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Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells
Author(s) -
Zhang Pingyu,
Chiu Cookson K. C.,
Huang Huaiyi,
Lam Yuko P. Y.,
Habtemariam Abraha,
Malcomson Thomas,
Paterson Martin J.,
Clarkson Guy J.,
O'Connor Peter B.,
Chao Hui,
Sadler Peter J.
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201709082
Subject(s) - chemistry , iridium , cancer cell , phosphorescence , oxidative phosphorylation , histidine , oxidative stress , enzyme , biochemistry , stereochemistry , cancer , fluorescence , biology , physics , quantum mechanics , genetics , catalysis
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 1 O 2 , 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.