A novel nitration product formed during the reaction of peroxynitrite with 2',3',5'-tri-O-acetyl-7,8-dihydro-8-oxoguanosine: N-nitro-N'-[1-(2,3,5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)- 2, 4-dioxoimidazolidin-5-ylidene]guanidine

Chem Res Toxicol. 2000 May;13(5):390-6. doi: 10.1021/tx0000318.

Abstract

A novel nitration product, formed during the reaction of peroxynitrite with 2',3',5'-tri-O-acetyl-7,8-dihydro-8-oxoguanosine, has been characterized using a combination of UV/vis, CD, and NMR spectroscopy and mass spectrometry. This compound has been identified as N-nitro-N'-[1-(2,3, 5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)-2, 4-dioxoimidazolidin-5-ylidene]guanidine (IV). Upon base hydrolysis, IV releases nitroguanidine (IVa) and an intermediate, 1-(2,3, 5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)-5-iminoimidazolidine -2, 4-dione (IVb). This intermediate is ultimately hydrolyzed to the stable 3-(2,3,5-tri-O-acetyl-beta-D-erythro-pentofuranosyl)oxaluric acid (IVc). IV can be reduced by sodium borohydride to a pair of stable diastereomers (IV(red)()). The formation of this product is rationalized in terms of initial oxidation of 2',3', 5'-tri-O-acetyl-7,8-dihydro-8-oxoguanosine to a quinonoid diimine intermediate, 3. Nucleophilic attack at C5 of 3 by peroxynitrite leads to formation of a C5-oxyl radical species, 5, which then undergoes a series of rearrangements to yield an ylidene radical, 7. Combination of this radical species with nitrogen dioxide results in the formation of product IV.

Publication types

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

MeSH terms

  • Circular Dichroism
  • Guanidines / analysis*
  • Guanosine / analogs & derivatives*
  • Guanosine / chemistry
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Nitrates / chemistry*
  • Oxidants / chemistry*
  • Spectrophotometry, Ultraviolet

Substances

  • 2',3',5'-tri-O-acetyl-7,8-dihydro-8-oxoguanosine
  • Guanidines
  • N-nitro-N'-(1-(2,3,5-tri-O-acetyl-erythro-pentofuranosyl)-2,4-dioxoimidazolidin-5-ylidene)guanidine
  • Nitrates
  • Oxidants
  • Guanosine
  • peroxynitric acid