title: Reactions of 9-substituted guanines with bromomalondialdehyde in aqueous solution predominantly yield glyoxal-derived adducts.
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 (1)H and (13)C 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,N(2)-(trans-1,2-dihydroxyethano)guanine adduct (6) predominated at pH < 6 and N(2)-carboxymethylguanine adduct (10a,b) at pH > 7. In addition to these, an N(2)-(4,5-dihydroxy-1,3-dioxolan-2-yl)methylene adduct (11a,b) and an N(2)-carboxymethyl-1,N(2)-(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,N(2)-ethenoguanine (5a-c) and N(2),3-ethenoguanine adducts (4a-c) were formed as minor products, and a transient accumulation of two unstable intermediates, tentatively identified as 1,N(2)-(1,2,2,3-tetrahydroxypropano)(8) and 1,N(2)-(2-formyl-1,2,3-trihydroxypropano)(9) adducts, was observed.
authors.affiliation: Department of Chemistry, University of Turku, FIN-20014 Turku, Finland.
authors.forename: Anne-Mari
authors.initials: AM
authors.lastname: Ruohola
authors.forename: Niangoran
authors.initials: N
authors.lastname: Koissi
authors.forename: Sanna
authors.initials: S
authors.lastname: Andersson
authors.forename: Ilona
authors.initials: I
authors.lastname: Lepistö
authors.forename: Kari
authors.initials: K
authors.lastname: Neuvonen
authors.forename: Satu
authors.initials: S
authors.lastname: Mikkola
authors.forename: Harri
authors.initials: H
authors.lastname: Lönnberg
mesh_terms: D002851:Chromatography, High Pressure Liquid; D006037:Glyoxal / Q000737:chemistry*; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008315:Malondialdehyde / Q000031:analogs & derivatives* / Q000737:chemistry; D015394:Molecular Structure; D012996:Solutions / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D012996:Solutions; D014867:Water; C083259:bromomalonaldehyde; D008315:Malondialdehyde; D006037:Glyoxal; D006147:Guanine; C014542:9-ethylguanine