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-CO substituents:  (S)-methyl-d 3 lactate, (S)-methyl-d 3 2-(methoxy-d 3)-propionate, di(methyl-d 3) d-tartrate, (S)-methyl-d 3 mandelate, (S)-methyl-d 3 O-(acetyl-d 3)-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-hydroxybutyrate, the net CH-stretching VCD intensity is small relative to that in the other molecules studied. Ab initio calculations of geometries, vibrational frequencies, and unpolarized infrared absorption (IR) and VCD intensities were carried out to identify the most abundant solution conformers from the VCD spectra and to correlate OH- and methine-stretching VCD intensity with molecular conformations. Factors leading to large methine-stretching VCD anisotropy ratios are assessed.

Vibrational circular dichroism (VCD) spectroscopy was used to investigate the solution conformations of cyclosporins A, C, D, G, and H in CDCl(3), in the amide I and NH/OH-stretching regions, and their corresponding magnesium complexes in CD(3)CN, in the amide I region. VCD spectra are sensitive to the chiral arrangement of Cdbond;O 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 CDCl(3) 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.