Theses and Dissertations at Montana State University (MSU)
Permanent URI for this collectionhttps://scholarworks.montana.edu/handle/1/733
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Item Solute partitioning into model biological membranes studied with time-resolved emission spectroscopy and calorimetry(Montana State University - Bozeman, College of Letters & Science, 2022) Duncan, Katelyn Marie; Chairperson, Graduate Committee: Robert Walker; This is a manuscript style paper that includes co-authored chapters.Bioaccumulation and bioconcentration are terms used to quantify the concentration of the solute in an organism with respect to the source of exposure. Empirical values are commonly used to predict a solutes tendency for bioconcentration. While they are useful zeroth order indicators, empirical values lack the chemical specificity required to fully understand the exact solute-solute and solute-lipid chemical interactions that occur when a solute is introduced to a biological membrane. The work described here uses fluorescence spectroscopy and thermoanalytical techniques to quantify solute partitioning into model biological membranes. The model membranes used in this study are lipid bilayer vesicles that are analyzed as a function of temperature from the rigid gel-phase through the transition temperature and into the fluid liquid-crystalline phase. Studies described in this work seek to create a quantitative, mechanistic description of solute behavior in heterogeneous chemical environments. Each body of work either altered the solute used for partitioning or altered the membrane to add chemical complexity. The first body of work describes a proof-of-concept study analyzing the change in partitioning behavior from small structural changes in the solute. This study found that small changes to the solute affects membrane permeability in a way that is not accounted for in empirical models. The subsequent study sought to understand how the addition of amino acids to the membrane changes partitioning tendencies. Further analysis was done to study the partitioning behavior of amino acid L-Phenylalanine. Studies showed L-Phenylalanine integrates into the membrane and experiences a conformationally restricted environment. Additional studies were done on a pharmaceutical candidate and found membrane permeability does not correlate with drug activity. The drug was predicted to interact with the target-protein directly. Furthermore, analysis on the herbicide Dicamba has shown some indication of membrane interaction; however, more studies are required to fully understand the partitioning behavior.Item Crystal pressure of pharmaceuticals in nanoscale pores(Montana State University - Bozeman, College of Engineering, 2017) Berglund, Emily Anne; Chairperson, Graduate Committee: James WilkingMany pharmaceutical compounds are poorly soluble in water. This is problematic because most pharmaceuticals are delivered orally and must dissolve in the gastrointestinal fluid to be absorbed by the body. Drug dissolution rate is proportional to surface area, so a common formulation strategy is to structure drugs as small as possible to maximize surface area. A simple approach to create very small particles is to structure the compounds within the nanoscale pore space of a colloidal packing. The resulting composite undergoes rapid disintegration in water and the exposed drug exhibits dramatically improved dissolution rates. We hypothesize that composite breakup is driven by the growth of nanoscale crystals, which exert a pressure on the walls of the confining pores. To test this hypothesis, we systematically vary the amount of water permitted into the composite and use calorimetry to monitor the evolution of the crystal size distribution as a function of water content. To exert sufficient pressure to overcome the tensile yield stress of the composite, the crystals must be fed by a supersaturated phase. Our results suggest that differences in crystal curvature due to crystal confinement and crystal size polydispersity generate the necessary supersaturation. These results are relevant not just for drug formulations, but for understanding physical processes such as salt damage to buildings and road damage due to frost heave.Item A new method of AC calorimetry using thermoelectric devices(Montana State University - Bozeman, College of Letters & Science, 1994) Pastalan, Gregory James