Kinetic studies of platinum complexes

Abstract

Since the chance discovery, in 1967, of the anti-tumour activity of cisplatin, cis-dichlorodiammineplatinum(II), research has focussed on studying the reactions of this and other related complexes in an effort to elucidate the nature of the biological activity. This thesis presents a study of the aqueous solution chemistry of some platinum(II) and platinum(IV) complexes in order to extend what is known about the simple chemistry of this biologically important class of compounds. The chloride ion anation of diaqua (cis-[Pt(OH₂)₂(N)₂]²⁺) complexes is investigated as is the bromide ion anation of the bromoaqua (cis-[PtBr(OH₂)(N)₂]⁺) and diaqua (cis-[Pt(OH₂)₂(N)₂]²⁺) species, all in 1.0 M HC1O₄. The kinetics are studied using UV/Vis spectroscopic methods - both conventional and stopped-flow. High-pressure stopped-flow is used for selected reactions to determine the effect of pressure on the anation process. The collective data are used to calculate activation parameters from which conclusions are drawn as to the mechanism of the reaction. The redox kinetics of the platinum(II)/platinum(IV) couple are investigated using a variety of redox agents. These data provide a basis on which to form mechanistic interpretations for both the oxidation and reduction processes. Extrapolations are made to the biological system for the reduction of anti-tumour active platinum(IV) drugs. Platinum(IV) complexes are known to be very inert. An investigation into the base hydrolysis of platinum(IV) complexes is presented and a mechanism proposed.