Experimental and theoretical studies on the selectivity of GGG triplets toward one-electron oxidation in B-form DNA

The selectivity of 5'-TGGGT-3' and 5'-CGGGC-3' sequences toward photoinduced one-electron oxidation was examined experimentally and by ab initio molecular orbital (MO) calculations. It was confirmed experimentally that Gz of 5'-TG(1)G(2)G(3)T-3' is more reactive than G(1), while for 5'-CG(1)G(2)G(3)C-3' the selectivity is reversed, that is, G(1) > G(2). The ab initio MO analyses were performed to elucidate the difference of the selectivities between 5'-TGGGT-3' and 5'-CGGGC-3' sequences. For the 5'-TGGG-3' sequence, the spin densities of G(1)(.) and G(2)(.) in neutral radical (5'-TG(1)G(2)G(3)-3')(.) have a similar pattern, and the shapes of the corresponding radical orbitals are also very similar. It was concluded that the selectivity is due to the stability of the (5'-TG(1)G(2)G(3)-3')(.) neutral radicals; that is, 5'-TG(1)G(2)(.)G(3)-3' is more stable in energy than 5'-TG(1)(.)G(2)G(3)-3'. For the 5'-CGGG-3' sequence, it was found that the spin density on NI of G(1)(.) in neutral radical (5'-CG(1)G(2)G(3)-3')(.) is distinguishably different from the corresponding spin density of G(2)(.) which has a pattern similar to those of G(1)(.) and G(2)(.) in 5'-TG(1)G(2)G(3)-3'. The radical orbital (SOMO) of G(1)(.) is delocalized on guanine base and up to the paired cytosine base, while the radical orbital of G(2)(.) is essentially localized on guanine base. This drastic difference of the electron population in the radical orbitals, caused by the stacking interaction with the 5'-side G of the opposite strand, can explain why G(1) is more reactive than G(2) in the 5'-CG(1)G(2)G(3)-3' sequence.