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The Potent Oxidant Anticancer Activity of Organoiridium Catalysts
Author(s) -
Liu Zhe,
RomeroCanelón Isolda,
Qamar Bushra,
Hearn Jessica M.,
Habtemariam Abraha,
Barry Nicolas P. E.,
Pizarro Ana M.,
Clarkson Guy J.,
Sadler Peter J.
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201311161
Subject(s) - chemistry , pyridine , ligand (biochemistry) , reactive oxygen species , catalysis , glutathione , iridium , cofactor , cisplatin , hydride , combinatorial chemistry , stereochemistry , gold compounds , chelation , medicinal chemistry , enzyme , metal , biochemistry , receptor , organic chemistry , biology , chemotherapy , genetics
Platinum complexes are the most widely used anticancer drugs; however, new generations of agents are needed. The organoiridium(III) complex [(η 5 ‐Cp xbiph )Ir(phpy)(Cl)] ( 1‐Cl ), which contains π‐bonded biphenyltetramethylcyclopentadienyl (Cp xbiph ) and C^N‐chelated phenylpyridine (phpy) ligands, undergoes rapid hydrolysis of the chlorido ligand. In contrast, the pyridine complex [(η 5 ‐Cp xbiph )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 H 2 O 2 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.