Low-Energy Electron (LEE)-Induced DNA Damage: Theoretical Approaches to Modeling Experiment

Abstract

Low-energy electrons (LEE) have been experimentally found to structurally alter DNA by induction of base damage, base release, and strand breaks. This has engendered a considerable number of theoretical studies of the mechanisms involved in this DNA damage. In this chapter, we discuss the various pathways for LEE interaction with DNA and the theoretical treatments most suited to A. Kumar ( ) • M.D. Sevilla Department of Chemistry, Oakland University, Rochester, MI, USA e-mail: kumar@oakland.edu; sevilla@oakland.edu © Springer Science+Business Media Dordrecht 2015 J. Leszczynski et al. (eds.), Handbook of Computational Chemistry, DOI 10.1007/978-94-007-6169-8_34-2 1 2 A. Kumar and M.D. Sevilla unravel these pathways. For example, inelastic electron scattering produces excitation, ionization, and transient negative ions (TNI) via shape, core-excited, and vibrational Feshbach resonances, which can all lead to DNA damage. Each of these pathways is distinguished, and their pertinence to the experimental results observed is described. Theoretical approaches used to explain these pathways are also described. Shape resonances can be understood as interactions with the electron with unoccupied molecular orbitals of neutral molecule, while coreexcited states involve excitation of inner shell electrons and can be treated with theoretical methods such as time-dependent density functional theory (TDDFT) or CASSCF. In treating the electron–molecule interaction, special care is needed to distinguish between diffuse and valence states of the TNI. The role of the vertical and adiabatic states of the radical anion is important as the electron adds to the neutral molecular framework, and reactions induced likely occur before equilibration to the adiabatic state. The effect of solvation is critical to both energetics of the interaction and the nature of the TNI formed. For example, gas-phase calculations show diffuse dipole-bound character for adenine, guanine, and cytosine anion radicals, but each of these is found to be in a valence state in aqueous solution by experiment. DNA base anion radicals often show ground states that are diffuse in character and that collapse to valence states on solvation. Such processes are shown to be accounted for inclusion of the polarized continuum model (PCM) for solvation. TD-DFT excited-state calculations including solvation show that the diffuse states rise in energy on solvation as expected. For LEE in the aqueous phase, new energy states become available such as conduction band or presolvated electrons, which may have sufficient energy to cause DNA damage. DNA radiosensitizers such as halogensubstituted uracils are being used to produce highly reactive uracil-5-yl radical, a precursor of DNA strand breaks, through its reaction with LEE.