Journal of Molecular Structure 1035 (2013) 260–266

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Journal of Molecular Structure

journal homepage: www.elsevier .com/locate /molstruc

Fine structures in vibrational circular dichroism spectra of chiral moleculeswith rotatable hydroxyl groups and their application in the analysisof local intermolecular interactions

Kohzo Konno a, Isamu Shiina b, Hiroharu Yui a,c,⇑a Department of Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japanb Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japanc PRESTO-JST, Sanbancyo 5, Chiyoda-ku, Tokyo 102-0075, Japan

h i g h l i g h t s

" Conformation of (�)-menthol in solution is addressed by VCD spectra and calculation." The rotation of polar hydroxyl group is found to sensitively affect the VCD activity." Boltzmann-weighted analysis improved the agreement with the experimental result." Fine structures in the OH vibrational region in the VCD spectra were detected." Intermolecular interactions corresponding to the fine structures are discussed.

a r t i c l e i n f o

Article history:Received 17 September 2012Received in revised form 10 November 2012Accepted 12 November 2012Available online 23 November 2012

Keywords:MentholConformationHydroxyl groupVibrational circular dichroism

0022-2860/$ - see front matter � 2012 Elsevier B.V. Ahttp://dx.doi.org/10.1016/j.molstruc.2012.11.025

⇑ Corresponding author at: Department of ChemistUniversity of Science, 1-3 Kagurazaka, Shinjuku-ku, T

E-mail address: yui@rs.kagu.tus.ac.jp (H. Yui).

a b s t r a c t

The effect of hydroxyl group on vibrational circular dichroism is addressed. (�)-Menthol is investigatedas a representative chiral molecule which has been widely used as a chiral starting material. Free rotationof the hydroxyl group in (�)-menthol allows it to exist in various conformations in solution. The varietyof conformations inevitably affects local intermolecular interactions and the resultant efficiency of asym-metric syntheses. However, the precise relationship between the conformations and intermolecularinteractions arising from rotation of the hydroxyl group has remained an unsolved issue despite the mol-ecule’s importance. Here, the conformations and interactions are investigated using vibrational circulardichroism (VCD). VCD is quite sensitive to slight differences in the conformation of chiral moleculesand their local environment. We examined various conformers in (�)-menthol and compared the VCDspectrum with that of (�)-menthone. It revealed the rotation of the polar hydroxyl group sensitivelyaffects the VCD activity, resulting in the emergence of various patterns in the corresponding VCD spectra,especially in the wavenumber regions at around 1064 cm�1 and 1254 cm�1. Among these regions, the lat-ter one is further investigated to examine the feasibility of applying the sensitive response to the analysison the local intermolecular environment. It includes solute–solvent interactions via hydroxyl groups,which is important for biomacromolecule structural stability and efficient stereoselective syntheses. Asa consequence, distinctive fine structures in the VCD spectra, including an unpredicted band, areobserved when varying temperature and concentration. Their possible assignment is also discussed.

� 2012 Elsevier B.V. All rights reserved.

1. Introduction

Hydroxyl group is one of the most important substituent moie-ties for the formation of higher structures for biomolecules. It isalso important for various materials in their surface modificationand resultant functionalization. The characteristic nature of the

ll rights reserved.

ry, Faculty of Science, Tokyookyo 162-8601, Japan.

hydroxyl group emerges from its high polarity and reactivity. Thus,clarification of the hydroxyl group’s local conformation in organicmolecules and of its chemical or physical states on the surface ofinorganic materials has been a fundamental issue [1–10]. Thearrangement of hydroxyl groups is also important for understand-ing the detailed mechanism of molecular recognition via hydro-gen-bonding in living bodies [11].

Among various organic molecules containing hydroxyl groups,(�)-menthol is one of the representative and best-known chiralmolecules. It has been used not only as a chiral auxiliary but also

K. Konno et al. / Journal of Molecular Structure 1035 (2013) 260–266 261

as a chiral starting material. Thus, it has been widely applied infood, cosmetic, and pharmaceutical products. For asymmetric syn-thesis, the hydroxyl group in (�)-menthol plays a dominant role asa reactive functional moiety [12].

However, in spite of the importance of the various conforma-tions of (�)-menthol, there have been few studies about its back-bone structure [13]. Difficulties in obtaining its single crystalhave precluded conformational determination by X-ray diffraction(XRD) [14]. Furthermore, in the solution phase, its conformationinherently varies due to the freely rotatable nature of the hydroxylgroup. On the other hand, VCD spectroscopy, which is based on achiral molecule’s differential absorption of left- and right-handedcircularly-polarized infrared radiation, is a promising tool to ad-dress the issue [15]. The combination of the experimentally-ob-served and theoretically-calculated VCD spectra [16] in thefingerprint region provides identification of and information onfine structural differences, especially regarding the absolute con-figurations of the chiral molecules in solutions [17]. Thus, VCDspectroscopy has gained attention as a new method for conforma-tional assignment with determination of the absolute stereochem-istry [18–25]. In addition, detailed three-dimensional structures ofmany chiral molecules in solution have been predicted by combin-ing experimental measurements and theoretical calculations of theVCD spectra [26–30]. As for (�)-menthol, its VCD spectrum wasmeasured as one example in the series of various chiral organiccompounds by Nafie et al. [31]. McCann et al. also investigatedthe precise conformation of (1S,2R,5S)-(+)-menthol by comparisonwith theoretical calculation in 1998 [32]. However, as for (�)-men-thol, a comparison with theoretical calculations in the fingerprintregion in the OH bending mode has not been carried out, thatshould be responsible for the local intermolecular interaction be-tween the solvent molecules or the other adjacent (�)-menthol.Furthermore, there has been little information on its local changesin its environments including intermolecular interactions in solu-tion when the temperature and concentration of the (�)-mentholsolution are changed.

Here the fundamental issue on the conformation of (�)-men-thol in solution was addressed comparing VCD spectra with theo-retical calculations for various rotational conformations ofsubstituent groups. It was revealed that the wavenumber regionsat around 1064 cm�1 and 1254 cm�1, which are related to thebending mode of the hydroxyl group, sensitively reflect the changein the conformations. By varying the concentration and the tem-perature of (�)-menthol solution, changes in the characteristic finestructures in the VCD spectra are measured in the wavenumberregion at around 1254 cm�1. By comparing the results to thosefrom the theoretical calculation, their possible assignments arediscussed.

Fig. 1. Comparison of the observed and calculated VCD spectra of (�)-menthol. Theobserved spectrum is offset for clarity.

2. Experimental methods

Measurements of infrared (IR) and VCD spectra. IR and VCD spec-tra were recorded with an FT-IR spectrometer (Thermo Fisher Sci-entific, Nicolet 8700) equipped with a VCD optical system.Thedetails of the optical system for VCD measurements were as fol-lows: the light from the interferometer was directed onto the focusmirror and passed through a linear polarizer and a ZnSe photoelas-tic modulator (PEM, Hinds Instruments, Type II/ZS50). The polari-zation of the IR light was modulated with the PEM operating at50 kHz. The light was then passed through the sample and focusedonto a liquid-nitrogen-cooled HgCdTe detector (Thermo Fisher Sci-entific, MCT-A�).

For the IR absorption and VCD spectra, 128 and 4000 scans wereadded, respectively. These spectra were recorded at a resolution of4 cm�1. The solution sample was held in a variable-path-length

BaF2 cell. (�)-Menthol (Tokyo Chemical Industry) was dissolvedin CCl4 (Wako Pure Chemical Industry) at a concentration of0.4 M. The VCD spectra of (�)-menthol were measured at a pathlength of 100 lm. The spectrum of (�)-menthone (Aldrich) wasmeasured at a path length of 25 lm. All reagents were used with-out further purification. The quarter-wave response of the PEMwas adjusted at 1300 cm�1 to maximize the signal.

Theoretical calculations. The geometries of all conformers wereoptimized using density functional theory (DFT) with the polariz-able continuum model (PCM). The conformational analysis of(�)-menthol was carried out at the B3PW91/6-311++G (d,p) level[33,34]. B3PW91 is one of the most popular functionals in DFT cal-culations [35,36]. At first, the geometries of molecules were opti-mized in vacuum. Then DFT/PCM calculations were performed onthe initial structures which were optimized in the first calculationsin vacuum. VCD spectra were calculated for the nine conformers atthe same level of theory. All calculations were performed using theGaussian 03 program [37].

For the optimization of the conditions for our VCD measure-ments and the confirmation of the reliability for the calculationmethod adopted in the present study, (+)-a-pinene [38] was exam-ined as a test sample first. (+)-a-Pinene has a rigid backbone struc-ture with few conformations. Since calculated band frequencies aregenerally higher than experimental values, the frequencies werescaled with a frequency-independent factor of 0.980. This scale fac-tor was determined by the best fits to frequencies between theexperimental and calculated spectra. After scaling, the calculatedspectrum agreed well with the experimental one, and gave confi-dence that the VCD measurement conditions and the DFT calcula-tion method adopted in the present study were appropriate. Afteroptimizing the system with (+)-a-pinene, the VCD spectrum of(�)-menthol was measured.

3. Results and discussion

Fig. 1 is a comparison of the experimental and calculated VCDspectra of (�)-menthol. Most bands in the observed (�)-mentholspectrum are in good agreement with the predicted spectrum.The relative peak intensities in Fig. 1, however, show partial butnon-negligible disagreement. For example, in the calculated spec-trum, no remarkable peaks are found in the region between 900and 1000 cm�1 (Fig. 1, region i), while there is a clear presence ofpeaks in this area in the observed spectrum. Moreover, the peak

Fig. 2. Assignment of peak ii (1064 cm�1) and peak iii (1254 cm�1) in Fig. 1. Red,green, and white balls represent oxygen, carbon, and hydrogen atoms, respectively.(For interpretation of the references to color in this figure legend, the reader isreferred to the web version of this article.)

Table 1Optimized dihedral angle of nine conformers.

Conformer Dihedral angle (degree)

Isopropyl Hydroxyl

I (G+,G+) 81.56 65.8II (T,G+) �151.44 65.13III (G�,G+) �66.64 64.65IV (G+,G�) 83.11 �53.35V (T,G�) 158.16 �58.19VI (G�,G�) �62.88 �56.54VII (G+,T) 79.12 175.53VIII (T,T) �162.02 172.17IX (G�,T) �69.05 173.05

262 K. Konno et al. / Journal of Molecular Structure 1035 (2013) 260–266

intensities of the observed negative bands at 1064 cm�1 (peak ii)and 1254 cm�1 (peak iii) do not agree with those calculated.

In general, molecules with rigid backbone structures, such asa-pinene and camphor, show excellent agreement between theirexperimental VCD and corresponding calculated spectra. Incontrast, (�)-menthol has three freely rotatable functional substit-uents on its carbocyclic skeleton. The rotation of these functional-ities causes backbone flexibility. The assignments of peaks ii and iiiare shown in Fig. 2. It can be noticed that these two modes involvevibrational coupling between the hydroxyl group and the carbocy-clic skeleton. These assignments suggest that the hydroxyl group in(�)-menthol affects non-negligible part in the discrepancy for thetheoretical and experimental VCD spectra. Interestingly, remark-able effects on the VCD spectrum of the various conformations ofthe hydroxyl group in the 6,60-dibromo-1,10-bi-2-naphthol systemwere reported by Polavarapu et al. [39] Thus, we considered thatthe relatively poor agreement in (�)-menthol might be due tothe free rotation of the functionalities, especially the hydroxylgroup.

For the investigation of the effect on free rotation of the func-tionalities on the VCD spectral patterns, the VCD spectra of (�)-menthol was calculated with respect to each conformer. At first,we considered the effect of the difference in axial and equatorialpositions of the isopropyl group on the carbocyclic skeleton onthe VCD spectrum. Most bulky substituents, such as the isopropylgroup on the carbocyclic skeleton, would generally locate in theequatorial position to avoid large steric hindrances with the carbo-cyclic skeleton. Thus, we assumed that conformers having the iso-propyl group in the equatorial position would be stable in solutionand that the flexibility of the backbone arises from rotational free-dom around the two single bonds: C2–C3 (isopropyl group) andC6–O7 (hydroxyl group) as shown in Fig. 3. The torsion angle ofthe isopropyl group was defined by the angle between the planesformed by atoms (H4, C3, C2) and atoms (C3, C2, H1). The torsionangle of the hydroxyl group was also defined by the angle betweenthe planes formed by atoms (H8, O7, C6) and atoms (O7, C6, H5).Three typical initial torsion angles, 60�, 180�, and �60� (labeledG+, T, and G�, respectively) were chosen, for the two single bonds.

Fig. 3. Structure of (�)-menthol and numbering the atoms for the definition oftorsion angles.

The optimized torsion angles of the isopropyl and hydroxyl groupsare shown in Table 1.

The representative nine conformers are generated by the step of120� rotations of the isopropyl or the hydroxyl groups. The corre-sponding calculated VCD spectra and the newman projections ofthe two single bonds are shown in Fig. 4. For the estimation ofthe effect on the rotation of the isopropyl group on the VCDspectral pattern at first, the calculated result for conformer I wascompared with those for conformers II and III, where the positionof the hydroxyl group was fixed. Although slight difference of thepatterns was observed, no large difference of the characteristicpeaks (peak ii and iii in Fig. 1) in these spectra appeared, as indi-cated with arrows. To the contrast, when the calculated result forconformer I was compared to those of IV and VII, where the posi-tion of the isopropyl group was fixed but that of hydroxyl groupwas varied, remarkable difference emerged in the characteristicpeaks in the VCD spectra was found. These remarkable differencesare also observed in other sets of (II, V, VIII) and (III, VI, IX), wherethe position of the isopropyl group was fixed but that of hydroxylgroup was varied. These results suggest that rotation of the hydro-xyl group, which has a large dipole when compared with the iso-propyl group, led to the great variations of the VCD spectralpatterns in (�)-menthol.

To confirm that the free rotation of the hydroxyl group led tothe various patterns in the VCD spectrum of (�)-menthol, we alsomeasured the VCD spectrum of (�)-menthone and compared them.Oxidation generates the ketone form of (�)-menthol, (�)-menth-one, and frees the VCD spectrum from influences of the variouspossible hydroxyl group conformations seen in (�)-menthol.Fig. 5 shows the comparison of the observed and calculated VCDspectra of (�)-menthone. The observed VCD spectral pattern for(�)-menthone showed excellent overall agreement with the corre-sponding theoretical result. This result confirms that the disagree-ment between the calculated and observed spectra of (�)-mentholis mainly attributed to the mixed population of the various hydro-xyl group conformations in solution at room temperature.

For the improvement of the agreement between the observedand calculated VCD spectra, our calculation procedure was ex-tended to account for conformational variation of the hydroxylgroup by calculating a linear combination of the VCD spectraweighted by a Boltzmann distribution at 298 K (Table 2). This addi-tional procedure should enhance the accuracy of the predictedspectra by accounting for the influence of conformational flexibil-ity in the experiment.

To consider the population of various conformations, the rela-tive energies of the nine conformers shown in Fig. 4 were calcu-lated and compared at 298 K. The calculated results on theseconformers are summarized in Table 2. The most stable three con-formers III, VI, and IX, have the same isopropyl torsion angle. Thenext three stable conformations, conformers I, IV and VII, alsoshare the same isopropyl torsion angle. The relative energies in

Fig. 4. Calculated VCD spectra of nine conformers of (�)-menthol. G+, T, and G� shows the typical initial torsion angles, 60�, 180�, and �60�, for isopropyl and hydroxylgroups, as shown as (isopropyl group, hydroxyl one).

Fig. 5. Comparison of the observed and calculated VCD spectra of (�)-menthone.The observed spectrum is offset for clarity.

Table 2Relative energies of nine conformers of (�)-menthol and their Boltzmanndistribution.

Conformer Relative energya Boltzmann distribution (%)b

I (G+,G+) 4.2 6.32II (T,G+) 9.74 0.68III (G�,G+) 0 34.49IV (G+,G�) 8.42 1.15V (T,G�) 12.29 0.24VI (G�,G�) 1.6 18.03VII (G+,T) 4.57 5.44VIII (T,T) 10.52 0.49IX (G�,T) 0.097 33.16

a Relative energy is in kJ/mol.b The Boltzmann distribution is calculated at 298 K.

K. Konno et al. / Journal of Molecular Structure 1035 (2013) 260–266 263

these sets of the conformers (III, VI, IX) and (I, IV, VII), are arrangedin the same order of the hydroxyl torsion angles, namely,(III < IX < VI) and (I < VII < IV) respectively. The ordering is consis-tent with the expected relative steric hindrance between the iso-propyl and hydroxyl moieties.

When (�)-menthol is in the most stable conformation, con-former III, the hydroxyl group is directed away from the CH bondof the isopropyl group. Thus, the steric interaction between the iso-propyl and the hydroxyl group is minimized in this conformer.Conformer IX has the second lowest steric hindrance. However,in the conformation with the highest relative energy, conformer

V, the hydroxyl group is directed toward one of the methyl substit-uents on the isopropyl group. Therefore, the relative energies arearranged in the order of the hydroxyl torsion angles such that60� < 180� < �60�.

Fig. 6 shows the comparison between the calculated recon-structed spectrum taking the Boltzmann distribution at 298 K intoaccount and the observed one. As a result, the agreement betweenthe experimental and calculated spectral features is remarkablyimproved, especially with regards to peak intensities. The residualerror of peak ii was reduced by half. Similarly, that of peak iii wasreduced by a third. These results demonstrate that accounting for aBoltzmann distribution of conformational populations in the calcu-lation improves the coincidence between experimental and calcu-lated VCD spectra.

However, non-negligible differences in the peak frequenciesstill remained. A probable reason for the discrepancy could beassignable to the difference in intermolecular interactions via polar

Fig. 6. Comparison of a calculated VCD spectrum weighted by a Boltzmannpopulation at 298 K with the observed one.

264 K. Konno et al. / Journal of Molecular Structure 1035 (2013) 260–266

hydroxyl group in solution. Although Ref. [32] describes the (+)-menthol, the enantiomer to the (�)-menthol, and the level of com-putation is somewhat different (Ref. [32]: DFT/B3LYP/6-31G(d,p),in the present paper: DFT/B3PW91/6-311++G (d,p)), it should beuseful to compare the results between that of Ref. [32] and thepresent results, especially in the spectral range including to theOH bending mode (1200–1300 cm�1). Although the sign is inverteddue to the comparisons between enantiomers, remarkable positive(in Ref. [32], negative) band at 1223 cm�1 and negative (in Ref.[32], positive) band at 1271 cm�1 show good accordance betweenthe presented result and that in Ref. [32]. Especially, clear twopeaks at around 1270–1290 cm�1 in the present computed spec-trum (Fig. 6) and that in Ref. [32] (Fig. 4b, numbered as 23 and24) showed excellent agreements. However, in the both cases,clear discrepancy between the computed band at around 1270–1290 cm�1 and experimentally obtained ones showed considerabledifference. These results indicate that only the taking the Boltz-mann distribution into account is not enough to explain the cleardifference between the experimentally obtained VCD band andcomputationally one at around 1270–1290 cm�1, including impor-tant information on the local environment and interaction of hy-droxyl group. Recently, intriguing VCD spectroscopic analyses ofchiral molecules with hydroxyl groups were reported by Yangand Xu [40]. They discussed the effects of hydrogen-bondingbetween glycidol and its surrounding water molecules on theVCD spectrum.

Then we focus now on the peaks appearing at 1270 cm�1 and1254 cm�1 in the calculated spectrum, which display non-negligi-ble differences with the experimental one. The former peak at1270 cm�1 is assigned to vibration of the carbocyclic skeletonbackbone, and the latter at 1254 cm�1 is assigned to a coupledvibration between the carbocyclic skeleton and a bending motionof the hydroxyl group. Vibrations for both modes are schematically

Fig. 7. Schematics of the vibrational modes corresponding to (a) 1254 cm�1 (OH bendbending with opposite phase to the peak at 1254 cm�1).

illustrated in Fig. 7. The intensity and/or vibrational frequency ofthe latter peak should change if the intermolecular interactionswith the hydroxyl group change. In other words, it is expected thatthe latter peak sensitively reflects changes in the local environ-ment and the interactions with neighboring solvent molecules.

However, although the peak at 1270 cm�1 was observed, thepeak at 1254 cm�1 could not be discerned in the experimentalVCD spectrum at the present conditions (0.4 M and 298 K). In gen-eral, vibrational frequencies of OH bending modes increase as theOH moiety forms stronger hydrogen bonds with neighboringatoms [41]. In our case, at high concentrations or lower tempera-tures, two (�)-menthol molecules can dimerize via hydrogenbonds between their hydroxyl groups. Thus, we considered thatunder the experimental conditions the peak at 1254 cm�1 couldshift to higher frequencies and may be superimposed with thestrong and broad peak at 1270 cm�1.

Spectral changes both with decreasing the (�)-menthol solutionconcentration and with increasing the solution temperature to in-crease the relative portion of the (�)-menthol monomer are exam-ined for the test of the assumption. These changes in the conditionsserve to simplify the local (�)-menthol environment. Fig. 8 showsthe results. Interestingly, spectra taken at both lower concentrationand higher temperature show the appearance of the peak at1254 cm�1, as predicted from the monomer (�)-menthol calcula-tions. The measured and calculated frequencies show good agree-ment, indicating that as the fraction of the (�)-menthol monomerform increases, the peak at 1254 cm�1 emerges. This peak can thusbe used as an indicator of the (�)-menthol monomer in solution.

Fig. 9 shows a comparison of the magnified spectra at around1270 cm�1 between the theoretically-calculated and experimen-tally-observed VCD spectrum at a solution temperature of 70 �C.Excellent agreement is not only observed for the peak at1272 cm�1, but also for the peaks at 1254 and 1282 cm�1. The lat-ter two peaks are assignable to OH bending modes with differentphases. However, interestingly, the appearance of an additionalwas noticed, unpredicted peak at 1262 cm�1 in the experimentalresult. Since the peak at 1262 cm�1 were observed in both low con-centration (0.1 M and 0.2 M) and high temperature (70 �C) condi-tions and their signal intensities (De) reached to 0.01 M�1cm�1

as well as the theoretically predicted and the measured peak at1254 cm�1, we can consider that the peak should also sensitivelyreflect the interaction of the (�)-menthol monomer to the sur-rounding solvent molecules via the hydroxyl group. However, atthe present, we do not have enough information to confirm withcertainty the assignment of this unpredicted peak at 1262 cm�1.We obtained the theoretical results, which lack this peak at1262 cm�1, under continuous model conditions to approximatethe solvent effect. To the contrast, in a real solute–solvent system,solvent molecules could have certain solvation structures, whichcan give rise to some differences from the calculation based onthe continuous model.

Next the possible assignment of the two discrete peaks appear-ing at 1254 and 1262 cm�1 was considered. As described, the fre-quency of the OH bending mode can vary with the interaction

ing), (b) 1270 cm�1 (vibration of the carbocyclic skeleton), and (c) 1282 cm�1 (OH

Fig. 8. Changes in the VCD spectra with (a) varying temperature and (b) varyingconcentration.

Fig. 9. Detailed comparison of the calculated and observed VCD spectra at asolution temperature of 70 �C in the region near 1270 cm�1.

Fig. 10. Proposed distinctive configurations and interactions between solute (�)-menthol and solvent carbon tetrachloride corresponding to the two distinctivepeaks. (a) Linear interaction between the positively polarized H atom in the polarhydroxyl group and a negatively polarized chlorine atom and (b) and (c)cooperative interactions between one hydroxyl group and two or three chlorineatoms, respectively.

K. Konno et al. / Journal of Molecular Structure 1035 (2013) 260–266 265

strength of the hydroxyl group. Thus, they could be assignable to atleast two distinctive configurations with different electrostaticstabilization between the hydroxyl group and negatively chargedchloride atoms of the solvent carbon tetrachloride molecules. Threepossible and responsible configurations are shown in Fig. 10. The

first is based on a linear interaction between the positively polar-ized H atom in the polar hydroxyl group and a negatively polarizedchloride atom (as is shown Fig. 10a). The second and third ones arebased on the cooperative interaction between the OH group andtwo or three chloride atoms (as are shown in Fig. 10b and c, respec-tively). These distinct configurations should induce different inter-molecular interaction strengths to the hydroxyl group. Althoughthe strength of the interaction corresponding to the last two config-urations (b) and (c) might be relatively close to each other com-pared to the first one (a), identification and confirmation of theassignment of the two discrete peaks require further examinationand consideration. However, the appearance of these distinctivefine structures in the VCD spectrum demonstrates the effectivenessof applying VCD spectroscopy for discriminating slight differencesin the local solvation environment and intermolecular interactionsin solution as well conformational analyses.

4. Conclusion

The effect of freely rotatable, polar hydroxyl groups on the VCDspectrum was investigated for the best-known chiral molecule,(�)-menthol. Non-negligible disagreements were observed in thepeak intensities for the experimental and calculated VCD spectra.Calculation of theoretical VCD spectra for various conformers and

266 K. Konno et al. / Journal of Molecular Structure 1035 (2013) 260–266

comparison of VCD spectra from (�)-menthol and (�)-menthonerevealed that the disagreement principally arises from the confor-mational variation of the hydroxyl group in solution. Use of aBoltzmann-weighted analysis to account for the various conform-ers improved the agreement between the theoretical and experi-mental results, but some discrepancies remained. This sensitivityshows the potential application for conformational selective anal-ysis of the local environment of the hydroxyl group in chiral mol-ecules and its interaction with neighboring solvent molecules. Byvarying the solute concentration and solution temperature, weidentified that the theoretically predicted peak at 1254 cm�1 isattributable to the monomer (�)-menthol OH bending mode insolution. In addition, an unpredicted peak at 1262 cm�1 was newlyobserved experimentally. The precise configuration that corre-sponds to this peak is now under investigation, but the appearanceof these two peaks suggests that the hydroxyl groups participate inat least two distinctly different types of solute–solvent interactionsin carbon tetrachloride. The present results are expected to en-hance the analyses on the conformational information of the chiralmolecules with freely rotatable hydroxyl groups and its intermo-lecular interactions, which are important for function expression,structural stability, and stereoselective reaction in solutions.

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