title: Distinct hydroxy-radical-induced damage of 3'-uridine monophosphate in RNA: a theoretical study.
abstract: RNA strand scission and base release in 3'-uridine monophosphate (UMP), induced by OH radical addition to uracil, is studied at the DFT B3LYP/6-31+G(d,p) level in the gas phase and in solution. In particular, the mechanism of hydrogen-atom transfer subsequent to radical formation, from C2' on the sugar to the C6 site on the base, is explored. The barriers of (C2'-)H2'(a) abstraction by the C6 radical site range from 11.2 to 20.0 kcal mol(-1) in the gas phase and 14.1 to 21.0 kcal mol(-1) in aqueous solution, indicating that the local surrounding governs the hydrogen-abstraction reaction in a stereoselective way. The calculated N1-C1' (N1-glycosidic bond) and beta-phosphate bond strengths show that homolytic and heterolytic bond-breaking processes are largely favored in each case, respectively. The barrier for beta-phosphate bond rupture is approximately 3.2-4.0 kcal mol(-1) and is preferred by 8-12 kcal mol(-1) over N1-glycosidic bond cleavage in both the gas phase and solution. The beta-phosphate bond-rupture reactions are exothermal in the gas phase and solution, whereas N1-C1' bond-rupture reactions require both solvation and thermal corrections at 298 K to be energetically favored. The presence of the ribose 2'-OH group and its formation of low-barrier hydrogen bonds with oxygen atoms of the 3'-phosphate linkage are highly important for hydrogen transfer and the subsequent bond-breakage reactions.
authors.affiliation: The Institute for Chemical Physics and School of Science, Beijing Institute of Technology, Beijing 100081, China.
authors.forename: Ru bo
authors.initials: Rb
authors.lastname: Zhang
authors.forename: Leif A
authors.initials: LA
authors.lastname: Eriksson
mesh_terms: D006859:Hydrogen / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D017665:Hydroxyl Radical / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics; D014542:Uridine Monophosphate / Q000737:chemistry*
chemical_list: D017665:Hydroxyl Radical; D012313:RNA; D006859:Hydrogen; D014542:Uridine Monophosphate