UBC Theses and Dissertations
A nuclear magnetic resonance study of molecular permeation through lipid membranes Males, Ryan Gordon
A theoretical description of the kinetics for the passive transport of both lipophobic and lipophilic nonelectrolytes, weak acids, and bases through membranes of large unilamellar vesicles (LUVs) is discussed. Equations are derived which may be used to obtain permeability coefficients and predict the extent of LUV entrapment of permeant molecules. By applying a diffusional approach rather than a simple first order kinetic approach to the problem of passive transport, some of the inconsistencies observed in other works are corrected. ¹H NMR methods are described for the measurement of permeability coefficients over a broad time scale. Employing these methods, the transmembrane permeability coefficients of glycolic acid as well as the environmentally sensitive arsenical, dimethylarsinic acid (DMA) have been measured in egg phosphatidylcholine (EPC) vesicles. The effects of temperature, pH, and membrane cholesterol content on permeability have been studied and a better understanding of how molecules traverse membranes has been attained. The importance of using permeability coefficients rather than n-octanol / water partition coefficients in the determination of the bioavailability and bioaccumulation of environmentally sensitive compounds is also discussed. The permeability of tetraphenylborate anion has been studied as well as its binding coefficient to EPC vesicles. This study illustrates how NMR may be applied to studies of lipophilic ions which transport rapidly across the membrane / water interface but move comparatively slower across the membranous region of a bilayer.
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