title: Addressing the competitive formation of tandem DNA lesions by a nucleobase peroxyl radical: a DFT-D screening.
abstract: The presence of two vicinal single-nucleotide oxidative lesions constitutes a pitfall case for DNA repair. Quantum mechanics calculations are performed to elucidate the formation of peroxyl-bridged adducts, where a purine and a pyrimidine base become covalently tethered. A dispersion-corrected density functional theory (DFT-D) screening along the 32 possible adducts built by a combination of the four different nucleobases outlines that guanine is a better tandem partner than adenine, in line with experimental data. In contrast, cytosine and thymine have an overall comparable reactivity as revealed by a highly localized spin density. For a given purine and pyrimidine combination, our computational approach also sketches some differences concerning the syn vs. anti configurations and the orientation strand.
authors.affiliation: Université de Lyon, Institut de Chimie de Lyon, CNRS, Ecole Normale Supérieure de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
authors.forename: C
authors.initials: C
authors.lastname: Dupont
authors.forename: C
authors.initials: C
authors.lastname: Patel
authors.forename: J L
authors.initials: JL
authors.lastname: Ravanat
authors.forename: E
authors.initials: E
authors.lastname: Dumont
mesh_terms: D003500:Cyclization; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D008958:Models, Molecular; D010545:Peroxides / Q000737:chemistry* / Q000494:pharmacology; D011687:Purines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D010545:Peroxides; D011687:Purines; D011743:Pyrimidines; C049375:perhydroxyl radical; D004247:DNA