New dinuclear cobalt(II) complexes as “self‐activating” chemical nuclease and inhibitor of tumor cell invasion: High selective cytotoxicity against NCI‐H460 cells

Abstract

Three new dinuclear Co(II) complexes [Co 2 (L 1 ) 2 Cl 2 ](PF 6 ) 2 (1), [Co 2 L 2 (OAc) 2 (CH 3 OH) 4 ](ClO 4 ) 2 (2), and [Co 2 L 3 (OAc) 2 (CH 3 OH) 4 ](ClO 4 ) 2 (3) were synthesized and structurally determined by X-ray single-crystal diffraction analysis as well as IR, elemental analysis, and mass spectrometry. All complexes exhibit efficiently self-activated cleavage activity with hydrolytic mechanism, which was accurately proved by addition of regular radical scavengers, anaerobic cleavage experiment, and 2-thiobarbituric acid reaction. Complex 1 exhibited higher selective cytotoxicity against tumor cells than normal cells, which is significantly better than that of cisplatin. Hoechst 33342 staining, intracellular ROS generation and mitochondrial membrane potential were conducted to assess the apoptosis-inducing activity of 1. The effect of complex 1 on cell invasion was observed by Transwell assay and angiogenesis experiment, and the results demonstrated that 1 could inhibit the cell invasion and angiogenesis. K E Y W O R D S crystal structures, dinuclear Co(II) complexes, invasion, selective cytotoxicity, self-activating Yong-Po Zhang and Qing He contributed equally to this work.