Research Project
6358672
The objective of the research proposed is the generation of organic, polymeric "molecular imprints" with novel-and improved-catalytic activities. To create a molecular imprint, a "template" molecule is first dissolved in a solution of monomers. These monomers contain chemical functionality that bonds either noncovalently (typically via hydrogen or ionic bonds) or covalently (via reversibly cleavable bonds such as imines or boronic esters) with the template molecule-formation of these bonds organize the monomers around the template. At this point, the mixture is polymerized to form a rigid, porous lattice-i.e., a plastic. The template molecule is then washed away from the polymer, leaving microscopic cavities (the "imprints") that are electrostatically and geometrically complementary to the template. The resultant molecular imprint can selectively bind the template molecule (in preference to its enantiomer, for example) or can act as a catalyst if the template molecule is appropriately designed (if it is a transition state analogue, for example). However, while molecular imprints with exquisite binding specificities can now be routinely generated, those with catalytic activity have displayed only modest rate accelerations. Here, three novel catalytic systems are proposed, each employing the covalent approach and each designed to incorporate a nucleophilic functionality, a mechanistic feature that can lead to huge rate accelerations in intramolecular model systems and a key to the accelerations effected by the best antibody catalysts isolated to date. The first of these systems involves the use of an imprint against a phenyl pyranoside derivative as a catalyst for the lactonization of the corresponding aldonic ester and amide; the second, the use of a Kemp's triacid derivative as a template to generate catalytic imprints for the hydrolysis of corresponding acyclic diacid-amides; and the third, the use of a vinylogous amide to generate catalysts for the aldol condensation of the corresponding aldehyde/ketone pair.
