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Three classes of VCD intensity models are presented to explore the nature of VCD spectra whose primary electric and magnetic-dipole contributions are due to the flow of electronic charge density associated with a single driving oscillator. The models, chosen as prototypic geometrical chiral structures, consists of a three-bond fragment, a helical structure and a closed-ring structure.

An improved procedure using vibrational circular dichroism spectroscopy for high-precision determinations of enantiomeric excess (ee) in chiral samples is described. Chiral trans-dideuteriocyclopropane is employed in the gas phase for percent ee measurements. This molecule is a member of the class of simple hydrocarbons made chiral by virtue of isotopic substitution for which no convenient and accurate alternative method of percent ee measurement is available. Percent ee determinations to within 1% are demonstrated for several ee values with and without contamination by the achiral cis-dideuteriocyclopropane species.

Compound A, a novel disubstituted pyrrolidine acid, is a member of a new class of agents that are potentially useful for the treatment of diabetes and dyslipidemia. The absolute configuration of this compound was determined by using vibrational circular dichroism (VCD). The results are in agreement with the assignments based on both X-ray analysis and the stereo-selective chemical synthesis. During VCD analysis, the solution conformation for a portion of compound A in CDCl3 was also established. The compound is found to associate as an H-bonded carboxylic acid “dimer” in CDCl3 solution, and VCD calculations on a model dimer fragment were required to establish the absolute configuration. Chirality, 2006. © 2006 Wiley-Liss, Inc.

CHFClI is among the more favorable molecules for parity violation (PV) measurements in molecules. Despite the fact that calculated PV effects are two orders of magnitude smaller than in some organometallic compounds, CHFClI displays interesting features which could make possible a new experimental PV test on this molecule. Indeed, ultrahigh resolution spectroscopy using an ultrastable CO(2) laser is favored by several intrinsic properties of this molecule. For example, the high vapor pressure of CHFClI allows investigation by supersonic beam spectroscopy. Indeed, the spectroscopic constants have been accurately determined by microwave and millimetre wave spectroscopy. This is important for the subsequent selection of an appropriate absorption band of CHFClI that could be brought to coïncide with the absorption of CO(2). Partially resolved (+)- and (-)-CHFClI enantiomers with respectively 63.3 and 20.5% ee's have been recently prepared and analyzed by molecular recognition using chiral hosts called cryptophanes. Finally, the S-(+)/R-(-) absolute configuration was ascertained by vibrational circular dichroïsm (VCD) in the gas phase.

The first use of near-infrared (NIR) Fourier transform vibrational circular dichroism (FT-VCD) to follow changes in the enantiomeric excess (EE) of chiral sample molecules in time using a flow-cell sampling apparatus is reported. Simultaneous changes in the fractional composition and the EE of a mixture of two different chiral molecules were monitored as a function of time. This simulates the progress of the chemical reaction from a chiral reactant to a chiral product where the mole fractions and EE values of both species may change with time. For the molecules studied, α-pinene, camphor, and borneol, the accuracy of following EE changes for one species alone is approximately 2%, while for simultaneously following EE changes in two species it is approximately 3% for 30 min sampling periods at 16 cm−1 spectral resolution. These findings demonstrate the potential for VCD to be used in the NIR region for real-time monitoring of the composition and %EE of chemical reactions involving the synthesis of chiral molecules.

Ultraviolet (UV) and infrared (IR) absorption and vibrational circular dichroism (VCD) spectroscopy were used to study conformational transitions in the double-stranded poly(rA). poly(rU) and its components-single-stranded poly(rA) and poly(rU) in buffer solution (pH 6.5) with 0.1M Na+ and different Mg2+ and Cd2+ (10(-6) to 10(-2) M) concentrations. Transitions were induced by elevated temperature that changed from 10 up to 96 degrees C. IR absorption and VCD spectra in the base-stretching region were obtained for duplex, triplex, and single-stranded forms of poly(rA) . poly(rU) at [Mg2+],[Cd2+]/[P] = 0.3. For single-stranded polynucleotides, the kind of conformational transition (ordering --> disordering --> compaction, aggregation) is conditioned by the dominating type of Me2+-polymer complex that in turn depends on the ion concentration range. The phase diagram obtained for poly(rA) . poly(rU) has a triple point ([Cd2+] approximately 10(-4)M) at which the helix-coil (2 --> 1) transition is replaced with a disproportion transition 2AU --> A2U + poly(rA) (2 --> 3) and the subsequent destruction of the triple helix (3 --> 1). The 2 --> 1 transitions occur in the narrow temperature interval of 2 degrees -5 degrees . Unlike 2 --> 1 and 3 --> 1 melting, the disproportion 2 --> 3 transition is a slightly cooperative one and observed over a wide temperature range. At [Me2+] approximately 10(-3) M, the temperature interval of A2U stability is not less than 20 degrees C. In the case of Cd2+, it increases with the rise of ion concentration due to the decrease of T(m) (2-->3). The T(m) (3-->1) value is practically unchanged up to [Cd2+] approximately 10(-3)M. Differences between diagrams for Mg(2+) and Cd2+ result from the various kinds of ion binding to poly(rA).poly-(rU) and poly(rA).

Electrospray ionization mass spectrometry-guided isolation of extracts from Didiscus aceratus led to the discovery of several new derivatives of the bioactive bisabolene-type sponge metabolite (S)-(+)-curcuphenol (1). The compounds obtained by this method included a mixture of known (2) and new (3) dihydroxylated analogs as well as a novel family of dimeric derivatives, dicurcuphenols A-E (4-8), and dicurcuphenol ether F (9). Dimers 4-9 were also subsequently obtained through a hemisynthetic method in which 1 was incubated with the enzyme laccase. Atropisomeric dimers 5 and 6 were subjected to vibrational circular dichroism analysis thereby establishing their absolute biaryl axial chirality as P and M, respectively. In contrast to 1, metabolites 2-9 exhibited weak or no cytotoxic or lipoxygenase inhibitory effects.

We report the first vibrational circular dichroism (VCD) spectra with continuous coverage from 800 cm−1 in the mid-infrared (MIR) region to 10 000 cm−1 in the near-infrared (NIR) region. This coverage is illustrated with MIR and NIR absorbance and VCD spectra of 2,2-dimethyl-dioxolane-4-methanol (DDM), α-pinene, and camphor that serve as calibration samples over this entire region. Commercially available, dual-source Fourier transform (FT) MIR and NIR VCD spectrometers were equipped with appropriate light sources, optics, and detectors, and were modified for dual-polarization-modulation (DPM) operation. The combination of liquid-nitrogen- and thermoelectric-cooled HgCdTe (MCT) detectors, as well as InGaAs and Germanium (Ge) detectors operating at room temperature, permitted collection of the desired absorbance and VCD spectra across the range of vibrational fundamental, combination band, and overtone frequencies. The spectra of DDM and α-pinene were measured as neat liquids and recorded for both enantiomers in the various spectral regions. Spectra for camphor were all measured in CCl4 solution at a concentration of 0.6 M, except for the carbonyl-stretching region, where a more dilute concentration was used. The typical anisotropy ratios ( g) of the three molecules were estimated with respect to their strongest VCD bands in each spectral region. It was found that for all three molecules in the spectral regions above 2000 cm−1, anisotropy ratios are approximately the same order (10−5) of magnitude. However, in the MIR region, the typical anisotropy ratios are significantly different for the three molecules. This study demonstrates that with modern FT-VCD spectrometers modified for DPM operation, VCD spectra can be measured continuously across a wide spectral range from the MIR to nearly the visible region with an unsurpassed combination of signal-to-noise ratio and spectral resolution.

Vibrational circular dichroism (VCD) spectroscopy was used to investigate the solution conformations of cyclosporins A, C, D, G, and H in CDCl3, in the amide I and NH/OH-stretching regions, and their corresponding magnesium complexes in CD3CN, in the amide I region. VCD spectra are sensitive to the chiral arrangement of CO and NH bonds in this cyclic undecapeptide. Calculations of molecular geometries, as well as IR and VCD intensities of model cyclosporin fragments that include the intramolecular hydrogen bonds of the crystal conformations of cyclosporins A and H (CsA and CsH), were carried out at the density functional theory (DFT; BPW91 functional/6-31G* basis set) level. The good agreement between IR and VCD spectra from experiment and DFT calculations provides evidence that the crystal conformation of CsA is dominant in CDCl3 solution; CsH, however, assumes both an intramolecularly hydrogen-bonded crystal conformation and more open forms in solution. Comparisons of the experimental and calculated VCD spectra in the NH/OH-stretching region of the noncomplexed cyclosporins indicate that conformers with both free and hydrogen-bonded NH and OH groups are present in solution. Differences between the IR and VCD spectra for the metal-free and magnesium-complexed cyclosporins are indicative of strong interactions between cyclosporins and magnesium ions. © 2003 Wiley Periodicals, Inc. Biopolymers 73: 163–177, 2004

Advances in the measurement, calculation, and application of vibrational circular dichroism (VCD) for the determination of absolute configuration are described. The purpose of the review is to provide an up-to-date perspective on the capability of VCD to solve problems of absolute stereochemistry for chiral molecules primarily in the solution state. The scope of the article covers the experimental methods needed for the accurate measurement of VCD spectra and the theoretical steps required to systematically deduce absolute configuration. Determination of absolute configuration of a molecule by VCD requires knowledge of its conformation or conformational distribution, and hence VCD analysis necessarily provides solution-state conformation information, in many cases available by no other method, as an additional benefit. Comparisons of the advantages and limitations of VCD relative to other available chiroptical methods of analysis are also presented.

The erythro isomer of 1-naphthyl-1-(2-piperidyl)methanol 4, an efficient chiral modifier for asymmetric heterogeneous hydrogenation, was obtained as the major isomer (95%) in two steps while the threo isomer can be obtained as the major isomer (67%) in three steps. erythro-4 and threo-4 were resolved on a CHIRALCEL OD-RH column. It has been shown by VCD that the diastereomer determined as the erythro by NMR was indeed the erythro and that the first eluted (-)-enantiomer on CHIRALCEL OD-R or -RH columns has the (1R,2S) configuration. The VCD studies identify the presence of at least five conformers in CDCl(3) solution. Moreover, this (-)-(1R,2S) absolute configuration found by VCD is consistent with the expected stereo-outcome of catalytic hydrogenation of pyruvate into lactate, which supported the (+)-(1S,2R) assignment.

A comparison of step-scan and rapid-scan Fourier transform vibrational circular dichroism (FT-VCD) spectroscopy in the hydrogen-stretching region has been carried out on Nicolet Magna 850 and Bruker IFS-55 FTIR spectrometers, each equipped with an accessory VCD bench. Single enantiomer VCD spectra of (+)- and (−)-camphor with flat baselines are obtained on each instrument, both in step-scan mode and rapid-scan mode. On both instruments, the RMS noise level is less than 1×10−6 (absorbance units) in less than two-hour collections, and the noise level obtained with the step-scan method is slightly lower than that for rapid-scan. The calibrated noise level of VCD spectra obtained on the Nicolet instrument is about twice that obtained on the Bruker instrument for a comparable collection time. Our preliminary results show that with an InSb detector on the Nicolet instrument, the noise level of VCD spectra is about a half of that obtained with an MCT detector.

There is an increasing need for new methods to determine percent enantiomeric excess (%ee) in chiral molecules. Four sets of determinations of %ee using Fourier transform infrared vibrational circular dichroism (FTIR-VCD) have been performed using three different instruments and several kinds of samples. These include measurements for neat α-pinene with two different FTIR spectrometers equipped with a mercury cadmium telluride (MCT) detector, measurements for lysine in H2O using one of the MCT instruments, and measurements for 3-methylcyclohexanone in CCl4 solution. We find that FT-VCD spectroscopy is capable of measuring %ee in the range of 1% or better for these samples using one to several hours of spectral collection time.

Vibrational circular dichroism (VCD) spectra of chiral α-hydroxy acids and related molecules have been investigated in the hydrogen stretching and midinfrared regions to probe factors influencing the VCD intensity of methine and hydroxyl stretching and bending motions. Ab initio calculations were carried out to identify low energy conformers and to calculate VCD intensity with the vibronic coupling VCD theory, utilizing DFT normal modes and geometry. Large methine stretching VCD intensity was correlated with the presence of an oxygen at the chiral center in conjunction with an O=C-C*-O dihedral angle near 0°. Vibrational transition current density plots for the methine stretch in deuteriated methyl lactate reveal angular and circulatory charge flow consistent with the positive rotational strength for the S-enantiomer.

Raman optical activity (ROA)1, the difference in Raman scattering intensity for right and left circularly polarized incident and/or Raman scattered radiation, has emerged as a technique for investigating the solution structure of chiral molecules, and has been applied to biomolecules in aqueous solution. 1, 2 Resonance Raman spectroscopy is well established as a technique for probing the structure and dynamics of appropriate chromophores in biomolecules. However, resonance Raman optical activity (RROA) has not been reported. Recently, the theory of Raman optical activity has been extended to the case of strong resonance with a single electronic state.3 The theory predicts that, in this limit, the RROA bands will all have the same sign (opposite in sign to the pure electronic circular dichroism of the resonant electronic transition) and will be proportional in intensity to the parent resonance Raman bands. We provide here evidence for both resonance and non-resonance ROA in the spectra of the analgesics naproxen and ibuprofen in basic and nonaqueous solution.

Infrared, vibrational circular dichroism, dual circular polarization Raman optical activity and Raman spectra have been used in conjunction for investigation of the vibrational modes of trans- and cis-pinane, and α- and β-pinene with a view of evaluating the usefulness of these techniques. It has been concluded that vibrational circular dichroism and Raman optical activity provide highly complementary and non-redundant information, of comparable spectral quality.

A modified design for a Fourier-transform vibrational circular dichroism (FT-VCD) spectrometer is presented. The FT-VCD instrument is based on a Nicolet Magna-IR 550 equipped with an external bench for the measurement of VCD spectra. VCD spectra of high signal quality were obtained with 20 minutes of collection time at 4 cm -1 resolution in the mid-infrared region by conventional sequential collection of rapid-scan VCD and transmission interferograms, the simultaneous collection of these rapid-scan interferograms and step-scan collection. Of these three methods the simultaneous rapid-scan exhibited the lowest levels of noise.

Vibrational circular dichroism (VCD) spectra in the region above 2000 cm−1 provides valuable information on absolute configuration or conformation of chiral molecules.1 Conventionally, VCD spectra in this region have been measured with dispersive instruments, since the high Fourier frequencies resulting from the rapid motion of a moving mirror in a conventional Fourier transform spectrometer may deteriorate the VCD signal. Step-scan FT-VCD, however, has no such difficulty (there is no Fourier frequency) and has advantages over dispersive VCD in terms of noise level, resolution, spectral coverage and repeatability. 2, 3 We have recently investigated a number of molecules of pharmaceutical interest using step-scan FT-VCD above 2000 cm−1. These molecules include S-(-)-propranolol, (S)-4-isobutyl-α- methylphenylacetic acid (ibuprofen) and (S)-6-methoxy-a-methyl-2-naphthalene- acetic acid (naproxen). The FTIR and VCD spectra have been measured and interpreted by comparison with ab initio calculations of geometry, vibrational frequency and intensity for a group of low-energy conformers of each compound. For the VCD spectra, intensities have been calculated with the locally distributed origin gauge (LDO) model and the vibronic coupling VCD theory.4

Vibrational circular dichroism (VCD), the difference in absorbance of left and right circularly polarized infrared radiation during vibrational excitation, provides information on the solution conformation of biological molecules.1,2 The fast time scale of vibrational excitation allows observation of discrete vibrational bands for conformers that are averaged on the NMR time-scale, and the added dimensions of sign and conformational sensitivity introduced with circular dichroism permit additional resolution of features that overlap in the parent infrared absorption spectra. We have recently investigated a series of molecules with two chiral centers and a variety of possible intramolecularly hydrogen-bonded conformations. These molecules include six ephedra drugs,3 where R and R’ are H or CH3, and the chirality at C1 is S and that at C2 is R for ephedrines and S for pseudoephedrines. The other molecules studied, related structurally to ephedrines, are the antiarrhythmic drug propranolol and a series of substituted 1,2-diphenylethanes Ephedrines [(R,R)-hydrobenzoin, (1R,2R)-diphenylethylenediamine and (1S,2S)-2-amino-l,2-diphenylethanol]. The absorbance and VCD spectra in the OH-and NH-stretching regions have been measured and interpreted by comparison with ab initio geometry, vibrational frequency and intensity calculations for a group of low energy conformers of each compound.

Raman optical activity (ROA), the circular intensity difference between right and left circularly polarized incident and/or Raman scattered radiation, provides a unique conformational probe of biological molecules in aqueous solution.1,2 In the classical measurement of ROA, the polarization of the incident laser radiation is modulated between the two circular polarization states, keeping the scattered linear polarization fixed, resulting in ICP-ROA. More recent methods developed in our laboratory include modulation only of the Raman scattered radiation, denoted SCP-ROA, or dual circular polarization modulation of both the incident laser and the Raman scattered radiation, either in- or out-of-phase, denoted DCPI- and DCPII-ROA, respectively. The depolarized backscattering DCPI-ROA measurement has been found to be particularly advantageous for biological samples. One emphasis of our recent research is to explore the sensitivity of ROA to locallized vs. longer range vibrational modes and to local vs. long-range stereochemistry. In addition, comparison of results from the various forms of measurement of ROA provides information on the relative importance of magnetic dipole vs. electric quadrupole mechanisms for ROA intensity. Two classes of molecules have been surveyed. Studies of simple peptides provide the opportunity to investigate the degree of localization of ROA features on specific residues and the effects of vibrational coupling among residues.3

The vibrational circular dichroism (VCD) spectra of (S)-1-amino-2-propanol and (S)-2-amino- 1-propanol in non-aqueous solution have been investigated. The vibrational frequencies, infrared intensities and VCD intensities have been calculated for all the hydrogen-bonded conformers with ab initio wave functions at a 6-31G (0.3 ) basis set level. The VCD intensities have been calculated with the vibronic coupling theory a priori formalism. Comparison of the experimental and calculated spectra allows correlation of the major VCD features with a few predominant conformers.

The solution conformations of a series of pentapeptides containing the unsaturated reside dehydrophenylalanine have been investigated by infrared, vibrational circular dichroism, electronic CD and NMR spectroscopies. VCD couplets in the NH-stretching region are identified as markers for the left or right-handed helical orientation of NH bonds in these peptides.

Vibrational circular dichroism (VCD) spectra provide information on the solution conformations of chiral molecules. The CH-, OH-, NH-, and C equals O-stretching VCD features are particularly useful conformational probes. Molecules of pharmaceutical interest studied by VCD include biomimetic iron carriers, unsaturated peptides, the anticancer drug taxol and a series of type I antiarrhythmic drugs.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Publisher Summary Raman optical activity (ROA) is the difference in the intensity of Raman scattered light with respect to right and left circularly polarized incident or scattered radiation, or both. The form of ROA defined with circular polarization modulation of the incident laser was first described theoretically in 1971 and was first measured in 1973. As with other forms of natural optical activity, a molecular sample must be chiral to possess a nonzero ROA spectrum. The measurement of an ROA spectrum requires particular care to avoid the presence of optical artifacts since ROA intensities are small, being typically three to four orders of magnitude below those of the parent Raman spectrum. The value of ROA as a spectroscopic technique lies in its particular sensitivity to chiral molecular environments. After nearly two decades of steady development, ROA is now emerging as an important new spectroscopic tool in the study of the stereo conformations of optically active molecules, including biological macromolecules and metal complexes. Advances in three principal areas have revolutionized the measurement of ROA spectra. These are (1) the use of alternative scattering geometries including backward scattering, (2) the use of charge-coupled device (CCD) detectors as nearly ideal, low-background, large area, multichannel detectors, and (3) the introduction of new polarization modulation techniques involving the measurement of circular polarization intensity differences associated with the scattered beam.

Publisher Summary A dissymmetric (chiral) molecule or molecular conformation—that is, one which is not superimposable on its mirror image—exhibits a differential interaction with left and right circularly polarized radiation. Circular dichroism, the difference in absorbance of left versus right circularly polarized light, can occur for both electronic and vibrational excitation of a chiral molecule. Although the infrared spectral region primarily encompasses vibrational transitions, low-lying electronic transitions in metal complexes can also occur in the infrared. This chapter uses the terms “infrared circular dichroism” (IRCD) to refer to both types of transitions and vibrational circular dichroism (VCD) to distinguish purely vibrational transitions. The first measurement of IRCD was reported in 1972 and that of VCD in 1973. Since that time, numerous advances in experimental techniques have expanded the region over which IRCD can be measured, and advances in interpretational and calculational approaches have provided a framework for correlating the observed spectra with specific molecular conformations and configurations. Metal complexes, metalloproteins, and metalloenzymes provide a particularly interesting area for IRCD investigation, because both conformational and configurational chirality can be present in the vicinity of the metal ion.

The solution conformations of three trispeptides--L,L,L-1,3,5-C6H3[CH2NHCOCH(X)-NHBoc++ +]3, X = CH3 (Ala) or CH2CH(CH3)2 (Leu), and L,L,L-N(CH2CH2NHCOCH[CH2-CH(CH3)2]NHBoc)3--have been determined from their ir and vibrational CD (VCD) spectra in the NH stretching and carbonyl stretching regions in apolar solution. The compounds containing L-Leu are shown to occur primarily in a propeller conformation with C3 symmetry that is stabilized by interchain hydrogen bonds. Through application of the coupled oscillator model of VCD, a right-handed sense for the hydrogen-bonded chains in the propeller is deduced, in agreement with previous empirical force field calculations. The spectra also provide evidence for interchain association between two chains, resulting in a C10-ring. For chains not involved in interchain association, the spectra reveal the presence of C7-rings within a chain. The trispeptide containing L-Ala is found to occur primarily in a random form.

Vibrational circular dichroism (VCD) and kinetic measurements have been carried out for several three-membered ring molecules that are optically active by virtue of isotopic substitution, (S,S)-cyclopropane-1,2-2H2, (2S,3S)-cyclopropane-1- 13C,2H-2,3-2H2, and (S,S)-oxirane-2,3-2H2.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Vibrational circular dichroism (VCD) spectra have been recorded in the NH and C equals O stretching regions for a series of tripodal peptides and peptides containing an unsaturated residue, in order to obtain information about solution conformations.© (1992) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Recent advances have led to dramatic improvements in the measurement of Raman optical activity (ROA). These include the use of new scattering geometries and improvements in polarization modulation methodology and multichannel-detector technology. Several new ROA experimental configurations are selected to illustrate the capabilities of a new ROA instrument constructed recently at Syracuse University. Both general and simplified theoretical expressions are used to identify fundamental aspects of various ROA experiments and to determine preferred configurations for the measurement of ROA. The authors find for their instrument that the optimum configuration is in-phase dual circular polarization (DCPI) ROA in backscattering geometry, as illustrated using (+)-fenchone. DCPI- ROA backscattering spectra are presented for aqueous solutions of L-alanine, glycyl-L-alanine and D-mannose. The large couplet arising from the bands between 800 and 900 cm-1 in the ROA spectrum of alanine is interpreted in terms of coupled methyl rocking and the methyl carbon-carbon stretching internal coordinates. The feasibility of applying ROA to the study of biological molecules is demonstrated by the high quality of the ROA spectra obtained for these molecules.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The trimethylene diradical (1-d{sub 0}) has long been considered a possible or even a likely short-lived reactive intermediate. The precise character of the trimethylene intermediate is of course not revealed unambiguously through the agreement between calculated relative lifetimes and measured lifetimes shown here. The local energetic minimum in the many-dimensional potential energy surface for the trimethylene intermediate is quite shallow, and the diradical may exist in a variety of conformational forms characterized by different C-C-C bond angles and H-C-C-H dihedral angles without any substantial variations in energy. For such a molecular entity, nearly a `twixtyl`, `a molecule or a range of molecular conformations` having no minimum on a potential energy surface but `which operationally behaves as a true intermediate`, isomerization rates and lifetimes may be dictated more by the requirement that various vibrational modes must attain appropriate phase relationships with one another rather than by any all-important activation energy criterion. 26 refs., 3 tabs.

The absolute configuration of the (−)-enantiomer of mirtazapine was determined by means of vibrational circular dichroism (VCD). The observed VCD of (−)-mirtazapine showed excellent correlation with the calculated VCD of the (R)-enantiomer. This is in agreement with the absolute configuration as determined by independent synthesis starting from (R)-phenylglycine.

Natural vibrational optical activity consists of two principal forms. The IR form is known as vibrational circular dichroism (VCD) and is simply the extension of electronic circular dichroism into the IR vibrational region of the spectrum. The Raman form, known as Raman optical activity (ROA), is a new form of optical activity that has no counterpart in the classical forms of optical activity. In this paper, the similarities and differences of the IR and Raman forms of vibrational optical activity will be examined. Although both VCD and ROA were discovered and confirmed in the period from 1973 to 1975, each field has evolved independently with key advances in theoretical description, instrumentation and application coming at different times over the past 20 years. The current relative strengths and weaknesses of VCD and ROA will be discussed, and specific examples of VOA spectra of (-)-alpha-pinene and the amino acid L-alanine, for which overlapping VCD and ROA data are available, will be presented.

Vibrational circular dichroism (VCD) spectra in the OH- and NH-stretching regions have been measured for six pharmaceutical molecules in the ephedra class, (1S,2R)-norephedrine, (1), (1S,2S)-norpseudoephedrine (2), (1S,2R)-ephedrine (3), (1S,2S)-pseudoephedrine (4), (1S,2R)-N-methylephedrine (5) and (1S,2S)-N-methylpseudoephedrine (6), all in dilute C2Cl4 solution. Ab initio calculations of geometries and vibrational frequencies for a number of conformers of 1 to 6 have been carried out. The recently developed locally distributed origin gauge model for VCD was used to calculate VCD spectra of the conformers for each drug. This ground-state ab initio model, which does not require sum-over-states, magnetic field perturbation or localized molecular orbitals, has been found to give good agreement with experiment in this frequency region. Composite spectra obtained from weighted averages of the calculated conformer spectra agree within a factor of two with observed IR and VCD intensities for five of the ephedra drugs. For (1S,2S)-pseudoephedrine, the discrepancy between experiment and calculation has been interpreted in terms of a coupled-oscillator effect absent in the other molecules.

A new formulation of the bond polarizability and vibronic coupling theories of Raman optical activity (ROA) is presented in which terms dependent upon the nuclear momentum are introduced for the first time. The new terms appear in the magnetic‐dipole electric‐dipole optical activity tensor and are directly analogous to the non‐Born–Oppenheimer, momentum‐dependent terms required in the formulation of the theory of vibrational circular dichroism. Through the use of simplifying approximations in the ROA vibronic coupling theory, a term‐for‐term correspondence with the bond polarizability theory is established. It is shown that the new terms are smaller than the original terms by the ratio of the vibrational transition frequency to the frequency of the incident radiation. The new terms also contribute oppositely to Stokes and anti‐Stokes ROA which provides a basis for their experimental isolation.

$^{1}$L. Laux, V. Fultz, S. Abbate, H. A. Havel, H. Overend, A. Moscowitz and D. A. Lightner, J. Am. Chem. Soc. 104, 4276 (1982).

Calcul du dichroisme circulaire vibrationnel a l'aide d'un modele d'orbitales moleculaires non localisees, dans l'approximation CNDO