A recent experimental report on the suppression of the oxidative decomposition of guanines in deoxyribonucleic acid (DNA) double helices due to the attachment of a phenyl group to a guanine [Nakatani, K.; Dohno, C.; Saito, I. J. Am. Chem. Soc. 2002, 124, 6802] is examined by semiempirical Hartree-Fock (HF) molecular orbital (MO) calculations and ab initio HF MO calculations with the STO-3G basis set. Because of this attachment, the energy level of MO localized on the guanine shifts to lower energy in a vacuum, whereas it shifts to higher energy in water. This is mainly because the energy reduction of MO levels by the water solvent becomes smaller when the solvent molecules are excluded by the phenyl group. Consequently, a hole trap is enhanced at the phenylated guanine base in water. The observed suppression of the oxidative decomposition of guanines around the phenylated guanine is thus explained by considering the solvent effects. In addition, we have observed that energy shifts due to a benzyl group or a tert-butyl group are similar to those due to the phenyl group in our calculation.

We examined the ionization potential (IP) corresponding to the free energy of a hole on duplex DNA by semiempirical molecular orbital theory with a continuum solvent model. As for the contiguous guanines (a guanine run), we found that the IP in the gas phase significantly decreases with the increasing number of nucleotide pairs of the guanine run, whereas the IP in water (OP, oxidation potential) only slightly does. The latter result is consistent with the experimental result for DNA oligomers in water. This decrease in the IP is mainly due to the attractive electrostatic interaction between the hole and a nucleotide pair in the duplex DNA. This interaction is reduced in water, which results in the small decrease in the IP in water. This mechanism explains the discrepancy between the experimental result and the previous computational results obtained by neglecting the solvent. As for the chemically modified guanine, the previous work showed that the removal of some solvent (water) molecules due to the attachment of a neutral functional group to a guanine in a duplex DNA stabilizes the hole on the guanine. One might naively have expected the opposite case, since a polar solvent usually stabilizes ions. This mechanism also explains this unexpected stabilization of a hole as follows. When some water molecules are removed, the attractive electrostatic interaction stabilizing the hole increases, and thus, the hole is stabilized. In order to design the hole energetics by a chemical modification of DNA, this mechanism has to be taken into account and can be used.