Browsing by Subject "porphyrins"
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Item Carbazole based anion receptors(2009) Mikkilineni, Vinay K.; Jonathan SesslerAnions are of great importance in the environment and health, thus it is no wonder that a great deal of research has been conducted to create synthetic receptors that can bind to various anions. In the past few decades, research and synthesis of novel receptors containing pyrrole, such as “expanded” porphyrins, has increased tremendously. These new synthetic molecules have been used as means for various applications including anion binding, sensing, transport and delivery. Previous work has shown some success in trying to use carbazole as a key component in combination with pyrrole for receptor synthesis. Carbazole has a large size, flourescent properties and a more acidic NH donor than the pyrrolic NH normally found in these analogues to bind ions. The synthesis and analysis of new carbazole-based receptors, “expanded” porphyrin macrocycles and amidopyrroles, is discussed with special attention paid to the modification of carbazole in an attempt to enhance binding and solubility of the receptors. Binding with various anions (chloride, benzoate, and dihydrogen phosphate) was studied and all molecules were shown to have an increased affinity for phosphate. However, there were notable differences in anion selectivity between the various receptors.Item Letter to H.B. Stenzel from Alex Comfort on 1962-08-13(1962-08-13) Comfort, AlexItem A Porphodimethene Chemical Inhibitor of Uroporphyrinogen Decarboxylase(PLOS One, 2014-02-25) Yip, Kenneth W.; Zhang, Zhan; Sakemura-Nakatsugawa, Noriko; Huang, Jui-Wen; Vu, Nhu Mai; Chiang, Yi-Kun; Lin, Chih-Lung; Kwan, Jennifer Y. Y.; Yue, Shijun; Jitkova, Yulia; To, Terence; Zahedi, Payam; Zahedi, Payam; Pai, Emil F.; Schimmer, Aaron D.; Lovell, Jonathan F.; Sessler, Jonathan L.; Liu, Fei-FeiUroporphyrinogen decarboxylase (UROD) catalyzes the conversion of uroporphyrinogen to coproporphyrinogen during heme biosynthesis. This enzyme was recently identified as a potential anticancer target; its inhibition leads to an increase in reactive oxygen species, likely mediated by the Fenton reaction, thereby decreasing cancer cell viability and working in cooperation with radiation and/or cisplatin. Because there is no known chemical UROD inhibitor suitable for use in translational studies, we aimed to design, synthesize, and characterize such a compound. Initial in silico-based design and docking analyses identified a potential porphyrin analogue that was subsequently synthesized. This species, a porphodimethene (named PI-16), was found to inhibit UROD in an enzymatic assay (IC50 = 9.9 µM), but did not affect porphobilinogen deaminase (at 62.5 µM), thereby exhibiting specificity. In cellular assays, PI-16 reduced the viability of FaDu and ME-180 cancer cells with half maximal effective concentrations of 22.7 µM and 26.9 µM, respectively, and only minimally affected normal oral epithelial (NOE) cells. PI-16 also combined effectively with radiation and cisplatin, with potent synergy being observed in the case of cisplatin in FaDu cells (Chou-Talalay combination index <1). This work presents the first known synthetic UROD inhibitor, and sets the foundation for the design, synthesis, and characterization of higher affinity and more effective UROD inhibitors.Item Synthesis of a boronic acid-based oligosaccharide receptor using a porphyrin scaffold(2008) Reyes, Ryan Noel; Eric AnslynThe multi-step synthesis of a boronic acid-based oligosaccharide receptor is described. The proposed molecule was synthesized with the aim of developing a sensor that could be tuned to bind specific oligosaccharides on the cell surface. This receptor consisted of a meso-substituted tetraphenylporphyrin scaffold. 5,15-bis(4-cyanophenyl)-10,20-bis(4-hydroxyphenyl) porphyrin was first coordinated to a zinc ion. Polyethylene glycol chains were then added to the phenols of the porphyrin with hopes of increasing water solubility. The alcohol groups of the PEG chains were then protected from base by dihydropyran, and reduction of the cyano groups with LiAlH4 followed. Subsequent refluxing in acid resulted in the removal of the alcohol-protecting groups and the zinc as well as the oxidation of any reduced porphyrin. The reductive amination of formylphenylboronic acid by the porphyrin resulted in the incorporation of two boronic acid functional groups. Upon purification, this porphyrin will be used in saccharide binding experiments to test the specific porphyrin-sugar interactions. These interactions will possibly be studied through the use of affinity chromatography, utilizing a solid phase such as Sephadex. This study may also ultimately provide a method for purification of the boronic acid porphyrin, which has not yet been easily conducted using conventional column chromatography.