Inhibition of autophagic flux by cyclometalated iridium(iii) complexes through anion transportationElectronic supplementary information (ESI) available: Syntheses and characterization data, anion transport assays, cell lines and culture conditions, cell viability assays, transmission electron microscopy, western blotting, flow cytometry analysis. CCDC 1814116 and 1814117. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c8sc04520h

• Main Authors: Chen, Mu-He, Zheng, Yue, Cai, Xiong-Jie, Zhang, Hang, Wang, Fang-Xin, Tan, Cai-Ping, Chen, Wen-Hua, Ji, Liang-Nian, Mao, Zong-Wan
• Format: Article
• Language: English
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c8sc04520h

Synthetic anion transporters that can interfere with the intracellular pH homeostasis are gaining increasing attention for tumor therapy, however, the biological mechanism of anion transporters remains to be explored. In this work, two phosphorescent cyclometalated Ir( iii ) complexes containing 2-phenylpyridine (ppy) as the cyclometalated ligand, and 2,2′-biimidazole (H 2 biim, Ir1 ) or 2-(1 H -imidazol-2-yl)pyridine (Hpyim, Ir2 ) as the ancillary ligands have been synthesized and characterized. Due to the protonation and deprotonation process of the N-H groups on H 2 biim and Hpyim, Ir1 and Ir2 display pH-dependent phosphorescence and can specifically image lysosomes. Both Ir1 and Ir2 can act as anion transporters mainly through the anion exchange mechanism with higher potency observed for Ir1 . Mechanism investigation shows that Ir1 and Ir2 can induce caspase-independent cell death through reactive oxygen species (ROS) elevation. As Ir1 and Ir2 can alkalinize lysosomes through anion disturbance, they can inhibit autophagic flux. Our work provides a novel anticancer mechanism of metal complexes, which gives insights into the innovative structure-based design of new metallo-anticancer agents. We report two phosphorescent cyclometalated iridium( iii ) complexes that can inhibit autophagic flux through anion transportation.