Energetics of Uracil Cation Radical and Anion Radical Ion-Molecule Reactions in the Gas Phase Frantis ˇek Turec ˇ ek* and Jill K. Wolken Department of Chemistry, Bagley Hall, Box 351700, UniVersity of Washington, Seattle, Washington 98195-1700 ReceiVed: May 4, 2001; In Final Form: July 9, 2001 The uracil cation radical was calculated to exist predominantly as the 1,3-dioxo tautomer 1 • + , similar to the most stable tautomer of neutral uracil (1). The enol forms of 1 • + were found to be 10-173 kJ mol -1 less stable than 1 • + and should not be significantly populated at 298 K thermal equilibrium. Cation radical 1 • + is a moderately strong gas-phase acid of topical acidities ΔH acid ) 829, 921, 916, and 879 kJ mol -1 for the H-1, H-3, H-5, and H-6 protons, respectively. Ion 1 • + is capable of exothermic protonation of adenine, guanine, and cytosine, and of the arginine, lysine, histidine, and tryptophan amino acid residues in proteins. The hydrogen atom affinities of 1 • + were -ΔH rxn ) 432, 371, and 360 kJ mol -1 for H-atom additions to O-4, O-2, and C-5, respectively. 1 • + was calculated to exothermically abstract the thiol hydrogen atom from CH 3 SH, the hydroxyl hydrogen from phenol, and an R-hydrogen atom from glycine N-methylamide. Uracil radicals formed by deprotonation of 1 • + were calculated to have large hydrogen atom affinities that should allow for exothermic abstraction of H-atoms from thiol groups, phenolic hydroxyls, and amino acid backbone R-methylene and methine groups. Protonation by a uracil cation radical followed by hydrogen atom abstraction can propagate radiation damage from the initial ionization site. In contrast to the highly reactive uracil cation radicals and radicals, the weakly bound uracil anion radical (1 • - ) was predicted to be much less reactive in the gas phase. Ion-molecule reactions of 1 • - by proton and hydrogen atom abstractions from thiols, phenol, and R-positions of amino acids were calculated to be endothermic and thus very slow in the gas phase. 1 • - can selectively deprotonate carboxylic groups as calculated for the reaction with glycine. Introduction Radiation damage in DNA and RNA occurs by direct or indirect action of high-energy photons or electrons on the nucleobase and, to a lesser extent, carbohydrate residues. 1 In the direct mechanism, the nucleobase is ionized by the radiation to form a cation radical. 1,2 The latter is a highly reactive species in the condensed phase that undergoes a variety of reactions that can chemically modify the nucleobase itself and the surrounding chemical moieties. In the indirect mechanism, the nucleobase captures a thermal electron produced by primary ionization to form an anion radical. 3 Further reactions of the anion radical then can result in chemical modifications of the nucleobase or other chemical moieties in the vicinity of the anion radical. Although redox and addition reactions of nucleobase radicals and ions have been studied extensively in aqueous solution as reviewed, 2 there are no reliable data on the reaction energetics. The gas phase represents a suitable reference medium in which the reaction energetics can be established in the absence of solvent effects and other interferences. There have been recent reports on ion-molecule reactions of gas-phase nucleobase cation radicals with several neutral counterparts 4a and neutral nucleobases with gas-phase radical cations that showed electron and proton transfer as well as radical addition reactions. 4b However, thermochemical data are currently unavailable for most ion-molecule reactions of interest to gas-phase ion chemistry and radiation damage. In this paper we examine by high-level ab initio calculations the energetics of gas-phase reactions of the cation radical and anion radical of the RNA nucleobase uracil. The reactions studied here comprise proton, hydrogen atom, hydride, and methanethiyl radical transfers. These reactions model interactions of nucleobase ion radicals with neutral nucleobases and also with the peptide backbone and amino acid side chains in proteins containing cysteine, cystine, and tyrosine residues that are considered the prime targets for radical-induced DNA- or RNA-protein reactions. 1 Calculations Standard ab initio and density functional theory calculations were performed using the Gaussian 98 suite of programs. 5 Geometries were optimized using Becke’s hybrid functional (B3LYP) 6 and the 6-31+G(d,p) basis set. Spin-unrestricted calculations (UB3LYP) were used for open-shell systems. Spin contamination in the UB3LYP calculations was small as judged from the 〈S 2 〉 operator expectation values that were 0.75-0.77. The optimized structures were characterized by harmonic frequency analysis as local minima (all frequencies real) or first- order saddle points (one imaginary frequency). Complete optimized structures in the Cartesian coordinate format and total energies are available from the corresponding author (F. T.) upon request. The B3LYP/6-31+G(d,p) frequencies were scaled by 0.963 (ref 7; for other scaling factors see ref 8) and used to calculate zero-point vibrational energies (ZPVE) and enthalpy corrections. The rigid-rotor harmonic oscillator approximation was used in all thermochemical calculations. Single-point energies were calculated at several levels of theory. In two sets * Corresponding author. Telephone: (206) 685-2041. Fax: (206) 685- 3478. E-mail: turecek@chem.washington.edu. 8740 J. Phys. Chem. A 2001, 105, 8740-8747 10.1021/jp0116860 CCC: $20.00 © 2001 American Chemical Society Published on Web 09/01/2001