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Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells
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 liv...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698709/ https://www.ncbi.nlm.nih.gov/pubmed/29047228 http://dx.doi.org/10.1002/anie.201709082 |
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author | 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. |
author_facet | 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. |
author_sort | Zhang, Pingyu |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5698709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56987092017-11-30 Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells 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. Angew Chem Int Ed Engl Communications 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. John Wiley and Sons Inc. 2017-10-19 2017-11-20 /pmc/articles/PMC5698709/ /pubmed/29047228 http://dx.doi.org/10.1002/anie.201709082 Text en © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Communications 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. Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells |
title | Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells |
title_full | Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells |
title_fullStr | Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells |
title_full_unstemmed | Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells |
title_short | Organoiridium Photosensitizers Induce Specific Oxidative Attack on Proteins within Cancer Cells |
title_sort | organoiridium photosensitizers induce specific oxidative attack on proteins within cancer cells |
topic | Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5698709/ https://www.ncbi.nlm.nih.gov/pubmed/29047228 http://dx.doi.org/10.1002/anie.201709082 |
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