A Theoretical Study of Electron Attachment to Uracil and 5-Halouracil

The 5-halouracils are an important class of compounds with potential applications as antiviral agents, antitumor agents, and radiosensitizers. In this study, we investigated electron attachment to uracil (U) and 5-halouracil (5-XU) in the gas and aqueous phases. In the gas phase, dipole-bound states were characterized using the EOM-EA-CCSD level of theory. These dipole-bound states showed very low electron-binding energies. We employed a nuclear charge stabilization method with regularized analytic continuation to determine the position and width of the ${\pi }^{\ast }$ and ${\sigma }_{C-X}^{\ast }$ resonances. The ${\pi }^{\ast }$ resonance of uracil is stabilized by the substitution of a halogen at the C5 carbon. The ${\sigma }_{C-\mathrm{Br}}^{\ast }$ resonance appears at a lower energy, indicating the dissociative nature of 5-bromouracil (5-BrU). In the aqueous phase, electron attachment showed that the anionic ground state corresponds to a stable ${\pi }^{\ast }$ state. Excited state analysis from the anionic ground state revealed that the low-lying ${\sigma }_{C-X}^{\ast }$ states contribute to efficient dissociative electron attachment in bromo- and iodo-substituted compounds, facilitating rapid bond cleavage. Ab initio molecular dynamics simulations in the aqueous phase revealed dissociation of the C─Br and C─I bonds, while the C─F and C─Cl bonds remained nondissociative throughout the simulation. The dissociative nature of 5-BrU and 5-IU makes them potential candidates for radiosensitivity.