Novel heterobimetallic Ir(III)-Re(I) complexes: design, synthesis and antitumor mechanism investigation.

Abstract

The reasonable design of binuclear or multinuclear metal complexes has demonstrated their potential advantages in the anticancer field. Herein, three heterobimetallic Ir(III)-Re(I) complexes, [Ir(C^N)2LRe(CO)3DIP](PF6)2 (C^N = 2-phenylpyridine (ppy, in IrRe-1), 2-(2-thienyl)pyridine (thpy, in IrRe-2) and 2-(2,4-difluorophenyl)pyridine (dfppy, in IrRe-3); L = pyridylimidazo[4,5-f][1,10]phenanthroline; DIP = 4,7-diphenyl-1,10-phenanthroline), were designed and synthesized. The heterobimetallic IrRe-1-3 complexes show pH-sensitive emission properties, which can be used for specific imaging of lysosomes. Additionally, IrRe-1-3 display higher cytotoxicity against tested tumor cell lines than the clinical chemotherapeutic drug cisplatin. Further mechanisms indicate that IrRe-1-3 can induce apoptosis and autophagy, increase intracellular reactive oxygen species (ROS), depolarize the mitochondrial membrane (MMP), block the cell cycle at the G0/G1 phase and inhibit cell migration. To the best of our knowledge, this is the first example of the synthesis of heterobimetallic Ir(III)-Re(I) complexes with superior anticancer activities and evaluation of their anticancer mechanisms.