A multi-methodological inquiry of the behavior of cisplatin-based Pt(IV) derivatives in the presence of bioreductants with a focus on the isolated encounter complexes

The study of Pt(IV) antitumor prodrugs able to circumvent some drawbacks of the conventional Pt(II) chemotherapeutics is the focus of a lot of attention. This paper reports a thorough study based on experimental methods (reduction kinetics, electrochemistry, tandem mass spectrometry and IR ion spectroscopy) and quantum–mechanical DFT calculations on the reduction mechanism of cisplatin-based Pt(IV) derivatives having two hydroxido ( 1 ), one hydroxido and one acetato ( 2 ), or two acetato ligands ( 3 ) in axial position. The biological reductants glutathione and ascorbic acid were taken into consideration. The presence of a hydroxido ligand resulted to play an important role in the chemical reduction with ascorbic acid, as verified by 15 N-NMR kinetic analysis using 15 N-enriched complexes. The reactivity trend ( 1 > 2 > 3 ) does not reflect the respective reduction peak potentials ( 1