The potent oxidant anticancer activity of organoiridium catalysts

Zhe Liu, Isolda Romero-Canelõn, Bushra Qamar, Jessica M. Hearn, Abraha Habtemariam, Nicolas P.E. Barry, Ana M. Pizarro, Guy J. Clarkson, Peter J. Sadler

Research output: Contribution to journalArticlepeer-review

219 Citations (Scopus)
103 Downloads (Pure)

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-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 2O2 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. Protective pyridine: A novel half-sandwich organoiridium(III) complex with a pyridine ligand is more potent than both its chloride analogue and cisplatin towards a wide range of cancer cells. The pyridine ligand protects the iridium complex from rapid reactions with glutathione, and its potency correlates with a substantial increase in the amount of reactive oxygen species in the cancer cells.

Original languageEnglish
Pages (from-to)3941-3946
Number of pages6
JournalAngewandte Chemie - International Edition
Volume53
Issue number15
Early online date11 Mar 2014
DOIs
Publication statusPublished - 7 Apr 2014

Keywords

  • anticancer drugs
  • biocatalysts
  • hydride transfer
  • iridium
  • reactive oxygen species

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Fingerprint

Dive into the research topics of 'The potent oxidant anticancer activity of organoiridium catalysts'. Together they form a unique fingerprint.

Cite this