Preferential DNA Cleavage under Anaerobic Conditions by a DNA-Binding Ruthenium Dimer

In the absence of dioxygen, the cationic complex [(phen)₂Ru(tatpp)Ru(phen)₂]⁴⁺ (P⁴⁺) undergoes in situ reduction by glutathione (GSH) to form a species that induces DNA cleavage. Exposure to air strongly attenuates the cleavage activity, even in the presence of a large excess of reducing agent (e.g., 40 equiv of GSH per P⁴⁺), suggesting that the complex may be useful in targeting cells with a low-oxygen microenvironment (hypoxia) for destruction via DNA cleavage. The active species is identified as the doubly reduced, doubly protonated complex H₂P⁴⁺, and a carbon-based radical species is implicated in the cleavage action. We postulate that the dioxygen concentration regulates the degree to which the carbon radical forms and thus regulates the DNA cleavage activity.