Abstract:

The hydrolysis of a potential antitumor Ru(III) complex trans-[RuIIICl4(2-NH2-5-Me-STz)2] (1) was investigated using density functional theory (DFT) combined with the conductor-like polarizable calculation model (CPCM). Full geometry optimizations and frequency calculations in vacuo for each related equilibrium geometry were carried out at the UB3LYP/(LanL2DZ+6-31G(d)) level. Single-point energies were calculated in the gas phase and in solution at the UB3LYP/(LanL2DZ(f)+6-311++G(3df,2dp) level on the optimized structures. The structural characteristics and detailed energy profiles for the hydrolysis processes of this complex were obtained. For the first hydrolysis step, complex 1 has an activation energy of 92.9 kJ·mol-1 in solution and this is similar to that of the reported Ru(III) complex trans-[RuIIICl4(2-NH2-Tz)2](2) (96.3 kJ·mol-1) and is in good agreement with experimental results. For the second hydrolysis step, the formation of cis-diaqua products is found to be thermodynamically preferred over the trans isomers. Similar to the hydrolysis action mechanismof cisplatin, a“cis effect”is present wherein the cis-diaqua products prefer binding to pertinent biomolecular targets. Therefore, cis-diaqua products can be expected to be important precursors for biological actions. These theoretical results should help in understanding the action mechanism of these potential Ru(III) drugs with pertinent biomolecular targets.

Key words: Density functional theory, Ru(III) complex, Anticancer activity, Hydrolysis, Conductor-like polarizable calculation model