Oxidation of 7-deazaguanine by one-electron and oxo-transfer oxidants: Mismatch-dependent electrochemistry and selective strand scission

Addition of oligonucleotides containing 7-deazaguanine (Z) to solutions con taining Ru(dmb)(3)(2+) (dmb = 4,4'-dimethyl-2,2'-bipyridine) produces an en hancement in the oxidative current in the cyclic voltammogram of the metal complex that can be used, through digital simulation, to determine the rate of oxidation of 7-deazaguanine by Ru(dmb)(3)(3+). The measured rate consta nts are about 10 times higher than those for oxidation of guanine by Ru(bpy )(3)(3+), even though the redox potential of Ru(dmb)(3)(3+/2+) is 200 mV lo wer. A potential of 0.75 V (vs Ag/ AgCl) can therefore be estimated for the oxidation of 7-deazagnanine, which can be selectively oxidized over guanin e when Ru(dmb)(3)(3+) is the oxidant. The rate of oxidation was much faster in sinele-stranded DNA, and the difference between rates of single-strande d and duplex DNA was higher than for guanine. The oxidation rate was also s ensitive to the presence of a single-base mismatch at the 7-deazaguanine in the order Z.C < Z.T < Z.G similar to Z.A < single-stranded. The Z.T mismat ch was much more readily distinguished than the G.T mismatch, consistent Wi th the overall greater sensitivity to secondary structure for Z. The oxidat ion reaction was also probed by monitoring piperidine-labile cleavage at th e Z nucleotide, which could be generated by treatment with either photogene rated Ru(bpy)(3)(3+) or the thermal oxidant Ru(tpy)(bpy)O2+ (tpy = 2,2',2"- terpyridine). These oxidants gave qualitatively similar selectivities to th e electron-transfer rates from cyclic voltammetry, although the magnitudes of the selectivities were considerably lower on the sequencing gels.