Hydrogen-bond acid/base catalysis: A density functional theory study of protonated guanine-(substituted) cytosine base pairs as models for nucleophilic attack on mitomycin in DNA

The mechanism of alkylation at the exocyclic nitrogen of guanine in G.C bas e pairs has been studied using density functional theory at the B3LYP/D95** level. Protonation of the amino group was used asa model for this reaction . The calculations indicate that the reaction is facilitated by a temporary transfer of the H-bonding hydrogen from the guanine amino position to the cytosine oxygen within the H-bond. Thus, the cytosine "loans" its basicity to the guanine within the H-bonded base pair. These calculations explain th e previously observed dependence of guanine alkylation upon the substituent at the 5-position of cytosine. The generality of catalysis via the tempora ry transfer of a H-bonding hydrogen within an H-bond, hydrogen-bond, acid/b ase catalysis (HBA/BC), is discussed. This form of catalysis might be impor tant in biochemistry, materials science, and the solid state.