Study of carvedilol by combined Raman spectroscopy and ab initio MO calculations

The novel cardioprotective drug carvedilol was studied by both Raman spectroscopy and ab initio molecular orbital methods (using the density functional theory approach). The spectra, acquired both for the solid samples and DMSO solutions as a function of pH, were assigned in view of the calculated wavenumbers and intensities, and also based on the experimental data obtained for individual compounds which comprise the molecule, namely carbazole and 1,2-dimethoxybenzene. The pH dependence of the Raman pattern of carvedilol was studied, and the pK(a) value of its secondary amine group was determined (pK(a) = 8.25) through pH titration experiments. This kind of information is of great significance for the understanding of the biochemical role of carvedilol, which is strongly determined by the acid-base behaviour of the molecule. Copyright (C) 2002 John Wiley Sons, Ltd.