A 2-iminohydantoin from the oxidation of guanine.
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.
Ye
Wenjie
W
Department of Environmental Sciences and Engineering CB7431, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7431, USA.
Sangaiah
R
R
Degen
Diana E
DE
Gold
Avram
A
Jayaraj
K
K
Koshlap
Karl M
KM
Boysen
Gunnar
G
Williams
Jason
J
Tomer
Kenneth B
KB
Ball
Louise M
LM
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*
D007097:Imines; D013141:Spiro Compounds; D006147:Guanine