Molecular Recognition in Water: Design, Synthesis, and Characterization of Rigid Molecular Receptors and Enzymatic Mechanistic Probes

Abstract

Molecular recognition can be defined as a selective and reversible binding between two or more molecules through non-covalent interactions. Multiple weakly attractive intermolecular forces work in concert to achieve selectivity in association. Such discrimination is critical to the physiological processes of catalysis, transport, antigen recognition, and storage. To better understand this phenomenon, acyclic synthetic molecular receptors also known as “molecular tweezers” were made to study the inclusion of small molecule guests from water. Three anionic tweezers derivatives with syn¬- cofacial orientation were constructed from a 1,2:4,5-bis-Trӧger’s Base skeleton that differed in the amount and distribution of negative charge about the receptors. These binding isomers were found to undergo self association to form dimers in solution by inclusion of the naphthalene wall of one tweezers into the cleft of another. Small molecule binding was evaluated at different ionic strengths and under concentration regimes in which either the desired monomeric tweezers or the dimeric complex predominated. Small molecules were also created in order to probe the mechanisms by which enzymes facilitate their transformations. Cinnamylidene pyruvate and fluorinated pyruvate derivatives were synthesized to better understand why SbADC, an ezyme classified as an acetoacetate decarboxylase, demonstrates aldolase activity. Enduracidinine is an unsaturated amino acid found in the potent antibiotics mannopeptimycin, teixobactin, and enduracidin. To investigate the biosynthesis of this amino acid, a new preparation of L-vinylglycine was devised. L-vinylglycine is a potential general precursor to the formation β,γ-unsaturated amino acids. Conditions were identified in which such unsaturated amino acids are formed by olefin metathesis of protected L-vinylglycine and alkenes including allylamine derivatives.