Data from He(I) UV photoelectron measurements have been used in conjunction with results from ab initio SCF molecular orbital calculations, and ab initio and semiempirical post-SCF calculations to describe the valence electronic structures of neutral and anionic 2'-deoxyguanosine 5'-phosphate (5'-dGMP). Analogous to 2'-deoxycytidine 5'-phosphate (Tasaki, K.; Yang, X.; Urano, S.; Fetzer, S.; LeBreton, P. R. J. Am. Chem. Soc. 1990, 112, 538-548), results from calculations on 5'-dGMP and 5'-dGMP-, carried out at the SCF level with a split-valence basis set, indicate that valence orbital electron distributions are localized on the base, sugar, or phosphate groups. This provides evidence that valence electron ionization in 5'-dGMP and 5'-dGMP- is similar to ionization in the model compounds 1,9-dimethylguanine (1), 3-hydroxytetrahydrofuran (2), trimethyl phosphate (3), methyl phosphate, and H3PO4 and in the model anions CH3HPO4- and H2PO4-. According to SCF calculations with the 6-31G basis set, the five upper occupied base orbitals and the two upper occupied sugar orbitals in 5'-dGMP and 5'-dGMP- are similar to orbitals appearing in 1 and 2. Supplementary semiempirical HAM/3 configuration interaction (CI) calculations on 1,9-dimethylguanine (1) and 3-hydroxytetrahydrofuran (2) indicate that three of the first five ionization potentials (IPs) in 1, and the first two IPs in 2 are associated with cation states which are qualitatively well described by Koopmans' theorem. The results of the HAM/3 CI calculations on 1 indicate that only two low-energy ionization events are influenced by CI effects. These cause hole-mixing associated with configurations arising from removal of electrons from the second and third highest occupied pi orbitals. In a parallel investigation of neutral and anionic phosphate, results from second-order Moller-Plesset perturbation (MP2) calculations and from ab initio configuration interaction calculations using the CI singles (CIS) method indicate that CI effects strongly influence the second lowest energy ionization event arising from removal of electrons from H3PO4 and the five lowest energy ionization events arising from removal of electrons from the closed shell anion H2PO4-. The similarity between valence orbital structure in the nucleotides and in the model compounds and anions makes it possible, employing experimental photoelectron data and computational results obtained at the post-SCF level for the model compounds and anions, to individually correct IPs calculated for 5'-dGMP and 5'-dGMP- at the 6-31G SCF level. For 5'-dGMP, this approach yields IPs of 8.4, 9.8, and 11.4-11.6 eV for the base, sugar, and phosphate groups, respectively. For 5'-dGMP-these groups have IPs of 5.9, 6.6, and 4.6 eV. A comparison of nucleotide IPs with alkylation patterns occurring in polynucleotide reactions of N-methyl-N-nitrosourea, dimethyl and diethyl sulfate, and methyl and ethyl methanesulfonate demonstrates that the percent alkylation which occurs at the different bases increases as the nucleotide base pi ionization potentials decrease. These results are consistent with the observation that these alkylating agents are soft electrophiles which exhibit increasing S(N)2 reactivity toward nucleotide bases with increasing pi polarizabilities.