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Inhibition of autophagic flux by cyclometalated iridium(III) complexes through anion transportation

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Abstract

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 (H2biim, Ir1) or 2-(1H-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 H2biim 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.

Graphical abstract: Inhibition of autophagic flux by cyclometalated iridium(iii) complexes through anion transportation

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Publication details

The article was received on 10 Oct 2018, accepted on 28 Jan 2019 and first published on 31 Jan 2019


Article type: Edge Article
DOI: 10.1039/C8SC04520H
Citation: Chem. Sci., 2019, Advance Article
  • Open access: Creative Commons BY license
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    Inhibition of autophagic flux by cyclometalated iridium(III) complexes through anion transportation

    M. Chen, Y. Zheng, X. Cai, H. Zhang, F. Wang, C. Tan, W. Chen, L. Ji and Z. Mao, Chem. Sci., 2019, Advance Article , DOI: 10.1039/C8SC04520H

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