ic0619714_si_003.pdf (229.69 kB)
Preferential DNA Cleavage under Anaerobic Conditions by a DNA-Binding Ruthenium Dimer
journal contribution
posted on 2007-04-30, 00:00 authored by Thamara K. Janaratne, Abhishek Yadav, Fiona Ongeri, Frederick M. MacDonnellIn 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.