Influence of Ligand and Nuclearity on the Cytotoxicity of Cyclometallated C^N^C Platinum(II) Complexes

A series of cyclometallated mono‐ and di‐nuclear platinum(II) complexes and the parent organic ligand, 2,6‐diphenylpyridine 1 (HC^N^CH), have been synthesized and characterized. This library of compounds includes [(C^N^C)Pt(II)(L)] (L=dimethylsulfoxide (DMSO) 2 and triphenylphosphine (PPh(3)) 3) and [((C^N^C)Pt(II))(2)(L‘)] (where L‘=N‐heterocycles (pyrazine (pyr) 4, 4,4‘‐bipyridine (4,4‘‐bipy) 5 or diphosphine (1,4‐bis(diphenylphosphino)butane (dppb) 6). Their cytotoxicity was assessed against four cancerous cell lines and one normal cell line, with results highlighting significantly increased antiproliferative activity for the dinuclear complexes (4–6), when compared to the mononucleated species (2 and 3). Complex 6 is the most promising candidate, displaying very high selectivity towards cancerous cells, with selectivity index (SI) values >29.5 (A2780) and >11.2 (A2780cisR), and outperforming cisplatin by >4‐fold and >18‐fold, respectively.