The Potent Oxidant Anticancer Activity of Organoiridium Catalysts

Authors:
  • JHJessica M. Hearn
    Jessica M. Hearn
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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 both1‐Cland cisplatin towards a wide range of cancer cells. The pyridine ligand protects1‐pyfrom rapid reaction with intracellular glutathione. The high potency of1‐pycorrelates 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 H2O2by 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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