title: Hydration process as an activation of trans- and cisplatin complexes in anticancer treatment. DFT and ab initio computational study of thermodynamic and kinetic parameters.
abstract: 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 x 10(-4) s(-1) in excellent accord with the experiment.
authors.affiliation: Department of Chemical Physics and Optics, Faculty of Mathematics and Physics, Charles University, Ke Karlovu 3, Prague 2, 121 16, Czech Republic. burda@karlov.mff.cuni.cz
authors.forename: Jaroslav V
authors.initials: JV
authors.lastname: Burda
authors.forename: Michal
authors.initials: M
authors.lastname: Zeizinger
authors.forename: Jerzy
authors.initials: J
authors.lastname: Leszczynski
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002945:Cisplatin / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D014867:Water; D002945:Cisplatin