Date of Thesis

2016

Description

It is well known that bile salts form micelles that are capable of stereospecific binding of binaphthyl guest molecules, but the precise structure of these aggregates, and the energetics of the intermolecular interactions are not well understood. Moreover, the dynamic nature of these complex micelle systems has made complete characterization elusive. Previous work has shown that sodium cholate (NaC) is capable of performing chirally selective micellar electrokinetic capillary chromatography (MEKC) separations of racemic binaphthyl compounds 1,1’-bi-2-naphthol (BN) and 1,1’-binaphthyl-2,2’- diylhydrogenphosphate (BNDHP). Furthermore, 1H NMR chemical shift analysis of NaC in the presence of binaphthyl guest molecules was shown to be a complementary technique for investigating chiral selectivity and micelle aggregation. In this work, isothermal titration calorimetry (ITC) is used to copiously describe the thermodynamics of micellization for sodium cholate, sodium deoxycholate (NaDC), and taurodeoxycholate (NaDC) as a function of temperature, ionic strength, and guest molecule concentration. The enthalpy of demicellization, ΔHdemic, of these bile salt micelle systems is directly measured and shown to be strongly temperature dependent, allowing for determination of the change in heat capacity of demicellization, ΔCрdemic. Using the psuedo-phase separation model, the free energy of demicellization, ΔGdemic, and entropy of demicellization, T∆Sdemic,were also calculated. ITC is also shown to be a sensitive reporter of chirally selective guest-host binding of model racemic 2 compounds BN and BNDHP to bile salt micelles. The S-isomer is shown to bind more tightly to the micelle in all cases, resulting in a larger binding enthalpy. Additionally, chiral selectivity appears to be enthalpically controlled. A model is proposed for interpreting ITC demicellization data in the absence and presence of a binaphthyl probe molecule, allowing for the quantitative determination of enthalpic difference in binding affinity that is on the order of 1 kJ mol-1. Furthermore, the racemic probe molecule BNDHP was found to mediate micellization at high concentrations and this observation is consistent with previous MEKC and NMR analyses of bile salt micelles. Lastly, the effect of temperature on the guest-host binding of R-BNDHP to cholate micelles was investigated. A change in temperature resulted in a change in the observed thermodynamics. However, further investigation over a wider temperature range is needed to fully characterize this effect. Overall, the results indicate that the micellization and chiral guest-host interactions of bile salt micelles are complex and dependent on various factors.

Keywords

bile salts, isothermal titration calorimetry, thermodynamics

Access Type

Masters Thesis (Bucknell Access Only)

Degree Type

Master of Science

Major

Chemistry

First Advisor

Timothy G. Strein

Second Advisor

David Rovnyak

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