Synthesis and characterization of platinum(II) complexes of diethyl [(methylsulfinyl)methyl]phosphonate: Potential drugs against bone tumors

Cisplatin is the most important metal-based drug used in tumor therapy; however, it suffers from severe side effects and a limited spectrum of activity. Since phosphonates are known to have a selective tropism for bones and calcified tissues, we have carried on the synthesis of different platinum complexes with a phosphonate ligand. The ligand used is diethyl [(methylsulfinyl)methyl]phosphonate (SMP), which can act as an O,S-donor towards Pt. Moreover, since the sulfur atom is a stable stereogenic center, the ligand is obtained in two enantiomeric forms. The synthesised complexes have the general formula [PtL2(SMP)], in which L-2 stands for a bidentate (dimethylmalonate, 1,2-diaminocyclohexane, ethylenedi-amine) or two monodentate (chloride) ligands. The formation of a five-membered chelate ring contributes to the chemical stability of complexes with SMP, and 2D NMR experiments have allowed determination of the ring puckering, which is dependent upon the chirality of the sulfur stereocenter. For the (S) configuration at the sulfur center (free ligand), the 6 puckering of the chelate ring is favoured. Preliminary studies have shown that these compounds are stable under physiological conditions. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).