title: Hydrogen abstraction from deoxyribose by a neighboring 3'-uracil peroxyl radical.
abstract: Theoretical examination of the reactivity of the uracil-5-peroxyl radical when abstracting a hydrogen atom from a neighboring 5'-deoxyribose in 5'-ApU-5-peroxyl-3' has been performed using density functional theory with the MPWB1K functional. Halogenated uracils are often used as radiosensitizers in DNA since the reactive uracil-5-yl radical is formed upon radiation and is known to create strand break and alkali-labile sites. Under aerobic conditions, such as in the cell, it has been proposed that the uracil-5-peroxyl radical is formed and would be the damaging agent. Our results show low reactivity for the uracil-5-peroxyl radical, determined by calculating the activation and reaction energies for the plausible hydrogen abstraction sites C1', C2', and C3' of the neighboring 5'-deoxyribose. These findings support the hypothesis that hydrogen abstraction primarily occurs by the uracil-5-yl radical, also under aerobic conditions, prior to formation of the peroxyl radical.
authors.affiliation: Division of Physical Chemistry, Arrhenius Laboratory, Stockholm University, 106 91 Stockholm, Sweden. patric.schyman@gmail.com
authors.forename: Patric
authors.initials: P
authors.lastname: Schyman
authors.forename: Leif A
authors.initials: LA
authors.lastname: Eriksson
authors.forename: Aatto
authors.initials: A
authors.lastname: Laaksonen
mesh_terms: D003855:Deoxyribose / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry*; D008958:Models, Molecular; D010545:Peroxides / Q000737:chemistry*; D013816:Thermodynamics; D014498:Uracil / Q000737:chemistry*
chemical_list: D010545:Peroxides; C049375:perhydroxyl radical; D003855:Deoxyribose; D014498:Uracil; D006859:Hydrogen