Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells

Zhang, Pingyu and Chiu, Cookson K. C. and Huang, Huaiyi and Lam, Yuko P. Y. and Habtemariam, Abraha and Malcomson, Thomas and Paterson, Martin J. and Clarkson, Guy J. and O'Connor, Peter B. and Chao, Hui and Sadler, Peter J. (2017) Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells. Angewandte Chemie, 129 (47). pp. 15094-15098. ISSN 0044-8249

Abstract

Strongly luminescent iridium(III) complexes, [Ir(C,N)2(S ,S )]+ (1 ) and [Ir(C,N)2(O,O)] (2 ), containing C,N (phenylquinoline), O,O (diketonate), or S,S (dithione) chelating ligands, have been characterized by X‐ray crystallography and DFT calculations. Their long phosphorescence lifetimes in living cancer cells give rise to high quantum yields for the generation of 1O2, with large 2‐photon absorption cross‐sections. 2 is nontoxic to cells, but potently cytotoxic to cancer cells upon brief irradiation with low doses of visible light, and potent at sub‐micromolar doses towards 3D multicellular tumor spheroids with 2‐photon red light. Photoactivation causes oxidative damage to specific histidine residues in the key proteins in aldose reductase and heat‐shock protein‐70 within living cancer cells. The oxidative stress induced by iridium photosensitizers during photoactivation can increase the levels of enzymes involved in the glycolytic pathway.