RUI: Molecular Characterization of Aggregation and Guest-Host Solvation by Bile Acids

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In this project, Professors David Rovnyak and Timothy Strein of Bucknell University are funded by the Chemical Structure, Dynamics and Mechanisms Program of the Division of Chemistry, to conduct a wide ranging study of bile acid aggregation using multiple techniques including nuclear magnetic resonance (NMR), fluorescence and electrophoresis. Bile acids are cholesterol-derived amphiphilic molecules in the liver which facilitate lipid and cholesterol transport. Predominant in aqueous solution as their salts (a.k.a. bile salts), fundamental physico-chemical properties of these important molecules are not well understood. Indeed it has been difficult to achieve consensus on bile aggregation, namely, the intermolecular interactions and dynamics that give rise to properties such as critical micelle concentration(s), aggregation number(s), gel formation, and guest-host interactions, beyond Small's model of bile aggregation proposed ca. 1968. Also, the capacity of bile aggregates to differentially solubilize the enantiomers of certain chiral compounds has not been characterized at a molecular level. This project will use the various techniques to detect and validate behaviors that have the potential to help explain seemingly disparate reports in the literature. For example, preliminary work has shown that NMR methods unambiguously delineate separate early and primary micellization stages that have not been clearly observed before. Further, planar fluorescent probes that exhibit strong solvatochromism are used to detect and characterize the presence of hydrophobic regions of the bile micelles. Micellar electrokinetic capillary electrophoresis will be used as a sensitive probe of aggregation stages and of guest-host interactions. Through the use of these complementary techniques, we a better understanding of the complicated intermolecular chemistry of bile salts will emerge. Bile acids are fascinating naturally produced molecules whose complex properties have challenged scientists for decades. Bile acids can interact strongly with certain classes of oils, form gels with desirable properties such as the capacity to promote topical drug delivery, and most recently are being found to play much wider roles in the maintenance of human health than previously understood. Bile acids can also help distinguish among isomers of compounds that would be difficult to separate by other means. Yet there is a need to explain bile acid properties and behaviors on the molecular scale. With deeper insights into the molecular scale behaviors of bile acids, there is the possibility to tap into greater potential for new applications of bile acids, and for better understanding of their broader roles in human biology. The undergraduate students working on these projects will be involved in all aspects of this project. They will acquire hands-on experience in the design of multifaceted experiments, the use of sophisticated spectroscopic instrumentation, and in analyzing and interpreting data collected using those instruments. This experience provides students preparation for further study or future employment.