title: A 2-iminohydantoin from the oxidation of guanine.
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.
authors.affiliation: Department of Environmental Sciences and Engineering CB7431, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7431, USA.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Ye
authors.forename: R
authors.initials: R
authors.lastname: Sangaiah
authors.forename: Diana E
authors.initials: DE
authors.lastname: Degen
authors.forename: Avram
authors.initials: A
authors.lastname: Gold
authors.forename: K
authors.initials: K
authors.lastname: Jayaraj
authors.forename: Karl M
authors.initials: KM
authors.lastname: Koshlap
authors.forename: Gunnar
authors.initials: G
authors.lastname: Boysen
authors.forename: Jason
authors.initials: J
authors.lastname: Williams
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Tomer
authors.forename: Louise M
authors.initials: LM
authors.lastname: Ball
mesh_terms: D006147:Guanine / Q000737:chemistry*; D007097:Imines / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D021241:Spectrometry, Mass, Electrospray Ionization; D013141:Spiro Compounds / Q000737:chemistry*
chemical_list: D007097:Imines; D013141:Spiro Compounds; D006147:Guanine