Hollow Helices as Enzyme-Like Catalysts

About This Grant

With the support of the Chemical Mechanism, Function, and Properties (CMFP) Program and the Chemical Catalysis Program in the Division of Chemistry, Professor Bing Gong of the State University of New York at Buffalo will be studying the function, properties, and catalytic behavior of short polyamides having spirally folded helical conformations. These slinky-like folding molecular chains, known as porous foldamers or “hollow helices”, feature an electrostatically negative, non-collapsible inner void (with a sub-nanometer diameter). These foldamers are expected to function as synthetic enzymes by accelerating chemical transformations by overcoming the energy barriers of targeted reactions within a defined pocket, similar to natural enzymes. The synthetic tunability of the hollow helices offers an adaptable structural platform for the development of enzyme-like catalysts with progressively enhanced efficiency and specificity. Broader impacts include fundamental knowledge, new catalysts, and workforce development through rigorous student training. The non-deformable inner pores of the aromatic oligoamides are strongly hydrogen-bonding and highly electronegative due to the presence of multiple inwardly oriented amide oxygen atoms. Cationic guest molecules exhibit high affinity binding to the inner pores of the hollow helices at up to 10e15/M, rivaling the tightest guest-binding systems observed in nature. This research aims to deepen our understanding of how hollow helices, with their exceptional ability to bind cationic species, can function as synthetic enzymes. By stabilizing the cationic transition states of targeted reactions, the helical foldamers are expected to facilitate the formation of acetals from aldehydes and ketones. The team will be looking at basic aspects of catalysis expected of the hollow helices. Catalytic efficiency will be tuned and enhanced by adjusting both the helical foldamers and the aldehyde/ketone substrates, along with the investigation and understanding of factors behind the observed changes in catalytic behavior. Another objective is to form mixed acetals—compounds with two distinct alkoxy groups—which are present in various medically significant natural products but continue to pose a considerable synthetic challenge. In the later stages of this project, efforts will made to develop hollow helices with biased (left or right) handedness, enabling the asymmetric synthesis of chiral mixed acetals. This project will combine the concepts and studies of molecular design, host-guest interaction, and enzyme kinetics to provide research training opportunities for undergraduate and graduate students. The research results will be publicized broadly in the scientific community and incorporated into undergraduate and graduate teaching. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.