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Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells

Title	Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells
Authors	Dr. Pingyu Zhang, Cookson K. C. Chiu, Dr. Huaiyi Huang, Yuko P. Y. Lam, Dr. Abraha Habtemariam, Thomas Malcomson, Prof. Martin J. Paterson, Dr. Guy J. Clarkson, Prof. Peter B. O'Connor, Prof. Hui Chao, Prof. Peter J. Sadler
Magazine	Angewandte Chemie (International Ed. in English)
Date	10/19/2017
DOI	10.1002/anie.201709082
Introduction	This research investigates highly luminescent iridium(III) complexes, specifically [Ir(C,N) 2( S, S)] + (1) and [Ir(C,N) 2(O,O)] (2), incorporating C,N (phenylquinoline), O,O (diketonate), or S,S (dithione) chelating ligands. These complexes underwent structural characterisation using X-ray crystallography and DFT calculations. Within living cancer cells, their extended phosphorescence lifetimes enable efficient generation of singlet oxygen (1O2) and exhibit substantial two-photon absorption cross-sections. While complex 2 demonstrates cellular nontoxicity, it exhibits potent cytotoxicity against cancer cells when briefly irradiated with low-dose visible light, proving effective at sub-micromolar concentrations in 3D multicellular tumour spheroids using two-photon red light. This photoactivation leads to oxidative damage targeting specific histidine residues in crucial proteins, such as aldose reductase and heat-shock protein-70, within living cancer cells. The oxidative stress generated by these iridium photosensitisers during light activation can also elevate the activity of enzymes participating in the glycolytic pathway.
Quote	Pingyu Zhang, Cookson K. C. Chiu and Huaiyi Huang et al. Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells. Angew. Chem. Int. Ed. Engl. 2017. Vol. 56(47):14898-14902. DOI: 10.1002/anie.201709082
Element	Iridium (Ir)
Materials	Chemical Compounds , Biomaterials
Topics	Photonic and Optoelectronic Materials
Industry	Pharmaceutical Industry , Research & Laboratory

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