The nucleobase guanine was oxidized with dimethyldioxirane (DMDO) to explore the role of epoxidizingagents in oxidative DNA damage. Treatment of guanine with 10% molar excess DMDO in aqueoussolution at 0
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 thebasis of mass spectrometry and NMR studies on
1 and its isotopomers generated by the oxidation of[4-
13C] and [7-
15N]guanine, which yield [5-
13C]
1 and [7-
15N]
1. The distribution of
13C and
15N labels inthe isotopomeric products supports initial epoxidation of the C4-C5 bond of guanine followed by a1,2-acyl migration of guanine C6. Compound
1 is suggested as a possible primary DNA lesion fromputative epoxidizing agents, including hydroperoxides present during biological processes such as lipidperoxidation.