Addressing the competitive formation of tandem DNA lesions by a nucleobase peroxyl radical: a DFT-D screening

Org Biomol Chem. 2013 May 14;11(18):3038-45. doi: 10.1039/c3ob40280k.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclization
  • DNA / drug effects
  • DNA Damage*
  • Models, Molecular
  • Peroxides / chemistry*
  • Peroxides / pharmacology
  • Purines / chemistry
  • Pyrimidines / chemistry
  • Quantum Theory*
  • Thermodynamics

Substances

  • Peroxides
  • Purines
  • Pyrimidines
  • perhydroxyl radical
  • DNA