For several years, applications of vibrational circular dichroism (VCD) were limited to studies of the chirality and conformation of small chiral organic molecules. Initial studies were more focused on developing a theoretical model to explain the sign and intensity patters observed for those spectra obtained. Other studies were oriented at developing spectral patterns for structurally related molecules so that correlations could be used for structural analysis in analogy to early electronic CD applications. Due to technological developments, near IR, CH, NH and OH stretching motions were the first studies transitions, with midIR (C=O stretch and CH deformations initially) developments coming later with improved modulators and detectors.

The simplest models were extensions of classical concepts of molecular vibrations and dipole moments, variously based on coupling oscillators or motions of charges. The basic problem with these methods was neglect of the non-Born-Oppenheimer aspect of VCD, wherein the electronic contribution to VCD for non-degenerate ground states disappears within that approximation. Two approaches to this problem were developed, and extended to the ab initio quantum mechanical level, one involving a sum over excited states and the other a perturbation treatment on the ground state. This latter, called magnetic field perturbation (MFP) theory, developed by Philip Stephens, has come to dominate current use of theory to stereochemical studies of small molecules. It is now implemented at the ab initio quantum mechanical level in the Gaussian 98 package of programs, and is used by a variety of labs, particularly at the density functional theory (DFT) level. Currently a major effort has developed based on these methods for determination of absolute configuration by combining experimental and computed VCD for relatively complex organic molecules, including drug candidates in the Stephens (USC), Nafie and Freedman (Syracuse), and Polavarapu (Vanderbilt) labs. Our group, in particular in collaboration with Petr Bour,(Academy of Science, Prague) has extended these to applications applicable to large molecules, focused in our group on peptides.

Many of our earlier studies involved chiral systems of C₂ or higher symmetry which were appropriate for coupled oscillator applications, should they work. These involved tartaric acid derivatives (with Eric Su), trans substituted cyclopropanes (with Vic Heintz and Sritana Yasui), and allenes (with Usha Narayanan). Several of our small molecule studies focused on the measurability and interpretation of chirality due to isotopic substitution. In collaboration with Jim Chickos at the University of Missouri St. Louis, we studies a series of four and five member rings that were doubly substituted with deuterium (with A. Annamali, Petr Malon, Cheok Tam and others). Some of these projects have continued, but they are now a minor part of our work.

To learn more about our earlier work on small molecules check out our Publications in this area, listed under Small Molecules.

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