UV photoelectron data for 1,9-dImethylguanine, 3-hydroxytetrahydrofuran, and water, and results from ab initio self-consistent field (SCF) and post-SCF molecular orbital calculations were employed to describe valence electrons in clusters of 2'-deoxyguanosine 5'-phosphate (5'-dGMP-) with four water molecules and a phosphate-bound sodium ion. Two clusters (A and B) were ex . In A, Na+ is coordinated to 5'-dGMP-. In B, Na+ and 5'-dGMP-are separated by water. In 5'-dGMP-clusters, the nucleotide valence ionization potentials (IPs) are different from those previously reported for isolated 5'-dGMP-. The smIllest IP in isolated 5'-dGMP-(4.6 eV) arises from the phosphate group; thesmallestIPs inA (8.2 eV) andB (7.9 eV) arise from the base. In the clusters, the IPs associated with the seven upper occupied base orbitals differ from corresponding IPs in 1,9-dimethylguanine by less than 0.4 eV. In A and B, the smaller ]IP of the base, compared with the phosphate group, is consistent with reactivity data indicating that DNA and RNA are subject to electrophilic SN2 attack by carcinogens such as N-methyl-Nnitrosourea, dimethyl and diethyl sulfate, and methyl and ethyl methanesulfonate, in which more than 75% of nucleotide alkylation occurs at the bases. While isolated nucleotides (1, 2, 4) have been investigated, nucleotides in the presence of water and counterions, which interact with DNA in physiological environments, have not. One goal of this investigation is to examine electrons in 2'-deoxyguanosine 5'-phosphate (5'-dGMP-) with 4 water molecules and a Na+ counterion. DNA binding occurs dynamically on a picosecond time scale (5, 6); nevertheless, information about solvent-counterion influences on nucleotide electronic structure can be obtained by examining statistically significant clusters. Fig. 1 shows two clusters (A and B) in which Na+ and 3 of the 4 water molecules bind to the phosphate group of 5'-dGMP-.X-ray (7,8), IR (9), and NMR (10) data indicate that phosphate in DNA is a principal hydration and Na+ binding site. In crystals of guanylyl (3'-5')cytidine nonahydrate, Na+ ions are octahedrally coordinated to the negative 0 atoms of phosphate and to H20 (11). Different theoretical approaches (5,(12)(13)(14)(15) indicate that Na+ binds in the grooves of DNA and along the backbone; however, recent molecular dynamics calculations point to the importance of Na+ binding at