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 (PPh₃) 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.