Mechanism of formation of ethenoguanine adducts from 2-haloacetaldehydes: 13C-labeling patterns with 2-bromoacetaldehyde.

The mechanism of formation of etheno (e) adducts of nucleic acid bases from 2-haloacetaldehydes is generally assumed to occur via initial Schiff base formation resulting from reaction of the aldehyde with an exocyclic amine. We recently revised the 1 H NMR assignments of the e protons of 1,N 2 -e-Guo (Guengerich, F. P., Persmark, M. P., and Humphreys, W. G. (1993) Chem. Res. Toxicol. 6, 635-648). In that work we also observed a facile and specific exchange of H7 of 1,N 2 -e-Guo and H5 of N 2 ,3-e-Gua with H 2 O. These findings raise questions about the mechanistic conclusions reached on the basis of labeling studies with deuterated ClCH 2 CHO (Sattsangi, P. D., Leonard, N. J., and Frihart, C. R. (1977) J. Org. Chem. 42, 3292-3296)