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 determination of standard redox potentials (E°) of nucleobases and of e-aq determine the extent of reaction of e-aq with nucleobases. In this work, E° 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° of e-aq (-2.86 V) is in excellent agreement with the experimental one (-2.87 V). The Gaussian-4-calculated E° 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° 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). Employing a model of e-aq-nucleobase complex with 6 water molecules, 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.

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“…Our G4-calculated E o vs. NHE of e aq − is −2.88 V which is in excellent agreement with the reported experimental values −2.87 V and −2.95 V, respectively (Kumar et al, 2016). The G4-calculated E o vs. NHE of G, A, C, T and U in DMF agree with the experimental values well with a mean unsigned error (MUE) with respect to experiment is 0.22 V (Kumar et al, 2016).…”

“…The G4-calculated E o vs. NHE of G, A, C, T and U in DMF agree with the experimental values well with a mean unsigned error (MUE) with respect to experiment is 0.22 V (Kumar et al, 2016). The G4-calculated E o vs. NHE of G, A, C, T and U in water are −2.84 V, −2.78 V, −2.44 V, −2.42 V and −2.33 V, respectively.…”

“…1.7 – 2.2 eV which is smaller than the VDE (3.3 eV) of solvated electron. The VDE and the electron affinity of the electron are two different quantities and well defined in the literature (Gu et al, 2012; Kumar et al, 2016; Kumar and Sevilla, 2010, 2012a). The VDE is the energy required to remove the electron vertically from liquid water into the gas phase, without structure relaxation, whereas, the adiabatic electron affinity (AEA) is the binding energy of the gas phase electron to the liquid water after full nuclear and electronic relaxation of the surrouinding water molecules.…”

“…The calculation of ΔG o directly leads to the evaluation of one-electron reduction potentials (E o vs. NHE) of e aq − and nucleobases. The procedures for calculation of ΔG o and E o vs. NHE are provided in our recent work (Kumar et al, 2016). …”

“…In addition, we also modeled the reaction of e aq − with nucleobases using an approximate ab initio molecular dynamics (MD) simulation (Kumar et al, 2016). In our MD simulations, we found that an e aq − residing in a cavity near to U, T and C is transferred within 30 fs and in adenine transfer occurs within 120 fs.…”