A DFT study on the hydrolysis mechanism of the potential antitumor Ru(III) complex TzNAMI

The hydrolysis process of Ru(III) complex [TzH][trans-RuCl4(DMSO)(Tz)]·(DMSO) (TzNAMI), a potential antitumor complex similar to the well-known antitumor agent NAMI-A, has been investigated by using density functional theory (DFT) method, and the solution effect was also considered and calculated by conductor-like polarizable calculation model (CPCM). The structural characteristics and the detailed energy profiles for the hydrolysis processes of this complex have been obtained. The analysis of thermodynamic and kinetic characteristics of hydrolysis reaction suggests the following: for the 1st hydrolysis step, the complex TzNAMI with thiazole ligand has slightly lower hydrolysis rate than NAMI-A with imidazole ligands, and such a calculated result is in good agreement with experimental one and reasonably explained in theory. For the 2nd hydrolysis step, the formation of cis-diaqua species is thermodynamically preferred to that of trans isomer. In addition, based on the analysis of electronic characteristics of species in the hydrolysis process, the trend in nucleophilic attack abilities (A) of hydrolysis products by pertinent biomolecules is revealed.