Step-Scan Fourier Transform Vibrational Circular Dichroism Spectra of Pharmaceutical Molecules

Abstract

Vibrational circular dichroism (VCD) spectra in the region above 2000 cm−1 provides valuable information on absolute configuration or conformation of chiral molecules.1 Conventionally, VCD spectra in this region have been measured with dispersive instruments, since the high Fourier frequencies resulting from the rapid motion of a moving mirror in a conventional Fourier transform spectrometer may deteriorate the VCD signal. Step-scan FT-VCD, however, has no such difficulty (there is no Fourier frequency) and has advantages over dispersive VCD in terms of noise level, resolution, spectral coverage and repeatability. 2, 3 We have recently investigated a number of molecules of pharmaceutical interest using step-scan FT-VCD above 2000 cm−1. These molecules include S-(-)-propranolol, (S)-4-isobutyl-α- methylphenylacetic acid (ibuprofen) and (S)-6-methoxy-a-methyl-2-naphthalene- acetic acid (naproxen). The FTIR and VCD spectra have been measured and interpreted by comparison with ab initio calculations of geometry, vibrational frequency and intensity for a group of low-energy conformers of each compound. For the VCD spectra, intensities have been calculated with the locally distributed origin gauge (LDO) model and the vibronic coupling VCD theory.4