Density functional study on the structural conformations and intramolecular charge transfer from the vibrational spectra of the anticancer drug combretastatin-A2

• Published in: Journal of Raman spectroscopy Vol. 40; no. 4; pp. 419 - 428
• Main Authors: Padmaja, L., Ravikumar, C., Sajan, D., Hubert Joe, I., Jayakumar, V. S., Pettit, G. R., Faurskov Nielsen, O.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.04.2009
• Subjects: combretastatin-A2; Combretum; density functional theory; intramolecular charge transfer; NIR FT-Raman spectra; PES
• ISSN: 0377-0486; 1097-4555
• DOI: 10.1002/jrs.2145

Combretastatin‐A2 (CA2), a potential anticancer drug in advanced preclinical development, is extracted from the medicinal plant Combretum caffrum. The NIR‐FT Raman and FT‐IR spectral studies of the molecule were carried out and ab initio calculations performed at the B3LYP/6‐31G(d) level to derive the equilibrium geometry as well as the vibrational wavenumbers and intensities of the spectral bands. The vibrational analysis showed that the molecule has a similar geometry as that of cis‐stilbene, and has undergone steric repulsion resulting in twisting of the phenyl ring with respect to the ethylenic plane. Vibrational analysis was used to investigate the lowering of the stretching modes, and enhancement of infrared band intensities of the C–H stretching modes of Me2 may be attributed to the electronic effects caused by back‐donation and induction from the oxygen atom. Analysis of phenyl ring modes shows that the CA2 stretching mode 8 and the aromatic C–H in‐plane bending mode are equally active as strong bands in both IR and Raman spectra, which can be interpreted as the evidence of intramolecular charge transfer (ICT) between the OH and OCH3groups via conjugated ring path and is responsible for bioactivity of the molecule. Copyright © 2008 John Wiley & Sons, Ltd. FT‐Raman and FT‐IR Spectra are used to investigate the potential anticancer drug Combretastatin‐A2. Stability of the molecule arising from hyperconjugative interactions leading to its bioactivity and intramolecular charge transfer (ICT) are analyzed using natural bond orbital (NBO) analysis. The potential energy surface scan results reveal that the molecule exists in the cis configuration, which is important for its bioactivity.