New copper(I) and heteronuclear copper(I)–ruthenium(II) complexes: Synthesis, structural characterization and cytotoxicity

A new family of copper(I) complexes of general formula [Cu(dppe)(NN)]+ have been synthesized and fully characterized, with dppe = 1.2-bis(diphenylphosphino)ethane and NN representing several bidentate heteroaromatic ligands: 2,2′-bipy = 2.2′-bipyridine (1), Me2bpy = 4.4′-dimethyl-2,2′-bipyridine (2), dpytz = 3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine (3), dpp = 2.3-bis(2-pyridyl)pyrazine (4), and the metallaligand [Ru(η5-C5H5)(PPh3)(dpp)]+ (5), yielding the bimetallic copper(I)-ruthenium(II) complex [Cu(dppe)(μ-dpp)Ru(η5-C5H5)(PPh3)]2 + (6). The single crystal structures of complexes (2) and (4) were determined by X-ray diffraction studies. All the complexes exhibit high cytotoxicity against the human cancer cells A2780 and MCF7 with IC50 values far lower than those found for the antitumor drug cisplatin in the same cell lines and even surpassing cisplatin resistance in the A2780cisR cells. They display IC50 values on the human embryonic kidney HEK293 non-tumoral cells of the same order of magnitude as those found for the tumoral cells. In the ovarian cells the compounds induce rapid production of reactive oxygen species (ROS) probably through mitochondrial pathways. According to the results reported here, these compounds can be considered as prospective antitumoral agents that deserve further evaluation.