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Organoiridium photosensitizers induce specific oxidative attack on proteins within cancer cells
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Zhang, Pingyu, Chiu, Cookson K. C., Huang, Huayi, Lam, Yuko P. Y., Habtemariam, Abraha, Malcomson, Thomas, Paterson, Martin J., Clarkson, Guy J., O'Connor, Peter B., Chao, Hui and Sadler, P. J. (2017) Organoiridium photosensitizers induce specific oxidative attack on proteins within cancer cells. Angewandte Chemie International Edition, 56 (47). pp. 14898-14902. doi:10.1002/anie.201709082 ISSN 1433-7851.
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Official URL: http://dx.doi.org/10.1002/anie.201709082
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.
Item Type: | Journal Article | |||||||||||||||||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | |||||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | |||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Cancer cells, Organoiridium compounds, Photosensitizing compounds | |||||||||||||||||||||
Journal or Publication Title: | Angewandte Chemie International Edition | |||||||||||||||||||||
Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA | |||||||||||||||||||||
ISSN: | 1433-7851 | |||||||||||||||||||||
Official Date: | 20 November 2017 | |||||||||||||||||||||
Dates: |
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Volume: | 56 | |||||||||||||||||||||
Number: | 47 | |||||||||||||||||||||
Page Range: | pp. 14898-14902 | |||||||||||||||||||||
DOI: | 10.1002/anie.201709082 | |||||||||||||||||||||
Status: | Peer Reviewed | |||||||||||||||||||||
Publication Status: | Published | |||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||||||||
Date of first compliant deposit: | 6 April 2018 | |||||||||||||||||||||
Date of first compliant Open Access: | 6 April 2018 | |||||||||||||||||||||
RIOXX Funder/Project Grant: |
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