Insight into the Electrochemical Reduction Mechanism of Pt(IV) Anticancer Complexes.

We carried out a theoretical study on the mechanism of electrochemical reduction of the prototypical platinum(IV) anticancer complex [Pt(NH)(CHCOO)Cl] to the corresponding platinum(II) [Pt(NH)Cl] derivative. Energies and geometric structures of the original Pt(IV) complex and all possible Pt(III) and Pt(II) intermediates and transition states involved in the reduction process have been calculated using density functional theory and Møller-Plesset perturbation theory. This study allowed us to formulate a detailed mechanism for the two-electron reduction of the [Pt(NH)(CHCOO)Cl] complex. The results show that, in agreement with the experimental evidence from cyclic voltammetry, the initial one-electron reduction of the [Pt(NH)(CHCOO)Cl] complex occurs through a stepwise mechanism via a metastable hexacoordinated platinum(III) [Pt(NH)(CHCOO)Cl] intermediate and a subsequent acetate ligand detachment with an activation free energy of 5.1 kcal mol. On the other hand, the second electron reduction of the resulting pentacoordinated [Pt(NH)(CHCOO)Cl] species occurs through a barrierless concerted process to the final [Pt(NH)Cl] derivative.