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.

Figure 1

(a) Schematic diagram showing the energetic cycle for the adiabatic electron solvation (AEA), the photoejection of the solvated electron (e^-_aq) into the gas phase (VDE), and the solvent reorganization to equilibrated water (SRE =1.8 eV). The VDE has the same geometry for the upper state as in the ground state. The difference between AEA and VDE gives the value of SRE. The SRE shows the solvent after photoejection of the electron is unstable by ca. 1.8 eV over a stable water phase geometry. (b) A comparison of the G4-calculated solvation free energy ΔG°_sol along with E° vs NHE of all the bases and solvated electron.

Figure 2

Total spin density plot of T-6H₂O^•-. The structure is optimized to a local minimum using the B3LYP/6-31++G** method including PCM.

Figure 3

Total spin density plot of T-6H₂O^•- at different time during MD simulation. (a) 0 fs (initial optimized starting structure for simulation), (b) 22 fs, (c) 23 fs, (d) 30 fs and (e) fully optimized structure. Structure (e) is stabilized by -0.88 eV over structure (a), see Table 3.

Figure 4

Total spin density plot of C-6H₂O^•- at different time during MD simulation. (a) 0 fs (initial optimized starting structure for simulation), (b) 10 - 14 fs, (c) 15 – 20 fs and (d) fully optimized structure. Structure (d) is stabilized by -0.64 eV over structure (a), see Table 3.

Figure 5

Total spin density plot of U-6H₂O^•- at different time during MD simulation. (a) 0 fs (initial optimized starting structure for simulation), (b) 7 fs, (c) 8 - 10 fs and (d) fully optimized structure. Structure (d) is stabilized by -0.93 eV than structure (a), see Table 3.

Figure 6

Total spin density plot of A-6H₂O^•- at different time during MD simulation. (a) 0 fs (initial optimized starting structure for simulation), (b) 100 fs, (c) 120 fs and (d) fully optimized structure. Structure (d) is stabilized by -0.25 eV than structure (a), see Table 3.

Figure 7

Total spin density plot of G-6H₂O^•- at different time during MD simulation. (a) 0 fs (initial optimized starting structure for simulation), (b) 625 fs and (c) 825 fs. The 6H₂O is located near the N7-C8 site of guanine.

Figure 8

Total spin density plot of G-6H₂O^•- at times during MD simulation. (a) 0 fs and (b) 60 fs. The 0 fs structure is generated from the 625 fs simulation (Figure 6(b)) by moving one water molecule (pink highlighted) to hydrogen bond with O6 of guanine. Structure (7c) is stabilized by -0.19 eV than structure shown in Figure 6(a), see Table 3.