Reactions of 9-substituted guanines with bromomalondialdehyde in aqueous solution predominantly yield glyoxal-derived adducts

Organic & Biomolecular Chemistry Pub Date: 2004-06-16 DOI: 10.1039/B405117C

Abstract

Reactions of 9-ethylguanine, 2′-deoxyguanosine and guanosine with bromomalondialdehyde in aqueous buffers over a wide pH-range were studied. The main products were isolated and characterized by 1H and 13C NMR and mass spectroscopy. The final products formed under acidic and basic conditions were different, but they shared the common feature of being derived from glyoxal. Among the 1 : 1 adducts, 1,N2-(trans-1,2-dihydroxyethano)guanine adduct (6) predominated at pH < 6 and N2-carboxymethylguanine adduct (10a,b) at pH > 7. In addition to these, an N2-(4,5-dihydroxy-1,3-dioxolan-2-yl)methylene adduct (11a,b) and an N2-carboxymethyl-1,N2-(trans-1,2-dihydroxyethano)guanine adduct (12) were obtained at pH 10. The results of kinetic experiments suggest that bromomalondialdehyde is significantly decomposed to formic acid and glycolaldehyde under the conditions required to obtain guanine adducts. Glycolaldehyde is oxidized to glyoxal, which then modifies the guanine base more readily than bromomalondialdehyde. Besides the glyoxal-derived adducts, 1,N2-ethenoguanine (5a–c) and N2,3-ethenoguanine adducts (4a–c) were formed as minor products, and a transient accumulation of two unstable intermediates, tentatively identified as 1,N2-(1,2,2,3-tetrahydroxypropano) (8) and 1,N2-(2-formyl-1,2,3-trihydroxypropano) (9) adducts, was observed.

Graphical abstract: Reactions of 9-substituted guanines with bromomalondialdehyde in aqueous solution predominantly yield glyoxal-derived adducts
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