Three areas of investigation are contemplated. Dr. Bruice will continue model work on the reactions catalyzed by organomercurial and mercuric reductase. In the former he has shown that the protonolysis rate is accelerated by bis- thiol ligation of the substrate mercury, and the generality of this reaction will now be explored. For the reductase, the one-electron and two-electron reduction potentials for various liganded mercuric ions will be determined in order to resolve the thermodynamics of the system. Studies will be initiated in the area of RNA self-splicing and self cleavage. The plausible role of metal ions as transition state stabilizers in the general base catalyzed displacement reactions of ribose 2' and 3' hydroxyl groups on phosphodiester linkages will be probed by the synthesis of suitable dinucleotide models. The relationships of structure to hammerhead self cleavage will be determined by molecular dynamics and energy minimization methods. A collaboration will be initiated with Drs. Lerner and Benkovic to produce porphyrin containing monoclonal antibodies to mimic heme dependent redox enzymes of another new direction.
