Structural characterization of chiral molecules using vibrational circular dichroism spectroscopy

Structural Characterization of Chiral Molecules Using Vibra- tional Circular Dichroism Spectroscopy Chiral molecules, i.e., molecules with handedness, are essential to biology, because most amino acids and sugars are chiral. A pair of molecules which are mirror images of each other have identical physical properties, but they differ in their interaction with other chiral molecules. This is the cornerstone of biological specificity. Chiral molecules also interact differently with different polarization states of electromagnetic radiation, because the absorption coefficient depends on the state of polarization. This is called dichroism and gives rise to several spectroscopic techniques targeting chiral molecules. This project is about application of one such technique, circular dichroism (CD) spectroscopy, which measures the difference in absorption of leftand right circularly polarized light—hence the name circular dichroism. This study has focused on the infrared (IR) range because there are many vibrational tran- sitions here compared to the number of electronic transitions in the ultraviolet or visible range—hence the term vibrational circular dichroism (VCD). VCD was used to identify the absolute configuration (chirality) and pre- dominant conformers of chiralmolecules by direct comparison of experimental and calculated spectra. Theoretical structures of the sample molecules were constructed and optimized using molecular mechanical force fields followed by the quantum mechanical method density functional theory (DFT). Calcula- tions of IR absorption and VCD spectra were then carried out using the same DFT methods. Here, VCD has the advantage over CD that time-independent DFT calculations are sufficient. During the course of this project, the above methodology has been ap- plied to a range of molecules. Some of them (nyasol, curcuphenol dimers and ginkgolide) are purely organic compounds of pharmaceutical interest. Oth- ers are transition metal complexes relevant for the search for parity-violation effects in vibrational spectroscopy (rhenium complexes), for asymmetric catal- ysis (Schiff-base complexes), or as model systems for metal centres in biology (Schiff-bases and heme). Proteins (primarily myoglobin) have been studied