title: Probing the reactivity of singlet oxygen with purines.
abstract: The reaction of singlet molecular oxygen with purine DNA bases is investigated by computational means. We support the formation of a transient endoperoxide for guanine and by classical molecular dynamics simulations we demonstrate that the formation of this adduct does not affect the B-helicity. We thus identify the guanine endoperoxide as a key intermediate, confirming a low-temperature nuclear magnetic resonance proof of its existence, and we delineate its degradation pathway, tracing back the preferential formation of 8-oxoguanine versus spiro-derivates in B-DNA. Finally, the latter oxidized 8-oxodGuo product exhibits an almost barrierless reaction profile, and hence is found, coherently with experience, to be much more reactive than guanine itself. On the contrary, in agreement with experimental observations, singlet-oxygen reactivity onto adenine is kinetically blocked by a higher energy transition state.
authors.affiliation: Laboratoire de Chimie, UMR 5182, Ecole Normale Supérieure de Lyon, Lyon France elise.dumont@ens-lyon.fr.
authors.forename: Elise
authors.initials: E
authors.lastname: Dumont
authors.affiliation: Laboratoire de Chimie, UMR 5182, Ecole Normale Supérieure de Lyon, Lyon France.
authors.forename: Raymond
authors.initials: R
authors.lastname: Grüber
authors.affiliation: Laboratoire de Chimie, UMR 5182, Ecole Normale Supérieure de Lyon, Lyon France Institut des Sciences Analytiques, Université de Lyon 1 and CNRS, Villeurbanne, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bignon
authors.affiliation: Institut des Sciences Analytiques, Université de Lyon 1 and CNRS, Villeurbanne, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Morell
authors.affiliation: iRTSV/CBM/MCT, CEA Grenoble, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Moreau
authors.affiliation: Theory-Modeling-Simulation, SRSMC, Université de Lorraine Nancy, Vandoeuvre-lès-Nancy, France CNRS, Theory-Modeling-Simulation, SRSMC, Vandoeuvre-lès-Nancy, France.
authors.forename: Antonio
authors.initials: A
authors.lastname: Monari
authors.affiliation: INAC-SCIB, Université Grenoble Alpes, F-38000 Grenoble, France CEA, INAC-SCIB-LAN, F-38000 Grenoble, France elise.dumont@ens-lyon.fr.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Ravanat
mesh_terms: D004247:DNA / Q000737:chemistry; D008962:Models, Theoretical; D056004:Molecular Dynamics Simulation; D010084:Oxidation-Reduction; D011687:Purines / Q000737:chemistry*; D011789:Quantum Theory; D026082:Singlet Oxygen / Q000737:chemistry*
chemical_list: D011687:Purines; D026082:Singlet Oxygen; D004247:DNA; C030985:purine