title: Do Solvated Electrons (e(aq)⁻) Reduce DNA Bases? A Gaussian 4 and Density Functional Theory-Molecular Dynamics Study.
abstract: The solvated electron (e(aq)⁻) is a primary intermediate after an ionization event that produces reductive DNA damage. Accurate standard redox potentials (E(o)) of nucleobases and of e(aq)⁻ determine the extent of reaction of e(aq)⁻ with nucleobases. In this work, E(o) values of e(aq)⁻ and of nucleobases have been calculated employing the accurate ab initio Gaussian 4 theory including the polarizable continuum model (PCM). The Gaussian 4-calculated E(o) of e(aq)⁻ (-2.86 V) is in excellent agreement with the experimental one (-2.87 V). The Gaussian 4-calculated E(o) of nucleobases in dimethylformamide (DMF) lie in the range (-2.36 V to -2.86 V); they are in reasonable agreement with the experimental E(o) in DMF and have a mean unsigned error (MUE) = 0.22 V. However, inclusion of specific water molecules reduces this error significantly (MUE = 0.07). With the use of a model of e(aq)⁻ nucleobase complex with six water molecules, the reaction of e(aq)⁻ with the adjacent nucleobase is investigated using approximate ab initio molecular dynamics (MD) simulations including PCM. Our MD simulations show that e(aq)⁻ transfers to uracil, thymine, cytosine, and adenine, within 10 to 120 fs and e(aq)⁻ reacts with guanine only when a water molecule forms a hydrogen bond to O6 of guanine which stabilizes the anion radical.
authors.affiliation: Department of Chemistry, Oakland University , Rochester, Michigan 48309, United States.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, Oakland University , Rochester, Michigan 48309, United States.
authors.forename: Amitava
authors.initials: A
authors.lastname: Adhikary
authors.affiliation: Department of Chemistry, Oakland University , Rochester, Michigan 48309, United States.
authors.forename: Lance
authors.initials: L
authors.lastname: Shamoun
authors.affiliation: Department of Chemistry, Oakland University , Rochester, Michigan 48309, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Sevilla
mesh_terms: D004247:DNA / Q000737:chemistry*; D004583:Electrons; D056004:Molecular Dynamics Simulation; D010084:Oxidation-Reduction
chemical_list: D004247:DNA