Addition of oligonucleotides containing 7-deazaguanine (Z) to solutions containing Ru(dmb)(3)(2+) (dmb = 4,4'-dimethyl-2,2'-bipyridine) produces an enhancement 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 constants 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 lower. 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 guanine 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-stranded and duplex DNA was higher than for guanine. The oxidation rate was also sensitive 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 mismatch was much more readily distinguished than the G.T mismatch, consistent With the overall greater sensitivity to secondary structure for Z. The oxidation reaction was also probed by monitoring piperidine-labile cleavage at the Z nucleotide, which could be generated by treatment with either photogenerated Ru(bpy)(3)(3+) or the thermal oxidant Ru(tpy)(bpy)O2+ (tpy = 2,2',2"-terpyridine). These oxidants gave qualitatively similar selectivities to the electron-transfer rates from cyclic voltammetry, although the magnitudes of the selectivities were considerably lower on the sequencing gels.