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The metal-centered Δ/Λ-chirality of four-coordinated, nonplanar Zn(A(^)B)(2) complexes is correlated to the chirality of the bidentate enantiopure (R)-A(^)B or (S)-A(^)B Schiff base building blocks [A(^)B = (R)- or (S)-N-(1-(4-X-phenyl)ethyl)salicylaldiminato-κ(2)N,O with X = OCH(3), Cl, Br]. In the solid-state the (R) ligand chirality induces a Λ-M configuration and the (S) ligand chirality quantitatively gives the Δ-M configuration upon crystallization as deduced from X-ray single crystal studies. The diastereoselections of the pseudotetrahedral zinc-Schiff base complexes in CDCl(3) solution were investigated by (1)H NMR and by vibrational circular dichroism (VCD) spectroscopy. The appearance of two signals for the Schiff-base -CH═N- imine proton in (1)H NMR indicates an equilibrium of both Δ- and Λ-diastereomers with a diastereomeric ratio of roughly 20:80% for all three ligands. VCD proved to be very sensitive to the metal-centered Δ/Λ-chirality because of a characteristic band representing coupled vibrations of the two ligand's C═N stretch modes. The absolute configuration was assigned on the basis of agreement in sign with theoretical VCD spectra from Density Functional Theory calculations.

Six novel monoterpene chromane esters were isolated from the aerial parts of Peperomia obtusifolia (Piperaceae) using chiral chromatography. This is the first time that chiral chromane esters of this kind, ones with a tethered chiral terpene, have been isolated in nature. Due to their structural features, it is not currently possible to assess directly their absolute stereochemistry using any of the standard classical approaches, such as X-ray crystallography, NMR, optical rotation, or electronic circular dichroism (ECD). Herein we report the absolute configuration of these molecules, involving four chiral centers, using vibrational circular dichroism (VCD) and density functional theory (DFT) (B3LYP/6-31G*) calculations. This work further reinforces the capability of VCD to determine unambiguously the absolute configuration of structurally complex molecules in solution, without crystallization or derivatization, and demonstrates the sensitivity of VCD to specify the absolute configuration for just one among a number of chiral centers. We also demonstrate the sufficiency of using the so-called inexpensive basis set 6-31G* compared to the triple-ζ basis set TZVP for absolute configuration analysis of larger molecules using VCD. Overall, this work extends our knowledge of secondary metabolites in plants and provides a straightforward way to determine the absolute configuration of complex natural products involving a chiral parent moiety combined with a chiral terpene adduct.

Vibrational circular dichroism (VCD) of a series of proteins in H2O solution with differing secondary structure are reported for the first time in the near-infrared (NIR) region as well as the NH-stretching region. The Fourier transform (FT) near-infrared (NIR) measurements were carried out between 6000 to 4000 cm−1. FT-VCD measurements were simultaneously carried out for the mid-infrared (mid-IR) region from 2000 to 800 cm−1 for direct comparison to VCD in the NIR region. The NIR VCD spectra of proteins show distinct spectral features for different protein structural motifs, indicating a valuable new method to study protein conformations. The principal VCD transitions in the NIR region are two combination bands, the amide A-II and B-II bands, of the amide A and B fundamentals with the amide II fundamental, and the second overtone of the amide II, referred to as the amide 3 X II band. VCD in the amide A and B band region consisting primarily of NH stretching motions were successfully obtained in H2O for the first time for an insulin fibril sample. Similar to the enhanced VCD signal observed in amide I and II regions, the amide A and B VCD of insulin fibril shows strong intensity enhancements, providing an additional valuable probe of protein fibril growth and development in solution. The relative sensitivities of the mid-IR, N–H stretching, and NIR regions are discussed.

We report a structural motif based on a C(3)-symmetric bowl-shaped core, on which three substituted amino acids on the periphery adopt either a folded or a spread-out conformation. This class of chiral folded structures is achieved by controlling the reactivity of the stereogenic protons on the nonplanar aromatic rings of trioxatricornan to afford predominantly C(3)-symmetric isomers. Bromination of trioxatricornan afforded a C(1)-symmetric and a C(3)-symmetric trisubstituted isomer, with the former being the major product as a statistical consequence during the reaction cascade. To obtain the C(3) symmetric isomer as the major product, C-H activation by means of ortho-lithiation with the bulky tert-butyl lithium and tetramethylethylenediamine was followed by a nucleophilic substitution that successfully reversed the statistically controlled regioselectivity. Further derivatization of the trioxatricornan with amino acids or menthol afforded diastereomers that were resolved by preparative chromatography. The absolute configurations of the diastereomers were determined by vibrational circular dichroism (VCD) in combination with density functional theory (DFT) and electronic circular dichroism (ECD). The folding structure of cysteine-derivatized trioxatricornan diastereomers was determined by two-dimensional NMR spectroscopy and molecular dynamics calculation, which revealed that one diastereomer has the amino acids folded toward the cavity of trioxatricornan and the other has a "spread-out" structure.

This work reports the use of water as a solvent to facilitate an efficient syntheses of amino acid-derivatized cyclobutenone. Kinetics studies in different solvents reveals that high dielectric constants of the solvents are the primary attribute for the high yielding and fast rate for this reaction. This class of substitution reactions in water also proceeds efficiently with a wide range of amino acids.

The paper concerns the structural and optical isomers of nonamethoxy-tribenzocyclononene (compound 1). In the first part of the paper it is shown that 1 exists in two structural isomers: a rigid crown (c-1) with C3 symmetry and a flexible saddle (s-1) with C1 symmetry. The latter, not previously known, can be prepared from the as-synthesized c-1 by quenching a hot solution (or the melt) followed by HPLC separation. The crown/saddle equilibrium, isomerization kinetics, and associated thermodynamic parameters in various organic solvents are reported. Carbon-13 MAS NMR, X-ray diffraction, and differential scanning calorimetry (DSC) of polycrystalline c-1 and s-1 racemates are also reported. The different melting points of the isomers and their rapid isomerization in the melt result in unconventional DSC thermograms involving multiple endothermic and exothermic transitions. The second part of the paper concerns the chiral properties of 1. Both the saddle and crown isomers are structurally chiral, but due to the fast pseudorotation of s-1 in solution, it cannot be separated into its enantiomers. Those of c-1 were separated by HPLC using a chiral column. Their X-ray structure and melting points differ considerably from those of the racemate. This and their fast racemization in the melt lead to complex DSC thermograms with multiple transitions. Solutions of the neat enantiomers exhibit a relatively small specific optical rotation. In the UV they show circular dichroism for the B1u and B2u transitions, with the latter exhibiting a clear couplet structure. Infrared and vibrational circular dichroism spectra of the enantiomers in solution are reported. Comparison of these spectra with quantum mechanical simulations provides unambiguous identification of the enantiomers.

(4 S ,7 R )-(−) and (4 S ,7 S )-(+)-4-isopropylidene-7-methyl-4,5,6,7-tetrahydro-2(1) H -indazoles 2a and 2b have been successfully separated by using HPLC over a Chiralpak AS column as the stationary phase, yielding up to 700 mg of each diastereomer. Their absolute configurations were determined by using vibrational circular dichroism (VCD) studies. This latter method proved not only very useful for determination of the conformers’ distribution, but also for analysis of the 1 H ,2 H tautomers.

Near-infrared (near-IR) and mid-infrared (mid-IR) vibrational circular dichroism (VCD) spectra in the region 800–10,000 cm−1 were recorded for nine enantiomeric pairs (or enantiomer and racemate pairs) of molecules with three ChiralIR Fourier transform (FT) VCD spectrometers equipped with various light sources and detectors and modified for dual polarization modulation (DPM) operation. Correlations across these sets of spectra permit conclusions regarding expected VCD intensities in the near-infrared compared to the conventional mid-IR regions. These VCD spectra also provide spectral standards for future studies in the near-infrared region. Compared with recent near-IR measurements carried out elsewhere using dispersive instrumentation, better signal-to-noise ratios were obtained for all but the frequency region above 8000 cm−1 where VCD spectra of comparable quality were obtained. These results are the first comprehensive set of VCD spectra for a set of simple chiral molecules with continuous coverage from the mid-infrared to nearly the visible region of the spectrum. This study demonstrates that with suitably equipped FT-VCD spectrometers, VCD and IR spectra can be measured with high quality across a wide spectral range.

Two-dimensional correlation spectroscopy (2D-COS) has been applied to Fourier transform (FT) vibrational circular dichroism (VCD) in multiple spectral regions for the first time. FT-IR and FT-VCD measurements of l -alanine in D 2 O have been carried out in the mid-IR (800–2000 cm −1 ) region, the hydrogen-stretching region (2000–4000 cm −1 ), and the near-IR region (4000–6000 cm −1 ) as a function of pD. A variety of different 2D-COS plots are possible from the IR and VCD spectral data in these three spectral regions, and examples are presented that show particularly interesting features of these spectra. Homo-spectral-region and hetero-spectral-region VCD–VCD and IR–IR 2D-COS plots are presented for l -alanine. Relative sensitivities to spectral changes in the methine and methyl vibrational regions are elucidated by analysis of both IR and VCD 2D-COS spectra. Near-IR band assignments are facilitated by hetero-spectral-region 2D-COS spectra that correlate the combination band region to that of the underling fundamental modes. These studies demonstrate that the method of 2D-COS IR-VCD is a useful tool that provides enhanced chemical information over traditional 1D spectra.

Near-infrared (near-IR) Fourier transform vibrational circular dichroism (FT-VCD) spectroscopy has been used to monitor the epimerization of (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-methanol (S-DDM). The near-IR-VCD spectra display clear isolated VCD bands at the range of 4700-5050 cm(-1) resulting from the OH stretch-bend combination bands of S-DDM, which were found to decrease in intensity with increasing reaction time. The near-IR-VCD spectra of 10 reference samples obtained were subjected to partial least-squares (PLS) regression analysis, and the results were used to build predictive models for enantiomeric excess (EE) determination. Multivariate regression was carried out on three different sets of spectra, corresponding to the epimerization of S-DDM in three different solvents: methylcyclohexane, carbon tetrachloride and tetrahydrofuran. The effects of solvent in DDM epimerization are discussed in terms of the relative stabilization of the reaction intermediate of the DDM epimerization reaction. The results of these near-IR-VCD studies for the determination of EE highlights the potential of VCD for in situ real-time process monitoring of the reaction kinetics of chiral molecules in solution.

Vibrational-circular-dichroism (VCD) studies of the solution conformations of three 2,2′-substituted biphenyls are reported. Biphenyls with only two substituents at the peri-position normally show rotation about their central axis of chirality at room temperature in solution. We previously found no evidence for rotation of (P,4S)-2-[4,5-dihydro-4-(1-methylethyl)oxazol-2-yl]-2′-(hydroxymethyl)-1,1′-biphenyl (1) in CDCl3 about its 1,1′- axis, due to stabilization by intramolecular H-bonding and the presence of the i-Pr substituent, but two conformers were found in solution that result from rotation of the heterocycle in 1 between OH⋅⋅⋅N (the form present in the solid state) and the OH⋅⋅⋅O H-bonded forms, with no rotation of the i-Pr group or (P) (M) twist [1]. For (P,S)-2, where the i-Pr substituent of 1 has been replaced by a Ph group, rotation of the heterocycle takes place in CDCl3 solution. For (P,S)-3 and (M,S)-4, where Me substitution at the two 6,6′-positions of (P,S)-1 prevents rotation about the central axis of chirality, rotation of the heterocycle is observed for the (P)-configuration ((P,S)-3), but not for the (M)-configuration ((M,S)-4). Only one rotamer involving the i-Pr group, which was found in the solid state of (P,S)-3, was also observed in solution, but (M,S)-4, obtained as an oil, was found to be a mixture of three rotamers of the i-Pr group.

The absolute configuration assignments of three antifungal agents, (+)-(2R,4S)-ketoconazole, (+)-(2R,4S)-itraconazole (with (S)-configuration at the sec-butyl group) and (+)-(S)-miconazole nitrate have been confirmed by using vibrational circular dichroism (VCD). For these three antifungal drugs, this study also provides evidence for the most abundant conformations of miconazole and for the relative conformations of the azole, dichlorophenyl, and methoxyphenyl groups in ketoconazole and itraconazole, in chloroform solution.

The first use of Fourier transform vibrational circular dichroism (FT-VCD) to follow changes in the percent enantiomeric excess (% EE) of chiral molecules in time using a flow cell sampling apparatus is reported. FT-VCD, as opposed to dispersive scanning VCD, eliminates the need to scan the VCD spectrum in time to monitor the % EE at more than one spectral location. The first use of partial least-squares chemometric analysis to determine % EE values from kinetic sets of VCD spectral data is also reported. These two advances have been used to monitor simultaneously changes in the fractional composition and the % EE of a mixture of two different chiral molecules. This simulates the progress of the chemical reaction from a chiral reactant to a chiral product where the % EE of both molecules can change with time. For the molecules studied, alpha-pinene, camphor, and borneol, the accuracy of following % EE changes for one species alone is approximately 1%, while for simultaneously following % EE changes in two species is approximately 2% for 10-20-min sampling periods at 4 cm(-)(1) spectral resolution. This accuracy can be increased for the same collection times or maintained for shorter periods of collection by lowering the spectral resolution. These findings demonstrate the potential for VCD to be used for real-time monitoring of the composition and % EE of chemical reactions involving the synthesis chiral molecules.

The configurations of three enantiopure tetrasubstituted α-fluoro cyclohexanones (–)-5Ia, (–)-5IIa and (–)-6a were determined by VCD and proved to be (–)-(2S,5R)-5Ia, (–)-(2R,5R)-5IIa, and (–)-(2R,5R)-6a. The VCD study also identified the conformers populated in CDCl3 solution, including higher-energy gas-phase conformers with equatorial fluorine for 5Ia and 5IIa that are stabilized in CDCl3 solution. Used as catalysts for epoxidation of trans olefins (β-methylstyrene, stilbene, methyl p-methoxy cinnamate) by oxone, it was found that (–)-5Ia is the most efficient for all trans olefins (providing, respectively, 62%, 90% and 66% ee) but that all three ketones provide high ee% with stilbene (78–90% ee). Moreover, the configurations predicted from the stereo outcome of the epoxidation reaction are identical to those determined by VCD. Chirality 16:467–474, 2004. © 2004 Wiley-Liss, Inc.

Biphenyls with only two substituents at the ‘peri'-position normally show rotation about their chiral axis at room temperature. Using vibrational circular dichroism (VCD), we found no evidence for rotation of (P)-2′-[(4S)-4,5-dihydro-4-(1-methylethyl)oxazol-2-yl][1,1′-biphenyl]-2-methanol ((P,S)-1) in CDCl3 about its chiral axis due to stabilization by intramolecular H-bonding. All rotamers of 1 were calculated at the DFT level, and, from these optimized structures, the VCD spectra were calculated and compared to the measured VCD spectra. The best agreement between calculated and measured spectra is obtained when two rotamers are present in solution. These rotamers differ primarily in their intramolecular H-bonding interactions, having either OH⋅⋅⋅N (the form present in the solid state) or OH⋅⋅⋅O H-bonds, i.e., a rotation of the heterocycle in 1 takes place in solution.

McN-5652-X, (+)-1, is a potent, selective inhibitor of serotonin reuptake in mammalian brain. When radiolabeled with 11C, it has served as a positron-emission tomography (PET) radiotracer for in vivo imaging of central serotonin transporters. We have determined the solid-state structures of (+)-1·HClO4 and (+)-1·(+)-(2R,3R)-tartrate by single-crystal X-ray diffraction, thereby confirming the trans relative configuration (Chemical Abstracts Service rules of nomenclature) and the 6S,10bR absolute configuration for (+)-1. Results from a vibrational circular dichroism (VCD) study on (+)-1 in CDCl3 are consistent with the 6S,10bR absolute configuration.

Vibrational circular dichroism (VCD) measurements and density functional theory (DFT) calculations were used to obtain the first definitive assignment of the absolute configuration for the polyphenolic binaphpthyl dialdehyde gossypol and a determination of the solution conformation in CDCl3. VCD spectra recorded for the two resolved enantiomers are near mirror images and excellent agreement between the observed IR and VCD spectra and intensity calculations carried out at the DFT (B3LYP/6-31G*) level establish the absolute configurations of (+)-gossypol as P and (−)-gossypol as M, with two conformations in CDCl3 solution that differ in isopropyl group orientation. Chirality 15:196–200, 2003. © 2003 Wiley-Liss, Inc.

Density functional theory calculations of the vibrational circular dichroism (VCD) spectra of a transition metal complex, (+)-tris(ethylenediaminato)cobalt(III) as a free ion and with associated chloride ions, are reported. By comparison with experimental data obtained in our laboratory in 1986 (Young et al. J. Am. Chem. Soc. 1986, 108, 7255) and new measurements, this study identifies, for the first time, the geometry and absolute configuration of the association complex as Λ-δδδ-Co(en)3Cl2+, in which two chloride ions each associate with three NH bonds along the C3-axis of a D3-symmetry complex. The DFT calculations, carried out with both the LanL2DZ and 6-31G(d)[C, H, N]/Stuttgart ECP [Co] basis sets, predict the energy order of ethylenediamine ring conformations as λλλ < λλδ < λδδ < δδδ for the free (gas phase) Λ-Co(en)33+ ion, an order opposite to that deduced from solution studies. The VCD studies identify the δ-conformation as the most prevalent in solution for halide and sulfate counterions, sugge...

We present the results of a study using vibrational circular dichroism (VCD) for (+)-1, which furnished an unambiguous determination of its absolute configuration as S. The most abundant conformation of (+)-1 in CDCl3 solution was also established. Chirality 14:215–219, 2002. © 2002 Wiley-Liss, Inc.

A new oxathiane, derived from 5-hydroxy-1-tetralone has been synthesized in eight steps, fully characterized as cis -fused rings by 1D and 2D NMR and resolved by preparative chiral chromatography (CHIRALCEL OD-R). The second eluting (+, MeOH)-isomer was assigned ( S , S )-configuration by VCD-ab initio simulation.

1,4-Oxazin-2-one 3 is obtained from 2-pinanone in 4 steps and 78% overall yield. Enantiopure (e.e. >99%) (R)-(+)-3 and (S)-(−)-3 were obtained through chiral supercritical fluid chromatography (using a semi preparative Chiralpak AS column) with almost quantitative recovery of material. The structure and the boat-conformation of the lactone ring have been determined by NMR and the absolute configuration determined by VCD.

Vibrational transition current density (TCD) plots and charge-weighted nuclear displacement vectors for selected vibrational modes of A and B symmetry in (2 S ,3 S )-oxirane-d 2 are used to visualize the electronic and nuclear contributions to infrared absorption and vibrational circular dichroism intensities. Vibrational TCD provides a vector field map of the integrand of the electronic contribution to the velocity-form electric dipole transition moment. Linear nuclear and electronic charge flow in planes parallel to the electric dipole transition moment vector provides visualization of contributions to IR intensity, while angular and circular charge flow perpendicular to this vector provide visualization of the magnetic dipole transition moment content of vibrational circular dichroism intensity. Four vibrational modes with several types of nuclear motion and the effect of basis set size on vibrational TCD are examined.

Vibrational transition current density (TCD) plots for the methine stretch of (S)-methyl-d3 lactate-Cd3 in four conformations are presented. A vibrational TCD map is a vector-field plot over a grid of points of the integrand of the electronic contribution to the velocity-form electric dipole transition moment. TCD plots allow visualization of the flow of electron density produced by nuclear motion, which can be used to identify angular and circular charge flow leading to the electronic magnetic dipole transition moment contribution to vibrational circular dichroism (VCD). For the methine stretch in (S)-methyl-d3 lactate-Cd3, nuclear motion is largely confined to the two atoms of the methine bond, but the electron current density is distributed throughout the molecule. The methine-stretching VCD intensity calculated for the (S)-methyl-d3 lactate-Cd3 conformers is interpreted in terms of the relative contributions from the nuclear electric- and magnetic-dipole transition moments, and from linear electron ch...

The CH- and OH-stretching vibrational circular dichroism (VCD) spectra of methyl lactate and related molecules in CCl4 solution have been investigated to identify solution conformations and establish a correlation between OH- and methine-stretching VCD intensity and molecular structure. Deuterium substitution was used when possible to remove overlapping absorption features in the CH-stretching region. Anisotropy ratios between +2.1 × 10-4 and +2.8 × 10-4 were measured for the methine-stretching VCD of the molecules with both α-oxy and α-CO substituents: (S)-methyl-d3 lactate, (S)-methyl-d3 2-(methoxy-d3)-propionate, di(methyl-d3) d-tartrate, (S)-methyl-d3 mandelate, (S)-methyl-d3 O-(acetyl-d3)-mandelate, and (S)-benzoin. The methine-stretching VCD intensity serves as a marker for both absolute configuration and solution conformation in these molecules, as previously demonstrated for amino acids and peptides. In (S)-methyl 2-chloropropionate, (R)-methyl 3-hydroxy-2-methylpropionate, and (S)-methyl 3-hydro...

Vibrational circular dichoism spectra recorded for (2S,3S)-1-13C-1,2,3-d3-cyclopropane and for mixtures of it and the three related stereoisomers prepared through gas-phase thermal stereomutation reactions at 407°C lead to the rate constant for racemization: kα = (4k1 + 4k12) = (3.12 ± 0.04) x 10-5 s-1. This and the rate constant measured for geometrical equilibration between the two chiral and the two achiral stereoisomers of 1-13C-1,2,3-d3-cyclopropane, ki = (8k1 + 4k12) = (4.63 ± 0.20) x 10-5 s-1, give two equations in two unknowns, and allow one to solve for one-center (k1) and two-center (k12) epimerization rate constants for cyclopropane stereomutations. They are nearly equal, a clear indication of closely competitive reaction pathways.Key words: cyclopropane stereomutations, thermal epimerizations, chirality through deuterium and carbon-13 labeling, vibrational circular dichroism.

We provide the first experimental evidence for resonance Raman optical activity (RROA). In non-aqueous solution (+)-naproxen ((S)-6-methoxy-α-naphthalenacetic acid) and its deuterated methyl ester exhibit monosignate negative RROA, whereas the RROA spectrum of (−)-naproxen sodium is monosignate positive (aqueous solution above pH 10), for 514 nm excitation. In all cases, the RROA bands exhibit the same relative intensities as those in the parent resonance Raman (RR) spectrum, and the ratio of RROA to RR is comparable in magnitude, but opposite in sign, to the electronic circular dichroism (CD) anisotropy ratio of the lowest energy electronic state near 330 nm. These findings are in accord with the theory of RROA in the limit of strong resonance with a single electronic state.

We present the first examples of ab initio calculations of electron transition current density (TCD) for vibrational transitions in molecules. The non-Born−Oppenheimer (non-BO) theoretical expressi...

We present the results of a new Fourier transform infrared vibrational circular dichroism (FT-IR-VCD) spectrometer optimized for performance in the near-infrared region above 2000 cm−1. The instrument is capable of operating in either the conventional rapidscan mode or the step-scan mode and is designed around the Bruker IFS 55 FT-IR spectrometer. We find that in the region of hydrogen stretching, the instrument performs as well as or better than (depending on the spectral coverage and resolution desired) a corresponding dispersive grating VCD spectrometer, with noise levels at approximately 10−6 Δ A units for a two-hour collection at 8-cm−1 resolution. The performance is approximately a factor-of-2 better in signal-to-noise ratio in optimized step-scan operation in comparison to the corresponding results in rapid-scan operation. The reasons are traced to advantages in electronic filtering and undersampling efficiency in step-scan mode. It is expected that the advantages of step-scan will increase with increasing optical transition frequency, such as the region of overtone and combination bands between 4000 and 8000 cm−1.

We report mid-infrared Fourier transform vibrational circular dichroism (FT-VCD) spectra obtained by using three different measurement schemes: the traditional sequential rapid-scan method, a new simultaneous rapid-scan method, and the step-scan method. We also provide a description of the optical setup used to obtain the VCD spectra. Using this optical layout, we are able to measure FT-VCD spectra for single enantiomers of the chiral sample with low levels of interfering artifacts and for collection times as fast as one minute. For approximately 20 min of spectral collection, the three FT-VCD measurements approaches tested here yield nearly the same signal quality. The approach with the highest quality, by a small margin, was the simultaneous rapid-scan method. Next was the sequential rapid-scan approach, followed closely by the step-scan method. VCD spectra and noise curves obtained with these different measurement techniques are presented and compared, and their relative advantages and disadvantages are discussed.

Infrared vibrational circular dichroism (VCD) and vibrational Raman optical activity (ROA) have been measured and compared quantitatively over the frequency range from 835 to 1345 cm−1 for trans-pinane, cis-pinane, α-pinene, and β-pinene. For these molecules in this region of spectral overlap between VCD and ROA, the average ratio of VCD or ROA to its parent vibrational intensity favors ROA by a factor of two to three. Several vibrational modes in each molecule yield both large VCD and large ROA, while several other modes show little propensity toward significant VCD or ROA intensity. Beyond this general property of a few strongly chiral and strongly achiral vibrational modes, little additional correlation between VCD and ROA intensity is found. This quantitative compilation of VCD, infrared, ROA, and Raman intensities provides an experimental basis for computational intensity studies of VCD, ROA, and their theoretical comparison.

The backscattering in-phase dual circular polarization (DCPI) Raman and Raman optical activity (ROA) for a series of terpene molecules is reported. The selected molecules were studied in three groups of closely related structures and correlations between ROA features and structural elements among molecules within these groups are discussed. One aim of this study was to uncover additional details regarding the sensitivity of ROA to stereostructural features in molecules and to elucidate further the degree of local character of this new stereochemical probe. Another was to compare the backscattering DCPI ROA intensities reported here with those obtained using depolarized right-angle incident circularly polarized (ICP) ROA for some of the same molecules more than a decade ago.

Vibrational optical activity (VOA) is a relatively newspectroscopic technique, which has two principal manifestations, ir vibrational CD and vibrational Raman optical activity. Progress in the study of oligopeptides using both of these forms of VOA is reviewed from the perspective of theoretical and instrumental techniques, spectral results, and structural interpretations. © 1994 John Wiley & Sons, Inc.

We report the measurement of backscattering in-phase dual circular polarization (DCPI) Raman optical activity (ROA) for the simple alanyl peptides L-alanyl-L-alanine ([L-Ala]2), L-alanylglycine (L-Ala-Gly), glycyl-L-alanine (Gly-L-Ala), and L-alanyl-L-alanyl-L-alanine ([L-Ala]3) in aqueous solutions. Empirical correlations between ROA features and the amino acid composition of the peptides are described. It is shown that the sum of the DCPIROA spectra for L-Ala-Gly and Gly-L-Ala is nearly the same as the corresponding ROA spectrum for (L-Ala)2. Additionally, the DCPIROA spectrum for (L-Ala)2 is very close to that of (L-Ala)3, as has been observed previously using backscattering unpolarized incident circular polarization (ICPu) ROA. The ROA contributions of the different L-Ala groups, which occur separately in the two glycyl peptides of alanine and jointly in (L-Ala)2, are described in terms of the extent of vibrational coupling between peptide subunits. From these results, it appears that ROA has a more local sensitivity to vibrational coupling than is found in VCD or electronic circular dichroism. © 1995 John Wiley & Sons, Inc.

Recent progress in the use of Raman optical activity (ROA) to study the stereochemical properties of biological molecules is described. The basic experimental, theoretical, instrumental and calculational methodology of backscattering ROA is presented together with examples of applications to amino acids and peptides in aqueous solution.

We report the first measurements of Raman optical activity (ROA) in ephedrine molecules. In-phase dual circular polarization (DCP I ) ROA spectra have been recorded for (1S,2R)-ephedrine, (1S,2R)-norephedrine, (1S,2S)-pseudoephedrine and (1S,2S)-norpseudoephedrine as hydrochloride salts in H 2 O solution. The spectra are interpreted in relation to the small changes in molecular structure among these four molecular species.

We report the first measurements of Raman optical activity (ROA) in ephedrine molecules. In-phase dual circular polarization (DCP I ) ROA spectra have been recorded for (1S,2R)-ephedrine, (1S,2R)-norephedrine, (1S,2S)-pseudoephedrine and (1S,2S)-norpseudoephedrine as hydrochloride salts in H 2 O solution. The spectra are interpreted in relation to the small changes in molecular structure among these four molecular species.

Vibrational optical activity (VOA) is a relatively newspectroscopic technique, which has two principal manifestations, ir vibrational CD and vibrational Raman optical activity. Progress in the study of oligopeptides using both of these forms of VOA is reviewed from the perspective of theoretical and instrumental techniques, spectral results, and structural interpretations. © 1994 John Wiley & Sons, Inc.

A new oxathiane, derived from 5-hydroxy-1-tetralone has been synthesized in eight steps, fully characterized as cis -fused rings by 1D and 2D NMR and resolved by preparative chiral chromatography (CHIRALCEL OD-R). The second eluting (+, MeOH)-isomer was assigned ( S , S )-configuration by VCD-ab initio simulation.

Vibrational circular dichroism (VCD) spectra of the antisymmetric stretch of azide ligated to the heme of a series of evolutionarily diverse and site-directed mutant hemoglobins and myoglobins are anomalously intense and demonstrate an intriguing sensitivity to subtle protein-ligand interactions. The antisymmetric stretch of the azide ligand covalently bound to the low-spin iron shows an anisotropy ratio of -9.5 X 10"4 for sperm whale and horse myoglobin which decreases to -8.0 X 10"4 for human and carp hemoglobin and Chironimus thummi thummi III monomeric hemoglobin. The VCD spectra of these heme-azide complexes depend upon the interactions of the azide ligand with distal heme pocket residues such as the E7 distal histidine and El 1 valine. The site-directed mutants of sperm whale (distal histidine substituted GIy E7) and human (distal valine substituted Asn El 1) myoglobin have vanishingly small anisotropy ratios (

Experimental and calculated (B3LYP/6-31G(d)) vibrational circular dichroism (VCD) and IR spectra are compared, illustrating that the structure and absolute configuration of ginkgolide B (GB) may be characterized directly in solution. A conformational search for GB using MacroModel and subsequent DFT optimizations (B3LYP/6-31G(d)) provides a structure for the lowest energy conformer which agrees well with the structure determined by X-ray diffraction. In addition, a conformer at an energy of 7 kJ mol−1 (B3LYP/6-311+G(2d,2p)) with respect to the lowest energy conformer is predicted, displaying different intramolecular hydrogen bonding. Differences between measured and calculated IR and VCD spectra for GB at certain wavenumbers are rationalized in terms of interactions with solvent, intermolecular GB-GB interactions, and the potential presence of more than one conformer. This is the first detailed investigation of the spectroscopic fingerprint region (850−1300 cm−1) of the natural product GB employing infrared absorption and VCD spectroscopy. Chirality, 2010. © 2009 Wiley-Liss, Inc.

International audience; Enantioenriched square-pyramidal oxo- and sulfidorhenium(V) complexes have been prepared and their stereochemistry studied by vibrational circular dichroism (VCD) spectroscopy.

Vibrational circular dichroism (VCD) spectra of an exceptionally simple chiral three-membered ring molecule, (S,S)-[2,3-2H2]oxirane, have been obtained for samples in the gas phase and in C2Cl4 and CS2 solution. The VCD band contours for the gas phase samples of this molecule with C2 symmetry follow those of the absorption spectra, with the modes of A symmetry species giving rise to bands with two sharp Q-branch maxima on either side of a distinct minimum, and the modes of B symmetry species giving rise to bands with a strong central Q-branch. The signs and relative intensities of the VCD bands can be understood in terms of chiral perturbation by the deuterium substitution of the vibrational modes of the parent oxirane molecule, which mixes modes of A1 and A2 symmetry, and modes of B1 and B2 symmetry, thus introducing angular charge oscillation about the direction of linear charge oscillation. Key words: vibrational circular dichroism, oxirane, chiral perturbation.

This work reports the use of water as a solvent to facilitate an efficient syntheses of amino acid-derivatized cyclobutenone. Kinetics studies in different solvents reveals that high dielectric constants of the solvents are the primary attribute for the high yielding and fast rate for this reaction. This class of substitution reactions in water also proceeds efficiently with a wide range of amino acids.

The use of isotopic difference spectra in vibrational optical activity is demonstrated as a supplemental aide in determining the absolute configuration of chiral molecules. It is shown that IR and VCD difference spectra associated with isotopic substitution observed in experimental spectra can be accurately reproduced by density functional theory calculations when the IR and VCD spectra of the original isotopomer are calculated to reasonable accuracy. Results for isotopically substituted nonamethoxy cyclotriveratrylene are presented to illustrate the degree of agreement between measured and calculated IR and VCD difference spectra for several isotopomers of this molecule. These findings highlight the utility of isotoptic substitution as an aide to verifying the determination of absolute configuration using vibrational optical activity. Chirality, 2008. © 2008 Wiley-Liss, Inc.