Pincer-Based Heterobimetallic Pt(II)/Ru(II), Pt(II)/Ir(III), and Pt(II)/Cu(I) Complexes: Synthesis and Evaluation of Antiproliferative Properties

Platinum pincer-based complexes [((ONO)-N-<^>-O-<^>)Pt(L)] (L = DMSO, pyridine, triphenylphosphine or 1,3-dimethylbenzimidazol-2-ylidene) carrying an ((NN)-N-<^>) coordination site were used as starting materials to synthesize a series of seven cationic heterobimetallic Pt(II)/Ru(II), Pt(II)/Ir(III), and Pt(II)/Cu(I) presenting a [(p-cymene)RuCl](+), a [(Cp*)IrCl](+)(Cp* = eta(5)-pentamethylcyclopentadienyl), and a [(NHCiPr)Cu](+){NHCiPr = 1,3-bis(2,6-diisopropylphenyl)imidazole-2-ylidene} moiety, respectively. The X-ray structure of one of the bimetallic Pt(II)/Ir(III) complexes showed a distortion of the organic platform to accommodate the coordination geometry of both metal centers, as already observed for previous Pt(II)/Re(I) complexes. The antiproliferative activity of the complexes was first screened on the triple negative breast cancer cell line MDA-MB-231. Then the IC(50)of the most active candidates was determined on a wider panel of human cancer cells (MDA-MB-231, MCF-7 and A2780) as well as on a non-tumorigenic cell line (MCF-10A). The most toxic compound, namely the Pt(II)/Cu(I) heterobimetallic complex4c, showed antiproliferative activity down to the nanomolar level.