NMR investigation of the spontaneous thermal- and/or photoinduced reduction of trans dihydroxido Pt(IV) derivatives

The initial aim of the present work was the synthesis of the axial disuccinato Pt(IV) derivative of [PtCl₂(cis-1,4-DACH)] (Kiteplatin, 1 in Figure 1) (DACH = diaminocyclohexane), which contains an isomeric form of the diamine ligand present in oxaliplatin (i.e., 1R,2R-DACH). The interest in this compound stems from its activity on several cisplatin and oxaliplatin-resistant cell lines. Oxidation of 1 with hydrogen peroxide affords cis,trans,cis-[PtCl₂(OH)₂(cis-1,4-DACH)] (2) which was treated with succinic anhydride in suitable solvents. To our surprise, in dimethylformamide (DMF) (50-70 C or under light irradiation) or in dimethylsulfoxide (DMSO) (under light irradiation) the formation of the succinato complex cis,trans,cis-[PtCl₂{OC(O)CH₂CH ₂C(O)OH}₂(cis-1,4-DACH)] (3) was accompanied by reduction to 1. It was found that solvolysis of 2 and formation of a μ-oxo dinuclear species (5) is the key step. The dinuclear species can then undergo reduction to a 1:1 mixture of 1 and 2 with concomitant elimination of oxygen (1/2 O ₂ in the form of H₂O₂). The whole process is fostered by heat and/or light, which could favor solvolysis of 2 as well as decomposition of hydrogen peroxide to water and oxygen so preventing the reoxidation of 1 to 2. Because of its peculiar behavior, compound 5 could be exploited also for the development of a technology for water splitting.