Chapter 15 - Vibrational optical activity in chiral analysis

Abstract

This chapter discusses vibrational optical activity (VOA) in chiral analysis. VOA spectra are rich in structural and stereo-specific information, coming from vibrational chromophores and extending over the entire molecular frame. The theory of vibrational circular dichroism (VCD) and raman circular dichroism (ROA) has advanced sufficiently in recent years to enable the accurate “ab initio” calculation of observed spectra for small- to medium-sized molecules. This opens the way for the use of VOA to solve the stereochemical problems involving absolute configuration and solution conformation in a direct way without the need to modify the molecule, to calculate excited electronic state properties or to crystallize the sample. The development of flow-cell techniques makes the monitoring of the reaction kinetics of chiral molecules in solution possible. As both FT-VCD and charged coupled devices-ROA(CCD-ROA) are multiplex techniques, it is possible to follow the evolution of the mole fraction and enantiomeric excess (EE) of multiple species as the reaction proceeds. No other form of optical activity currently possesses this capability. Extension of VCD into the near-infrared (IR) region further enhances the potential for VCD to be used routinely to monitor processes involving the synthesis, manufacture, and processing of pharmaceutical products containing chiral active pharmaceutical ingredients (APIs). The commercialization of hardware and software for the measurement and calculation of VCD and ROA opens the way for these two forms of VOA to be broadly available for all those interested in solving problems involving molecular chirality and chiral analysis.