Glutathione activation of an organometallic half-sandwich anticancer drug candidate by ligand attack

Abstract

In contrast to the clinical drug cisplatin, the anticancer complex [Os(η⁶-p-cymene)(4-(2-pyridylazo)-N,N-dimethylaniline)I]⁺ [1-I] is inert towards hydrolysis and targets cancer cell metabolism rather than DNA. A combination of DFT calculations and X-ray absorption spectroscopy (XAS) suggests that hydrolytic activation of 1-I involves catalytic attack by the intracellular tripeptide glutathione (GSH) on the azo bond of the chelating ligand in the complex.