Long-range oxidation of guanine by Ru(III) in duplex DNA

Theoretical and experimental studies have demonstrated that 5'-GG-3' sequences in DNA are 'hot spots' for oxidative damage, but few studies have definitively addressed whether oxidative damage to DNA may arise from a distance via long-range charge migration. Towards this end, we have prepared tethered ruthenium (Ru)-oligonucleotide duplexes and used a flash-quench strategy to demonstrate long-range charge transport through the DNA double helix.

DNA assemblies containing a tethered Ru(II) intercalator have been synthesized. Ru(III), generated in situ in the presence of externally bound electron-transfer quenchers, promotes base damage selectively at the 5'-G of a 5'-GG-3' doublet located approximately 37 A from the binding site of the oxidant. In the absence of a guanine doublet, oxidative damage occurs equally at all guanine bases in the strand. Oxidative damage is also observed at long range for guanine in a G.A mismatch but not in a G.T mismatch.

The present study expands the scope of long-range electron-transfer chemistry in terms of experiments, applications, and possible reactions within the cell. Here we demonstrate oxidative damage to DNA occurring with a high quantum yield over a distance of approximately 37ůsing a ground-state oxidant. These results point to the equilibration of the radical across the DNA duplex to the sites of lowest energy. In addition, this charge migration is sensitive to the intervening pi-stack formed by DNA base pairs and hence may be useful for the detection of mismatches.