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 language | English |
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Pages (from-to) | 3941-3946 |
Number of pages | 6 |
Journal | Angewandte Chemie - International Edition |
Volume | 53 |
Issue number | 15 |
Early online date | 11 Mar 2014 |
DOIs | |
Publication status | Published - 7 Apr 2014 |
Keywords
- anticancer drugs
- biocatalysts
- hydride transfer
- iridium
- reactive oxygen species
ASJC Scopus subject areas
- Catalysis
- General Chemistry
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The potent oxidant anticancer activity of organoiridium catalysts
1/03/14 → 26/03/14
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