Synthesis of polymerizable and deuterated phosphatidylcholines for use in membrane studies.
Item
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Title
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Synthesis of polymerizable and deuterated phosphatidylcholines for use in membrane studies.
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Identifier
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AAI9218287
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identifier
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9218287
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Creator
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Xu, Zhenchun.
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Contributor
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Adviser: Robert Bittman
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Date
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1992
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Language
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English
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Publisher
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City University of New York.
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Subject
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Engineering, Chemical | Health Sciences, Pharmacology
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Abstract
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In this Dissertation, (Z)-1-methoxybut-1-en-3-yne has served as a useful synthon for the synthesis of the positional isomers and homologues of conjugated diacetylenic alcohols and acids. This new and efficient way is an alternative to the use of the Cadiot-Chodkiewicz heterocoupling reaction for the preparation of diacetylenic carboxylic acids. The butadiyne-synthon approach to conjugated diacetylenic alcohols has been extended to the preparation of the identical-acid, mixed-acid, mixed-ether, and ether/ester phosphatidylcholines (PC) containing conjugated diacetylene chains by using previous methods for PC synthesis. The ether-containing PCs are prepared by using diacetylenic alcohols as nucleophiles in the ring-opening reaction of various chiral glycidyl derivatives. The chiral purity of each stereoisomer of the ring-opened products was established by examination of the diastereomeric mixture of the (R)-(+)-{dollar}\alpha{dollar}-methoxy-{dollar}\alpha{dollar}-(trifluoromethyl)-phenylacetic acid ester by chiral high-pressure liquid chromatography.;Liposomes prepared from four diacetylenic PCs containing eighteen-carbon chains have been examined in terms of lamellar structure, polymerizability, and permeability properties. The structures of bilayers of these lipids were determined at low resolution by low angle X-ray diffraction. Among these PC's, only 1,2-di-(4{dollar}\sp\prime{dollar},6{dollar}\sp\prime{dollar}-octadecadiynoyl)-sn-glycero-3-phosphocholine polymerized effectively upon UV irradiation at room temperature, as estimated by Dr. David G. Rhodes. The results of permeation experiments of PC liposomes indicate that unpolymerized and polymerized liposomes of 1,2-di-(4{dollar}\sp\prime{dollar},6{dollar}\sp\prime{dollar}-octadecadiynoyl)-sn-glycero-3-phosphocholine underwent osmotic swelling with acetamide, glycerol, and urea more rapidly than did liposomes of stearoyl-oleoyl PC, but the initial rates of swelling of polymerized liposomes of 1,2-di-(4{dollar}\sp\prime{dollar},6{dollar}\sp\prime{dollar}-octadecadiynoyl)-sn-glycero-3-phosphocholine were 3-10 times lower than those of unpolymerized liposomes of 1,2-di-(4{dollar}\sp\prime{dollar},6{dollar}\sp\prime{dollar}-octadecadiynoyl)-sn-glycero-3-phosphocholine. The molecular packing of monolayers of three diacetylenic PCs at the air/water interface was studied by pressure/area measurements, and their domain structure was analyzed using 1% phosphatidylethanolamine-rhodamine labeled monolayers by fluorescence microscopy by Hui et al.;Three partially deuterated PCs were prepared by acetylenic coupling reaction, catalytic reduction with deuterium, and conversion of the deuterium-labeled fatty acids into PC. One of the PC-d{dollar}\sb8{dollar} isomers was used recently in the direct determination of conformational disorder in bilayer membranes by FT-infrared spectroscopy (Mendelsohn, R.; Davies, M. A.; Schuster, H. F.; Xu, Z.; Bittman, R. Biochemistry 1991, 30, 8558-8563). The quantitative detection of a specific, position-dependent kink (gtg') and isolated gauche (gtt) rotamer has been performed using CD{dollar}\sb2{dollar} rocking modes.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
