Hydration process as an activation of trans- and cisplatin complexes in anticancer treatment. DFT and ab initio computational study of thermodynamic and kinetic parameters

The thermodynamic and kinetic aspects of hydration reactions of cis‐/transplatin were explored. The polarizable continuum model was used for estimation of solvent effects. Using the B3LYP/6‐31+G(d) method, the structures were optimized and vibrational frequencies estimated. Interaction energies and activation barriers were determined at the CCSD(T)/6‐31++G(d,p) level within the COSMO approach. An associative mechanism was assumed with a trigonal‐bipyramidal structure of the transition state. Within the applied model, all the hydration reactions are slightly endothermic. The Gibbs energies of cisplatin hydration amount to 7.0 and 14.2 kcal/mol for the chloride and ammonium replacement, respectively. Analogous values for the transplatin reactions are 6.8 and 11.9 kcal/mol. The determined rate constants are by several (three to four) orders of magnitude larger for the dechlorination process than for deammination. The cisplatin dechlorination rate constant was established as 1.3 · 10−4 s−1 in excellent accord with the experiment. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 907–914, 2005