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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

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Official URL: http://dx.doi.org/10.1002/anie.201709082

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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
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of 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:
DateEvent
20 November 2017Published
19 October 2017Available
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
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
EP/P001459/1[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
EP/G006792[EPSRC] Engineering and Physical Sciences Research Councilhttp://dx.doi.org/10.13039/501100000266
21471164 [NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
21525105[NSFC] National Natural Science Foundation of Chinahttp://dx.doi.org/10.13039/501100001809
2015CB856301[MSTPRC] Ministry of Science and Technology of the People's Republic of Chinahttp://dx.doi.org/10.13039/501100002855
Newton International Fellowship[RS] Royal Societyhttp://dx.doi.org/10.13039/501100000288

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