Bifunctional Catalysis in the Nucleotide-Catalyzed Hydrolysis of (+/-)-7β,8α-Dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzopyrene

Article abstract of DOI:10.1021/jo00226a016

The rates of reaction of (+/-)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzopyrene (DE-2) in 1:9 dioxane-water (v/v) solutions containing the 2'-, 3'-, and 5'-monophosphate derivatives of guanosine, adenosine, and cytidine have been determined.From plots of k_obsd vs. concentration of nucleotide at several different pH values, it could be concluded that the monohydrogen phosphate ionization state was responsible for catalyzing the hydrolysis of DE-2.It was therefore assumed that the monohydrogen phosphate group acted as a general acid catalyst in the epoxide hydrolysis reaction.The second-order rate constants for the general acid catalyzed hydrolysis of DE-2 by the nucleotides listed above were determined.The 2'- and 5'-monophosphates of guanosine and adenosine are better general acid catalysts than the corresponding 3'-isomers, although the 3'-isomers are stronger acids.The guanosine and adenosine nucleotides are better catalysts than the cytidine monophosphates.It is concluded that not only does the monohydrogen phosphate group act as a general acid but the secondary interactions of a stacking nature between the aryl group of DE-2 and the base are important for catalytic effectiveness.