Effects of base stacking on guanine electron transfer: Rate constants for G and GG sequences of oligonucleotides from catalytic electrochemistry

The electron-transfer rate constants for oligonucleotides containing adjace nt guanines were determined by digital simulation of cyclic voltammograms o f Ru(bpy)(3)(2+) in the presence of the oligonucleotides (bpy = 2,2'-bipyri dine). These experiments showed that sequences containing an isolated guani ne (included in a 5'-AGT segment) gave a rate constant of 1.4 x 10(5) M-1 S -1 (in terms of guanine concentration) while sequences containing a 5'-GG s egment gave an overall rate constant of 7.5 x 10(5) M-1 s(-1). Both rate co nstants were independent of DNA concentration in the simulations. By assumi ng that the 3'-G of the GG doublet exhibits the same rate constant as the i solated guanine, we estimate the ratio of rate constants for the 5'-G of th e GG doublet to the 3'-G to he k(GG)/k(G) = 12 +/- 2 This value was indepen dent of DNA concentration and scan rate. Similar experiments using oligonuc leotides containing inosine (I) in place of guanosine gave the same rate co nstant for a 5'-IG doubler as for isolated guanine (k(IG)/k(G) = 1.0 +/- 0. 2) but Save significant enhancement for the 5'-GI sequence (k(GI)/k(G) = 2. 8 +/- 0.4). These experiments show that it is in fact the 5'-G that is enha nced and support the assumption that the 3'-G of the GG doublet gives the s ame rate constant as isolated guanine. stacking of guanines on the 5' side of 7-deazaguanine did not produce current enhancements as large as those fo r the GG segments, strongly supporting the idea that favorable placement of the electronegative N7 atom of the 3' base in the doubler is responsible f or the increased electron donor reactivity.