Planta Med 2012; 78 - CL45
DOI: 10.1055/s-0032-1320280

Determination of absolute configuration of chiral molecules using vibrational optical activity

Y He 1, B Wang 1, RK Dukor 1, LA Nafie 2
  • 1BioTools Inc., 17546 Beeline Hwy, Jupiter, FL 33458
  • 2Department of Chemistry, 1–014 CST, Syracuse University, Syracuse, NY 13244

Determination of absolute configuration (AC) of chiral molecules is an important step in any field related to chirality, especially in the pharmaceutical industry. Vibrational optical activity (VOA) has become a powerful tool for the determination of absolute configuration of chiral molecules in solution state after 30 years of evolution. VOA offers a novel alternative to X-ray crystallography, permitting AC determinations on neat liquid, oil, and solution samples. By comparing the sign and intensity of the experimental VOA spectrum with the ab initio DFT calculated VOA of a chosen configuration, one can unambiguously assign the absolute configuration of a chiral molecule. Comparing measured VOA spectra with calculated VOA spectra of all the conformers can also provide solution-state conformational populations. VOA consists of vibrational circular dichroism (VCD) and Raman optical activity (ROA). VCD is used routinely by researchers of various backgrounds including basic study of chirality, asymmetric synthesis or catalysis, drug screening, pharmacology and natural products. Although the application of ROA in AC determination lags behind that of the VCD, with the recent implementation of ROA calculation method into the commercial calculation software, ROA will in the future complement VCD for AC determination. In this presentation basic principles of the application of VCD to the determination of absolute configuration in chiral molecules are described. The steps required for VCD spectral measurement and calculation are outlined followed by recent applications of AC in small organic, pharmaceutical and natural product molecules.