Enzymes catalyze reactions in ways that often seem extraordinary. For many decades their unique properties have captured the fancy of chemists, biochemists, and biologists. Although remarkable insights into their mode of action have been gained, only recently have the technical capabilities of organic chemists been sufficient to meet the challenge of trying to synthesize artificial enzymes - which are often called enzyme mimics. Our research involves those enzyme mimics (host molecules) (a) that can be constructed by total synthesis from readily available starting materials (b) that have molecular weights significantly lower than those of the enzymes, and (c) that possess the enzyme-like properties of binding guest molecules in a chemically and stereochemically selective fashion and then catalyzing their transformation to products.

The essential requirements for a host molecule to possess enzyme-like activity are (a) a cavity complementary in size and shape to that of the guest molecule in order to bind the guest and (b) appropriately positioned functional groups to interact with specific sites of the guest molecule in order to catalyze the conversion of guest to products. The cavity-containing compounds used in our research are macrocycles called calixarenes (shown below) which provide the basic basket-like framework to which functional groups are affixed at appropriate positions. An account of how the calixarenes came to be used for enzyme mimic-building is given in the first entry in the list of selected publications.

Aldolase is an enzyme that catalyzes the interaction of dihydroxyacetone phosphate (DHAP) and glyceraldehyde phosphate (GAP) to form fructose-1,6-phosphate. This process is employed in the forward direction in the photosynthesizing green leaf and in the reverse direction in the metabolizing mammal. Our research goals are well illustrated by our continuing attempts to fashion an aldolase mimic that is designed with the knowledge that the enzyme itself employs a positively charged group to bind the phosphate of DHAP, a primary amino group to form a Schiff base with DHAP which activates it for reaction, and a basic group to abstract the [[alpha]]-H of DHAP. A calixarene-based compound that may possess these features is illustrated. The construction of this molecule poses a formidable challenge, reflecting the fact that organic synthesis is an extremely important ingredient of enzyme mimic research. Once the target molecule has been made its complex-forming ability and catalytic potential can then be measured. Over the course of research of this sort students gain experience and expertise in a wide variety of areas including synthetic and physical organic chemistry, analytical techniques (NMR, UV/vis, and mass spectrometry, HPLC), X-ray crystallography, and computer modeling.