Binding to DNA purine bases and amino acid residues of a ruthenium(II) antitumor complex: A density functional study

The hydrolyzed α-[Ru(azpy)2Cl2] (azpy is 2-(phenylazo)pyridine; α indicates that the isomer in which the coordinating pairs Cl, N(py), and N(azo) are cis, trans, and cis, respectively) binding to guanine (G), adenine (A), methionine (Met), and histidine (His) residues were investigated by using density functional theory. Reactant complexes (RC), product complexes (PC), and transition states (TS) involved were fully characterized. The calculated energy profiles showed that the activation free energies for the substitutions of hydrolyzed α-[Ru(azpy)2Cl2] with Met was apparently lower than those of guanine and adenine. This indicate that the hydrolyzed α-[Ru(azpy)2Cl2] compounds may preferentially bind to the sulfur-containing amino acids residues in vivo. Moreover, the natural orbital population analysis (NPA) showed that the Ru atom gained the greatest negative charges in the reactions of hydrolyzed α-[Ru(azpy)2Cl2] with Met, which may contribute to their remarkably low activation free energies partially.