title: The potent oxidant anticancer activity of organoiridium catalysts.
abstract: 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 H2 O2 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.
authors.affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL (UK).
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.forename: Isolda
authors.initials: I
authors.lastname: Romero-Canelón
authors.forename: Bushra
authors.initials: B
authors.lastname: Qamar
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Hearn
authors.forename: Abraha
authors.initials: A
authors.lastname: Habtemariam
authors.forename: Nicolas P E
authors.initials: NP
authors.lastname: Barry
authors.forename: Ana M
authors.initials: AM
authors.lastname: Pizarro
authors.forename: Guy J
authors.initials: GJ
authors.lastname: Clarkson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sadler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002384:Catalysis; D002945:Cisplatin / Q000737:chemistry*; D006801:Humans; D007495:Iridium / Q000737:chemistry*; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry*; D017382:Reactive Oxygen Species; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D007495:Iridium; D002945:Cisplatin
keywords: anticancer drugs; biocatalysts; hydride transfer; iridium; reactive oxygen species