595 5 minus2 013 772 7 987 9 1593 minus3 0

ACM14 722 732 minus10 1101 1127 minus26 1424 1435 minus12 015 771 35 39 1130 24 3 1431 14 minus4 016 703 minus29 1149 22 1451 15 0

MCa 17 750 748 2 1067 1093 minus26 1418 1423 minus5 018 726 16 minus22 1072 39 minus21 1432 10 9 0

Aa 19 784 732 52 1097 1127 minus30 1357 1435 minus78 120 763 35 31 1087 24 minus40 1410 14 minus26 1

Na21 742 766 minus24 1015 977 38 1601 1597 4 122 767 10 1 1150 22 173 1600 5 3 123 702 minus64 1068 91 1675 78 3

lowastTD total deviations

data and properly compare musk to nonmusk moleculesUsing this approach GGAPW91 computed spectra showedno discriminating patterns between musks and nonmusksB3LYP data showed theoretical frequencies and the threediagnostic bands to bematching while nitro andmacrocyclicnonmusks failed in at least one of such comparisons

It was therefore possible to conclude that no specificmodealone is responsible for the discrimination of themusky odorInstead when a great amount of frequencies expressing weakor medium intensities were found along the 700ndash1700 cmminus1range musk odor occurs At this range observedmodes wereCH2

wag and scissor bending modes C=C stretches andsymmetric nitro stretching modes

This trial scanning over IR vibrational modes and theirrelation to musk odor perception brings new informationaltowards the understanding and application of vibrationaltheoryrsquos ideas and opens the possibility to a more extensivestudy in which a broader number of molecules may bemodeled so as to come to a quantitative proposal for amusky-like novel odorant regarding their IR vibrational modes

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The authors thank Professor Ines Sabioni Resck (fromInstituto de Quımica Brasılia Brazil) for initial ideas andreliance

References

[1] M Eh ldquoNew alicyclic musks the fourth generation of muskodorantsrdquoChemistryamp Biodiversity vol 1 no 12 pp 1975ndash19842004

[2] P Saiyasombati andG BKasting ldquoTwo-stage kinetic analysis offragrance evaporation and absorption from skinrdquo InternationalJournal of Cosmetic Science vol 25 no 5 pp 235ndash243 2003

[3] G B Kasting and P Saiyasombati ldquoA physico-chemical prop-erties based model for estimating evaporation and absorptionrates of perfumes from skinrdquo International Journal of CosmeticScience vol 23 no 1 pp 49ndash58 2001

[4] M Shirasu K Yoshikawa Y Takai et al ldquoOlfactory receptor andneural pathway responsible for highly selective sensing of muskodorsrdquo Neuron vol 81 no 1 pp 165ndash178 2014

[5] J Reisert and H Zhao ldquoResponse kinetics of olfactory receptorneurons and the implications in olfactory codingrdquo Journal ofGeneral Physiology vol 138 no 3 pp 303ndash310 2011

12 Advances in Chemistry

[6] J-P Rospars Y Gu A Gremiaux and P Lucas ldquoOdourtransduction in olfactory receptor neuronsrdquo Chinese Journal ofPhysiology vol 53 no 6 pp 364ndash372 2010

[7] B Malnic and A F Mercadante ldquoThe odorant signaling path-wayrdquo Annual Review of Biomedical Sciences vol 11 pp T86ndashT94 2009

[8] K Snitz A Yablonka T Weiss I Frumin R M Khan andN Sobel ldquoPredicting odor perceptual similarity from odorstructurerdquo PLoS Computational Biology vol 9 no 9 Article IDe1003184 2013

[9] B K Lavine CWhite NMirjankar CM Sundling and CMBreneman ldquoOdor-structure relationship studies of tetralin andindan musksrdquo Chemical Senses vol 37 no 8 pp 723ndash736 2012

[10] Y Zou H Mouhib W Stahl A Goeke Q Wang and PKraft ldquoEfficient macrocyclization by a novel oxy-oxonia-copereaction synthesis and olfactory properties of new macrocyclicmusksrdquo Chemistry vol 18 no 23 pp 7010ndash7015 2012

[11] S Liu ldquoStudy on the relationship between molecular odour ofpolycyclic musksrdquo Xiangliao Xiangjing Huazhuangpin vol 6pp 24ndash29 2004

[12] S-Y Takane and J B O Mitchell ldquoA structure-odor relation-ship study using EVA descriptors and hierarchical clusteringrdquoOrganicampBiomolecular Chemistry vol 2 no 22 pp 3250ndash32552004

[13] K J Rossiter ldquoStructure-odour relationshipsrdquo ChemicalReviews vol 96 no 8 pp 3201ndash3240 1996

[14] M Zarzo ldquoThe sense of smell molecular basis of odorantrecognitionrdquoBiological Reviews vol 82 no 3 pp 455ndash479 2007

[15] A Kato and K Touhara ldquoMammalian olfactory receptorspharmacologyGprotein coupling anddesensitizationrdquoCellularandMolecular Life Sciences vol 66 no 23 pp 3743ndash3753 2009

[16] L Turin and F Yoshii ldquoStructure-odor relations a modernperspectiverdquo in Handbook of Olfaction and Gustation R LDoty Ed pp 275ndash294 Marcel Dekker New York NY USA2003

[17] L Turin ldquoA spectroscopic mechanism for primary olfactoryreceptionrdquo Chemical Senses vol 21 no 6 pp 773ndash791 1996

[18] M A Reed ldquoInelastic electron tunneling spectroscopyrdquo Mate-rials Today vol 11 no 11 pp 46ndash50 2008

[19] L Turin ldquoA method for the calculation of odor character frommolecular structurerdquo Journal ofTheoretical Biology vol 216 no3 pp 367ndash385 2002

[20] L J W Haffenden V A Yaylayan and J Fortin ldquoInvestigationof vibrational theory of olfaction with variously labelled ben-zaldehydesrdquo Food Chemistry vol 73 no 1 pp 67ndash72 2001

[21] J C Brookes F Hartoutsiou A P Horsfield and A MStoneham ldquoCould humans recognize odor by phonon assistedtunnelingrdquo Physical Review Letters vol 98 no 3 Article ID038101 2007

[22] M I Franco L Turin A Mershin and E M C SkoulakisldquoMolecular vibration-sensing component in Drosophila mela-nogaster olfactionrdquo Proceedings of the National Academy ofSciences vol 108 no 9 pp 3797ndash3802 2011

[23] I A Solovrsquoyov P-Y Chang and K Schulten ldquoVibrationallyassisted electron transfer mechanism of olfaction myth orrealityrdquo Physical Chemistry Chemical Physics vol 14 no 40 pp13861ndash13871 2012

[24] S GaneDGeorganakis KManiati et al ldquoMolecular vibration-sensing component in human olfactionrdquo PLoS ONE vol 8 no1 Article ID e55780 2013

[25] D L Pavia G M Lampman G S Kriz and J R VyvyanIntroduction to Spectroscopy Cengage Learning Sao PauloBrazil 2010

[26] D A Lerner D Berthomieu and E R Maia ldquoModeling of theconformational flexibility and EZ isomerism of thiazoximicacid and cefotaximerdquo International Journal of Quantum Chem-istry vol 111 no 6 pp 1222ndash1238 2011

[27] A P Scott andL Radom ldquoHarmonic vibrational frequencies anevaluation of Hartree-Fock Moslashller-Plesset quadratic configu-ration interaction density functional theory and semiempiricalscale factorsrdquoThe Journal of Physical Chemistry vol 100 no 41pp 16502ndash16513 1996

[28] S Gabler J Soelter T Hussain S Sachse and M SchmukerldquoPhysicochemical vs vibrational descriptors for prediction ofodor receptor responsesrdquo Molecular Informatics vol 32 no 9-10 pp 855ndash865 2013

[29] Materials Studio SW and Insight II SW Acelrys San DiegoCalif USA

[30] M J Frisch G W Trucks H B Schlegel et al ldquoGaussian 09Revision A02rdquo Gaussian Inc Wallingford Conn USA 2009

[31] H Sun ldquoCompass an ab initio force-field optimized forcondensed-phase applicationsmdashoverview with details onalkane and benzene compoundsrdquo Journal of Physical ChemistryB vol 102 no 38 pp 7338ndash7364 1998

[32] P Dauber-Osguthorpe V A Roberts D J Osguthorpe J WolfM Genest and A T Hagler ldquoStructure and energetics of ligandbinding to proteins Escherichia coli dihydrofolate reductase-trimethoprim a drug-receptor systemrdquo Proteins StructureFunction and Genetics vol 4 no 1 pp 31ndash47 1988

[33] DH JMackay A J Cross andA THagler ldquoThe role of energyminimization in simulation strategies of biomolecular systemsrdquoin Prediction of Protein Structure and the Principles of ProteinConformation D G Fasman Ed pp 317ndash358 Plenum PressNew York NY USA 1990

[34] R Fletcher and C M Reeves ldquoFunction minimization byconjugate gradientsrdquo The Computer Journal vol 7 no 2 pp149ndash154 1964

[35] WH Press B P Flannery S A Teukolsky andW T VetterlingNumerical Recipes in C the Art of Scientific Computing Cam-bridge University Press London UK 1988

[36] J J P Stewart ldquoMopac a semiempirical molecular orbitalprogramrdquo Journal of Computer-Aided Molecular Design vol 4no 1 pp 101ndash105 1990

[37] J A Pople D P Santry and G A Segal ldquoApproximate self-consistent molecular orbital theory I Invariant proceduresrdquoThe Journal of Chemical Physics vol 43 no 10 pp S129ndashS1351965

[38] J A Pople and G A Segal ldquoApproximate self-consistentmolecular orbital theory III CNDO results for AB

2

and AB3

systemsrdquo The Journal of Chemical Physics vol 44 no 9 pp3289ndash3296 1966

[39] M J S Dewar E G Zoebisch E F Healy and J J P StewartldquoAM1 a new general purpose quantum mechanical molecularmodelrdquo Journal of the American Chemical Society vol 107 no13 pp 3902ndash3909 1985

[40] B Delley ldquoAn all-electron numerical method for solving thelocal density functional for polyatomic moleculesrdquoThe Journalof Chemical Physics vol 92 no 1 pp 508ndash517 1990

[41] B Delley ldquoFast calculation of electrostatics in crystals and largemoleculesrdquo Journal of Physical Chemistry vol 100 no 15 pp6107ndash6110 1996

Advances in Chemistry 13

[42] B Delley ldquoDMol methodology and applicationsrdquo in DensityFunctional Methods in Chemistry J W Andzelm and J KLabanowski Eds pp 101ndash108 Springer New York NY USA1991

[43] B Delley ldquoCalculated electron distribution for Tetrafluoroter-phthalonitrile (TFT)rdquo Chemical Physics vol 110 no 2-3 pp329ndash338 1986

[44] YWang and J P Perdew ldquoCorrelation hole of the spin-polarizedelectron gas with exact small-wave-vector and high-densityscalingrdquo Physical Review B vol 44 no 24 pp 13298ndash13307 1991

[45] P J Stephens F J Devlin C F Chabalowski and M J FrischldquoAb Initio calculation of vibrational absorption and circulardichroism spectra using density functional force fieldsrdquo Journalof Physical Chemistry vol 98 no 45 pp 11623ndash11627 1994

[46] G Schaftenaar and J H Noordik ldquoMolden a pre- and post-processing program for molecular and electronic structuresrdquoJournal of Computer-Aided Molecular Design vol 14 no 2 pp123ndash134 2000

[47] Xming ldquoXming X server for Windowsrdquo 2012 httpwwwstraightrunningcomXmingNotes

[48] K Nara L R Saraiva X Ye and L B Buck ldquoA large-scaleanalysis of odor coding in the olfactory epitheliumrdquo Journal ofNeuroscience vol 31 no 25 pp 9179ndash9191 2011

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Advances in Chemistry 9

Table 4 Deviations estimated over differences between experimen-tal and theoretical wavenumbers forGGAPW91 andB3LYP IRdata

Method Deviation 1 (cmminus1) Deviation 2 (cmminus1)GGAPW91 13 124B3LYP 43 145

Experimentaldata

GGAPW91

B3LYP

3500 3000 2500 2000 1500 1000 500 0

Figure 4 Ranges for important vibrational modes collected forcompounds 1ndash23 through experimental data versus GGAPW91results versus B3LYP results Vibrational modes come in accordanceto bonding atoms and bond order in green CndashH modes in darkgreen C=C modes in light pink CndashO in burgundy C=O and inblue N=O modes

For each musk group the central frequencies averages(ave (5)) and their standard deviations (std (6)) wereestimated these values are plotted at the right side of thecentral frequency listThe next column on the right shows thedifferences between each central frequencies and the averageof central frequencies (diff (7)) Consider

avegroup =1

119899

119891

sum

119899=1

cf119899

(5)

where cf119899

represents the central frequencies found for eachgroup (MCM PCM etc) having herein been defined lowerand upper limits for 119899 so that 119899 = 1 5 for MCM 119899 = 6 10for PCM 119899 = 11 13 for NM and 119899 = 14 16 for ACMConsider

stdgroup = radic119891

sum

119899=1

[(cf119899

minus avegroup)2

] (6)

diff119899

= cf119899

minus avegroup (7)

The values found for the avegroup and stdgroup of theMCMgroup were the same as those found for theMCa group thosebelonging to NM were repeated for Na and data calculatedfor ACM were taken as parameters for Aa

Finally each diff119899

value was allowed to be lower or twotimes its stdgroup value as stated in

diff119899

le 2 times stdgroup (8)

If this happens it is possible to say that theoretical datafit vibrational theoryrsquos demands over study band if not theydo not agree When repeating this process for all three bandsunder the spectra values for the Total Deviations (TD) arecollected The zero input (0) means that all three bandsobeyed (8) Logically TD inputs between 1 and 3 indicate howmany of the bands presented a diff

119899

value that was higher thanthe stdgroup doubled value

34 Absence of the 2000ndash2400 cmminus1 Band None of the pre-vious tables bring a mode among the 2000ndash2400 cmminus1 rangeThe 2200 cmminus1 band was described by Turin as the carbonylstretching mode which only occurred at this range whenworking with NDDOAM1 Hamiltonian Through ab initiocalculation the mentioned mode was observed at the rangeof 1680ndash1810 cmminus1 and it was only taken into account forcfs estimates when dealing with the 1550ndash1950 cmminus1 band fornitro compounds Regarding structural features compounds6 7 12 and 13 do not possess the carbonyl group and arereal musks while compounds 17 18 19 20 and 23 containthe carbonyl group and are odorless Therefore carbonylstretches cannot be taken as criteria for IR data-muskybehavior profile

35 GGAPW91 cf rsquos Plots and Musk Activity Table 5 (withGGAPW91 results) presents only two molecules nonmusks20 and 23 which failed to express a complete match betweentheoretical data and the signed bands of the vibrational the-ory For nonmusk 20 the cf value estimated near 1000 cmminus1was higher than its avegroup value this compound had bothOndashCsp2 stretching modes occurring at high intensities andfrequencies below 1200 cmminus1 (which are precisely the 1090and 1144 cmminus1 wavenumbers) On the other hand musks 14ndash16 and nonmusk 19 have presented a stretch mode (or at leastone of them) outside the 1000 plusmn 200 cmminus1 range Concerningnonmusk 23 it can be said that it showed a lower cf valuewhich remained around the 700 cmminus1 band and a higher cfvalue near the 1000 cmminus1 band This can be explained by thefact that (i) referring to the 700 cmminus1 band 23 had an averagefor intensity modes that was lower than the average valuesfor the other Na and NM compounds and therefore lowerweight values (see (4)) and lower cf and (ii) referring to the1000 cmminus1 band the OndashCsp3 stretch mode at 1073 cmminus1 hadan intensity value that was 87 times higher than the secondmost intensemode generating the observed overestimated cfvalue

That being said and according to mathematical approachadopted in this paper no relationship was found betweenIR properties and the presence of musky odor throughGGAPW91 It does not mean that GGAPW91 calculationleads to affirm that musks and nonmusks have indistinguish-able spectra Itmeans that considering theweighted-averagesvalues resource in order to simplify the adoption of alltheoretical peaks under analysis resulting central frequenciesare similar among musks and nonmusks Such observationmay be due the fact that GGAPW91 spectra had narrowerbands for each vibrational mode rather than B3LYP spectraAs GGAPW91 proved to be a more accurate method itrequires a more accurate statistical tools so to properly dealwith all theoretical modes as to affirm (or deny) a possibledifference on musks and nonmusks IR spectra

36 B3LYP cf rsquos Plots and Musk Activity On the other handTable 6 (with B3LYP data) shows that all musks from 1 to16 have had theoretical central frequencies that fitted thefrequencies demanded at 700 1000 and 1500 (or 1750) cmminus1

10 Advances in Chemistry

Table 5 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for GGAPW91 collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd

Diff Around 1000 Avestd

Diff Around 1500 Avestd

Diff

MCM

1 742 743 minus1 1030 1049 minus19 1429 1411 18 02 761 12 18 1096 31 47 1404 11 minus7 03 748 5 1047 minus2 1417 6 04 734 minus9 1016 minus33 1405 minus6 05 730 minus13 1057 8 1402 minus9 0

PCM

6 751 733 18 1046 1020 26 1423 1480 minus57 07 769 34 36 1051 48 31 1424 54 minus56 08 678 minus55 977 minus43 1527 47 09 731 minus2 1066 46 1532 52 010 736 3 959 minus61 1495 15 0

NM11 735 755 minus20 1033 1019 14 1634 1589 45 012 763 17 8 1002 16 minus17 1567 39 minus22 013 766 11 1023 4 1567 minus22 0

ACM14 784 784 0 1084 1086 minus2 1402 1411 minus9 015 762 23 minus22 1079 9 minus7 1401 16 minus10 016 807 23 1096 10 1429 18 0

MCa 17 751 743 8 1067 1049 17 1405 1411 minus7 018 726 12 minus17 1049 31 0 1417 11 6 0

Aa 19 779 784 minus6 1073 1086 minus13 1411 1411 0 020 757 23 minus28 1105 9 19 1403 16 minus8 1

Na21 733 755 minus21 1033 1019 13 1557 1589 minus32 022 757 17 2 1006 16 minus13 1549 39 minus40 023 717 minus38 1060 41 1655 66 2

lowastTD total deviations

in the vibrational theory Simultaneously Aa and Na showedthat at least one of their cfs was too shifted from theiraverages Molecule 23 for instance is the only nonmusk pos-sessing an aldehyde functional group and its C=O stretchingmode is found at the 1550ndash1950 cmminus1 range under studyNevertheless nitromusk 11 also holds an aldehyde functionalgroup and though its cf at 1750 cmminus1 is indeed higher than theother cfs for the NM it is still 70 cmminus1 lower than 23rsquos cf Stillconcerning the analysis of Table 6 we can say that the acyclicanalogs 19 and 20 have had their central frequencies shiftedto lower values at the 1500 cmminus1 diagnostic band the onlyone in which there was no agreement between theoreticalresults and expectations deriving from the vibrational theoryAt the 1500 plusmn 200 cmminus1 range hydrocarbon scissoring modesand alkenearomatic C=C stretching modes are found and19 and 20 lack the gem-methyl at the cyclohexane that areobserved in 14 and 15 moreover although in 16 this gem-methyl is also absent it possesses two alkene groups forwhich its stretching modes are also found at this rangeFinally macrocyclic analogs showed the same spectra dataas macrocyclic musks as compounds 18 and 19 differ fromMCM in that they lack two methylene groups it is possibleto suggest that such loss leads the moleculersquos CndashH vibrational

mode sum to be too low to be detected by its OR as suggestedelsewhere [23] Besides both 18 and 19 present awoody smellby being smaller they may be able to bind to a variety ofdifferent ORs which do not reassemble the behavior of themusk detected by possibly only one OR or just a few more[48]

4 Conclusions

This paper worked on developing a method which couldstate the following (i) whether musky molecules had theirIR theoretical spectra fitted into the four bands assigned byvibrational theory in 2002 Turinrsquos paper and (ii) whethernonmuskymolecules did not have their IR theoretical spectrafitted into same criteria It was first concluded that only threebands were useful for discriminating musk from nonmuskodorants The fourth IR band refers to a carbonyl stretchingmode and data here presented showed that this mode cannotbe taken as criteria when building a muskiness profile

Present work was carried out with two different func-tionals applying DFT calculation level and both were ableto accurately predict IR spectra A mathematical strategyhas been adopted in order to summarize IR theoretical

Advances in Chemistry 11

Table 6 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for B3LYP collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd Diff Around 1000 Ave

std Diff Around 1500 Avestd Diff

MCM

1 754 748 6 1142 1093 48 1407 1423 minus16 02 768 16 20 1066 39 minus27 1428 10 5 03 749 1 1116 23 1421 minus2 04 744 minus3 1099 5 1430 6 05 723 minus25 1044 minus49 1429 6 0

PCM

6 749 722 28 1068 1019 49 1450 1476 minus26 07 752 51 31 1052 62 33 1450 32 minus27 08 692 minus30 971 minus48 1461 minus15 09 646 minus75 1069 50 1499 23 010 768 47 936 minus83 1520 44 0

NM11 754 766 minus12 952 977 minus26 1602 1597 5 012 771 10 5 993 22 16 1595 5 minus2 013 772 7 987 9 1593 minus3 0

ACM14 722 732 minus10 1101 1127 minus26 1424 1435 minus12 015 771 35 39 1130 24 3 1431 14 minus4 016 703 minus29 1149 22 1451 15 0

MCa 17 750 748 2 1067 1093 minus26 1418 1423 minus5 018 726 16 minus22 1072 39 minus21 1432 10 9 0

Aa 19 784 732 52 1097 1127 minus30 1357 1435 minus78 120 763 35 31 1087 24 minus40 1410 14 minus26 1

Na21 742 766 minus24 1015 977 38 1601 1597 4 122 767 10 1 1150 22 173 1600 5 3 123 702 minus64 1068 91 1675 78 3

lowastTD total deviations

data and properly compare musk to nonmusk moleculesUsing this approach GGAPW91 computed spectra showedno discriminating patterns between musks and nonmusksB3LYP data showed theoretical frequencies and the threediagnostic bands to bematching while nitro andmacrocyclicnonmusks failed in at least one of such comparisons

It was therefore possible to conclude that no specificmodealone is responsible for the discrimination of themusky odorInstead when a great amount of frequencies expressing weakor medium intensities were found along the 700ndash1700 cmminus1range musk odor occurs At this range observedmodes wereCH2

wag and scissor bending modes C=C stretches andsymmetric nitro stretching modes

This trial scanning over IR vibrational modes and theirrelation to musk odor perception brings new informationaltowards the understanding and application of vibrationaltheoryrsquos ideas and opens the possibility to a more extensivestudy in which a broader number of molecules may bemodeled so as to come to a quantitative proposal for amusky-like novel odorant regarding their IR vibrational modes

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The authors thank Professor Ines Sabioni Resck (fromInstituto de Quımica Brasılia Brazil) for initial ideas andreliance

References

[1] M Eh ldquoNew alicyclic musks the fourth generation of muskodorantsrdquoChemistryamp Biodiversity vol 1 no 12 pp 1975ndash19842004

[2] P Saiyasombati andG BKasting ldquoTwo-stage kinetic analysis offragrance evaporation and absorption from skinrdquo InternationalJournal of Cosmetic Science vol 25 no 5 pp 235ndash243 2003

[3] G B Kasting and P Saiyasombati ldquoA physico-chemical prop-erties based model for estimating evaporation and absorptionrates of perfumes from skinrdquo International Journal of CosmeticScience vol 23 no 1 pp 49ndash58 2001

[4] M Shirasu K Yoshikawa Y Takai et al ldquoOlfactory receptor andneural pathway responsible for highly selective sensing of muskodorsrdquo Neuron vol 81 no 1 pp 165ndash178 2014

[5] J Reisert and H Zhao ldquoResponse kinetics of olfactory receptorneurons and the implications in olfactory codingrdquo Journal ofGeneral Physiology vol 138 no 3 pp 303ndash310 2011

12 Advances in Chemistry

[6] J-P Rospars Y Gu A Gremiaux and P Lucas ldquoOdourtransduction in olfactory receptor neuronsrdquo Chinese Journal ofPhysiology vol 53 no 6 pp 364ndash372 2010

[7] B Malnic and A F Mercadante ldquoThe odorant signaling path-wayrdquo Annual Review of Biomedical Sciences vol 11 pp T86ndashT94 2009

[8] K Snitz A Yablonka T Weiss I Frumin R M Khan andN Sobel ldquoPredicting odor perceptual similarity from odorstructurerdquo PLoS Computational Biology vol 9 no 9 Article IDe1003184 2013

[9] B K Lavine CWhite NMirjankar CM Sundling and CMBreneman ldquoOdor-structure relationship studies of tetralin andindan musksrdquo Chemical Senses vol 37 no 8 pp 723ndash736 2012

[10] Y Zou H Mouhib W Stahl A Goeke Q Wang and PKraft ldquoEfficient macrocyclization by a novel oxy-oxonia-copereaction synthesis and olfactory properties of new macrocyclicmusksrdquo Chemistry vol 18 no 23 pp 7010ndash7015 2012

[11] S Liu ldquoStudy on the relationship between molecular odour ofpolycyclic musksrdquo Xiangliao Xiangjing Huazhuangpin vol 6pp 24ndash29 2004

[12] S-Y Takane and J B O Mitchell ldquoA structure-odor relation-ship study using EVA descriptors and hierarchical clusteringrdquoOrganicampBiomolecular Chemistry vol 2 no 22 pp 3250ndash32552004

[13] K J Rossiter ldquoStructure-odour relationshipsrdquo ChemicalReviews vol 96 no 8 pp 3201ndash3240 1996

[14] M Zarzo ldquoThe sense of smell molecular basis of odorantrecognitionrdquoBiological Reviews vol 82 no 3 pp 455ndash479 2007

[15] A Kato and K Touhara ldquoMammalian olfactory receptorspharmacologyGprotein coupling anddesensitizationrdquoCellularandMolecular Life Sciences vol 66 no 23 pp 3743ndash3753 2009

[16] L Turin and F Yoshii ldquoStructure-odor relations a modernperspectiverdquo in Handbook of Olfaction and Gustation R LDoty Ed pp 275ndash294 Marcel Dekker New York NY USA2003

[17] L Turin ldquoA spectroscopic mechanism for primary olfactoryreceptionrdquo Chemical Senses vol 21 no 6 pp 773ndash791 1996

[18] M A Reed ldquoInelastic electron tunneling spectroscopyrdquo Mate-rials Today vol 11 no 11 pp 46ndash50 2008

[19] L Turin ldquoA method for the calculation of odor character frommolecular structurerdquo Journal ofTheoretical Biology vol 216 no3 pp 367ndash385 2002

[20] L J W Haffenden V A Yaylayan and J Fortin ldquoInvestigationof vibrational theory of olfaction with variously labelled ben-zaldehydesrdquo Food Chemistry vol 73 no 1 pp 67ndash72 2001

[21] J C Brookes F Hartoutsiou A P Horsfield and A MStoneham ldquoCould humans recognize odor by phonon assistedtunnelingrdquo Physical Review Letters vol 98 no 3 Article ID038101 2007

[22] M I Franco L Turin A Mershin and E M C SkoulakisldquoMolecular vibration-sensing component in Drosophila mela-nogaster olfactionrdquo Proceedings of the National Academy ofSciences vol 108 no 9 pp 3797ndash3802 2011

[23] I A Solovrsquoyov P-Y Chang and K Schulten ldquoVibrationallyassisted electron transfer mechanism of olfaction myth orrealityrdquo Physical Chemistry Chemical Physics vol 14 no 40 pp13861ndash13871 2012

[24] S GaneDGeorganakis KManiati et al ldquoMolecular vibration-sensing component in human olfactionrdquo PLoS ONE vol 8 no1 Article ID e55780 2013

[25] D L Pavia G M Lampman G S Kriz and J R VyvyanIntroduction to Spectroscopy Cengage Learning Sao PauloBrazil 2010

[26] D A Lerner D Berthomieu and E R Maia ldquoModeling of theconformational flexibility and EZ isomerism of thiazoximicacid and cefotaximerdquo International Journal of Quantum Chem-istry vol 111 no 6 pp 1222ndash1238 2011

[27] A P Scott andL Radom ldquoHarmonic vibrational frequencies anevaluation of Hartree-Fock Moslashller-Plesset quadratic configu-ration interaction density functional theory and semiempiricalscale factorsrdquoThe Journal of Physical Chemistry vol 100 no 41pp 16502ndash16513 1996

[28] S Gabler J Soelter T Hussain S Sachse and M SchmukerldquoPhysicochemical vs vibrational descriptors for prediction ofodor receptor responsesrdquo Molecular Informatics vol 32 no 9-10 pp 855ndash865 2013

[29] Materials Studio SW and Insight II SW Acelrys San DiegoCalif USA

[30] M J Frisch G W Trucks H B Schlegel et al ldquoGaussian 09Revision A02rdquo Gaussian Inc Wallingford Conn USA 2009

[31] H Sun ldquoCompass an ab initio force-field optimized forcondensed-phase applicationsmdashoverview with details onalkane and benzene compoundsrdquo Journal of Physical ChemistryB vol 102 no 38 pp 7338ndash7364 1998

[32] P Dauber-Osguthorpe V A Roberts D J Osguthorpe J WolfM Genest and A T Hagler ldquoStructure and energetics of ligandbinding to proteins Escherichia coli dihydrofolate reductase-trimethoprim a drug-receptor systemrdquo Proteins StructureFunction and Genetics vol 4 no 1 pp 31ndash47 1988

[33] DH JMackay A J Cross andA THagler ldquoThe role of energyminimization in simulation strategies of biomolecular systemsrdquoin Prediction of Protein Structure and the Principles of ProteinConformation D G Fasman Ed pp 317ndash358 Plenum PressNew York NY USA 1990

[34] R Fletcher and C M Reeves ldquoFunction minimization byconjugate gradientsrdquo The Computer Journal vol 7 no 2 pp149ndash154 1964

[35] WH Press B P Flannery S A Teukolsky andW T VetterlingNumerical Recipes in C the Art of Scientific Computing Cam-bridge University Press London UK 1988

[36] J J P Stewart ldquoMopac a semiempirical molecular orbitalprogramrdquo Journal of Computer-Aided Molecular Design vol 4no 1 pp 101ndash105 1990

[37] J A Pople D P Santry and G A Segal ldquoApproximate self-consistent molecular orbital theory I Invariant proceduresrdquoThe Journal of Chemical Physics vol 43 no 10 pp S129ndashS1351965

[38] J A Pople and G A Segal ldquoApproximate self-consistentmolecular orbital theory III CNDO results for AB

2

and AB3

systemsrdquo The Journal of Chemical Physics vol 44 no 9 pp3289ndash3296 1966

[39] M J S Dewar E G Zoebisch E F Healy and J J P StewartldquoAM1 a new general purpose quantum mechanical molecularmodelrdquo Journal of the American Chemical Society vol 107 no13 pp 3902ndash3909 1985

[40] B Delley ldquoAn all-electron numerical method for solving thelocal density functional for polyatomic moleculesrdquoThe Journalof Chemical Physics vol 92 no 1 pp 508ndash517 1990

[41] B Delley ldquoFast calculation of electrostatics in crystals and largemoleculesrdquo Journal of Physical Chemistry vol 100 no 15 pp6107ndash6110 1996

Advances in Chemistry 13

[42] B Delley ldquoDMol methodology and applicationsrdquo in DensityFunctional Methods in Chemistry J W Andzelm and J KLabanowski Eds pp 101ndash108 Springer New York NY USA1991

[43] B Delley ldquoCalculated electron distribution for Tetrafluoroter-phthalonitrile (TFT)rdquo Chemical Physics vol 110 no 2-3 pp329ndash338 1986

[44] YWang and J P Perdew ldquoCorrelation hole of the spin-polarizedelectron gas with exact small-wave-vector and high-densityscalingrdquo Physical Review B vol 44 no 24 pp 13298ndash13307 1991

[45] P J Stephens F J Devlin C F Chabalowski and M J FrischldquoAb Initio calculation of vibrational absorption and circulardichroism spectra using density functional force fieldsrdquo Journalof Physical Chemistry vol 98 no 45 pp 11623ndash11627 1994

[46] G Schaftenaar and J H Noordik ldquoMolden a pre- and post-processing program for molecular and electronic structuresrdquoJournal of Computer-Aided Molecular Design vol 14 no 2 pp123ndash134 2000

[47] Xming ldquoXming X server for Windowsrdquo 2012 httpwwwstraightrunningcomXmingNotes

[48] K Nara L R Saraiva X Ye and L B Buck ldquoA large-scaleanalysis of odor coding in the olfactory epitheliumrdquo Journal ofNeuroscience vol 31 no 25 pp 9179ndash9191 2011

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

10 Advances in Chemistry

Table 5 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for GGAPW91 collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd

Diff Around 1000 Avestd

Diff Around 1500 Avestd

Diff

MCM

1 742 743 minus1 1030 1049 minus19 1429 1411 18 02 761 12 18 1096 31 47 1404 11 minus7 03 748 5 1047 minus2 1417 6 04 734 minus9 1016 minus33 1405 minus6 05 730 minus13 1057 8 1402 minus9 0

PCM

6 751 733 18 1046 1020 26 1423 1480 minus57 07 769 34 36 1051 48 31 1424 54 minus56 08 678 minus55 977 minus43 1527 47 09 731 minus2 1066 46 1532 52 010 736 3 959 minus61 1495 15 0

NM11 735 755 minus20 1033 1019 14 1634 1589 45 012 763 17 8 1002 16 minus17 1567 39 minus22 013 766 11 1023 4 1567 minus22 0

ACM14 784 784 0 1084 1086 minus2 1402 1411 minus9 015 762 23 minus22 1079 9 minus7 1401 16 minus10 016 807 23 1096 10 1429 18 0

MCa 17 751 743 8 1067 1049 17 1405 1411 minus7 018 726 12 minus17 1049 31 0 1417 11 6 0

Aa 19 779 784 minus6 1073 1086 minus13 1411 1411 0 020 757 23 minus28 1105 9 19 1403 16 minus8 1

Na21 733 755 minus21 1033 1019 13 1557 1589 minus32 022 757 17 2 1006 16 minus13 1549 39 minus40 023 717 minus38 1060 41 1655 66 2

lowastTD total deviations

in the vibrational theory Simultaneously Aa and Na showedthat at least one of their cfs was too shifted from theiraverages Molecule 23 for instance is the only nonmusk pos-sessing an aldehyde functional group and its C=O stretchingmode is found at the 1550ndash1950 cmminus1 range under studyNevertheless nitromusk 11 also holds an aldehyde functionalgroup and though its cf at 1750 cmminus1 is indeed higher than theother cfs for the NM it is still 70 cmminus1 lower than 23rsquos cf Stillconcerning the analysis of Table 6 we can say that the acyclicanalogs 19 and 20 have had their central frequencies shiftedto lower values at the 1500 cmminus1 diagnostic band the onlyone in which there was no agreement between theoreticalresults and expectations deriving from the vibrational theoryAt the 1500 plusmn 200 cmminus1 range hydrocarbon scissoring modesand alkenearomatic C=C stretching modes are found and19 and 20 lack the gem-methyl at the cyclohexane that areobserved in 14 and 15 moreover although in 16 this gem-methyl is also absent it possesses two alkene groups forwhich its stretching modes are also found at this rangeFinally macrocyclic analogs showed the same spectra dataas macrocyclic musks as compounds 18 and 19 differ fromMCM in that they lack two methylene groups it is possibleto suggest that such loss leads the moleculersquos CndashH vibrational

mode sum to be too low to be detected by its OR as suggestedelsewhere [23] Besides both 18 and 19 present awoody smellby being smaller they may be able to bind to a variety ofdifferent ORs which do not reassemble the behavior of themusk detected by possibly only one OR or just a few more[48]

4 Conclusions

This paper worked on developing a method which couldstate the following (i) whether musky molecules had theirIR theoretical spectra fitted into the four bands assigned byvibrational theory in 2002 Turinrsquos paper and (ii) whethernonmuskymolecules did not have their IR theoretical spectrafitted into same criteria It was first concluded that only threebands were useful for discriminating musk from nonmuskodorants The fourth IR band refers to a carbonyl stretchingmode and data here presented showed that this mode cannotbe taken as criteria when building a muskiness profile

Present work was carried out with two different func-tionals applying DFT calculation level and both were ableto accurately predict IR spectra A mathematical strategyhas been adopted in order to summarize IR theoretical

Advances in Chemistry 11

Table 6 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for B3LYP collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd Diff Around 1000 Ave

std Diff Around 1500 Avestd Diff

MCM

1 754 748 6 1142 1093 48 1407 1423 minus16 02 768 16 20 1066 39 minus27 1428 10 5 03 749 1 1116 23 1421 minus2 04 744 minus3 1099 5 1430 6 05 723 minus25 1044 minus49 1429 6 0

PCM

6 749 722 28 1068 1019 49 1450 1476 minus26 07 752 51 31 1052 62 33 1450 32 minus27 08 692 minus30 971 minus48 1461 minus15 09 646 minus75 1069 50 1499 23 010 768 47 936 minus83 1520 44 0

NM11 754 766 minus12 952 977 minus26 1602 1597 5 012 771 10 5 993 22 16 1595 5 minus2 013 772 7 987 9 1593 minus3 0

ACM14 722 732 minus10 1101 1127 minus26 1424 1435 minus12 015 771 35 39 1130 24 3 1431 14 minus4 016 703 minus29 1149 22 1451 15 0

MCa 17 750 748 2 1067 1093 minus26 1418 1423 minus5 018 726 16 minus22 1072 39 minus21 1432 10 9 0

Aa 19 784 732 52 1097 1127 minus30 1357 1435 minus78 120 763 35 31 1087 24 minus40 1410 14 minus26 1

Na21 742 766 minus24 1015 977 38 1601 1597 4 122 767 10 1 1150 22 173 1600 5 3 123 702 minus64 1068 91 1675 78 3

lowastTD total deviations

data and properly compare musk to nonmusk moleculesUsing this approach GGAPW91 computed spectra showedno discriminating patterns between musks and nonmusksB3LYP data showed theoretical frequencies and the threediagnostic bands to bematching while nitro andmacrocyclicnonmusks failed in at least one of such comparisons

It was therefore possible to conclude that no specificmodealone is responsible for the discrimination of themusky odorInstead when a great amount of frequencies expressing weakor medium intensities were found along the 700ndash1700 cmminus1range musk odor occurs At this range observedmodes wereCH2

wag and scissor bending modes C=C stretches andsymmetric nitro stretching modes

This trial scanning over IR vibrational modes and theirrelation to musk odor perception brings new informationaltowards the understanding and application of vibrationaltheoryrsquos ideas and opens the possibility to a more extensivestudy in which a broader number of molecules may bemodeled so as to come to a quantitative proposal for amusky-like novel odorant regarding their IR vibrational modes

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The authors thank Professor Ines Sabioni Resck (fromInstituto de Quımica Brasılia Brazil) for initial ideas andreliance

References

[1] M Eh ldquoNew alicyclic musks the fourth generation of muskodorantsrdquoChemistryamp Biodiversity vol 1 no 12 pp 1975ndash19842004

[2] P Saiyasombati andG BKasting ldquoTwo-stage kinetic analysis offragrance evaporation and absorption from skinrdquo InternationalJournal of Cosmetic Science vol 25 no 5 pp 235ndash243 2003

[3] G B Kasting and P Saiyasombati ldquoA physico-chemical prop-erties based model for estimating evaporation and absorptionrates of perfumes from skinrdquo International Journal of CosmeticScience vol 23 no 1 pp 49ndash58 2001

[4] M Shirasu K Yoshikawa Y Takai et al ldquoOlfactory receptor andneural pathway responsible for highly selective sensing of muskodorsrdquo Neuron vol 81 no 1 pp 165ndash178 2014

[5] J Reisert and H Zhao ldquoResponse kinetics of olfactory receptorneurons and the implications in olfactory codingrdquo Journal ofGeneral Physiology vol 138 no 3 pp 303ndash310 2011

12 Advances in Chemistry

[6] J-P Rospars Y Gu A Gremiaux and P Lucas ldquoOdourtransduction in olfactory receptor neuronsrdquo Chinese Journal ofPhysiology vol 53 no 6 pp 364ndash372 2010

[7] B Malnic and A F Mercadante ldquoThe odorant signaling path-wayrdquo Annual Review of Biomedical Sciences vol 11 pp T86ndashT94 2009

[8] K Snitz A Yablonka T Weiss I Frumin R M Khan andN Sobel ldquoPredicting odor perceptual similarity from odorstructurerdquo PLoS Computational Biology vol 9 no 9 Article IDe1003184 2013

[9] B K Lavine CWhite NMirjankar CM Sundling and CMBreneman ldquoOdor-structure relationship studies of tetralin andindan musksrdquo Chemical Senses vol 37 no 8 pp 723ndash736 2012

[10] Y Zou H Mouhib W Stahl A Goeke Q Wang and PKraft ldquoEfficient macrocyclization by a novel oxy-oxonia-copereaction synthesis and olfactory properties of new macrocyclicmusksrdquo Chemistry vol 18 no 23 pp 7010ndash7015 2012

[11] S Liu ldquoStudy on the relationship between molecular odour ofpolycyclic musksrdquo Xiangliao Xiangjing Huazhuangpin vol 6pp 24ndash29 2004

[12] S-Y Takane and J B O Mitchell ldquoA structure-odor relation-ship study using EVA descriptors and hierarchical clusteringrdquoOrganicampBiomolecular Chemistry vol 2 no 22 pp 3250ndash32552004

[13] K J Rossiter ldquoStructure-odour relationshipsrdquo ChemicalReviews vol 96 no 8 pp 3201ndash3240 1996

[14] M Zarzo ldquoThe sense of smell molecular basis of odorantrecognitionrdquoBiological Reviews vol 82 no 3 pp 455ndash479 2007

[15] A Kato and K Touhara ldquoMammalian olfactory receptorspharmacologyGprotein coupling anddesensitizationrdquoCellularandMolecular Life Sciences vol 66 no 23 pp 3743ndash3753 2009

[16] L Turin and F Yoshii ldquoStructure-odor relations a modernperspectiverdquo in Handbook of Olfaction and Gustation R LDoty Ed pp 275ndash294 Marcel Dekker New York NY USA2003

[17] L Turin ldquoA spectroscopic mechanism for primary olfactoryreceptionrdquo Chemical Senses vol 21 no 6 pp 773ndash791 1996

[18] M A Reed ldquoInelastic electron tunneling spectroscopyrdquo Mate-rials Today vol 11 no 11 pp 46ndash50 2008

[19] L Turin ldquoA method for the calculation of odor character frommolecular structurerdquo Journal ofTheoretical Biology vol 216 no3 pp 367ndash385 2002

[20] L J W Haffenden V A Yaylayan and J Fortin ldquoInvestigationof vibrational theory of olfaction with variously labelled ben-zaldehydesrdquo Food Chemistry vol 73 no 1 pp 67ndash72 2001

[21] J C Brookes F Hartoutsiou A P Horsfield and A MStoneham ldquoCould humans recognize odor by phonon assistedtunnelingrdquo Physical Review Letters vol 98 no 3 Article ID038101 2007

[22] M I Franco L Turin A Mershin and E M C SkoulakisldquoMolecular vibration-sensing component in Drosophila mela-nogaster olfactionrdquo Proceedings of the National Academy ofSciences vol 108 no 9 pp 3797ndash3802 2011

[23] I A Solovrsquoyov P-Y Chang and K Schulten ldquoVibrationallyassisted electron transfer mechanism of olfaction myth orrealityrdquo Physical Chemistry Chemical Physics vol 14 no 40 pp13861ndash13871 2012

[24] S GaneDGeorganakis KManiati et al ldquoMolecular vibration-sensing component in human olfactionrdquo PLoS ONE vol 8 no1 Article ID e55780 2013

[25] D L Pavia G M Lampman G S Kriz and J R VyvyanIntroduction to Spectroscopy Cengage Learning Sao PauloBrazil 2010

[26] D A Lerner D Berthomieu and E R Maia ldquoModeling of theconformational flexibility and EZ isomerism of thiazoximicacid and cefotaximerdquo International Journal of Quantum Chem-istry vol 111 no 6 pp 1222ndash1238 2011

[27] A P Scott andL Radom ldquoHarmonic vibrational frequencies anevaluation of Hartree-Fock Moslashller-Plesset quadratic configu-ration interaction density functional theory and semiempiricalscale factorsrdquoThe Journal of Physical Chemistry vol 100 no 41pp 16502ndash16513 1996

[28] S Gabler J Soelter T Hussain S Sachse and M SchmukerldquoPhysicochemical vs vibrational descriptors for prediction ofodor receptor responsesrdquo Molecular Informatics vol 32 no 9-10 pp 855ndash865 2013

[29] Materials Studio SW and Insight II SW Acelrys San DiegoCalif USA

[30] M J Frisch G W Trucks H B Schlegel et al ldquoGaussian 09Revision A02rdquo Gaussian Inc Wallingford Conn USA 2009

[31] H Sun ldquoCompass an ab initio force-field optimized forcondensed-phase applicationsmdashoverview with details onalkane and benzene compoundsrdquo Journal of Physical ChemistryB vol 102 no 38 pp 7338ndash7364 1998

[32] P Dauber-Osguthorpe V A Roberts D J Osguthorpe J WolfM Genest and A T Hagler ldquoStructure and energetics of ligandbinding to proteins Escherichia coli dihydrofolate reductase-trimethoprim a drug-receptor systemrdquo Proteins StructureFunction and Genetics vol 4 no 1 pp 31ndash47 1988

[33] DH JMackay A J Cross andA THagler ldquoThe role of energyminimization in simulation strategies of biomolecular systemsrdquoin Prediction of Protein Structure and the Principles of ProteinConformation D G Fasman Ed pp 317ndash358 Plenum PressNew York NY USA 1990

[34] R Fletcher and C M Reeves ldquoFunction minimization byconjugate gradientsrdquo The Computer Journal vol 7 no 2 pp149ndash154 1964

[35] WH Press B P Flannery S A Teukolsky andW T VetterlingNumerical Recipes in C the Art of Scientific Computing Cam-bridge University Press London UK 1988

[36] J J P Stewart ldquoMopac a semiempirical molecular orbitalprogramrdquo Journal of Computer-Aided Molecular Design vol 4no 1 pp 101ndash105 1990

[37] J A Pople D P Santry and G A Segal ldquoApproximate self-consistent molecular orbital theory I Invariant proceduresrdquoThe Journal of Chemical Physics vol 43 no 10 pp S129ndashS1351965

[38] J A Pople and G A Segal ldquoApproximate self-consistentmolecular orbital theory III CNDO results for AB

2

and AB3

systemsrdquo The Journal of Chemical Physics vol 44 no 9 pp3289ndash3296 1966

[39] M J S Dewar E G Zoebisch E F Healy and J J P StewartldquoAM1 a new general purpose quantum mechanical molecularmodelrdquo Journal of the American Chemical Society vol 107 no13 pp 3902ndash3909 1985

[40] B Delley ldquoAn all-electron numerical method for solving thelocal density functional for polyatomic moleculesrdquoThe Journalof Chemical Physics vol 92 no 1 pp 508ndash517 1990

[41] B Delley ldquoFast calculation of electrostatics in crystals and largemoleculesrdquo Journal of Physical Chemistry vol 100 no 15 pp6107ndash6110 1996

Advances in Chemistry 13

[42] B Delley ldquoDMol methodology and applicationsrdquo in DensityFunctional Methods in Chemistry J W Andzelm and J KLabanowski Eds pp 101ndash108 Springer New York NY USA1991

[43] B Delley ldquoCalculated electron distribution for Tetrafluoroter-phthalonitrile (TFT)rdquo Chemical Physics vol 110 no 2-3 pp329ndash338 1986

[44] YWang and J P Perdew ldquoCorrelation hole of the spin-polarizedelectron gas with exact small-wave-vector and high-densityscalingrdquo Physical Review B vol 44 no 24 pp 13298ndash13307 1991

[45] P J Stephens F J Devlin C F Chabalowski and M J FrischldquoAb Initio calculation of vibrational absorption and circulardichroism spectra using density functional force fieldsrdquo Journalof Physical Chemistry vol 98 no 45 pp 11623ndash11627 1994

[46] G Schaftenaar and J H Noordik ldquoMolden a pre- and post-processing program for molecular and electronic structuresrdquoJournal of Computer-Aided Molecular Design vol 14 no 2 pp123ndash134 2000

[47] Xming ldquoXming X server for Windowsrdquo 2012 httpwwwstraightrunningcomXmingNotes

[48] K Nara L R Saraiva X Ye and L B Buck ldquoA large-scaleanalysis of odor coding in the olfactory epitheliumrdquo Journal ofNeuroscience vol 31 no 25 pp 9179ndash9191 2011

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Advances in Chemistry 11

Table 6 Calculated central frequencies for bands near 700 1000 and 1500 cmminus1 for 1ndash23 compounds for B3LYP collected data

MuskCentral frequency (cmminus1)

TDlowastAround 700 Avestd Diff Around 1000 Ave

std Diff Around 1500 Avestd Diff

MCM

1 754 748 6 1142 1093 48 1407 1423 minus16 02 768 16 20 1066 39 minus27 1428 10 5 03 749 1 1116 23 1421 minus2 04 744 minus3 1099 5 1430 6 05 723 minus25 1044 minus49 1429 6 0

PCM

6 749 722 28 1068 1019 49 1450 1476 minus26 07 752 51 31 1052 62 33 1450 32 minus27 08 692 minus30 971 minus48 1461 minus15 09 646 minus75 1069 50 1499 23 010 768 47 936 minus83 1520 44 0

NM11 754 766 minus12 952 977 minus26 1602 1597 5 012 771 10 5 993 22 16 1595 5 minus2 013 772 7 987 9 1593 minus3 0

ACM14 722 732 minus10 1101 1127 minus26 1424 1435 minus12 015 771 35 39 1130 24 3 1431 14 minus4 016 703 minus29 1149 22 1451 15 0

MCa 17 750 748 2 1067 1093 minus26 1418 1423 minus5 018 726 16 minus22 1072 39 minus21 1432 10 9 0

Aa 19 784 732 52 1097 1127 minus30 1357 1435 minus78 120 763 35 31 1087 24 minus40 1410 14 minus26 1

Na21 742 766 minus24 1015 977 38 1601 1597 4 122 767 10 1 1150 22 173 1600 5 3 123 702 minus64 1068 91 1675 78 3

lowastTD total deviations

data and properly compare musk to nonmusk moleculesUsing this approach GGAPW91 computed spectra showedno discriminating patterns between musks and nonmusksB3LYP data showed theoretical frequencies and the threediagnostic bands to bematching while nitro andmacrocyclicnonmusks failed in at least one of such comparisons

It was therefore possible to conclude that no specificmodealone is responsible for the discrimination of themusky odorInstead when a great amount of frequencies expressing weakor medium intensities were found along the 700ndash1700 cmminus1range musk odor occurs At this range observedmodes wereCH2

wag and scissor bending modes C=C stretches andsymmetric nitro stretching modes

This trial scanning over IR vibrational modes and theirrelation to musk odor perception brings new informationaltowards the understanding and application of vibrationaltheoryrsquos ideas and opens the possibility to a more extensivestudy in which a broader number of molecules may bemodeled so as to come to a quantitative proposal for amusky-like novel odorant regarding their IR vibrational modes

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

Acknowledgment

The authors thank Professor Ines Sabioni Resck (fromInstituto de Quımica Brasılia Brazil) for initial ideas andreliance

References

[1] M Eh ldquoNew alicyclic musks the fourth generation of muskodorantsrdquoChemistryamp Biodiversity vol 1 no 12 pp 1975ndash19842004

[2] P Saiyasombati andG BKasting ldquoTwo-stage kinetic analysis offragrance evaporation and absorption from skinrdquo InternationalJournal of Cosmetic Science vol 25 no 5 pp 235ndash243 2003

[3] G B Kasting and P Saiyasombati ldquoA physico-chemical prop-erties based model for estimating evaporation and absorptionrates of perfumes from skinrdquo International Journal of CosmeticScience vol 23 no 1 pp 49ndash58 2001

[4] M Shirasu K Yoshikawa Y Takai et al ldquoOlfactory receptor andneural pathway responsible for highly selective sensing of muskodorsrdquo Neuron vol 81 no 1 pp 165ndash178 2014

[5] J Reisert and H Zhao ldquoResponse kinetics of olfactory receptorneurons and the implications in olfactory codingrdquo Journal ofGeneral Physiology vol 138 no 3 pp 303ndash310 2011

12 Advances in Chemistry

[6] J-P Rospars Y Gu A Gremiaux and P Lucas ldquoOdourtransduction in olfactory receptor neuronsrdquo Chinese Journal ofPhysiology vol 53 no 6 pp 364ndash372 2010

[7] B Malnic and A F Mercadante ldquoThe odorant signaling path-wayrdquo Annual Review of Biomedical Sciences vol 11 pp T86ndashT94 2009

[8] K Snitz A Yablonka T Weiss I Frumin R M Khan andN Sobel ldquoPredicting odor perceptual similarity from odorstructurerdquo PLoS Computational Biology vol 9 no 9 Article IDe1003184 2013

[9] B K Lavine CWhite NMirjankar CM Sundling and CMBreneman ldquoOdor-structure relationship studies of tetralin andindan musksrdquo Chemical Senses vol 37 no 8 pp 723ndash736 2012

[10] Y Zou H Mouhib W Stahl A Goeke Q Wang and PKraft ldquoEfficient macrocyclization by a novel oxy-oxonia-copereaction synthesis and olfactory properties of new macrocyclicmusksrdquo Chemistry vol 18 no 23 pp 7010ndash7015 2012

[11] S Liu ldquoStudy on the relationship between molecular odour ofpolycyclic musksrdquo Xiangliao Xiangjing Huazhuangpin vol 6pp 24ndash29 2004

[12] S-Y Takane and J B O Mitchell ldquoA structure-odor relation-ship study using EVA descriptors and hierarchical clusteringrdquoOrganicampBiomolecular Chemistry vol 2 no 22 pp 3250ndash32552004

[13] K J Rossiter ldquoStructure-odour relationshipsrdquo ChemicalReviews vol 96 no 8 pp 3201ndash3240 1996

[14] M Zarzo ldquoThe sense of smell molecular basis of odorantrecognitionrdquoBiological Reviews vol 82 no 3 pp 455ndash479 2007

[15] A Kato and K Touhara ldquoMammalian olfactory receptorspharmacologyGprotein coupling anddesensitizationrdquoCellularandMolecular Life Sciences vol 66 no 23 pp 3743ndash3753 2009

[16] L Turin and F Yoshii ldquoStructure-odor relations a modernperspectiverdquo in Handbook of Olfaction and Gustation R LDoty Ed pp 275ndash294 Marcel Dekker New York NY USA2003

[17] L Turin ldquoA spectroscopic mechanism for primary olfactoryreceptionrdquo Chemical Senses vol 21 no 6 pp 773ndash791 1996

[18] M A Reed ldquoInelastic electron tunneling spectroscopyrdquo Mate-rials Today vol 11 no 11 pp 46ndash50 2008

[19] L Turin ldquoA method for the calculation of odor character frommolecular structurerdquo Journal ofTheoretical Biology vol 216 no3 pp 367ndash385 2002

[20] L J W Haffenden V A Yaylayan and J Fortin ldquoInvestigationof vibrational theory of olfaction with variously labelled ben-zaldehydesrdquo Food Chemistry vol 73 no 1 pp 67ndash72 2001

[21] J C Brookes F Hartoutsiou A P Horsfield and A MStoneham ldquoCould humans recognize odor by phonon assistedtunnelingrdquo Physical Review Letters vol 98 no 3 Article ID038101 2007

[22] M I Franco L Turin A Mershin and E M C SkoulakisldquoMolecular vibration-sensing component in Drosophila mela-nogaster olfactionrdquo Proceedings of the National Academy ofSciences vol 108 no 9 pp 3797ndash3802 2011

[23] I A Solovrsquoyov P-Y Chang and K Schulten ldquoVibrationallyassisted electron transfer mechanism of olfaction myth orrealityrdquo Physical Chemistry Chemical Physics vol 14 no 40 pp13861ndash13871 2012

[24] S GaneDGeorganakis KManiati et al ldquoMolecular vibration-sensing component in human olfactionrdquo PLoS ONE vol 8 no1 Article ID e55780 2013

[25] D L Pavia G M Lampman G S Kriz and J R VyvyanIntroduction to Spectroscopy Cengage Learning Sao PauloBrazil 2010

[26] D A Lerner D Berthomieu and E R Maia ldquoModeling of theconformational flexibility and EZ isomerism of thiazoximicacid and cefotaximerdquo International Journal of Quantum Chem-istry vol 111 no 6 pp 1222ndash1238 2011

[27] A P Scott andL Radom ldquoHarmonic vibrational frequencies anevaluation of Hartree-Fock Moslashller-Plesset quadratic configu-ration interaction density functional theory and semiempiricalscale factorsrdquoThe Journal of Physical Chemistry vol 100 no 41pp 16502ndash16513 1996

[28] S Gabler J Soelter T Hussain S Sachse and M SchmukerldquoPhysicochemical vs vibrational descriptors for prediction ofodor receptor responsesrdquo Molecular Informatics vol 32 no 9-10 pp 855ndash865 2013

[29] Materials Studio SW and Insight II SW Acelrys San DiegoCalif USA

[30] M J Frisch G W Trucks H B Schlegel et al ldquoGaussian 09Revision A02rdquo Gaussian Inc Wallingford Conn USA 2009

[31] H Sun ldquoCompass an ab initio force-field optimized forcondensed-phase applicationsmdashoverview with details onalkane and benzene compoundsrdquo Journal of Physical ChemistryB vol 102 no 38 pp 7338ndash7364 1998

[32] P Dauber-Osguthorpe V A Roberts D J Osguthorpe J WolfM Genest and A T Hagler ldquoStructure and energetics of ligandbinding to proteins Escherichia coli dihydrofolate reductase-trimethoprim a drug-receptor systemrdquo Proteins StructureFunction and Genetics vol 4 no 1 pp 31ndash47 1988

[33] DH JMackay A J Cross andA THagler ldquoThe role of energyminimization in simulation strategies of biomolecular systemsrdquoin Prediction of Protein Structure and the Principles of ProteinConformation D G Fasman Ed pp 317ndash358 Plenum PressNew York NY USA 1990

[34] R Fletcher and C M Reeves ldquoFunction minimization byconjugate gradientsrdquo The Computer Journal vol 7 no 2 pp149ndash154 1964

[35] WH Press B P Flannery S A Teukolsky andW T VetterlingNumerical Recipes in C the Art of Scientific Computing Cam-bridge University Press London UK 1988

[36] J J P Stewart ldquoMopac a semiempirical molecular orbitalprogramrdquo Journal of Computer-Aided Molecular Design vol 4no 1 pp 101ndash105 1990

[37] J A Pople D P Santry and G A Segal ldquoApproximate self-consistent molecular orbital theory I Invariant proceduresrdquoThe Journal of Chemical Physics vol 43 no 10 pp S129ndashS1351965

[38] J A Pople and G A Segal ldquoApproximate self-consistentmolecular orbital theory III CNDO results for AB

2

and AB3

systemsrdquo The Journal of Chemical Physics vol 44 no 9 pp3289ndash3296 1966

[39] M J S Dewar E G Zoebisch E F Healy and J J P StewartldquoAM1 a new general purpose quantum mechanical molecularmodelrdquo Journal of the American Chemical Society vol 107 no13 pp 3902ndash3909 1985

[40] B Delley ldquoAn all-electron numerical method for solving thelocal density functional for polyatomic moleculesrdquoThe Journalof Chemical Physics vol 92 no 1 pp 508ndash517 1990

[41] B Delley ldquoFast calculation of electrostatics in crystals and largemoleculesrdquo Journal of Physical Chemistry vol 100 no 15 pp6107ndash6110 1996

Advances in Chemistry 13

[42] B Delley ldquoDMol methodology and applicationsrdquo in DensityFunctional Methods in Chemistry J W Andzelm and J KLabanowski Eds pp 101ndash108 Springer New York NY USA1991

[43] B Delley ldquoCalculated electron distribution for Tetrafluoroter-phthalonitrile (TFT)rdquo Chemical Physics vol 110 no 2-3 pp329ndash338 1986

[44] YWang and J P Perdew ldquoCorrelation hole of the spin-polarizedelectron gas with exact small-wave-vector and high-densityscalingrdquo Physical Review B vol 44 no 24 pp 13298ndash13307 1991

[45] P J Stephens F J Devlin C F Chabalowski and M J FrischldquoAb Initio calculation of vibrational absorption and circulardichroism spectra using density functional force fieldsrdquo Journalof Physical Chemistry vol 98 no 45 pp 11623ndash11627 1994

[46] G Schaftenaar and J H Noordik ldquoMolden a pre- and post-processing program for molecular and electronic structuresrdquoJournal of Computer-Aided Molecular Design vol 14 no 2 pp123ndash134 2000

[47] Xming ldquoXming X server for Windowsrdquo 2012 httpwwwstraightrunningcomXmingNotes

[48] K Nara L R Saraiva X Ye and L B Buck ldquoA large-scaleanalysis of odor coding in the olfactory epitheliumrdquo Journal ofNeuroscience vol 31 no 25 pp 9179ndash9191 2011

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

12 Advances in Chemistry

[6] J-P Rospars Y Gu A Gremiaux and P Lucas ldquoOdourtransduction in olfactory receptor neuronsrdquo Chinese Journal ofPhysiology vol 53 no 6 pp 364ndash372 2010

[7] B Malnic and A F Mercadante ldquoThe odorant signaling path-wayrdquo Annual Review of Biomedical Sciences vol 11 pp T86ndashT94 2009

[8] K Snitz A Yablonka T Weiss I Frumin R M Khan andN Sobel ldquoPredicting odor perceptual similarity from odorstructurerdquo PLoS Computational Biology vol 9 no 9 Article IDe1003184 2013

[9] B K Lavine CWhite NMirjankar CM Sundling and CMBreneman ldquoOdor-structure relationship studies of tetralin andindan musksrdquo Chemical Senses vol 37 no 8 pp 723ndash736 2012

[10] Y Zou H Mouhib W Stahl A Goeke Q Wang and PKraft ldquoEfficient macrocyclization by a novel oxy-oxonia-copereaction synthesis and olfactory properties of new macrocyclicmusksrdquo Chemistry vol 18 no 23 pp 7010ndash7015 2012

[11] S Liu ldquoStudy on the relationship between molecular odour ofpolycyclic musksrdquo Xiangliao Xiangjing Huazhuangpin vol 6pp 24ndash29 2004

[12] S-Y Takane and J B O Mitchell ldquoA structure-odor relation-ship study using EVA descriptors and hierarchical clusteringrdquoOrganicampBiomolecular Chemistry vol 2 no 22 pp 3250ndash32552004

[13] K J Rossiter ldquoStructure-odour relationshipsrdquo ChemicalReviews vol 96 no 8 pp 3201ndash3240 1996

[14] M Zarzo ldquoThe sense of smell molecular basis of odorantrecognitionrdquoBiological Reviews vol 82 no 3 pp 455ndash479 2007

[15] A Kato and K Touhara ldquoMammalian olfactory receptorspharmacologyGprotein coupling anddesensitizationrdquoCellularandMolecular Life Sciences vol 66 no 23 pp 3743ndash3753 2009

[16] L Turin and F Yoshii ldquoStructure-odor relations a modernperspectiverdquo in Handbook of Olfaction and Gustation R LDoty Ed pp 275ndash294 Marcel Dekker New York NY USA2003

[17] L Turin ldquoA spectroscopic mechanism for primary olfactoryreceptionrdquo Chemical Senses vol 21 no 6 pp 773ndash791 1996

[18] M A Reed ldquoInelastic electron tunneling spectroscopyrdquo Mate-rials Today vol 11 no 11 pp 46ndash50 2008

[19] L Turin ldquoA method for the calculation of odor character frommolecular structurerdquo Journal ofTheoretical Biology vol 216 no3 pp 367ndash385 2002

[20] L J W Haffenden V A Yaylayan and J Fortin ldquoInvestigationof vibrational theory of olfaction with variously labelled ben-zaldehydesrdquo Food Chemistry vol 73 no 1 pp 67ndash72 2001

[21] J C Brookes F Hartoutsiou A P Horsfield and A MStoneham ldquoCould humans recognize odor by phonon assistedtunnelingrdquo Physical Review Letters vol 98 no 3 Article ID038101 2007

[22] M I Franco L Turin A Mershin and E M C SkoulakisldquoMolecular vibration-sensing component in Drosophila mela-nogaster olfactionrdquo Proceedings of the National Academy ofSciences vol 108 no 9 pp 3797ndash3802 2011

[23] I A Solovrsquoyov P-Y Chang and K Schulten ldquoVibrationallyassisted electron transfer mechanism of olfaction myth orrealityrdquo Physical Chemistry Chemical Physics vol 14 no 40 pp13861ndash13871 2012

[24] S GaneDGeorganakis KManiati et al ldquoMolecular vibration-sensing component in human olfactionrdquo PLoS ONE vol 8 no1 Article ID e55780 2013

[25] D L Pavia G M Lampman G S Kriz and J R VyvyanIntroduction to Spectroscopy Cengage Learning Sao PauloBrazil 2010

[26] D A Lerner D Berthomieu and E R Maia ldquoModeling of theconformational flexibility and EZ isomerism of thiazoximicacid and cefotaximerdquo International Journal of Quantum Chem-istry vol 111 no 6 pp 1222ndash1238 2011

[27] A P Scott andL Radom ldquoHarmonic vibrational frequencies anevaluation of Hartree-Fock Moslashller-Plesset quadratic configu-ration interaction density functional theory and semiempiricalscale factorsrdquoThe Journal of Physical Chemistry vol 100 no 41pp 16502ndash16513 1996

[28] S Gabler J Soelter T Hussain S Sachse and M SchmukerldquoPhysicochemical vs vibrational descriptors for prediction ofodor receptor responsesrdquo Molecular Informatics vol 32 no 9-10 pp 855ndash865 2013

[29] Materials Studio SW and Insight II SW Acelrys San DiegoCalif USA

[30] M J Frisch G W Trucks H B Schlegel et al ldquoGaussian 09Revision A02rdquo Gaussian Inc Wallingford Conn USA 2009

[31] H Sun ldquoCompass an ab initio force-field optimized forcondensed-phase applicationsmdashoverview with details onalkane and benzene compoundsrdquo Journal of Physical ChemistryB vol 102 no 38 pp 7338ndash7364 1998

[32] P Dauber-Osguthorpe V A Roberts D J Osguthorpe J WolfM Genest and A T Hagler ldquoStructure and energetics of ligandbinding to proteins Escherichia coli dihydrofolate reductase-trimethoprim a drug-receptor systemrdquo Proteins StructureFunction and Genetics vol 4 no 1 pp 31ndash47 1988

[33] DH JMackay A J Cross andA THagler ldquoThe role of energyminimization in simulation strategies of biomolecular systemsrdquoin Prediction of Protein Structure and the Principles of ProteinConformation D G Fasman Ed pp 317ndash358 Plenum PressNew York NY USA 1990

[34] R Fletcher and C M Reeves ldquoFunction minimization byconjugate gradientsrdquo The Computer Journal vol 7 no 2 pp149ndash154 1964

[35] WH Press B P Flannery S A Teukolsky andW T VetterlingNumerical Recipes in C the Art of Scientific Computing Cam-bridge University Press London UK 1988

[36] J J P Stewart ldquoMopac a semiempirical molecular orbitalprogramrdquo Journal of Computer-Aided Molecular Design vol 4no 1 pp 101ndash105 1990

[37] J A Pople D P Santry and G A Segal ldquoApproximate self-consistent molecular orbital theory I Invariant proceduresrdquoThe Journal of Chemical Physics vol 43 no 10 pp S129ndashS1351965

[38] J A Pople and G A Segal ldquoApproximate self-consistentmolecular orbital theory III CNDO results for AB

2

and AB3

systemsrdquo The Journal of Chemical Physics vol 44 no 9 pp3289ndash3296 1966

[39] M J S Dewar E G Zoebisch E F Healy and J J P StewartldquoAM1 a new general purpose quantum mechanical molecularmodelrdquo Journal of the American Chemical Society vol 107 no13 pp 3902ndash3909 1985

[40] B Delley ldquoAn all-electron numerical method for solving thelocal density functional for polyatomic moleculesrdquoThe Journalof Chemical Physics vol 92 no 1 pp 508ndash517 1990

[41] B Delley ldquoFast calculation of electrostatics in crystals and largemoleculesrdquo Journal of Physical Chemistry vol 100 no 15 pp6107ndash6110 1996

Advances in Chemistry 13

[42] B Delley ldquoDMol methodology and applicationsrdquo in DensityFunctional Methods in Chemistry J W Andzelm and J KLabanowski Eds pp 101ndash108 Springer New York NY USA1991

[43] B Delley ldquoCalculated electron distribution for Tetrafluoroter-phthalonitrile (TFT)rdquo Chemical Physics vol 110 no 2-3 pp329ndash338 1986

[44] YWang and J P Perdew ldquoCorrelation hole of the spin-polarizedelectron gas with exact small-wave-vector and high-densityscalingrdquo Physical Review B vol 44 no 24 pp 13298ndash13307 1991

[45] P J Stephens F J Devlin C F Chabalowski and M J FrischldquoAb Initio calculation of vibrational absorption and circulardichroism spectra using density functional force fieldsrdquo Journalof Physical Chemistry vol 98 no 45 pp 11623ndash11627 1994

[46] G Schaftenaar and J H Noordik ldquoMolden a pre- and post-processing program for molecular and electronic structuresrdquoJournal of Computer-Aided Molecular Design vol 14 no 2 pp123ndash134 2000

[47] Xming ldquoXming X server for Windowsrdquo 2012 httpwwwstraightrunningcomXmingNotes

[48] K Nara L R Saraiva X Ye and L B Buck ldquoA large-scaleanalysis of odor coding in the olfactory epitheliumrdquo Journal ofNeuroscience vol 31 no 25 pp 9179ndash9191 2011

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Advances in Chemistry 13

[42] B Delley ldquoDMol methodology and applicationsrdquo in DensityFunctional Methods in Chemistry J W Andzelm and J KLabanowski Eds pp 101ndash108 Springer New York NY USA1991

[43] B Delley ldquoCalculated electron distribution for Tetrafluoroter-phthalonitrile (TFT)rdquo Chemical Physics vol 110 no 2-3 pp329ndash338 1986

[44] YWang and J P Perdew ldquoCorrelation hole of the spin-polarizedelectron gas with exact small-wave-vector and high-densityscalingrdquo Physical Review B vol 44 no 24 pp 13298ndash13307 1991

[45] P J Stephens F J Devlin C F Chabalowski and M J FrischldquoAb Initio calculation of vibrational absorption and circulardichroism spectra using density functional force fieldsrdquo Journalof Physical Chemistry vol 98 no 45 pp 11623ndash11627 1994

[46] G Schaftenaar and J H Noordik ldquoMolden a pre- and post-processing program for molecular and electronic structuresrdquoJournal of Computer-Aided Molecular Design vol 14 no 2 pp123ndash134 2000

[47] Xming ldquoXming X server for Windowsrdquo 2012 httpwwwstraightrunningcomXmingNotes

[48] K Nara L R Saraiva X Ye and L B Buck ldquoA large-scaleanalysis of odor coding in the olfactory epitheliumrdquo Journal ofNeuroscience vol 31 no 25 pp 9179ndash9191 2011

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of