The hydrolysis process of the anticancer complex [ImH][trans-RuCl4(Im)2]:: a theoretical study

A hydrolysis process of the anticancer drug [ImH][trans-RuCl4(Im)(2)] (ICR, Im = imidazole) has been investigated using density functional theory (DFT), and the aqueous solution effect has been considered and calculated by the conductor-like polarizable calculation model (CPCM). The stationary points on the potential energy surfaces for the first and second hydrolysis steps (including two different paths) were fully optimized and characterized. The results show that the computed values of free energy barriers Delta G degrees (aq) and rate constants (k) in aqueous solution, in particular for the first hydrolysis step, are in excellent agreement with the experimental results. The analysis of electronic characteristics of species in the hydrolysis process suggests that the nucleophilic attack abilities (A) of hydrolysis products by biomolecular targets is in the sequence of A(P1) < A(P2-1) < A(P2-2) (P1, P2-1 and P2-2 express the hydrolysis products of the first hydrolysis step, and of the second hydrolysis step through path 1 and path 2, respectively). On the basis of our present limited work, the following can reasonably be suggested: path 1 in the second hydrolysis step has thermodynamic preference over path 2, and thus the cis-diaqua species P2-1 may dominate. The theoretical results provide the structural properties as well as the detailed energy pro. les for the hydrolysis process of ICR, so such results may contribute to understanding the reaction mechanism of this drug with the biomolecular target.