Kinetics and mechanism for reduction of halo- and haloam(m)ine platinum(IV) complexes by l-ascorbate

Reduction of the model platinum(IV) complexes cis-[PtCl4(NH3)2] (1), trans-[PtCl4(NH3)2] (2), trans-[PtCl2(en)2]2+ (3), trans-[PtBr2(NH3)4]2+ (4), [PtCl6]2− (5), and [PtBr6]2− (6) with l-ascorbic acid (H2Asc) in 1.0 M aqueous medium at 25 °C in the region 1.75≤pH≤7.20 has been investigated using stopped-flow spectrophotometry. The redox reactions follow the rate law: −d[Pt(IV]/dt=k[H2Asc]tot[Pt(IV)] where k is a pH-dependent second-order rate constant and [H2Asc]tot, the total concentration of ascorbic acid. The pH-dependence of k is attributed to parallel reduction of Pt(IV) by the protolytic species HAsc− and Asc2−. Analysis of the kinetics data reveals that the ascorbate anion Asc2− is up to seven orders of magnitude more reactive than HAsc− while H2Asc is unreactive. Electron transfer from HAsc−/Asc2− to the Pt(IV) compounds is suggested to take place by a mechanism involving a reductive attack on any one of the mutually trans-halide ligands by Asc2− and/or HAsc− forming a halide-bridged activated complex. The rapid reduction of these complexes supports the assumption that ascorbate Asc2− might be an important reductant at physiological conditions for anticancer active Pt(IV) pro-drugs capable of undergoing reductive trans elimination. The parameters ΔH≠ and ΔS≠ for reduction of Pt(IV) with Asc2− have been determined from the study of the temperature dependence of k.