Do Solvated Electrons (eaq-) Reduce DNA Bases? A Gaussian 4 and Density Functional Theory- Molecular Dynamics Study

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 (-2.87V). 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 06 of guanine which stabilizes the anion radical.