title: Mechanism of the OH Radical Addition to Adenine from Quantum-Chemistry Determinations of Reaction Paths and Spectroscopic Tracking of the Intermediates.
abstract: The OH radical is a well-known mediator in the oxidation of biological structures like DNA. Over the past decades, the precise events taking place after reaction of DNA nucleobases with OH radical have been widely investigated by the scientific community. Thirty years after the proposal of the main routes for the reaction of•OH with adenine ( Vieira , A. ; Steenken , S. J. Am. Chem. Soc. 1990 , 112 , 6986 - 6994 ), the present work demonstrates that the OH radical addition to C4 position is a minor pathway. Instead, the dehydration process is mediated by the A5OH adduct. Conclusions are based on density functional theory calculations for the ground-state reactivity and highly accurate multiconfigurational computations for the excited states of the radical intermediates. The methodology has been also used to study the mechanism giving rise to the mutagens 8-oxoA and FAPyA. Taking into account the agreement between the experimental data and the theoretical results, it is concluded that addition to the C5 and C8 positions accounts for at least ∼44.5% of the total•OH reaction in water solution. Finally, the current findings suggest that hydrophobicity in the DNA/RNA surroundings facilitates the formation of 8-oxoA and FAPyA.
authors.affiliation: Instituto de Ciencia Molecular, Universitat de València , P.O. Box 22085, 46071 València, Spain.
authors.forename: Antonio
authors.identifier: 0000-0001-8232-4989
authors.initials: A
authors.lastname: Francés-Monerris
authors.affiliation: Instituto de Ciencia Molecular, Universitat de València , P.O. Box 22085, 46071 València, Spain.
authors.forename: Manuela
authors.initials: M
authors.lastname: Merchán
authors.affiliation: Instituto de Ciencia Molecular, Universitat de València , P.O. Box 22085, 46071 València, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Roca-Sanjuán
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D017665:Hydroxyl Radical / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D011743:Pyrimidines / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D011743:Pyrimidines; C002992:8-hydroxyadenine; D017665:Hydroxyl Radical; C039544:4,6-diamino-5-N-formamidopyrimidine; D000225:Adenine