U. Notre Dame This CAREER award is made in the Organic Dynamics Program in support of the research and teaching activities of Dr. Bradley Smith. The theme of the research is the design and synthesis of allosteric supramolecular assemblies, i.e systems whose chemical activity is altered by conformational changes remote to the site of the activity. In each system proposed, the allosteric mechanism will involve chair-chair interconversion of cis-1,3-cyclohexanedicarboxylic acids. These switchable moieties will be incorporated into cyclophanes, polar lipids, and self assembling ion channels. The allosteric molecular switches will be triggered by pH changes and/or metal cations. Depending on the design of the supramolecular assembly, triggered-release of drugs, transport of ions, and signal transduction will be achieved. Dr. Smith's teaching plan will involve the development of a laboratory manual for a new Biological Organic Chemistry course for biology majors and the development of a new course in Organic Structure Elucidation. A workbook will be prepared for the latter based on modern spectroscopic methods and directed towards senior undergraduates. This study of allosteric supramolecular assemblies will lead to the development of useful molecular devices such as triggered-release liposomes for gene therapy, targeted carriers for drug delivery and switchable ion channels with antibiotic potential. The involvement of graduate and undergraduate students in the research will have a significant educational value.
