computational approach on architecture and tailoring of organic metal complexes derived from...

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Full PaperReceived: 23 April 2011 Revised: 2 August 2011 Accepted: 2 August 2011 Published online in Wiley Online Library: 7 September 2011

(wileyonlinelibrary.com) DOI 10.1002/aoc.1838

Computational approach on architecture andtailoring of organic metal complexes derivedfrom streptomycin and Zn, Cd and Pb:antimicrobial effectivenessKumar Rajiva,b∗ and Johar Rajnic

Streptomycin has been used to derive organic metal complexes (OMCs) after metallation with ZnCl2, CdCl2 and PbCl2 andcharacterized by elemental analysis, electronic and vibrational spectroscopy, 1H and 13C NMR, mass spectroscopy (time-of-flightMS), magnetic measurement, thermal decomposition analysis (TGA, DTA), molecular modeling and X-ray powder diffraction.OMCs are monomeric. Crystal system, lattice parameters, unit cell, particle size and volume of crystalline OMCs have beendetermined using X-ray powder diffraction pattern analysis. The geometries of complexes were optimized on the basis ofmolecular modeling. Kinetic parameters were computed from thermal analysis, confirming first-order kinetics. Molecular modelshave been optimized by MM2 calculations. Architecture and tailoring of the rationally designed and synthesized supramolecularmodels having covalent bonded oxygen or other molecular contacts extended through Huckel Charge Distribution in highestoccupied molecular orbit (HOMO). Antimicrobial effectiveness of OMCs has been reported. Copyright c© 2011 John Wiley &Sons, Ltd.

Supporting information may be found in the online version of this article.

Keywords: streptomycin; organic metal complexes (OMCs); thermal decomposition; molecular modeling; XRPD

Introduction

Streptomycin, a well-known antibiotic, possesses the prop-erty of inhibiting the growth and even destroying microor-ganisms. Interaction between such drugs and metal ion(s)has been utilized as a new methodology in design and for-mation of new class of organometallic complexes.[1,2] Phar-macological activity of such drugs and complexes, in manycases, is strictly interaction dependent. Because of this, bio-organometallic chemistry and the design of new organometalliccomplexes having higher antimicrobial effectiveness are gain-ing interest. However, synthesis and characterization of suchcomplexes with streptomycin have not yet been investigated,except for a neutral Cu(II) complex with Cu–O–bond.[3] Fur-thermore, there is no consensus in the literature on theuse of streptomycin as a ligand; in particular, for the forma-tion of organometallic complexes with metal–ligand bindingsites.

The molecular architecture is a determining factor that controlsmany of the physical properties of ligands and associatedorganic metal complexes (OMCs). In order to develop efficientdevices having conductance, sensing and other importantmedicinal properties simultaneously, advanced organic syntheticprotocols for a both better architectured formulation and formedicinal development are in demand. To ascertain metalbinding sites in streptomycin with Zn, Cd and Pb metal ion(s)(Fig. 1) through solvent accessible surface model (Fig. 2) basedon spectral characterization and molecular modeling of ligandand derived organometallic complexes (OMCs) are describedherein.

Experimental

Materials and Instruments

All chemicals and solvent used in this study were of analyticalreagent grade and used as procured from Aldrich after dryingover 4 Å molecular sieves. Solvents were purified using standardprocedures.[4]

The stoichiometric analysis (C, H and N) of OMCs wasperformed using a Carlo-Ebra 1106 elemental analyzer. Metalcontent was estimated on a AA-640-13 Shimadzu flame atomicabsorption spectrometer in a solution prepared by decomposingthe respective complex in hot concentrated HNO3. IR spectrawere recorded on a PerkinElmer Fourier transform infrered (FTIR)spectrometer in KBr. The electronic spectra were recorded inwater on a Beckman DU-64 spectrometer with quartz cells. 1Hand 13C NMR spectra were recorded at ambient temperatures onBruker AMX400 and DRX500 spectrometers with tetramethylsilane

∗ Correspondence to: Kumar Rajiv, Department of Chemistry, University of Delhi,Delhi 110007, India. E-mail: chemistry [email protected]

This article is dedicated to Prof. David A. Atwood, Editor-in-Chief, Main GroupChemistry, Department of Chemistry, University of Kentucky, Lexington, KY,USA, who has inspired the authors to do this research article.

a Department of Chemistry, University of Delhi, Delhi 110007, India

b Department of Chemistry, SC, University of Delhi, New Delhi 110027, India

c Department of Chemistry, Guru Gobind Singh Indraprastha University, NewDelhi 110002, India

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K. Rajiv and J. Rajni

Figure 1. Stereo-structure of streptomycin ligand.

Figure 2. Solvent-accessible surface model of streptomycin.

(TMS) as internal reference and D2O as solvent. Chemical shifts(δ) were expressed in parts per million (ppm) relative to TMS.A Rigaku model 8150 thermoanalyzer (Thermaflex) was used forsimultaneous recording of TGA–DTA curves at a heating rate of10 ◦C min−1. For TGA, the instrument was calibrated using calciumoxalate, whereas for DTA calibration was done using indium metal,both of which were supplied along with the instrument. A flat-bed aluminium crucible was used with α-alumina (99% pure)as the reference material for DTA. The activation energy andArrhenius constant of the degradation process were obtained byCoats–Redfern method.

The crystals needed for X-ray powder diffraction analysis wereused to produce three-dimensional crystalline models as follows:1 g bismuth OMC was dissolved at 40 ◦C in a minimum amount ofmethanol. A clear solution was obtained and heated for 4–5 minunder reflux and was then filtered off at a high temperature.

The solution was cooled to room temperature and closed with asemi-permeable membrane so that methanol could not evaporatebut still maintaining a very slow evaporation. The mixtures werestored at room temperature for a period of 3–5 weeks. Very smallcrystals were filtered off and dried.

Pharmacology: In Vitro Antifungal Assay

Antimicrobial activities (antifungal) of drug along with OMC-1to OMC-3 were screened against Aspergillus niger by preparingtheir stock solutions in DMSO according to the required concen-trations for the experiments. To ensure the effect of solvent onbacterial growth, a control test was performed with test mediumsupplemented with DMSO.

Growth of fungus was measured by reading the diameter ofthe fungal colony. Screening for antifungal activity was carriedout in vitro against Aspergillus niger, following the procedureoutlined,[5] and relative inhibitory ratios (%) were determinedusing the mycelium growth rate method. On completion ofmycelial growth, diameters were measured and inhibition ratewas calculated according to the formula

I = (DI − Do)

DI× 100

where I is inhibition rate, DI is average diameter of mycelia in theblank test and Do is average diameter of mycelia in the presenceof OMC-1 to OMC-3.

X-ray Powder Diffraction (XRPD) Measurements

XRPD patterns were recorded on a vertical-type Philips 1130/00X-ray diffractometer, operated at 40 kV and 50 mA generatorusing a Cu-Kα line at radiation 1.54 source. The sample wasscanned between 5◦ and 70◦ (2θ ) at 25 ◦C. Crystallographic datawere analyzed using the Crysfire-2000 powder indexing softwarepackage and the space group was found using the CHECK CELLprogram. The Debye–Scherer relation was derived with the helpof 100% peak width to determine the particle size. Experimentaldensity was observed by the Archimedes method.

3D Molecular Modeling

The correct sequence of atoms was obtained to obtain reasonablelow-energy molecular models to determine their molecularrepresentation in three dimensions. Complications of moleculartransformations could be explored using the output obtained. Togain a better insight into the molecular structure of the ligand andOMCs, geometric optimization and conformational analysis wereperformed using an MM+2 force field.[6]

The potential energy of the molecule was the sum of thefollowing terms: E = Estr + Eang + Etor + Evdw + Eoop + Eele, whereall Es represent energy values found corresponding to given typesof interaction. The subscripts str, ang, tor, vdw, oop and eledenote bond stretching, angular bonding, torsion deformation,van der Waals interactions, out-of-plane bending and electronicinteraction, respectively.

Preparation of OMCs

ZnCl2 (OMC-1)

OMC of ZnCl2 was prepared by dissolving equimolar amounts ofstreptomycin (0.2905 g, 0.5 mmol) and ZnCl2 (0.068 g, 0.5 mmol) in

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Organic metal complexes derived from streptomycin and Zn, Cd and Pb

Table 1. Analytical data (%) of OMCs

Analysis: found (calculated) (%)

OMC Empirical formula C H N M

[Zn(L)(H2O)2] C21H41N7O14Zn 37.13 (37.03) 6.11 (6.07) 14.41 (14.40) 9.60 (9.60)

OMC-1

[Cd(L)(H2O)2] C21H41N7O14Cd 34.61 (34.65) 5.65 (5.68) 13.46 (13.47) 15.42 (15.44)

OMC-2

[Pb(L)(H2O)2] C21H41N7O14Pb 30.61 (30.65) 5.11 (5.02) 11.91 (11.92) 25.17 (25.18)

OMC-3

a minimum quantity of CH3OH (25 mL, absolute) in a 100 mL round-bottomed flask. The mixture was heated for 5 h at ∼81–82 ◦C ona water bath to reduce the volume of the solution to ∼12 mL. Asolid mass was separated out on cooling at ∼5 ◦C and kept in arefrigerator for better crystallization. It was then filtered, washedwith CH3OH, and dried over P2O5 under vacuum. The crystals wereredissolved for recrystallization with warm methanol, resulting ina clear solution; this was kept undistributed for several weeksand very small crystals were formed. Various attempts to obtainsingle crystals were unsuccessful. XRPD studies indicated thecrystalline nature of the OMCs. The compounds were soluble inpolar solvents.

CdCl2 (OMC-2)

The procedure used for OMC-1 was employed for OMC-2 withequimolar amounts of streptomycin (0.2905 g, 0.5 mmol) andCdCl2 (0.092 g, 0.5 mmol).

PbCl2 (OMC-3)

The procedure used for OMC-1 was employed for OMC-3 withequimolar amounts of streptomycin (0.2905 g, 0.5 mmol) andPbCl2 (0.139 g, 0.5 mmol).

Results and Discussion

Satisfactory results of elemental analysis have been obtained andare summarized in Table 1. Their chemical composition confirmedthe purity and stoichiometry of neat and encapsulated OMCs.Loss of water or other molecules after oligomerization andpolymerization affected the final accuracy of C, H and N analyticalresults. In our study all elemental analytical results were linearwithout deviation as per oligomerization and polymerization.Further mass spectra of OMCs supported the same. These studiesrevealed that OMC-1, 2, and 3 were of high purity and monomeric innature. Various attempts to obtain single crystals have so far beenunsuccessful. XRPD studies of OMCs indicated their crystallinenature. OMCs were soluble in polar solvents.

The thermal decomposition analysis of OMCs proved theelimination of two H2O molecules. In the case of polymerization,two or more ligands or OMC moieties changed the ratio of waterelimination and the ratio of atoms concerned, i.e. O and H woulddiffer significantly from the values obtained. Mass spectral findingsfurther correspond to the monomeric composition nature of OMCs.Thus the molecular formula of OMCs is [ML(H2O)2], where M = Zn,Cd or Pb, and L = streptomycin. On the basis of the above findings,it can be clearly stated that the reported molecular formula andthe presented molecular models are in accordance.

Infrared Spectra

IR spectra of complexes were recorded as KBr disks. In the IRspectrum of streptomycin, medium to strong absorption bandswere observed at 1750–1050 cm−1 and 1042 cm−1, indicatingthe presence of <C O and –C–O–C–groups. The stretchingfrequencies of –OH groups were observed at 3434 cm−1 and3368 cm−1 in the form of broad vibration bands with a shoulder atabout 3550 cm−1. Very strong stretching vibration bands appearedin the IR spectra of streptomycin at 3435–3429 cm−1, showing thepresence of –NH2. The same bands appeared for studied OMCs atthe same wave number, ruling out the participation of nitrogenatoms in coordination.

The conclusion has been drawn that oxygen of the –OH group isinvolved in the coordination with metals after comparing the IR ofstreptomycin and OMCs. The vibrational bands due to rockingand wagging modes of water and metal–oxygen stretchingmodes were observed at 800–350 cm−1 for OMCs and confirmedcoordinated water molecules.[7] New stretching vibrational bandsof OMCs were observed at 516–315 cm−1 in the far IR region dueto ν(M–O), indicating involvement of oxygen of the –OH groupin new bonds to the metals (–O–M–). The presence of watermolecules was confirmed by the appearance of an intense broadband centered at 3400 cm−1 in OMCs. IR spectra of OMCs werecomplicated and suggestions were made regarding the structuralfeatures of OMCs. Related infrared spectral data are presented inTable 2.

1H NMR Spectra

The proton NMR spectra of streptomycin and its diamagneticOMCs were recorded in D2O using TMS as internal standard andshowed well-resolved signals in accordance with their relatedresonance and integrated intensities. The chemical shifts of ligandprotons and its diamagnetic OMCs are discussed comparatively.On comparison, it was concluded that certainly there were somechanges in observed regions of hydroxyl (OH) groups due todeprotonation. The formation of new bonds (–O–M) betweenligand moiety and metal used was compared.[8] The OH signalfor two protons (O22,38 –H) at δ 2.2 ppm as singlet in the ligandspectrum completely disappeared in the spectra of OMCs, whichindicated involvement of OH groups in chelation with ZnCl2, CdCl2and PbCl2, followed by displacement of protons. Another newsignal observed at 3.33 ppm in 1H NMR spectra of diamagneticOMCs was absent in 1H NMR spectra of streptomycin, with anintegration corresponding to four protons assigned to two watermolecules.

1H NMR of streptomycin (D2O): δ 9.72 (s, 1H, OC21 –H), 5.4 (d,1H, J = 9.1 Hz, C10 –H), 5.03 (d, 1H, J = 6.8 Hz, C18 –H), 4.4 (d, 1H,

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Table 2. Assignment of relevant IR absorption bands of OMCs

OMCs ν(<N–H) ν(OH) ν(OH) ν(NH2) ν(NH2) ν(M–O) ν(Ph–O–H)

[Zn(L)(H2O)2] 3429 (s, b) 3434, 3368, 1635 (m) 1515 (s) 1215 (m) 695 (s) 516 (s) 1750, 1050

OMC-1

[Cd(L)(H2O)2] 3435 (s, b) 3445, 3419, 1646 (m) 1509 (m) 1217 (w) 696 (s) 514 (s), 420, 365 1745, 1045

OMC-2

[Pb(L)(H2O)2] 3429 (s, b) 3446, 3420, 1622 (m) 1479 (s) 1216 (w) 698 (s) 425 (s), 350, 315 1746, 1042

OMC-3

C9 –H), 4.14–4.20 (m, 2H, C3,12 –H), 3.95 (d, 2H, J = 7 Hz C37 –H),3.86 (m, 1H, J = 4.5 Hz, C6 –H), 3.88 (m, 1H, J = 6.9 Hz, C14 –H),3.81 (d, 1H, J = 6.9 Hz, C17 –H), 3.52–3.55 (m, 1H, C2 –H), 3.51 (d,1H, J = 6.8 Hz, C15 –H), 3.57 (t, 1H, J = 10.2 Hz, C5 –H), 3.53 (m, 1H,J = 6.1 Hz, C16 –H), 3.57 (m, 1H, J = 7.1 Hz, C4 –H), 2.52–2.58 (m,1H, C1 –H), 2.10–2.75 (bs, 9H, NH or NH2, N28,29,32,33,34 –H), 2.55 (s,3H, C39 –H), 2.4 (s, 2H, O25,35 –H), 2.3 (s, 2H, O23,24 –H), 2.2 (s, 2H,O22,38 –H), 2.18 (s, 1H, O36 –H), 1,25 (d, 3H, J = 7 Hz, C20 – H).

From the data obtained it was clear that chemical shifts of pro-tonated species were very similar to those of metallic derivatives,suggesting similar structure and conformation. Change observedin the region δ 2.2 ppm indicated interaction of streptomycin withmetal ions in competition with protonation in solution.

13C NMR Spectrum of OMCs

In 13C NMR spectra of streptomycin and OMCs, well-resolved sig-nals were detected. A group of sharp peaks at 165.39–160.11 ppmwere found, confirming the presence of carbon atoms withinazomethine linkages ( C–N> and –N C>). A group ofsharp peaks was also observed at 76.22–65.12 ppm and44.12–40.33 ppm corresponding to ether (–O–CH2 –) and cen-tral methylene (–CH2 –) linkages respectively.[9,10] Another groupof peaks observed was as follows. 13C NMR (D2O, ppm): 165–C31,160–C27, 98–C8, 95–C10, 43.9–C6, 42–C2, 68.5–C4, 63.2–C37,65–C5, 31.6–C39, 54.0–C17, 70.8–C16, 65.8–C15, 63.1–C1, 12–C20,62.6–C18, 61–C3, 72.5–C14, 90–C21, 65–C12 and 75–C9.

Electronic Spectra

Electronic spectra of ligand and OMCs showed transitions at190–800 nm. A shoulder band was observed at 275 nm in thespectrum of ligand assigned to n→n∗ transition within –OH groupof hydroxyl moiety in free ligand. A little deviation observed inOMCs for these transitions appeared for –OH groups in the spectraof free ligand. It revealed that the involvement of –OH groups inchelation due to deprotonation confirmed the formation of newoxygen–metal (–O–M–) bond. Owing to this, new transitionswere observed at 240–280 nm assigned to –O–M(II) as assignedligand-to-metal charge transfer (LMCT).[11]

The spectrum is featureless in the visible region, for d10 Cd(II)ion; however, this complex showed some intense absorptionsin UV, readily assignable to –O–Cd(II) as LMCT.[12] The intensityof Cd–O–absorption in other isolated sites has been shownat 240 nm to be roughly consistent with new bond formation(Cd–O–).[13] Magnetic measurements suggested OMCs of Zn(II),Cd(II)and Pb(II) to be diamagnetic in nature. On the basis of theabove discussion, the proposed molecular structure for OMCs(Fig. 3) clears its tetrahedral geometry.

Figure 3. Stereo-structure of OMCs (M = Zn, Cd, Pb).

Thermal Decomposition and Kinetics

TGA was used to determine rate-dependent parameters of solidstate non-isothermal decomposition reactions. TGA and DTAanalyses were carried out for OMCs under ambient conditions.TGA revealed that OMC of Zn(II) lost nearly 15% of total massbetween 65 and 140 ◦C, followed by considerable decompositionup to 600 ◦C, leaving metal oxide (ZnO) as residue. OMCs ofCd(II) and Pb(II) decomposed to nearly 9% of total mass up to atemperature of 170 ◦C, followed by considerable decompositionof ligand molecule up to 650 ◦C, leaving metal oxide (CdO and PbOrespectively) as residue. On the basis of thermal decomposition,the kinetic analysis parameters such as activation energy (E∗),enthalpy of activation (�H∗), entropy of activation (�S∗), and freeenergy change of decomposition (�G∗) were evaluated graphicallyby employing the Coats–Redfern relation:[14,15]

log[− log(1 − α)/T2] = log[AR/θE∗(1 − 2RT/E∗)] − E∗/2.303RT(1)

where α is mass lost up to temperature T , R is the gas constant,E∗ is activation energy in J mol−1, θ is linear heating rate and theterm (1 − 2RT/E∗) ∼= 1.

A straight-line plot of the left-hand side of the equa-tion (1) against 1/T gives the value of E∗, while its intercept cor-responds to A (Arrhenius constant). Coats–Redfern linearization


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Table 3. Thermodynamic activation parameters of OMCs

OMCs Order/n Steps E∗ (J mol−1) A (s−1) �S∗ (J K−1 mol−1) �H∗ (J mol−1) �G∗ (kJ mol−1)

[Zn(L)(H2O)2] 1 I 34.09 8.27 × 105 −25.096 84.10 96.62

OMC-1 II 39.75 2.16 × 105 −146.69 1205.89 106.53

[Cd(L)(H2O)2] 1 I 9.814 2.501 × 105 −1.641 218.76 5.801

OMC-2 II 6.76 1.71 × 104 −1.611 52.691 2.348

[Pb(L)(H2O)2] 1 I 39.18 2.28 × 106 −11.083 709.35 3.566

OMC-3 II 67.82 1.42 × 106 −12.431 25.1077 10.547

plots confirmed the first-order kinetics for the decompositionprocess. The calculated values of thermodynamic activation pa-rameters for decomposition steps of OMCs have been reported inTable 3.

According to the kinetic data obtained from TG curves,activation energy is related to thermal stability of OMCs. Amongmetal complexes, activation energy increases as OMC-2 < OMC-1and OMC-3, and the same trends have been obtained for thermalstability curves of OMCs.[16] All these OMCs have negative entropy,which clearly indicates spontaneous formation of these complexes.

The negative value of entropy indicated a more orderedactivated state that may be possible through chemisorption ofoxygen and other decomposition products. The negative valuesof entropy of activation were compensated by values of enthalpiesof activation, leading to almost the same values for free energy ofactivation.

Time-of-Flight (TOF) Mass Spectra

MS has been successfully used to investigate molecular ion species[M]+ and various other peaks corresponding to fragmentationpatterns of OMCs in solution. The patterns of the mass spectrumgive a clear impression of successive degradation of targetcompound, with series of peaks corresponding to variousfragments. The intensity of a corresponding peak is directly relatedto the stability of corresponding fragments. In the mass spectra ofOMCs, molecular ion peaks corresponding to fragments (ligand orfragments of the ligand with metal or metal + ligand) have beenobserved, which further confirmed their molecular formula.[17]

In initial peaks, it can be easily observed that the ligandused degraded and broke down into various fragments suchas [C8H15NO5], showing a molecular ion peak at 196.4797 (m/zvalues) with low intensity and many more similar fragments.Owing to degradation, another fragment pattern appeared at163.3124/196.4797/206.3986 (m/z) (OMC-1, OMC-3, OMC-2) withdifferent intensity, and a very strong peak was also observedat 263/264/284 with 100% intensity separately, which has acorrelation with the fragmentation patterns of streptomycin(OS) and OMC-3, OMC-1 and OMC-2 respectively. The resultsobtained represented the degradation and demetallation patternsof reported OMCs.

In TOF mass spectra of OMC-2 and OMC-3, initial fragmentationpatterns were found similar to the ligand and also showed anadditional peak indicating mass loss of two water molecules anddegradation of double bonded nitrogen fragments >N–C NHfrom parent molecule of streptomycin observed at 690.0010and 687.7129 (ligand fragments + metal) for these complexesrespectively. Mass degradation patterns provide most importantinformation about fragmentations of a particular compound inthe studied spectra and proved the presence of an isotropic ratio

corresponding to metals, i.e. Cd(II) and Pb(II) with ligand fragments.On the basis of the above discussion, a mononuclear nature ofstudied OMCs has been proved and may be assigned as [M+(ligand fragments)].

In the mass spectra of OMC-2 and OMC-3, molecular ion peaks(ligand + metal) were observed at 730.1101 and 824.4311 (m/z)respectively, which represented the final molecular ion peak (m/z)for reported compounds. (Scanned graphs of TOF mass spectraof OMC-2 and OMC-3 were added and are presented as onlinesupporting information in supplementary graphs S-1 and S-2respectively).

XRPD Analysis

XRPD is a powerful technique in structural determination ofmolecular solids. While single crystal methodologies (directmethods and Patterson synthesis) have proved successful insolving structures from XRPD data, the systematic or accidentaloverlap of diffraction peaks leads to inevitable problems inattempting to extract intensities of individual reflections.

In the absence of single crystals, XRPD data are especiallyuseful and are used to deduce accurate cell parameters of studiedsolid compounds. The diffraction patterns revealed the crystallinenature of OMCs. The indexing procedure was performed using(CCP4, UK) the Crysfire program,[18,19] giving different crystalsystems with varying space group. Merit of fitness and particlesize of OMCs have been calculated from XRPD spectra of OMC-2(scanned graph given in supplementary graph S-3 for Cd(II)-SM. The cell dimensions and other related parameters of OMCsobtained are shown in Table 4.

Molecular Modeling of OMCs

It is good to see simple mechanical models presented here.The current models, therefore, are proposed as a standardby which specific interactions in real molecules might bejudged. If deviations in distances, angles or torsion are inevidence, then specific electronic interactions should perhapsbe pursued. In order to ascertain structural features and otherrelated preferences to confirm observed spectral reports aboutcoordination behavior of streptomycin with metal ion(s) understudy, molecular mechanics calculations have been done for thesame. The energy minimization values for optimized structures ofstudied OMCs-1, 2 and 3 were determined and found to be 35.12,25.31 and 38.24 kcal mol−1 respectively. Selected bond lengthsand bond angles of OMCs between metal ion(s) and –O–atom ofhydroxyl are illustrated in Table 5.

However, the following structural features inspire continuedresearch: (a) has two hydroxyl groups that may be completelydependent on certain conditions; (b) these groups may induce


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Table 4. Crystallographic data of OMCs

OMC-1 OMC-2 OMC-3

Formula C21H41N7O14Zn C21H41N7O14Cd C21H41N7O14Pb

FW 679.20 729.17 823.25

Temp. (K) 293 293 293

Wavelength 1.54056 1.54056 1.54056

Crystal system Monoclinic Triclinic Monoclinic

Space group P 2/M P 1 P 2/M

Unit cell dimensions

a (Å) 14.1937 6.709547 12.961

b (Å) 10.5175 9.231634 13.184

c (Å) 9.26918 8.685700 7.224

α 90.0000 118.1240 90

β 110.8413 97.8563 106.36

γ 90.000 49.1991 90

Volume (Å3) 1293.19 347.14 1184.36

θ range (◦) 13.811-61.987 10-65 12-67

Limiting indices −6 ≤ h ≤ 4 −3 ≤ h ≤ 1 −7 ≤ h ≤ 5

0 ≤ k ≤ 7 −4 ≤ k ≤ 4 0 ≤ k ≤ 8

0 ≤ l ≤ 4 0 ≤ l ≤ 4 0 ≤ l ≤ 5

Particle size (nm) 80.82 55.99 10.92

Intensity (%) 5.9–100 4.5–100 3.4–100

R indices 0.0000615 0.0000754 0.0000362

Density 1.7437 1.034 1.151

Z 2 1 1

core aggregation via versatile bridging abilities (c) hydroxyl is agood tool for construction of novel organometallic complexes;because of this, active groups could bind central metal ion(s) andform a –O–M–bond, confirming the stability of main group OMCs.Data analysis for bond lengths and angles of studied compoundsreveals the following remarks.

Selected bond lengths of OMC-1, OMC-2, and OMC-3 between–O–and metal ion(s) were as follows: O(23)–Zn(39), 1.8896;O(23)–Cd(39), 2.1200; and O(23)–Pb(39), 2.1102 respectively.This variation indicates that all the OMCs have different

metal ion(s). The bond angles of OMC-1, OMC-2, and OMC-3 metal to donor atom moiety were altered somewhatupon coordination; bonds angles O(41)–Zn(39)–O(23), 130.888;O(25)–Cd(39)–O(23), 120.0647; and O(25)-Pb(39)-O(23), 109.4584respectively.

All active groups taking part in coordination had bonds longerthan that already existing in the ligand (like –O–and <O → M–).Coordination significantly shortens for O(23)–Zn(39), which was1.8896, as compared to O(23)–Cd(39), which was 2.1200. This isbecause bond lengths between donor atoms and metal ion(s) areprobably affected by variation in the atomic size of metal ion(s).There was a large variation in bond lengths on complexation. Itbecomes slightly longer as coordination takes place via the O atomof <O → M–.

Taking account of the above factors, in this paper we reported anovel three-dimensional structure with their topological networksseparately represented by a common molecular structure forOMCs. The optimized structure of OMC-3 as a molecular modelingmodel is presented in Fig. 4. The process to determine energyminimization was repeated several times to find the globalminimum minimization energy.[20,21] The optimized structuresof OMC-1, OMC-2, and OMC-3 showed respective tetrahedralgeometry.

Pharmaceutical Effectiveness of OMCs

Pharmaceutical effectiveness of OMC-1, OMC-2, and OMC-3depends on the connectivity of ligand to metal ion(s). Moreover,coordination reduces polarity of used positively charged metalion(s) and negatively charged donor atoms in drug used as ligand.Antifungal activity of drug formed metal complexes (OMC-1, OMC-2 and OMC-3) and was performed by agar plate technique againstAspergillusniger; results obtained are displayed graphically in Fig. 5.OMC-1, OMC-2, and OMC-3 were directly mixed in a medium ofdifferent concentrations. The fungus was positioned in mediumwith the help of an inoculum needle.[22] Petri dishes wrapped inpolythene sheets containing some drops of C2H5OH were placedin an incubator at 30±3 ◦C for 70–90 h. Enlargement of the fungalcolony was measured by its diameter.

Table 5. Selected bond lengths (Å) and bond angles (◦) of OMCs

OMCs Selected bond lengths Selected bond angles

C21H41N7O14Zn Zn(39)–O(41) 1.8 O(41)–Zn(39)–O(25) 99.50

Zn(39)–O(40) 1.8 O(41)–Zn(39)–O(23) 130.8

O(25)–Zn(39) 1.8 O(40)–Zn(39)–O(25) 120.0

O(23)–Zn(39) 1.8 O(40)–Zn(39)–O(23) 120.0

O(25)–Zn(39)–O(23) 119.9

C21H41N7O14Cd Cd(39)–O(43) 2.1 O(43)–Cd(39)–O(25) 111.5

Cd(39)–O(40) 2.1 O(43)–Cd(39)–O(23) 122.9

O(25)–Cd(39) 2.1 O(40)–Cd(39)–O(25) 119.9

O(23)–Cd(39) 2.1 O(40)–Cd(39)–O(23) 119.9

O(25)–Cd(39)–O(23) 120.0

C21H41N7O14Pb Pb(39)–O(43) 2.1 O(43)–Pb(39)–O(40) 109.4

Pb(39)–O(40) 2.1 O(43)–Pb(39)–O(25) 109.4

O(25)–Pb(39) 2.1 O(43)–Pb(39)–O(23) 109.4

O(23)–Pb(39) 2.1 O(40)–Pb(39)–O(25) 109.4

O(40)–Pb(39)–O(23) 109.4

O(25)–Pb(39)–O(23) 109.4


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Figure 4. Optimized molecular model of Pb(II)-OMC (color code: C, blackish gray; N, blue; O, red; yellowish gray, Pb).

Figure 5. Comparative aspects of antifungal findings.

Antifungal activity significantly increased after complexationwith metal ion(s) because it is strictly interaction dependent andso new bonds (O–M) in OMCs inhibit enzymatic activity. This iswell known that enzymes required certain group for enhancingconcerned activity. It was thus susceptible to deactivation by metalion(s) on coordination.[23] Results indicated that OMC-1, OMC-2,and OMC-3 had the potential to generate a novel antimicrobialagent by displaying moderate to high affinities for most of thereceptors, particularly in the case of Zn-OMC-1.

Conclusions

After elemental analysis, the studied OMCs of streptomycin werefound to be monomeric in nature. A better insight into the natureof the intricate organic moiety of ligand and OMC molecularstructures could be achieved using a multidimensional approachof spectroscopic investigations. In the Results and Discussionsections, modern spectral investigations observations at molecularlevel has been provided. This helps in furthering an understandingof the atomic arrangements of target compounds, especiallyin investigating the adjustability of the concerned ligand orconnectivity or its selection abilities towards metal ion(s) throughits specific coordination sites.[24]

The spectral results confirmed coordination of metal ion(s) withoxygen atoms of the hydroxyl group of the tetrahydrofuran ringand neighboring tetrahydropyran ring. Architecture and tailoringof multidimensional networks of novel organometallic complexes(OMCs) of Zn(II), Pb(II) and Cd(II) ion(s) derived from streptomycinhaving O-donor sites were presented. This occurred because ofdeprotonation of the hydroxyl group in the presence of metalion(s), which plays a key role, as reported earlier,[25] wherethe same class of compounds consisted of the same bondingpattern, i.e. –O–bonded H2O molecules and –O–bonded withthe metals. These coordination modes and intriguing architectureenable the possibility of rationally designing and synthesizingsupramolecular architectures based on covalent bonded oxygenatoms or other supramolecular contacts, as reported for Cd(II)compounds.[26,27] Vibrational spectra and 1H NMR spectral studies

confirmed the same bond set-up by showing the disappearance ofsome hydroxyl group protons, especially from substituent groupsof tetrahydrofuran and the neighboring cyclic ring having the–O–group as linkage.

Cell parameters were observed from XRPD spectra to determinecrystallographic features, and molecular modeling has been doneto discover the optimization energies corresponding to themodels.

Acknowledgments

One of the authors (Rajiv Kumar) gratefully acknowledges hisyounger brother Bitto for motivation. Special thanks to papa(Mohan Pal Singh) for helping and interpretation of 1H and 13CNMR spectra. The authors acknowledge CSL Delhi University Delhifor providing computer facilities, DRDO, New Delhi for financialassistance, IIT Bombay and IIT Delhi for recording EPR and 1H and13C NMR spectra, respectively.

Supporting information

Supporting information may be found in the online version of thisarticle.

References

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[17] Y. Bandala, J. Avina, T. Gonzalez, I. A. Rivero, E. Juaristi, J. Phys. Org.Chem. 2008, 21, 349.

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