title: Copper/H2O2-mediated oxidation of 2'-deoxyguanosine in the presence of 2-naphthol leads to the formation of two distinct isomeric adducts.
abstract: Exposure of cells to phenolic compounds through exogenous and endogenous sources can lead to deleterious effects via nucleobase modifications of DNA occurring under oxidative conditions. 2'-Deoxyguanosine (dG) is the most electron rich of the four canonical bases and includes many nucleophilic sites; it is also susceptible to oxidation with numerous reactive oxygen species. In these studies, dG was allowed to react with 2-naphthol in the presence of copper or iron salts yielding two principal isomeric products. Spectroscopic analysis and reactions with alkylated nucleosides support the assignment of compound 1a/1b as a pair of atropisomer N(2) adducts and compound 2a/2b as a diastereomeric mixture of tricyclic [4.3.3.0] adducts. Both products are the result of an overall four-electron oxidation process and consequently have the same masses, though drastically different structures, providing mechanistic insight into their formation. Thus, dG alkylation by 2-naphthol under oxidative conditions yields products whose structural properties are altered, leading to potentially mutagenic effects in genomic DNA.
authors.affiliation: Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Fleming
authors.forename: Arunkumar
authors.initials: A
authors.lastname: Kannan
authors.forename: James G
authors.initials: JG
authors.lastname: Muller
authors.forename: Yi
authors.initials: Y
authors.lastname: Liao
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Burrows
mesh_terms: D003300:Copper / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry*; D004583:Electrons; D006861:Hydrogen Peroxide / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D009284:Naphthols / Q000737:chemistry*; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D019800:Phenol / Q000737:chemistry
chemical_list: D009284:Naphthols; D016877:Oxidants; D019800:Phenol; D003300:Copper; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine; C028405:2-naphthol