Research

My research group is pursuing studies in several different areas. In our major effort we are trying to prepare artificial enzymes that can imitate the function of natural enzymes. Students typically design a potential catalyst on the computer, synthesize it, then determine its catalytic effectiveness and the mechanism involved. One of the most interesting recent successes is the preparation of such enzyme mimics that carry out selective oxidations of bound substrates with geometric control of the position attacked. In this way we override the natural reactivities of the substrate by using the geometric control imposed by defined binding to the catalyst.

A related study involves the synthesis of mimics of antibodies or of biological receptor sites, constructing molecules that will bind to polypeptides with sequence selectivity in water, using mainly hydrophobic interactions. These could be very useful in modulating the activity of peptide hormones, for instance.

Reactions in water can be influenced by the hydrophobic effect. We are studying the use of this effect to promote and direct chemical reactions, and also to furnish information about the geometries of transition states. The results have been striking, furnishing information not available by other techniques.

We have had a long-standing program to develop novel compounds that can induce cells to differentiate. These have important potential in cancer treatment, and are now in human trials. One of these compounds has now been approved by the U. S. Food and Drug Agency for use by cancer patients.         

In our earliest work we extended the range of aromatic compounds, and synthesized other compounds that we showed to be antiaromatic. We are still pursuing studies on antiaromatic compounds, particularly those with triplet ground states that have potential applications in materials science.