Effects of Microsolvation on the Adenine-Uracil Base Pair and Its Radical Anion: Adenine-Uracil Mono- and Dihydrates ² Sunghwan Kim and Henry F. Schaefer, III* Center for Computational Chemistry, UniVersity of Georgia, Athens, Georgia 30602 ReceiVed: April 6, 2007; In Final Form: May 25, 2007 Microhydration effects upon the adenine-uracil (AU) base pair and its radical anion have been investigated by explicitly considering various structures of their mono- and dihydrates at the B3LYP/DZP++ level of theory. For the neutral AU base pair, 5 structures were found for the monohydrate and 14 structures for the dihydrate. In the lowest-energy structures of the neutral mono- and dihydrates, one and two water molecules bind to the AU base pair through a cyclic hydrogen bond via the N 9 -H and N 3 atoms of the adenine moiety, while the lowest-lying anionic mono- and dihydrates have a water molecule which is involved in noncyclic hydrogen bonding via the O 4 atom of the uracil unit. Both the vertical detachment energy (VDE) and adiabatic electron affinity (AEA) of the AU base pair are predicted to increase upon hydration. While the VDE and AEA of the unhydrated AU pair are 0.96 and 0.40 eV, respectively, the corresponding predictions for the lowest-lying anionic dihydrates are 1.36 and 0.75 eV, respectively. Because uracil has a greater electron affinity than adenine, an excess electron attached to the AU base pair occupies the π* orbital of the uracil moiety. When the uracil moiety participates in hydrogen bonding as a hydrogen bond acceptor (e.g., the N 6 -H 6a ‚‚‚O 4 hydrogen bond between the adenine and uracil bases and the O w -H w ‚‚‚N and O w -H w ‚‚‚O hydrogen bonds between the AU pair and the water molecules), the transfer of the negative charge density from the uracil moiety to either the adenine or water molecules efficiently stabilizes the system. In addition, anionic structures which have C-H‚‚‚O w contacts are energetically more favorable than those with N-H‚‚‚O w hydrogen bonds, because the C-H‚‚‚O w contacts do not allow the unfavorable electron density donation from the water to the uracil moiety. This delocalization effect makes the energetic ordering for the anionic hydrates very different from that for the corresponding neutrals. Introduction Carcinogenic and mutagenic effects 1-8 of high-energy radia- tion arise from the ability of photons to produce lethal DNA lesions such as modified bases, 9-11 abasic sites, 12-15 interstrand cross-links, 16-19 and single- and double-strand breaks (SSBs and DSBs). 20-22 At an initial step of radiation-induced DNA damage, radiation generates positive holes within the DNA duplex by ionizing the nucleic acid bases (NABs). 23-30 Migration of these positive charges tends toward guanine sites, leading to formation of various oxidative products. 31-37 On the other hand, ionizing radiation can cause DNA damage not only through the direct hit by high-energy quanta, but also through the interaction of DNA components with low-energy electrons (LEEs), 38-44 which are mainly generated by radiolysis of water. 45 Moreover, many experimental and theoretical studies proved that LEEs even at energies of zero or near-zero eV can induce DNA damage. 46-52 Recently, Sanche and co-workers 53 qualitatively analyzed various radiation products that were generated by irradiating solid thin films of tetrameric nucleotides with 10 eV electrons under ultrahigh vacuum. On the basis of the distribution of the radiation products, Sanche suggested that an initial step in DNA damage by LEEs involves electron attachment to the NABs, followed by electron transfer to the sugar-phosphate backbone and subsequent dissociation of the phosphodiester bond. Simi- larly, in recent theoretical studies using density functional theory (DFT), Leszczynski and co-workers 49,50 demonstrated that the attachment of LEEs to NABs can give rise to DNA strand breaks by C3′-O3′ or C5′-O5′ σ-bond cleavage. In this respect, the electron affinities of the NABs are of importance in understand- ing the mechanism of radiation-induced DNA damage. While most of early ab initio studies predicted negative adiabatic electron affinities for all NABs, Adamowicz and co- workers 54-56 suggested the existence of the dipole bound anions in which an electron is trapped in a dipole field of the neutral molecule. Desfrancois et al. 57 employed Rydberg electron transfer (RET) spectroscopy to detect the dipole-bound anions of uracil, thymine, and adenine. The adiabatic electron affinities (AEAs) arising from these dipole-bound anionic states were determined to be 0.054 ( 0.035, 0.068 ( 0.020, and 0.012 ( 0.005 eV for uracil, thymine, and adenine, respectively. Using negative ion photoelectron spectroscopy, Bowen and co- workers 58 also detected the dipole-bound anions of uracil and thymine. However, the existence of the dipole bound states in aqueous phases seems improbable, because the former are strongly destabilized in condensed or aqueous phases due to their diffuse character. 59 Instead, the valence-bound anions are thought to be the predominant form of NAB negative ions in aqueous solution and in living organisms. While the gas-phase AEAs of the NABs arising from the valence anionic states are thought to be negative or near zero eV, 60 hydration effects in aqueous solution are known to increase the AEAs of NABs. 61-64 Using photodetachment-photoelectron spectroscopy, Schiedt, Weinkauf, Neumark, and Schlag 61 found ² Part of the special issue "Robert E. Wyatt Festschrift". * Corresponding author. E-mail: hfs@uga.edu. 10381 J. Phys. Chem. A 2007, 111, 10381-10389 10.1021/jp072727g CCC: $37.00 © 2007 American Chemical Society Published on Web 08/18/2007