A New Entry to Asymmetric Platinum(IV) Complexes via Oxidative Chlorination

Pt­(IV) complexes are usually prepared by oxidation of the corresponding Pt­(II) counterparts, typically using hydrogen peroxide or chlorine. A different way to synthesize asymmetrical Pt­(IV) compounds is the oxidative chlorination of Pt­(II) counterparts with N-chlorosuccinimide. The reaction between cisplatin cis-[PtCl2(NH3)2], carboplatin, cis-[PtCl2(dach)] and cis-[Pt­(cbdc)­(dach)] (cbdc = cyclobutane-1,1′-dicarboxylato; dach = cyclohexane-1R,2R-diamine) with N-chlorosuccinimide in ethane-1,2-diol was optimized to produce the asymmetric Pt­(IV) octahedral complexes [PtA2Cl­(glyc)­X2] (A2 = 2 NH3 or dach; glyc = 2-hydroxyethanolato; X2 = 2 Cl or cbdc) in high yield and purity. The X-ray crystal structure of the [Pt­(cbdc)­Cl­(dach)­(glyc)] complex is also reported. Moreover, the oxidation method proved to be versatile enough to produce other mixed Pt­(IV) derivatives varying the reaction medium. The two trichlorido complexes easily undergo a pH-dependent hydrolysis reaction, whereas the dicarboxylato compounds are stable enough to allow further coupling reactions for drug targeting and delivery via the glyc reactive pendant. Therefore, the coupling reaction between the [Pt­(cbdc)­Cl­(dach)­(glyc)] and a model carboxylic acid, a model amine, and selectively protected amino acids is reported.