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

Area of Science:

• Chemical Physics
• Computational Chemistry
• Radiation Chemistry

Background:

• The solvated electron (e(aq)⁻) is a crucial intermediate in reductive DNA damage following ionization.
• Accurate standard redox potentials (E(o)) for nucleobases and e(aq)⁻ are essential for understanding e(aq)⁻ reactions with DNA.
• Previous methods lacked precision in determining these critical electrochemical parameters.

Purpose of the Study:

• To accurately calculate the standard redox potentials (E(o)) of the solvated electron and DNA nucleobases.
• To investigate the reaction mechanisms and dynamics of e(aq)⁻ with nucleobases using computational methods.
• To improve the understanding of electron transfer processes in DNA damage.

Main Methods:

• Ab initio Gaussian 4 theory combined with the polarizable continuum model (PCM) for E(o) calculations.
• Inclusion of explicit water molecules to refine calculations of nucleobase redox potentials.
• Approximate ab initio molecular dynamics (MD) simulations of e(aq)⁻-nucleobase complexes.

Main Results:

• Gaussian 4 calculations yielded highly accurate E(o) for e(aq)⁻, closely matching experimental values.
• Calculated E(o) for nucleobases in DMF showed good agreement with experimental data, significantly improved by including water molecules (MUE = 0.07 V).
• MD simulations demonstrated rapid e(aq)⁻ transfer to uracil, thymine, cytosine, and adenine within 10-120 fs, with guanine reaction dependent on specific water-mediated hydrogen bonding.

Conclusions:

• The study provides highly accurate computational predictions of redox potentials relevant to DNA damage.
• Computational modeling, especially with explicit water, is effective for studying electron transfer dynamics in biological systems.
• Understanding these electron transfer mechanisms is vital for predicting and potentially mitigating radiation-induced DNA damage.