Molecular structure, vibrational spectra and first-order molecular hyperpolarizabilities of potential anti-cancer drug, combretastatin-A1

Combretastatin-A1, a potential anti-cancer drug in advanced preclinical development possessing the ‘selective’ anti-cancer activity specifically targeting the blood vessels supplying malignant tumors while other drugs tend to attack both healthy and diseased cells, is subjected to vibrational spectral investigation using NIR-FT Raman, FT-IR and SERS. The geometry and vibrational spectrum of combretastatin-A1 have been computed using B3LYP/6-311G(d,p) basis set. The vibrational analysis shows that the molecule is having similar geometric behavior as that of cis-stilbene, and has undergone steric repulsion resulting in phenyl ring twisting with respect to the ethylenic bridge. Vibrational analysis is used to investigate the lowering of asymmetric and symmetric stretching modes and enhancement of infrared band intensities of CH stretching modes of Me2 in CA1 may be attributed to the electronic effects caused by back donation from the oxygen atom. The calculated first hyperpolarizability of CA1 is 2.165 × 10−30 esu, predicted for the first time in this new class of compounds which is 9.6 times that of urea. Analysis of phenyl ring modes shows that CC stretching mode 8 and aromatic CH in-plane bending modes are found equally active as strong bands in both IR and Raman which can be interpreted as the evidence of intramolecular charge transfer between OH and OCH3 groups via conjugated ring path which is responsible for hyperpolarizability enhancement leading to NLO activity. The SERS spectral investigations have been performed to predict the adsorption geometry of the compound on the silver surface and the phenyl ring Ph2 is found to possess a flat orientation on the metal surface.