NIR-FT Raman and FT-IR spectral studies and ab initio calculations of the anti-cancer drug combretastatin-A4

Combretastatin-A4, a potential anti-cancer drug in advanced preclinical development, is extracted from the medicinal plant Combretum caffrum. NIR-FT Raman and FT-IR spectral studies were carried out and ab initio calculations were performed at the HF/6-31G(d) level to derive equilibrium geometry and vibrational wavenumbers and intensities. The vibrational analysis shows that the molecule exhibits similar geometric behavior to cis-stilbene, and has undergone steric repulsion resulting in phenyl ring twisting with respect to the ethylenic plane. The spectral behavior of the methoxy groups is influenced by the oxygen lone pair-aryl p_z orbital conjugation and back-donation. Chelation of the OH group with the oxygen lone pair of the methoxy group produces separate bands for free OH and associated OH vibrations.