Synthesis and characterization of receptors to bind anionic components of bacterial membranes

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Jayasinghe, Champika P.
Burns, Dennis H.

Small molecules that can selectively recognize phospholipids would likely be useful as tools for chemical biology and may have application as pharmaceuticals. Inspired by the phospholipid binding of antimicrobial peptids found in nature, we have begun to develop synthetic receptors for the head group of phosphatidylglycerol. Among neutral receptors, attention is centered to systems containing the urea subunit. This study reports the re-synthesis of bis-phenolic-oxygen–ether-linked macrocycles and their binding studies towards phosphate anion and phosphatidylglycerol anion by means of 1H NMR and Isothermal Titration Calorimetry (ITC) experiments. Control receptor 8 binds to the inorganic H2PO4- anion in 1:1 binding stoichiometry with a moderate to high binding constant while receptor 7 bind s to PG anion with a moderate binding constant in 1:1 binding stoichiometry. Then it describes the synthesis and characterization of pre-organized neutral anion receptors which could contain a linker with four methylene unit between two aromatic rings. This link could be obtained by olefin ring closing metathesis utilizing Grubb’s catalyst. Finally it describes the study to determine the scope and the utilization of single step ureidoalkylation reaction using N-ethoxymethylene-N’-hexylurea 18 on different types of aromatic rings.

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Thesis (Ph.D.)--Wichita State University, College of Liberal Arts and Sciences, Dept. of Chemistry