Understanding Molecular-Recognition Properties of Helical Pores under Non-equilibrium Conditions

Professor Bing Gong of the State University of New York at Buffalo and Professor Xiao Cheng Zeng of the University of Nebraska-Lincoln collaborate to develop novel approaches to sensing differences among sugar molecules. In this project, the team designs and synthesizes long-chain molecules that coil up like springs. The interior space of these "molecular springs" interact with different kinds of sugar molecules with different strengths. By embedding these "molecular springs" in a cell wall and monitoring the passage of sugar molecules through the interior spaces, the research team aims to develop a method to recognize and sense sugars in water. The results of this research may have implications in separations and medical diagnostics. The broader impacts involve training graduate and undergraduate students, incorporating research into teaching, conducting workshops, reaching out to underrepresented groups, and broadly disseminating this work to the scientific community. With the support from the Macromolecular, Supramolecular and Nanochemistry Program of the Chemistry Division, this project aims to probe and understand molecular recognition of sugar and sugar alcohols in aqueous media under non-equilibrium conditions. The research team prepares aromatic oligoamide foldamers that form helical coils. When embedded in membranes, the oxygen-rich, electrostatically negative inner pores of these coils provide thruways for ions to pass through the membrane. In addition, the presence of numerous amide oxygen atoms in the inner pores of the membrane-bound foldamers serve as hydrogen-bond acceptors that enable multiple hydrogen-bonding interactions with sugars and sugar alcohols in different strengths. Such interactions, being dynamic and transient, especially in water, result in the perturbation of ion currents through the transmembrane pores. Depending on their structures and properties, different types of carbohydrates perturb the flow of ions through the pores differently, which can be detected very sensitively. By measuring the changes in transmembrane ion conductance in the presence of different saccharides and their derivatives, the research aims to monitor and understand molecular recognition of these molecules under non-equilibrium conditions. Specifically, this work focuses on synthesizing oligoamides of different lengths (8mer, 16mer, 32mer, and 64mer) and examining the effects of various sugars and sugar alcohols on the transmembrane ion currents through the pore-forming foldamers. Vesicle-based assays are performed to provide a rapid but qualitative screening of the effects of chosen carbohydrates, followed by measurement of single-channel currents to reveal the signatures of different carbohydrate molecules. 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.