Vibrational circular dichroism in ephedra molecules. Experimental measurement and ab initio calculation

Abstract

Vibrational circular dichroism (VCD) spectra in the OH- and NH-stretching regions have been measured for six pharmaceutical molecules in the ephedra class, (1S,2R)-norephedrine, (1), (1S,2S)-norpseudoephedrine (2), (1S,2R)-ephedrine (3), (1S,2S)-pseudoephedrine (4), (1S,2R)-N-methylephedrine (5) and (1S,2S)-N-methylpseudoephedrine (6), all in dilute C₂Cl₄ solution. Ab initio calculations of geometries and vibrational frequencies for a number of conformers of 1 to 6 have been carried out. The recently developed locally distributed origin gauge model for VCD was used to calculate VCD spectra of the conformers for each drug. This ground-state ab initio model, which does not require sum-over-states, magnetic field perturbation or localized molecular orbitals, has been found to give good agreement with experiment in this frequency region. Composite spectra obtained from weighted averages of the calculated conformer spectra agree within a factor of two with observed IR and VCD intensities for five of the ephedra drugs. For (1S,2S)-pseudoephedrine, the discrepancy between experiment and calculation has been interpreted in terms of a coupled-oscillator effect absent in the other molecules.