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

The reasonable design of binuclear or multinuclear metal complexes has demonstrated their potential advantages in the anticancer field. Herein, three heterobimetallic Ir(si)-Re(i) complexes, (Ir(C<^>N)(2)LRe (CO)(3)DIPHPF6)(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.

Automated summary

By rational design, three heterobimetallic complexes with pH-sensitive emission properties were synthesized, which showed superior anticancer activities compared to cisplatin. The complexes induced apoptosis and autophagy, increased intracellular ROS, depolarized MMP, arrested the cell cycle, and inhibited cell migration.