Theoretical determination of the aquation reaction mechanism of cyclometalated benzimidazole Ru(II) and Ir(III) anticancer complexes

Abstract

The free energy profiles for the hydrolysis reaction mechanism of two synthesized C,N-cyclometalated benzimidazole chorido-Ir(III) and Ru(II) anticancer complexes, which have shown promising anticancer activity, have been explored theoretically employing density functional theory (DFT). Analogous calculations have been carried out for the complexes obtained by the substitution of either the H atom in R4 position of the phenyl ring of the 2-phenylbenzimidazole chelating ligand with the electron-withdrawing CF3 group or the chloride ligand with pyridine with the purpose to probe the influence of such substitutions on the hydrolysis profiles. Results show that for the unsubstituted complexes displacement of the labile chloride ligand by water requires that low energy barriers are surmounted for the aquation process to occur. Substitution with either the CF3 group in peripheral position or chloride with pyridine causes an increase of barriers heights. The only complex with an hydrolysis barrier comparable with that of cisplatin is the pyridine leaving ligand ruthenium complex.