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Cite this:DOI: 10.1039/c8cc01052h

Conformational control over an aldehydefragment by selective vibrational excitation ofinterchangeable remote antennas†

A. J. Lopes Jesus, ab Claudio M. Nunes, a Rui Fausto a and Igor Reva *a

We apply interchangeable vibrational antennas (OH or NH2 group)

to achieve unprecedented conformational control over the heavy

aldehyde fragment in 2-formyl-2H-azirine. The two aldehyde con-

formers were manipulated bi-directionally, using selective vibra-

tional excitation with narrowband near-infrared (NIR) light tuned at

the wavenumbers corresponding to OH and NH2 stretching over-

tones and combination modes.

The possibility of inducing conformational changes by vibrationalexcitation has been known since the 1960s, when Pimentel andco-authors found that the matrix-isolated molecules of HONOisomerized when illuminated with broadband infrared (IR)light.1,2 Optical parametric oscillators (OPO) brought this researchfield to a new level. By providing access to NIR or IR narrowbandirradiation, Khriachtchev and co-authors proved possible to selec-tively excite a chosen conformer to induce conformational control.3

The first report of this kind describes selective excitation of the OHstretching overtone of the most stable form of formic acid, allowinggeneration of a higher-energy rotamer.4 After formic acid, manyother carboxylic acids5–14 were shown to undergo conformationalisomerization upon their selective vibrational excitation. Other typesof matrix-isolated molecules such as alcohols,14–18 amino acids,19–22

nucleic acid bases,23–25 and the carboxyl radical26 were also success-fully subjected to conformational control.

The conformational isomerizations described above concernedthe internal rotation of a light H atom in the vibrationally excitedOH group, or torsion around the CC bond adjacent to that OHgroup, or both (see Scheme 1). Such conformational changesare typically associated with torsional barriers no higher than60 kJ mol�1.9 The energy required to surmount the torsional barrierwas introduced in those systems via vibrational excitation of the OHgroup, in the overtone spectral range (7150–6600 cm�1 equivalent of

80–85 kJ mol�1).27 These cases suggest that there is an efficientcoupling between the stretching of the OH group and the torsionalmotion around the geminal OC and vicinal CC bonds.

In the last few years there has been growing interest in discover-ing other patterns of vibrationally induced conformational control.It has been demonstrated that selective vibrational excitation of the2nOH or 2nNH2 modes28 may lead to conformational rotameriza-tion in a remote fragment of a molecule, separated by severalchemical bonds.29,30 However, both of these conformationalchanges concerned the flip of a remote light H atom.29,30 Ourparticular attention has been focused on the possibility of confor-mational isomerizations involving remote fragments with heavyatoms. The first reactivity pattern of such kind was found for theheavy hydroxymethyl (–CH2OH) fragment. Vibrationally inducedisomerization of this fragment was observed for kojic acid.31 Here,a remote OH group (Scheme 2a, red) played the role of antenna, by

Scheme 1 Conformational changes in hydroxyacetone induced by vibra-tional excitation of the OH group. Green arrow: flip of the OH group; bluearrow: torsion around the CC bond adjacent to the excited OH group.

Scheme 2 Conformational isomerizations involving heavy-atom fragments(shown in blue) induced by remote vibrational 2nOH and 2nNH excitations(shown in red): (a) Torsion of a heavy –CH2OH fragment in kojic acid; (b) torsionof a heavy –OCH3 fragment in 6-methoxyindole.

a CQC, Department of Chemistry, University of Coimbra, 3004-535, Coimbra,

Portugal. E-mail: reva@qui.uc.ptb CQC, Faculty of Pharmacy, University of Coimbra, 3004-295, Coimbra, Portugal

† Electronic supplementary information (ESI) available: Additional experimentalresults, IR assignments, and computational data. See DOI: 10.1039/c8cc01052h

Received 6th February 2018,Accepted 27th March 2018

DOI: 10.1039/c8cc01052h

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transferring the energy deposited in its stretching overtone to thetorsional movement of the –CH2OH fragment (Scheme 2a, blue)around the CC bond.

The second reactivity pattern concerns a heavy methoxy (–OCH3)fragment. The conformational changes of this fragment, reported sofar only for indoles (substituted at positions 5 or 6), were induced byvibrational excitations of the NH stretching overtone (Scheme 2b).Here, the NH group served as a remote vibrational antenna,permitting bi-directional conformational control.32,33 To thebest of our knowledge, no other types of NIR-induced rotamer-izations involving displacements of remote fragments withheavy atoms have been reported to date.

In the present communication, we demonstrate that conforma-tional control can be achieved in a third type of fragment with heavyatoms, by means of vibrational excitation of a remote antenna.Namely, the conformation of the aldehyde (–CHO) fragment attached

at position 2 of a 2H-azirine ring is controlled via OH or NH2

antennas attached at position 3 of the ring. To the best of ourknowledge, the use of interchangeable vibrational antennas toachieve conformational control is also unprecedented.

3-Amino-2-formyl-2H-azirine (3) and 3-hydroxy-2-formyl-2H-azirine (4) were generated in situ by UV irradiation of 3-amino-isoxazole (1) and 3-hydroxy-isoxazole (2), respectively, isolated inargon matrixes at 15 K (Scheme 3). This methodology was previouslyused to generate other 2H-azirines from irradiation of matrix-isolated isoxazoles.34–37 The identification of 3 and 4, resulting fromthe UV-irradiation of 1 and 2, was established by the comparisonof the experimental mid-IR spectra of the photoproducts with thetheoretical spectra calculated for 3 and 4 (Fig. S1 and S2, ESI†). Theassignments of the most prominent IR bands of formyl-2H-azirines3 and 4 are given in Tables S1 and S2 (ESI†). Particularly character-istic are the very intense IR bands centered around 1830–1820 cm�1

(due to the nCQN vibration in the three-membered azirine ring)38

and around 1740–1725 cm�1 (due to the nCQO mode in the formylgroup).39 These bands appear broad and/or split, which suggests thegeneration of more than one conformer.

The relaxed scans of potential energy calculated at the MP2/6-311++G(3df,3pd) level (Fig. S3, ESI†) for the internal torsionaround the N–C–CQO dihedral angle in 3 and 4 reveal that each

Scheme 3 Generation of 2-formyl-2H-azirines (3, 4) from isoxazoles(1, 2) in an Ar matrix at 15 K (1 - 3, l = 228 nm; 2 - 4, l = 224 nm).

Fig. 1 (a) Anharmonic wavenumbers (unscaled) and IR intensities calcu-lated at the B3LYP/6-311++G(d,p) level for the 2naNH2, (na + ns)NH2, and2nsNH2 transitions of 3A (blue, K) and 3B (red, ’; intensities multiplied by �1),compared with the spectral changes resulting from the NIR irradiation of 3:(b) at 6850 cm�1 and (c) at 6822 cm�1. Positive features in the differencespectra show the growing bands. Irradiations at wavenumbers shownby red (b) and blue (c) arrows produced the 3B - 3A and the opposite3A - 3B conformational changes, respectively.

Fig. 2 Experimental mid-infrared (a) and near-infrared (b) spectrarecorded: immediately after the deposition of 2 in an Ar matrix at 15 K(trace 1, black); after photogeneration of 4 from 2 (trace 2, red); and after asubsequent NIR irradiation at 6915 cm�1 (trace 3, blue). (c) Differencespectrum [trace b3 ‘‘minus’’ trace b2]. (d) Anharmonic wavenumbers(unscaled) and IR intensities calculated at the B3LYP/6-311++G(d,p) levelfor the 2nOH transitions of conformers 4A (blue, K) and 4B (red, ’).Irradiation at 6920 cm�1 produces an opposite change (see Scheme 4).

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molecule exhibits two conformers, A and B, regarding the orienta-tion of the aldehyde group with respect to the azirine ring. Inconformers 3A and 4A, the CQO bond is synperiplanar relative tothe ring. In conformers 3B and 4B, the CQO bond is antiperiplanarrelative to the ring. For each of the 2H-azirines, conformer B ispredicted to be the most stable form by 6–7 kJ mol�1 (QCISD/6-311++G(3df,3pd) values, see Tables S3 and S4, ESI†). The energybarriers for the conversion of the less stable forms A into themost stable conformers B were estimated to be over 17 kJ mol�1

(Fig. S3, ESI†).The infrared signatures of both conformers A and B in each of 3

and 4 were successfully identified in the experiments. In the case of3, particularly interesting is the identification of the bands due tothe nNH2 and 2nNH2 stretching modes of the NH2 antenna. Thebands due to the antisymmetric NH2 stretching mode (naNH2) werelocated at 3532 and 3545 cm�1 for conformers 3A and 3B, respec-tively (see Fig. S1 and Table S1, ESI†). The bands due to thesymmetric NH2 stretching mode (nsNH2) were identified at3410 (A) and 3440 cm�1 (B). In the NIR region, six bands due tophotoproduct 3 were found in the 7100–6700 cm�1 range (Fig. 1band c), typical of 2nNH2 vibrations.30 Taking into account the resultsof anharmonic vibrational calculations carried out for conformers3A and 3B (Fig. 1a), the absorptions at 6993/7029 cm�1 and at6737/6761 cm�1 can be ascribed to the first overtones of theantisymmetric (2naNH2) and symmetric (2nsNH2) stretching vibra-tions, while those at 6822/6850 cm�1 can be ascribed to thecombination bands [(na + ns)NH2].

In the case of 4, i.e. a molecule with an OH antenna, thestretching nOH modes of conformers 4A and 4B are partiallyoverlapped, appearing as a doublet band at 3546/3544 cm�1

(Fig. 2a). This experimental observation is consistent with a closeproximity of the wavenumbers calculated for the nOH vibrations of

conformers 4A and 4B (predicted difference of 4.3 cm�1, seeTable S2, ESI†). In the 2nOH region, a feature covering the6925–6910 cm�1 range was identified (Fig. 2b). The close proximityof the 2nOH frequencies observed for conformers 4A and 4B agreeswith the anharmonic calculations, which predict these two con-formers having their overtones separated by 15 cm�1 (Fig. 2d).

The possibility of conformational control over the aldehydegroup was then demonstrated by NIR excitations at the wavenum-bers identified for NH2 and OH vibrational antennas. The effects ofthese excitations were followed by recording mid-IR and near-IRspectra. For 3, particularly significant spectral modifications weredetected when the OPO output was tuned at 6822 and 6850 cm�1

(boldfaced arrows in Fig. 1), i.e., at the positions assigned to the(na + ns)NH2 transitions of conformers 3A and 3B, respectively. Thespectral modifications resulting from irradiation are illustrated inFig. 1 (near-IR) and Fig. 3 (mid-IR) as difference spectra. Theircomparison with the spectra calculated for the two conformersleaves no doubt that excitation at 6822 cm�1 induces the 3A - 3Bconversion, while the reverse transformation 3B - 3A is observedupon excitation at 6850 cm�1. Reversible conformational changescould be also introduced upon selective excitations at the wave-numbers assigned to the 2naNH2 (6993/7029 cm�1) and 2nsNH2

(6737/6761 cm�1) stretching overtones of the two conformers, whichwere followed by comparison of the mid-IR spectra of 3 (Fig. S4,ESI†). These results clearly show that the energy transfer, from thevibrationally excited NH2 antenna to the C–CHO torsional motion,occurs successfully. Moreover, selective narrow-band NIR irradiationat the frequencies of several vibrational modes of the NH2 antennacan be used to control the conformation of the aldehyde fragment(Scheme 4a).

Regarding 4, the conformational changes upon irradiation weremore pronounced when the NIR frequency was tuned to the edges

Fig. 3 (a) Simulated IR spectra for 3A (blue, intensities multiplied by �1)and 3B (red) based on the B3LYP/6-311++G(d,p) harmonic vibrationalcalculations. Spectral changes resulting from irradiation of 3 isolated inan Ar matrix at 15 K: (b) at 6822 cm�1 and (c) at 6850 cm�1. The positivebands grow upon NIR irradiations. See Fig. S4 (ESI†) for further details.

Fig. 4 (a) Simulated IR spectra for 4A (blue, intensities multiplied by �1)and 4B (red) based on B3LYP/6-311++G(d,p) harmonic vibrational calcula-tions. Spectral changes resulting from irradiation of 4 isolated in an Armatrix at 15 K: (b) at 6920 cm�1 and (c) at 6915 cm�1. The positive bandsgrow upon NIR irradiations. See Fig. S5 in the ESI† for an extended version.

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of the 2nOH absorption band, at 6915 and 6920 cm�1. Thespectral variations within the nOH (Fig. 2a) and 2nOH (Fig. 2band c) profiles, resulting from the NIR excitation at 6915 and6920 cm�1 (Fig. 2), confirm that the lower-frequency compo-nent is due to conformer B, while the higher-frequency compo-nent is due to conformer A, in accord with the anharmoniccalculations (Fig. 2d). The comparison of the experimentaldifference spectra with the spectra calculated for the twoconformers (Fig. 4a) proves in a very clear way that the4A - 4B isomerization is triggered by exciting the matrix-isolated 4 at 6920 cm�1 (Fig. 4b), while the opposite transfor-mation 4B - 4A takes place upon excitation at 6915 cm�1

(Fig. 4c). Therefore, the conformational control in 4 is bidirec-tional and reversible as in 3 (Scheme 4b).

In conclusion, we discovered a molecular framework whereinternal rotation of a heavy atom aldehyde –CHO fragment couldbe achieved, for the first time,40 by vibrational excitation of inter-changeable remote NH2 and OH antennas. In 2-formyl-2H-azirine,the conformational changes were found to be selective and rever-sible upon excitations of the XH (X = NH, O) stretching overtones orcombination modes.

This work was supported by the Portuguese ‘‘Fundaçao para aCiencia e a Tecnologia’’ (FCT). The Coimbra Chemistry Centre issupported by the FCT through the project UID/QUI/0313/2013,cofunded by COMPETE. C. M. N. and I. R. acknowledge the FCTfor Postdoctoral Grant No. SFRH/BPD/86021/2012 and an Inves-tigador FCT grant, respectively.

Conflicts of interest

There are no conflicts to declare.

Notes and references1 J. D. Baldeschwieler and G. C. Pimentel, J. Chem. Phys., 1960, 33,

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6 E. M. S. Maçoas, L. Khriachtchev, M. Pettersson, J. Lundell, R. Fausto andM. Rasanen, Vib. Spectrosc., 2004, 34, 73–82.

7 E. M. S. Maçoas, L. Khriachtchev, M. Pettersson, R. Fausto andM. Rasanen, J. Phys. Chem. A, 2005, 109, 3617–3625.

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can also be used for vibrational excitations. However, since fewerconformational barriers can be reached by MIR than by NIR excita-tions, fewer processes are promoted effectively by MIR radiation. SeeS. Coussan and G. Tarczay, Chem. Phys. Lett., 2016, 644, 189–194.

28 The 2n vibrational states of the NH2 group include three modes: theantisymmetric 2na and symmetric 2ns stretching overtones, and the(na + ns) combination mode.

29 B. Kovacs, N. Kus-, G. Tarczay and R. Fausto, J. Phys. Chem. A, 2017,121, 3392–3400.

30 A. Halasa, L. Lapinski, H. Rostkowska and M. J. Nowak, J. Phys.Chem. A, 2015, 119, 9262–9271.

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an aldehyde group in the indole framework were not successful. Seehere: I. Reva, L. Lapinski, A. J. Lopes Jesus and M. J. Nowak, J. Chem.Phys., 2017, 147, 194304.

Scheme 4 Observed conformational interconversions of the remoteCHO group induced by selective NIR excitations of the 2nNH2 modesof 3, and of the 2nOH modes of 4. Note the conformer-specific colorcodes (A, blue and B, red) for (a) 3-amino-2-formyl-2H-azirine 3 and(b) 3-hydroxy-2-formyl-2H-azirine 4.

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