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

Abstract

We report two phosphorescent cyclometalated iridium(iii) complexes that can inhibit autophagic flux through anion transportation.

Iridium(III) Complexes Targeting Apoptotic Cell Death in Cancer Cells

“…Two cyclometalated iridium complexes 38 and 39 (Figure 11) were developed by Chen, Tan, Mao and coworkers [51]. With a 2,2′-biimidazole N^N ligand functionalized for anion binding, the iridium complex 38 served as an anion transporter to regulate lysosomal pH through hydrogen transfer, resulting in autophagic flux suppression.…”

Thiourea and Guanidine Compounds and Their Iridium Complexes in Drug‐Resistant Cancer Cell Lines: Structure‐Activity Relationships and Direct Luminescent Imaging

“…We believe that these observations may also shed light on the behaviour of the non‐metallated molecules; there is already precedent for minor components of the Ir coordination sphere to drive subcellular location, and in our case, due to reduced bond rotation arising from intramolecular hydrogen bonding in the free ligands, it is possible that the metal complex also preserves the conformation of the uncoordinated molecule. Complex stability, a prerequisite for this hypothesis, is reported to be good for similar Ir complexes …”

“…Complex stability, a prerequisite for this hypothesis, is reported to be good for similar Ir complexes. [52,53] All compounds tested showed notable toxicity. On the one hand, this shows that use of similar thiourea and guanidine structures in materials applications should be accompanied by caution about release.…”

Phosphorescent metal complexes as theranostic anticancer agents: combining imaging and therapy in a single molecule

“…Interestingly, both 22 and 23 can act as anion transporters to inhibit autophagic ux by alkalinizing lysosomes. 51 By structural optimization, we developed a series of Ir(III) complexes as stimuli-activatable PSs targeting lysosomes. 15 Complex 24 (Scheme 2) shows enhanced phosphorescence emission and 1 O 2 generation in tumour/lysosome-related acidic environments (pH # 6.5) and exhibits a high photocytotoxicity (PI > 833) in human lung adenocarcinoma (A549) cells upon visible light exposure.…”