<p>The parasite <i>Echinococcus granulosus</i> causes hydatid disease, a major zoonosis. A fatty-acid-binding protein, EgFABP1, is important for the parasite, as it must acquire almost all its lipids from its environment or the host. The structure of EgFABP1 has been solved and refined to 1.6 Å resolution. The structure reveals that EgFABP1 has the 10-stranded β-barrel fold typical of the family of intracellular lipid-binding proteins. </p><p>Human semicarbazide-sensitive amine oxidase (SSAO; EC 1.4.3.6), also known as vascular adhesion protein-1, is a copper-containing monoamine oxidase that occurs both as a membrane-bound protein and in a soluble form in plasma. SSAO has been implicated in glucose transport in adipocytes, the differentiation of adipose cells and the leukocyte extravasation process. Toxic reaction products have been suggested to cause some of the vascular complications associated with diabetes and SSAO is therefore of pharmaceutical interest.</p><p>The structure of a truncated, soluble form of human SSAO has been determined to 2.5 Å resolution. The structure reveals that a leucine residue located adjacent to the active site could function as a gate controlling its accessibility. An RGD motif is displayed on the surface where it could be involved in integrin binding and possibly play a role in the shedding of SSAO from the membrane. Carbohydrate moieties are observed at five out of six potential N-glycosylation sites. Carbohydrates attached to Asn 232 flank the active site entrance and might influence substrate specificity. The structure also reveals a vicinal disulfide bridge, which we hypothesise could act as a redox switch involved in the protein’s mechanism of action. The structure of a complex of SSAO and the irreversible inhibitor 2-hydrazinopyridine has been solved and refined to 2.9 Å resolution. Both structures together will aid efforts to identify natural substrates, provide valuable information for the design of specific inhibitors and direct further studies. </p>

The parasite Echinococcus granulosus causes hydatid disease, a major zoonosis. A fatty-acid-binding protein, EgFABP1, is important for the parasite, as it must acquire almost all its lipids from its environment or the host. The structure of EgFABP1 has been solved and refined to 1.6 Å resolution. The structure reveals that EgFABP1 has the 10-stranded β-barrel fold typical of the family of intracellular lipid-binding proteins. Human semicarbazide-sensitive amine oxidase (SSAO; EC 1.4.3.6), also known as vascular adhesion protein-1, is a copper-containing monoamine oxidase that occurs both as a membrane-bound protein and in a soluble form in plasma. SSAO has been implicated in glucose transport in adipocytes, the differentiation of adipose cells and the leukocyte extravasation process. Toxic reaction products have been suggested to cause some of the vascular complications associated with diabetes and SSAO is therefore of pharmaceutical interest. The structure of a truncated, soluble form of human SSAO has been determined to 2.5 Å resolution. The structure reveals that a leucine residue located adjacent to the active site could function as a gate controlling its accessibility. An RGD motif is displayed on the surface where it could be involved in integrin binding and possibly play a role in the shedding of SSAO from the membrane. Carbohydrate moieties are observed at five out of six potential N-glycosylation sites. Carbohydrates attached to Asn 232 flank the active site entrance and might influence substrate specificity. The structure also reveals a vicinal disulfide bridge, which we hypothesise could act as a redox switch involved in the protein’s mechanism of action. The structure of a complex of SSAO and the irreversible inhibitor 2-hydrazinopyridine has been solved and refined to 2.9 Å resolution. Both structures together will aid efforts to identify natural substrates, provide valuable information for the design of specific inhibitors and direct further studies.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

The synthesis of dipyridyl functionalized polysulfones with improved hydrophilicity, enhanced membrane morphology and excellent ATRP polymeric ligand properties was conducted by the following method: (a) the formation of lithiated polysulfone from unmodified polysulfone and the subsequent reaction with 2,2'-vinylidenedipyridine in tetrahydrofuran at -78 oC under argon atmosphere to afford the corresponding dipyridyl functionalized polysulfone. The stoichiometry of the reaction affects the degree of functionalization of the product. When equimolar amounts of 2,2'-vinylidenedipyridine are added to the lithiated polysulfone, the degree of functionalization obtained was 45%. However, the addition of 10% and 20% molar excess of 2,2'-vinylidenedipyridine to the corresponding lithiated polysulfone produced dipyridyl functionalized polysulfones with degrees of functionalization of 80% and 95%, respectively; and (b) the membranes obtained from unmodified polysulfone as well as dipyridyl functionalized polysulfones were characterized by atomic force microscopy, scanning electron microscopy, pure water permeation measurements and contact angle measurements. Amine chain end functionalized polystyrene and poly(methyl methacrylate) were prepared by Atom Transfer Radical Polymerization (ATRP) methods as follows: (a) •-Aminophenyl functionalized polystyrene was prepared in quantitative yields by ATRP methods using a new primary amine functionalized initiator adduct, formed in situ by the reaction of 1-(4-aminophenyl)-1-phenylethylene and (1-bromoethyl)benzene in the presence of copper (I) bromide/2,2'-bipyridyl as catalyst in diethyl ether at 110 oC, for the polymerization of styrene.(b) New •-bis(aminophenyl) and •,ω-tetrakis(aminophenyl) functionalized polymers were prepared in quantitative yields by the ATRP method using the following synthetic strategy: (i) the initiation of styrene polymerization with a new primary diamine functionalized initiator adduct, generated in situ by the reaction of stoichiometric amounts of 1,1-bis(4-aminophenyl)ethylene with (1-bromoethyl)benzene in the presence of copper (I) bromide/2,2'-bipyridyl as catalyst, afforded •-bis(aminophenyl) functionalized polystyrene; and (ii) •-bis(aminophenyl) functionalized poly(methyl methacrylate) was prepared by the ATRP method using the primary diamine functionalized initiator adduct as initiator for methyl methacrylate polymerization; and (iii) well defined •,ω-tetrakis(aminophenyl) functionalized polystyrene was prepared by the post ATRP chain end modification reaction of •-bis(aminophenyl) functionalized polystyrene with 1,1-bis(4-aminophenyl)-ethylene at the completion of the polymerization reaction. (c) Similarly, •-bis(4-dimethylaminophenyl) functionalized polystyrene was prepared by using a new tertiary diamine functionalized initiator adduct, formed in situ by treatment of equimolar amounts of 1,1-bis[(4-dimethylamino)phenyl]-ethylene with (1-bromoethyl)benzene in the presence of copper (I) bromide/2,2'-bipyridyl as the catalyst in diphenyl ether at 110 oC for the initiation of styrene polymerization by the ATRP method. Furthermore, the ATRP of methyl methacrylate, initiated by the new tertiary diamine functionalized initiator adduct, produced •-bis(4-dimethylaminophenyl) functionalized poly(methyl methacrylate). In addition, •,ω-tetrakis(4-dimethylaminophenyl) functionalized polystyrene was synthesized via a post ATRP chain end modification reaction of •-bis(4-dimethylaminophenyl) functionalized polystyrene with equimolar amounts of 1,1-bis[(4-dimethylamino)phenyl]ethylene at the completion of the polymerization process. vi Quantitative yields of the different amine functionalized polymers with predictable number average molecular weights (Mn = 1.3 x 103 – 16.4 x103 g/mol), narrow molecular weight distributions (Mw/Mn = 1.03 – 1.29) and controlled chain end functionality were obtained. Polymerization kinetics data was employed to determine the controlled/living character of each ATRP reaction leading to the formation of the different amine chain end functionalized polymers. The polymerization processes were monitored by gas chromatographic analyses. Polymerization kinetics measurements for all reactions show that the polymerizations follow first order rate kinetics with respect to monomer consumption. The number average molecular weight of the amine functionalized polymers increases linearly with percentage monomer conversion and polymers with narrow molecular weight distribution were obtained. The ATRP of styrene, catalyzed by a novel dipyridyl functionalized polysulfone/CuBr supported catalyst system, afforded well defined polystyrene with predictable number average molecular weight and narrow molecular weight distribution in a controlled/living free radical polymerization process. The substituted 1,1-diphenylethylene initiator precursor derivatives and the functionalized polymers were characterized by nuclear magnetic resonance spectrometry, fourier transform infrared spectroscopy, thin layer chromatography, column chromatography, size exclusion chromatography, non-aqueous titrations, differential scanning calorimetry and thermogravimetrical analysis. / Chemistry / M. Sc. (Chemistry)

La plateforme ferrocène est fréquemment utilisée en chimie de coordination et en catalyse pour son excellente résistance aux conditions de réaction poussées. Le squelette ferrocène permet de maîtriser l’agencement de plusieurs groupes fonctionnels d’intérêt. Des ansa-ferrocènes et des ferrocènes à conformation contrainte, permettant par leur structure de contrôler une proximité des groupes fonctionnels, ont été décrits.La première partie de cette thèse traite de la synthèse de cyclopentadiényles borylés disubstitués et de leur réaction d’assemblage pour la formation de métallocènes borylés à conformation contrainte. Des analyses par RMN et des calculs par DFT ont permis de mettre en évidence la diastéréosélectivité inédite de la synthèse.À partir de cette approche, la deuxième partie traite de l’agencement de fonctions acides/bases de Lewis sur une plateforme ferrocénique à conformation contrainte. La synthèse de cyclopentadiényles (P/B) trisubstitués a été initiée. La synthèse de ligands ambiphiles (P/B) par assemblage de cyclopentadiénures et l’influence des tertio-butyles sur leur conformation ont été explorées. Une nouvelle forme de couplage de spin à trois centres sans liaison covalente, impliquant la lacune du bore dans la transmission de spin 31P31P, a été observée en RMN pour un P,P,B-ferrocène très original.La troisième partie traite de la synthèse de ferrocènes (P/B) et (N/B) à conformation contrainte. La voie de synthèse alternative et diastéréosélective proposée s’est révélée efficace alors que le rôle des tertio butyles dans le contrôle conformationnel a été démontré. L’étude de leur réactivité de type paire frustrée de Lewis a été initiée avec le CO2. / Ferrocene platforms are useful in coordination chemistry and catalysis thanks to their robustness and versatile functionalization. Ferrocene backbone allows the implantation of several key functional groups in a restricted space, inducing close proximity and potential polyfunctional cooperation (see for instance ferrocenyl polyphosphine chemistry). Ansa ferrocene and ferrocene bearing conformational control inducing groups maximizing the proximity of key groups have been widely reported.The first part of this thesis focuses on the synthesis of new borylated cyclopentadienyl, and their use in formation of borylated metallocenes bearing conformational constraints. NMR analysis and DFT calculation exhibits the diastereoselectivity of assembly reaction.The second part deals with the arrangement of several Lewis acids and bases on a constraint ferrocene platform. Synthesis of trisubstituted cyclopentadienyl (P/B) has been initiated. Synthesis of ambiphilic ligands (P/B) by assembly reaction of cyclopentadienides and the influence of tert-butyl groups on their conformation have been explored. A new 31P31P spin coupling transmitted “through-space (nonbonded spin-spin coupling transmission) involving for the first time an empty orbital has been observed.The third part describes the synthesis of heteroannular (P/B) and (N/B) ferrocene directly from ferrocene functionalization. An efficient and diastereoselective synthesis has been developed and the influence of tert-butyl groups on the conformational control has been highlighted in both solid and solution state. Studies of the frustrated Lewis pair reactivity of these new ambiphilic ligands have been initiated by addition of CO2.

L’objectif de cette thèse est de développer un matériau à base de polyméthacrylate de méthyle (PMMA) amorcé par une réaction redox à température ambiante pour produire des composites thermoplastiques. Plus particulièrement, notre travail a consisté à étudier le mécanisme d’amorçage afin d’améliorer la formulation de la résine en terme de cinétique de polymérisation. Afin d’atteindre cet objectif, les paramètres d’Arrhenius de la décomposition d’amorceur ont été déterminés et intégrés dans un modèle de simulation numérique décrivant la polymérisation du MMA à température ambiante développé à l’aide du logiciel PREDICI. Basé sur cette simulation, des différents paramètres ont été testés dans le but de diminuer le temps de polymérisation. En complément de la détermination des paramètres du système d’amorçage, une étude de copolymérisation avec un grand nombre de comonomères a été effectuée. Cette étude a conduit à l’identification d’un monomère permettant d’accélérer la vitesse de polymérisation : le méthacrylate d’acetoacetoxyethyle (AAEMA). Une étude cinétique de ce monomère a été réalisée avec l’identification du coefficient de la vitesse de propagation kp ainsi que les paramètres de copolymérisation avec MMA, rMMA et rAAEMA. Les paramètres cinétiques, qui ont été déterminés expérimentalement, ont été vérifiés par une simulation numérique de copolymérisation de MMA et AAEMA. / Composite materials are used for decades as high-performance materials in industry. Up to date these materials were based on non-recyclable thermoset polymers. Nowadays, environmental and economical restrictions enhance the development of recyclable composite materials. For answering that demand, research focuses on the development of recyclable thermoplastic polymer composites. Within this context, the work of this thesis focuses on the development of a material based on a poly(methyl methacrylate) (PMMA) resin initiated with a redox initiation system at room temperature in order to prepare thermoplastic composites. More precisely, our work consisted of studying this initiation system and to improve the kinetics of the resin formulation. For that purpose, the Arrhenius parameters of the initiator decomposition reaction were determined and implemented in a simulation model that describes the polymerization of MMA at room temperature. Based on the simulation carried out on the software PREDICI, several conditions were tested aiming in the decrease of the polymerization times. Besides investigating parameters concerning the initiation system, a copolymerization study, using a large variety of comonomers, was conducted. This study led to the identification of an interesting fast polymerizing methacrylate: acetoacetoxyethyl methacrylate (AAEMA). The kinetics of this monomer were studied including the determination of the propagation rate coefficient kp and the copolymerization parameters with MMA rMMA and rAAEMA. The determined kinetic parameters were finally verified by a copolymerization simulation of MMA and AAEMA.

Die vorliegende Arbeit befasst sich in erster Linie mit der Synthese hochreaktiver Allenylisothiocyanate, wobei nicht nur das bereits ausführlich untersuchte Propa-1,2-dienylisothiocyanat – die einfachste Verbindung dieser Substanzklasse – sondern vor allem neue, höher substituierte Allene dargestellt werden sollen. Die Herstellung erfolgt während einer Gasphasenthermolyse (Blitzvakuum- oder Solution-Spray-Blitzvakuumpyrolyse) über die [3,3]-sigmatrope Umlagerung der entsprechenden Propargylthiocyanat-Vorstufen. Im Anschluss werden die so gewonnenen Allenylisothiocyanate in verschiedenen 2- und 3-Komponenten-Reaktionen eingesetzt. Dabei soll das Hauptaugenmerk auf der Synthese neuer 2-Amino-1,3-thiazol-Strukturen liegen, welche aufgrund ihrer vielseitigen biologischen Wirkung mittlerweile einen hohen Stellenwert in der organischen Chemie einnehmen. Zum besseren Verständnis einiger unklarer mechanistischer Abläufe verschiedener Umsetzungen werden vor allem NMR-spektroskopische Experimente durchgeführt (z. B.: 2D-NMR, Doppel-resonanz-Experimente, Tieftemperatur-NMR-Verfolgung). Des Weiteren wird der Grundkörper – Propa-1,2-dienylisothiocyanat – mit diversen sterisch gehinderten, sekundären Aminen umgesetzt, wobei die Grenzen der Reaktivität ausgelotet werden sollen. Mit Hilfe der NMR-spektroskopischen Charakterisierung der zuvor synthetisierten 2-Amino-1,3-thiazole wird die Möglichkeit zur Durchführung von Konkurrenz-Reaktionen mit jeweils zwei verschiedenen Aminen eröffnet. Auf diesem Weg können relative Faktoren zum Abschätzen der Bildungsgeschwindigkeiten der Thiazole ermittelt und ähnliche Substituenten hinsichtlich ihres sterischen Anspruchs miteinander verglichen werden.

Die Phasengleichgewichte (Flüssigkeit-Dampf und Flüssigkeit-Flüssigkeit) der binären, ternären und quaternären Mischungen bestehend aus Wasser, Toluen, Anilin und Cyclohexylamin wurden experimentell bestimmt und modelliert bzw. vorausberechnet. Die Bestimmung der Flüssigkeit-Dampf-Gleichgewichte erfolgte mit Hilfe der dynamischen Methode, die dafür notwendige Mess- und Regeltechnik wurde erweitert und modernisiert. Die Flüssigkeit-Flüssigkeit-Gleichgewichte wurden durch Trübungstitration und Analyse der koexistierenden Phasen bestimmt. Die Beschreibung der binären Systeme und die Vorausberechnung der Mehrkomponentensysteme erfolgte mit den Aktivitätskoeffizientenmodellen UNIQUAC und NRTL und der Zustandsgleichung, entwickelt von Elliott, Suresh und Donohue (ESD). Die ESD-Zustandsgleichung enthält neben einem Attraktions- und einem Repulsionsterm auch einen Term, der assoziative Wechselwirkungen explizit berücksichtigt. Die Beschreibung der binären Systeme gelingt mit den getesteten Modellen sehr gut. Dabei werden mit den Aktivitätskoeffizientenmodellen bessere Ergebnisse erreicht als mit der ESD-Zustandsgleichung. Diese Bild kehrt sich bei der Vorausberechnung der Mehrkomponentensysteme um. Bei Verwendung der NRTL-Gleichung treten deutlich höhere Abweichungen auf als bei Berechnungen mit der ESD-Zustandsgleichung bzw. der UNIQUAC-Gleichung. Die Erwartung durch explizite Berücksichtigung der Assoziation mit der ESD-Zustandsgleichung einen deutlichen Vorteil in der Vorhersage von Phasengleichgewichten in Systemen mit assoziierenden Komponenten zu erhalten konnte in den untersuchten Mischungen nicht eindeutig bestätigt werden. / Phase equilibria (vapor-liquid and liquid-liquid) of binary, ternary and quaternary systems consisting of water, toluene, aniline and cyclohexylamine were determined experimentally and modeled resp. predicted. Vapor-liquid equilibria were determined by the dynamic method, the necessary measuring and control systems were extended and modernized. Liquid-liquid equilibria were investigated by turbidity titration and analyses of coexisting phases. The calculation of the binary systems and the prediction of the multicomponent systems were performed with the activity coefficient models UNIQUAC and NRTL and the equation of state developed by Elliott, Suresh and Donohue (ESD). The ESD equation of state includes beside an attractive and a repulsive term a term for explicit consideration of associative interaction. The description of the binary systems succeeded very well with the tested models. Better results were achieved with the activity coefficient models than with the ESD equation of state. These findings are inversed in the case of prediction of multicomponent phase equilibria. On application of the NRTL equation the deviations are notable greater than with the ESD equation of state or the UNIQUAC equation. The expectation to get a significant advantage in prediction of phase equilibria in systems with associating components with the ESD equation of state could not be answered definitely.

No description available.

Electrochemical diazonium grafting offers versatile functionalization of chemically inert graphite under mild condition, which is particularly suitable for CNT composite modification. Tetrafluorinated carboxylphenyl diazonium grafting provides the most controllable functionalization chemistry allowing near monolayer levels of functionality on carbon nanotubes. The functional density was successfully quantified by anion selective dye-assay and X-ray photoelectron spectroscopy (XPS) of thiol-Au self-assembled monolayers (SAM) as a calibration reference. This technique enables monolayer functionality at the tips of carbon nanotube membranes for biomimetic pumps and valves as well as thin conductive layers for CNT-based high area electrochemical support electrodes. Double-walled carbon nanotube (DWCNT) membranes were functionalized with sterically bulky dye molecules with amine termination in a single step functionalization process. Non-faradic (EIS) spectra indicated that the functionalized gatekeeper by single-step modification can be actuated to mimic protein channel under bias. This functional chemistry on membranes resulted in rectification factors of up to 14.4 with potassium ferricyanide in trans-membrane electrochemical measurements. One step functionalization by electrooxidation of amines provides simple and promising functionalization chemistry for the application of CNT membranes. Carbon nanotubes (CNTs) are considered a promising catalyst support due to high surface area, conductivity and stability. But very few cases of asymmetric catalysis have been reported using CNTs as support. Three noncovalent functionalization approaches have been carried out to immobilize Rh-Josiphos complex on CNTs for asymmetric hydrogenation of dimethyl itaconate. Coordinated Rh catalyst on CNTs exhibited excellent activity and reuse ability even after seventh run in hydrogenation but no enantiomeric excess as expected for lacking a chiral directing ligand. The catalyst using pyrene absorption gave 100% yield and excellent enantiomer excess (>90%) but suffered from leaching into solution. The phosphotungstic acid (PTA) anchored catalyst gave 100% yield and higher ee (99%) and better reusability over pyrene absorbed catalyst but had significant leaching after the second run. At this point it remains a significant challenge to utilize CNTs as a chiral catalyst support.