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    The potent oxidant anticancer activity of organoiridium catalysts

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    Publication date
    2014-04
    Author
    Liu, Z.
    Romero-Canelón, I.
    Qamar, B.
    Hearn, J.M.
    Habtemariam, A.
    Barry, Nicolas P.E.
    Pizarro, A.M.
    Clarkson, G.J.
    Sadler, P.J.
    Keyword
    Anticancer drugs; Biocatalysts; Hydride transfer; Iridium; Reactive oxygen species
    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.
    Peer-Reviewed
    Yes
    
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    Abstract
    Platinum 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.
    URI
    http://hdl.handle.net/10454/11201
    Version
    Published version
    Citation
    Liu 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.
    Link to publisher’s version
    http://dx.doi.org/10.1002/anie.201311161
    Type
    Article
    Collections
    Life Sciences Publications

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