Copper/H2O2-mediated oxidation of 2'-deoxyguanosine in the presence of 2-naphthol leads to the formation of two distinct isomeric adducts

J Org Chem. 2011 Oct 7;76(19):7953-63. doi: 10.1021/jo201423n. Epub 2011 Aug 25.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Copper / chemistry*
  • Deoxyguanosine / chemistry*
  • Electrons
  • Hydrogen Peroxide / chemistry*
  • Hydrogen-Ion Concentration
  • Isomerism
  • Naphthols / chemistry*
  • Oxidants / chemistry
  • Oxidation-Reduction
  • Phenol / chemistry

Substances

  • Naphthols
  • Oxidants
  • Phenol
  • Copper
  • Hydrogen Peroxide
  • Deoxyguanosine
  • 2-naphthol