With support from the Organic Dynamics Program, Dr. Menger will utilize both experimental and theoretical approaches to identify the origins of intramolecular and enzymatic reactivity. The systems chosen for study are constructed so that two functional groups are held by a rigid molecular scaffold in a manner such that their mutual geometric relationship is well defined. Three additional projects will be undertaken: (i) the chemistry of "clumps", an evolutionary approach to catalysis, (ii) construction of a cyclodextrin-based system that contains three catalytic entities, and (iii) an attempt to explain why general base catalyses in organic models, but not in enzymes, display such small effective molarities (EMs). %%% The long-term goal of Dr. Menger's research program is to identify the various structural and configurational factors that determine reactivity in intramolecular and enzymatic reactions. Dr. Menger has designed several systems that utilize "enforced proximity" in an effort to learn how two or more functional groups behave when covalent and noncovalent bonding force them to reside in close mutual proximity. The results obtained from such studies are expected to be germane not only to chemical dynamics in solution but also to enzymatic systems, where the binding to the enzyme forces substrate molecules into close contact with catalytic groups.