Computational Investigation of Fluoride and Superoxide Radical Anion Interactions with the Thymine Nucleobase

Abstract

We present the first computational investigation of the intermolecular interactions between the fluoride anion (F⁻) and the superoxide radical anion (O₂⁻) with the thymine nucleobase. Calculations were performed using density functional theory (DFT) with the B3LYP functional and the aug-cc-pVDZ correlation-consistent basis set. Full geometry optimizations were carried out for the thymine–F⁻ and thymine–O₂⁻ complexes, accompanied by radial and angular potential energy surface scans, vibrational frequency analyses, and dissociation energy evaluations. Particular attention was given to proton transfer processes from thymine’s acidic N–H sites to F⁻ and O₂⁻, leading to the formation of hydrogen-bonded and proton-transferred complexes. Comparative analysis between these two hard anionic bases reveals differences in hydrogen-bond strength, site selectivity, and proton-transfer propensity. These results provide new insight into the molecular mechanisms underlying oxidative and anionic nucleobase damage, contributing to a deeper understanding of DNA reactivity with reactive oxygen species (ROS)