Novel cis-[(NHC)(NHC)(L)Cl]platinum(ii) complexes - synthesis, structures, and anticancer activities.

A general synthesis of novel platinum(ii) complexes bearing two different, cis-oriented, N-heterocyclic carbene (NHC) ligands is presented. Easily accessible cis-[Pt(NHC)(DMSO)] precursor complexes were converted to either cis-[Pt(NHC)Cl] complexes such as 5a and 5b, or to novel mixed cis-[Pt(NHC)(NHC)Cl] complexes such as 5c-h by successive introduction of the individual carbene ligands. The 'symmetric' complexes 5a and 5b were also converted to cationic cis-[Pt(NHC)(PPh)Cl]Cl complexes 8a and 8b. The structures of the ten new complexes, comprising benzylated and alkylated imidazol-2-ylidene ligands, were analysed by H, C and Pt NMR spectroscopy and also by X-ray diffraction for 5a, 5d, 5h, and 8a. The neutral complexes 5 were cytotoxic against a panel of seven human cancer cell lines with IC values in the low micromolar range, while the cationic complexes 8 reached even nanomolar IC values. Complex 5h carrying the substitution pattern of the natural antitumoral agent Combretastatin A-4 showed a conspicuous specificity for cancer cell lines sensitive to this drug. In electrophoretic mobility shift assays, the cis-biscarbene complexes 5b and 8b led to an unwinding or aggregation of plasmid DNA, while the trans-biscarbene complex 1b showed no such effect.