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dc.contributor.authorLiu, Z.*
dc.contributor.authorRomero-Canelón, I.*
dc.contributor.authorQamar, B.*
dc.contributor.authorHearn, J.M.*
dc.contributor.authorHabtemariam, A.*
dc.contributor.authorBarry, Nicolas P.E.*
dc.contributor.authorPizarro, A.M.*
dc.contributor.authorClarkson, G.J.*
dc.contributor.authorSadler, P.J.*
dc.date.accessioned2017-01-27T15:44:18Z
dc.date.available2017-01-27T15:44:18Z
dc.date.issued2014-04
dc.identifier.citationLiu Z, Romero-Canelón I, Qamar B et al (2014) The potent oxidant anticancer activity of organoiridium catalysts. Angewandte Chemie International Edition. 53(15): 3941-3946.en_US
dc.identifier.urihttp://hdl.handle.net/10454/11201
dc.descriptionYesen_US
dc.description.abstractPlatinum complexes are the most widely used anticancer drugs; however, new generations of agents are needed. The organoiridium(III) complex [(η5-Cpxbiph)Ir(phpy)(Cl)] (1-Cl), which contains π-bonded biphenyltetramethylcyclopentadienyl (Cpxbiph) and C^N-chelated phenylpyridine (phpy) ligands, undergoes rapid hydrolysis of the chlorido ligand. In contrast, the pyridine complex [(η5-Cpxbiph)Ir(phpy)(py)]+ (1-py) aquates slowly, and is more potent (in nanomolar amounts) than both 1-Cl and cisplatin towards a wide range of cancer cells. The pyridine ligand protects 1-py from rapid reaction with intracellular glutathione. The high potency of 1-py correlates with its ability to increase substantially the level of reactive oxygen species (ROS) in cancer cells. The unprecedented ability of these iridium complexes to generate H2O2 by catalytic hydride transfer from the coenzyme NADH to oxygen is demonstrated. Such organoiridium complexes are promising as a new generation of anticancer drugs for effective oxidant therapy.en_US
dc.description.sponsorshipWe thank the ERC (247450), SNSF (PA00P2_145308 for N.P.E.B.), IAS (for I.R.C.), BBSRC (for J.M.H.), Science City (AWM and ERDF), and the EPSRC for support, and Prof. Timothy Bugg and members of EC COST Action CM1105 for stimulating discussions. We also thank Professor Pat Unwin, Mike Snowden, and Rob Lazenby for their help with the electrochemical experiments and the National Cancer Institute for NCI-60 human tumor cell panel screening.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1002/anie.201311161en_US
dc.rights©2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.en_US
dc.subjectAnticancer drugs; Biocatalysts; Hydride transfer; Iridium; Reactive oxygen speciesen_US
dc.titleThe potent oxidant anticancer activity of organoiridium catalystsen_US
dc.status.refereedYesen_US
dc.date.Accepted2014
dc.date.application2014-03-11
dc.typeArticleen_US
dc.type.versionPublished versionen_US
refterms.dateFOA2018-07-26T09:23:02Z


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