REACTION-MECHANISMS OF FORMALDEHYDE WITH ENDOCYCLIC IMINO GROUPS OF NUCLEIC-ACID BASES

Four different possible mechanisms of formaldehyde reacting with the e ndocyclic imino groups of nucleic acid bases leading to hydroxymethyla ted nucleic acid adducts were investigated. The potential energy surfa ce for each mechanism was characterized using the technique of ab init io quantum chemistry. A water-assisted mechanism involving concerted i nteractions among the deprotonated nucleic acid base, formaldehyde, an d a water molecule was found to be energetically most favorable. This mechanism also accounts for the experimentally observed features of th ese reactions, namely, that they are fast and reversible and both the forward and backward reactions are base catalyzed.