Chemistry, University of Illinois at Chicago, Chicago, IL, USA. The evaluation of nucleotide photoionization threshold energies provides useful information for understanding mechanisms of carcinogenesis. A comparison of aqueous photoionization energies with gas-phase ionization potentials indicates that hydration lowers these energies by 3.31 to 3.83 eV for the nucleobases, 2.92 to 3.11 eV for the nucleosides and alters the ionization events for the nucleotides. Nucleotides in gas-phase are ionized at the phosphate moiety but hydration favors base ionization, which is consistent with experimental data indicating that at 77 K in aqueous perchlorate glasses, the primary photoionization pathway involves base ionization followed by deprotonation. The gas-phase ionization potentials were calculated using the B3LYP/6-31þG* density functional method. Solvation energy calculations were performed employing the SM8 continuum solvation model. The photoionization energies in aqueous solution are estimated to be 4.78, 5.08, and 4.96, and 5.26 eV for 5’dGMP-, 5’dCMP-, 5’dAMP-, and 5’dTMP-, respectively. For the test molecules indole and tryptophan the aqueous photoionization energies (4.26 and 4.18 eV, respectively) are in agreement with the experimental values (4.35 and 4.45 eV). The SN2 transition states of the methylation reaction of guanine with dimethyl sulfate, the vapors of which may cause severe inflammation and necrosis of the eyes, mouth, and respiratory tract of humans and tumors in the nasal passages, lungs, and thorax of animals, were examined in the gas-and aqueous-phases at N7, N3 and O6 sites employing the same theoretical approach. Results show that the transition states in water are influenced by steric interactions, and the activation barriers are lower by 4.0 to 11.0 kcal/mol than in the gas-phase.