Synthesis, crystal structure and cytotoxic activity of 2,2′-bipyridine / 1,10-Phenanthroline based Copper(II) complexes with diphenylphosphinic acid

Mixed-ligand 2,2′-bipyridine, 1,10-phenanthroline based copper(II) complexes are often considered as potential antitumor agents. This research was aimed at synthesis and finding the cytotoxic potential of copper(II) complexes with diphenylphosphinic acid (HL) and 2,2′-bipyridine, 1,10-phenanthroline derivatives – [Cu(phen)(H₂O)L₂]·H₂O (1), [Cu(dmphen)(H₂O)L₂] (2), [Cu(Cl-phen)(H₂O)₂L]L·EtOH (3), [Cu(bipy)(H₂O)L₂] (4) and Cu(dmbipy)(H₂O)L₂ (5) (phen – 1,10-phenanthroline, dmphen – 4,7-dimethyl-1,10-phenanthroline, Cl-phen – 5-chloro-1,10-phenanthroline, bipy – 2,2′-bipyridine, dmbipy – 4,4′-dimethyl-2,2′-bipyridine). Obtained mononuclear compounds have been characterized by EPR and IR-spectroscopy, elemental, thermogravimetric, single-crystal and powder X-ray diffraction analyses. According to single-crystal X-ray diffraction data, complexes possess distorted trigonal bipyramidal or square pyramidal geometry. 2,2′-Bipyridine and 1,10-phenanthroline derivatives have been shown to be chelating agents in these complexes, while anion of diphenylphosphinic acid acts as a monodentate ligand. Complexes 1–5 have been monitored for their solution stability using UV–vis spectroscopy. In the present study, cytotoxic activity of the complexes has been investigated on 2D human cell culture models (larynx carcinoma Hep2, hepatocellular carcinoma HepG2, breast carcinoma MCF-7 and non-tumor lung fibroblasts MRC5) and 3D HepG2 human cell model. 1,10-Phenanthroline based complexes have demonstrated the highest cytotoxicity superior to the reference drug cisplatin. The level of reactive oxygen species generation in Hep2 cells has been shown to increase after incubation with complexes.