Gas-phase ionization potentials (IPs) were evaluated for anionic 2’-deoxyguanosine 5’-phosphate (5’-dGMP(-)) and for 5’-dGMP(-) in water, counterion clusters with Na+. Gas-phase IPs of isolated 5’-dGMP(-) and of 5’-dGMP(-) in clusters containing Naf and 4, 8, 11, 12, and 14 water molecules, obtained from ab initio self-consistent field (SCF) molecular orbital calculations, were corrected by employing gas-phase UV photoelectron data on the model compounds 1,9-dimethylguanine, 3-hydroxytetrahydrofuran, and water together with results from second-order Moller-Plesset and configuration interaction singles calculations on the model anion CH3HPO4-. The correction procedure depends on results from recent investigations (Kim, H. S.; Yu, M.; Jiang, Q.; LeBreton, P. R. J. Am. Chem. Sec. 1993, 115, 6169-6183. Kim, Il. S.; LeBreton, P. R. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 3725-3729), which indicate that the upper occupied nucleotide valence orbitals described by SCF calculations with split valence basis sets are largely localized on the base, sugar, or phosphate groups. In the gas-phase, the nucleotide environment strongly influences the IPs. For the gas-phase cluster 5’-dGMP(-). 14H(2)O . Na+ (cluster I), in which Na+ is bound to phosphate, the lowest energy base, sugar, and phosphate IPs are 2.2, 2.3, and 3.7 eV smaller than corresponding IPs in 5’-dGMP(-) without H2O or Na+, and the energetic ordering of IPs is different. In 5’-dGMP(-), the lowest energy base IP (5.8 eV) is 0.4 eV larger than that of the phosphate group. In cluster I, the base IP (8.0 eV) is 1.1 eV smaller than that of the phosphate group. Gibbs free energies associated with ionization in aqueous solution (aci,,;,(solution)) were obtained by adding the difference (Delta Delta G(hyd)) between the hydration energies of 5’-dGMP(-) or of the 5’-dGMP(-) clusters, before and after ionization, to the corrected gas phase IPs : Delta G(ioniz)(solution) approximate to IP + Delta Delta G(hyd). Differences between corresponding values of Delta G(ioniz)(solution) for ionization from 5’-dGMP(-) versus 5’-dGMP(-) in clusters are smaller than differences between gas-phase IPs. In cluster I, values of Delta G(ioniz)(solution) for the lowest energy base and phosphate ionization events (6.7 and 8.3 eV, respectively) are 0.1 and 0.9 eV larger than for 5’-dGMP(-). In the cluster, the lowest sugar ionization energy (8.6 eV) is 0.3 eV smaller than in 5’-dGMP(-). Nucleotide reactivities toward the carcinogen, N-methyl-N-nitrosourea, which methylates DNA via a reactive methane diazonium ion (CH3N2+), increase as nucleotide base it ionization potentials decrease. Employing transition-state geometries obtained from semiempirical MNDO calculations for gas-phase reactions of CH3N2+ With nucleoside model compounds (9-methylguanine, 9-methyladenine, I-methylcytosine, and 1-methylthymine), results from single-point ab initio 4-31G and 6-31G SCF calculations provide evidence that the activation barriers are strongly influenced by hydration, and that nucleotide base pi polarization effects, modulated by steric interactions, play an important role in determining DNA methylation patterns.