A 2-iminohydantoin from the oxidation of guanine

Chem Res Toxicol. 2006 Apr;19(4):506-10. doi: 10.1021/tx0600144.

Abstract

The nucleobase guanine was oxidized with dimethyldioxirane (DMDO) to explore the role of epoxidizing agents in oxidative DNA damage. Treatment of guanine with 10% molar excess DMDO in aqueous solution at 0 degrees C and pH 7.5 followed by workup under mild conditions gave 5-carboxamido-5-formamido-2-iminohydantoin (1) as the sole isolable product in 71% yield. The structure of 1 was established on the basis of mass spectrometry and NMR studies on 1 and its isotopomers generated by the oxidation of [4-(13)C] and [7-(15)N]guanine, which yield [5-(13)C]1 and [7-(15)N]1. The distribution of 13C and 15N labels in the isotopomeric products supports initial epoxidation of the C4-C5 bond of guanine followed by a 1,2-acyl migration of guanine C6. Compound 1 is suggested as a possible primary DNA lesion from putative epoxidizing agents, including hydroperoxides present during biological processes such as lipid peroxidation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Guanine / chemistry*
  • Imines / chemistry*
  • Magnetic Resonance Spectroscopy
  • Oxidation-Reduction
  • Spectrometry, Mass, Electrospray Ionization
  • Spiro Compounds / chemistry*

Substances

  • Imines
  • Spiro Compounds
  • Guanine