title: The Effect of Solvation on the Radiation Damage Rate Constants for Adenine.
abstract: It is well known that water plays an important part in almost all biological systems and that inclusion of solvation effects might therefore be of utmost importance in studies of radiation damage to DNA. In the present investigation, we have studied the effect of different solvation models in calculations of Gibbs free energies and reaction rates for the reaction between the OH radical and the DNA nucleobase adenine by conducting density functional theory calculations at the ωB97X-D/6-311++G(2df,2pd) level with the Eckart tunnelling correction. The solvent, water, was included through either the implicit polarizable continuum model (PCM) or through explicit modelling of micro-solvation by a single water molecule at the site of reaction as well as by the combination of both. Scrutiny of the thermodynamics and kinetics of the individual sub-reactions suggests that the qualitative differences introduced by the solvation models do not significantly alter the conclusions made based solely on simple gas-phase calculations. Abstraction of the amine hydrogen atoms H61and H62and addition onto C8remain the most likely reaction pathways.
authors.affiliation: Department of Chemistry, University of Copenhagen, DK-2100, Copenhagen Ø, Denmark. birgittemilhoj@gmail.com.
authors.forename: Birgitte O
authors.identifier: http://orcid.org/0000-0001-5875-0187
authors.initials: BO
authors.lastname: Milhøj
authors.affiliation: Department of Chemistry, University of Copenhagen, DK-2100, Copenhagen Ø, Denmark. sauer@kiku.dk.
authors.forename: Stephan P A
authors.identifier: http://orcid.org/0000-0003-4812-0522
authors.initials: SP
authors.lastname: Sauer
mesh_terms: D000225:Adenine / Q000737:chemistry*; D004249:DNA Damage; D017665:Hydroxyl Radical / Q000737:chemistry; D011789:Quantum Theory; D012995:Solubility; D013816:Thermodynamics
chemical_list: D017665:Hydroxyl Radical; D000225:Adenine
keywords: DNA damage; density functional calculations; kinetics; nucleobases; radicals