Peroxynitrite reacts with 8-nitropurines to yield 8-oxopurines

Chem Res Toxicol. 2002 Jan;15(1):7-14. doi: 10.1021/tx010093d.


Peroxynitrite reacts with 2'-deoxyguanosine to yield several major products, including 8-oxo-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine (8-nitroGua). While the terminal products formed during the reaction of 8-oxodG with peroxynitrite have been previously characterized, those formed from 8-nitroGua have not. To identify these products, 9-ethyl-8-nitroxanthine was used as a model for 8-nitroGua, since the former could be easily synthesized in high yield, and facilitated reversed-phase HPLC separation of the resulting products. Using this model substrate, the products formed during the peroxynitrite reaction were identified as the ethyl derivatives of oxaluric acid, 5-iminoimidazolidin-2,4-dione, III, [N-nitro-N'-[2,4-dioxo-imidazolidine-5-ylidene]-urea, V, dehydroallantoin, parabanic acid, cyanuric acid, and uric acid. Upon the basis of the previous studies with 8-oxodG, these products were recognized as those expected to arise from peroxynitrite-mediated uric acid oxidation. Furthermore, the presence of uric acid in the reaction mixture led us to propose a model in which the 8-nitropurine is first converted to the 8-oxopurine which is further oxidized by peroxynitrite to give the observed final products. We have also provided evidence suggesting that the peroxynitrite anion, acting as a nucleophile, might be responsible for the initial conversion of the 8-nitropurine to the 8-oxopurine and that a hydroxyl radical or oxidative process is less likely to explain this conversion.

Publication types

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

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Chromatography, High Pressure Liquid
  • DNA Adducts / analysis
  • DNA Adducts / chemistry*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / analysis
  • Deoxyguanosine / chemistry*
  • Guanine / analogs & derivatives*
  • Guanine / analysis
  • Guanine / chemical synthesis
  • Guanine / chemistry*
  • Nitrates / chemistry*
  • Xanthine / analysis
  • Xanthine / chemistry*
  • Xanthines


  • 8-nitroguanine
  • 9-ethyl-8-nitoxanthine
  • DNA Adducts
  • Nitrates
  • Xanthines
  • Xanthine
  • peroxynitric acid
  • Guanine
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine