Abstract:

    The storage of genetic information, is entrusted to the bio-polymers of RNA and DNA which owe their great stability to phosphate diester linkages (R'O-P(O₂^-)OR). Many of the enzymes responsible for the cleavage of RNA and DNA have dinuclear or trinuclear metal ion active sites. We have been interested in biomimetic chemistry which involves synthesizing and studying small molecules designed to approximate the catalytic components of the active site of such enzymes, and studying the mechanisms by which these cleave models for RNA and DNA. Unfortunately, despite many literature reports of the catalytic abilities of various dinuclear complexes to hydrolyze phosphate diesters in water, almost none of the existing catalysts are  substantially better than hydroxide ion in catalyzing the decomposition of RNA models.

In this seminar we will present new results concerning the abilities of a simple dinuclear catalytic systems (1) to promoted the cleavage of a series of RNA models (2) in a medium of methanol and ethanol under pH controlled conditions. It is shown that 1 can promote the cleavage of of these by many orders of magnitude relative to the methoxide catalyzed cleavages, and at least 10¹² -old relative to the background reactions at near neutral pH in methanol. The mechanism by which the catalytic reaction occurs and the biological ramifications of this remarkable catalytic effect are discussed.