The Dual and Simultaneous Roles of Nucleophilic Delivery and Assistance of Leaving Group Departure by Metal Ions in Phosphate Transfer from Phosphate Diesters

Our research has centered around the very difficult problem of the catalysis Of hydrolysis of phosphate diesters. The study may be divided into two parts. The first deals with the design synthesis and study of new catalytic systems which incorporate a duality of functional groups designed to deliver a nucleophile, preferably metal bound water, and to stabilized the leaving alkoxide, preferably by metal cation. One completed study has been published and others are in progress one nears completion. The second part of the problem is the design, synthesis, and study of compounds which we call microgonotropens which bind in the minor groove of dsDNA at A.T rich regions and direct a catalytic configuration of nucleophile and electrophile to particular dsDNA phosphodiester linkages. We have published one paper, three additional papers dealing with dien-microgonotropens will be published this summer and two on tren-microgonotropens approach completion. We are interested in how the microgonotropens change the shape of dsDNA and this has led us to computer studies of the structures of peptide nucleic acid complexes with dsDNA. Two papers on this topic have been accepted for publication and will appear before the end of 1993.