Date of Thesis

Summer 2020

Description

Bile salts are naturally occurring amphiphilic molecules that are synthesized in the liver and can solubilize hydrophobic molecules. Bile salts are of particular interest due to emerging applications including topical drug delivery, separations, and nanomaterials processing. Little is known about bile micelle formation processes including number of monomers per aggregate, the structure of the various micellar aggregates, and the mechanisms by which micelles bind chiral guest molecules. Bile salts are also distinguished from other amphiphiles in that they undergo multiple stepwise aggregation events. This work gains insight into the structure of cholate aggregates by monitoring changes in heteronuclear single quantum coherence (2D-HSQC) NMR signals with varied cholate concentrations in the absence and presence of a chiral guest molecule. Changes in the chemical shifts with cholate concentration (1-100 mM) reveal changing local environments around particular nuclei, revealing the extent to which particular regions of the structure participate in the dynamic processes of micelle formation and guest-host binding. In addition, fitting the chemical shift data from HSQC spectra to a phase transition model reveals stepwise, discrete critical micelle concentrations (CMCs), and corresponding differences in interaction surfaces as a function of stepwise aggregation, indicating which locations on the cholate structure “see” changes during each aggregation step. Several trends arise in the chemical shift perturbation data which illuminate the evolving landscape of the micelle structure with successive CMCs and 2 supports a stepwise model of aggregation. The chemical shift perturbations also allow for further understanding of the interaction and chiral selectivity of bile salts with chiral guest molecules.

Keywords

NMR, capillary electrophoresis, bile salts

Access Type

Masters Thesis (Bucknell Access Only)

Degree Type

Master of Science

Major

Chemistry

First Advisor

Timothy Strein

Second Advisor

David Rovnyak

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