Substituent and Solvent Effects on the Structural Bioactivity and Anticancer Characteristic of Catechin as a Bioactive Constituent of Green Tea M. MONAJJEMI, 1,2 M. KHOSRAVI, 3 B. HONARPARVAR, 3 F. MOLLAAMIN 1 1 Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran 2 Department of Chemistry and Biochemistry, Institute for Theoretical Chemistry, The University of Texas at Austin, Austin, Texas 3 Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran Received 11 December 2009; accepted 22 January 2010 Published online 18 May 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/qua.22612 ABSTRACT: In this study, quantum chemical calculations using density functional theory and 6-311G (d) basis set have been applied to analyze the substituent effect on the electronic structural properties including thermochemical parameters as well as anticancer characteristics of catechin as a bioactive constituent of green tea. It has been found out that different substituents with two kinds of electron donating and electron withdrawing groups including ANO 2 , ANH 2 , ACl, AOCH 3 , and ACH 3 leaded to different structural stabilities. The catechin with chloro substituents has been referred to the most stable catechin derivatives based on the minimum energy of investigated compounds. In this study, the calculated values have been compared in gas phase and different solvent media with a wide range of solvent dielectrics using the self-consistent reaction field method with polarizable continuum model. Relative interaction energies between solute and solvent as well as dipole moment values have been analyzed. The results of solvent effect study revealed that the formation of hydrogen bonds accounts for the stabilization of catechin. These calculated data were found to be a logical way in predicting the relative stability of catechin derivatives and can be useful for drug design of anticancer drugs and would open a new door for the researchers who are interested in natural products. The results presented in this article will be helpful to improve existing model and will open up a whole new arena of study to understand the anticancer characteristic of these antioxidant drugs derived from natural products against the photosensitizing DNA damage induce by catechin extracts and enable a Correspondence to: F. Mollaamin; e-mail: smollaamin@gmail. com International Journal of Quantum Chemistry, Vol 111, 2771–2777 (2011) V C 2010 Wiley Periodicals, Inc.