Theses and Dissertations from UMD

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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

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Author: search.filters.author.Okunola, Oluyomi AdeolaSubject: search.filters.subject.nitrate

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    USING "SMALL" MOLECULES AS TRANSMEMBRANE ANION TRANSPORTERS
    (2009) Okunola, Oluyomi Adeola; Davis, Jeffery T; Chemistry; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Functional, "small" molecule anion transporters have been identified and developed from natural products and synthetic organic compounds. The major discoveries include the design of a transmembrane Cl- transporter whose activity is pH-tunable, a NO3- transporter that displays unique selectivity for NO3- over Cl- anions, and a series of small molecules that efficiently transport HCO3- across liposomal membranes via a HCO3-/Cl- exchange mechanism. An assay for detecting transmembrane HCO3- transport using paramagnetic Mn2+ and 13C NMR is also described. Modulated Cl- transport was achieved by lipophilic calix[4]arene amides 2.2-2.4, all in the cone conformation. Modulation was achieved through functional group modification to one of the four side-chains. The cone conformation was confirmed by both 1H NMR and X-ray crystallography. Significantly, Cl- transport was gated by pH in the presence of triamido calixarene TAC-OH 2.3, which possesses a phenolic hydroxyl group. Using fluorescence assays, the rate of Cl- transport by TAC-OH 2.3 across liposomal membranes decreased with increasing pH, while transport rate by cone-H 2.2a, lacking an OH group, was not affected by pH. Nitrate was selectively transported over Cl- in the presence of nitro tripod 3.1, a small molecule receptor for both anions. The selective transport of NO3- by 3.1 is a significant discovery as most known synthetic Cl- transporters also transport NO3- ions and vice versa. Nitrate transport across liposomal membranes was confirmed by enzyme-coupled and fluorescence assays. Tripod 3.1 induced an increase in the intravesicular pH of liposomes that were not experiencing a pH gradient, while no pH changes occurred in the presence of calixarene 2.1 a known Cl- and NO3- transporter. This result suggests that 3.1 is an H+/NO3- symporter. Transmembrane HCO3- transport was achieved using the natural product, prodigiosin, 4.1, and synthetic isophthalamides 4.2-4.4. The Cl-/HCO3- exchange mechanism by which compounds 4.1-4.4 transport HCO3- was elucidated by ISE and NMR assays. The 13C NMR assay provided direct evidence for HCO3- transport in the presence of paramagnetic Mn2+ ions, and was adaptable to various assay conditions.