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.

Reactions of mRNA 5'-cap model compounds were studied to evaluate the potential of these reactions in the development of artificial RNases. Diadenosine triphosphate was used as a model for the triphosphate bridge, and its hydrolysis was studied in the presence of several Cu2+ complexes. The results of the kinetic experiments show that bifunctional catalysis by phosphate bound Cu2+ complexes is involved. The most efficient catalysis is achieved with complexes with acidic aqua ligands, and a metal ion-bound hydroxo ligand most probably acts as a nucleophile in the reaction. A detailed mechanism cannot, however, be suggested on the basis of the data. N-7-methylguanosine and its 5'-monophosphate and diphosphate were used to study the reactions of the N-7-methylguanine base of the mRNA 5'-cap moiety. While Cu2+ complexes efficiently enhance the hydrolysis of the triphosphate bridge, little effect on the reactions of the N-7-methylguanine base was observed: neither the cleavage of the imidazole ring or the depurination of the nucleoside were enhanced to any significant extent.