Molecular mechanical and quantum chemical study on the species involved in the hydrolysis of cis-diaminedichloro-platinum(II) and substituted bis(ethylenediamine)dichloro-platinum(II) complexes. Part I. Reactans and products

Abstract

Cisplatin and its substituted ethylenediamine derivatives, cis-PtCl₂(R₂en) (en = ethylenediamine, R = H, Ph (phenyl), 2-, 3- and 4-PhOH) have been studied with respect to the first step of their hydrolysis reaction. The geometry of the reactants and products was determined by molecular mechanics (MM). The MM optimized structures were used to calculate by the extended Huckel method the charge distribution and relative electronic energies. The MM and EH calculations were carried out with different ligand conformations. Due to increased non-bonded repulsion, with increasing ligand bulkiness, the square planar arrangement is the preferred geometry also by the MM results. This additlonal (to the electronic) stabilization of the square planar arrangement around Pt(II) is unfavorable for the aquation process. The thermodynamic stabilities correlate with the rate of hydrolysis of meso-, (+)- and (-)-[1,2-bis(2hydroxyphenyl)ethylenediamine]dichloroplatinum(II) (3-PtCI₂). The slower rate of hydrolysis of the meso diastereoisomer as compared with that of the d, I species of 3-PtCI₂ is explained by the presence of a 5th Pt-0 contact in the meso diastereoisomer which hinders the entrance of the water molecule and makes the hydrolysis slower.