Antiproliferative activity of a series of cisplatin-based Pt(IV)-acetylamido/carboxylato prodrugs.

We report studies of a novel series of Pt(IV) complexes exhibiting an asymmetric combination of acetylamido and carboxylato ligands in the axial positions. We demonstrate efficient synthesis of a series of analogues, differing in the alkyl chain length and hence lipophilicity, from a stable acetylamido/hydroxido complex formed by reaction of cisplatin with peroxyacetimidic acid (PAIA). NMR spectroscopy and X-ray crystallography confirm the identity of the resulting complexes, and highlight subtle differences in the structure and stability of acetylamido complexes compared to the equivalent acetato complexes.

Unprecedented one-pot synthesis of an unsymmetrical cisplatin-based Pt(IV)-acetamidato complex.

We describe herein a novel Pt(IV)-acetamidato complex as a result of the one-pot reaction between cisplatin and the highly reactive peroxyacetimidic acid generated in situ. This is the first example of a Pt(IV) complex containing a N-donor ligand coordinated during the Pt(II) → Pt(IV) oxidation step. Remarkably, the Pt(IV)-amidato compound is highly soluble and stable in water; it represents an interesting building block for the further development of Pt(IV) antitumor prodrugs.

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.