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The potent oxidant anticancer activity of organoiridium catalysts
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.
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.
Publication Date
2014-04
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©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.
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2014
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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.
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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.
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