Thesis (Ph. D.)--Columbia University, 1931. / Biographical. Bibliography: p. 45.

Thesis (Ph. D.)--Columbia University, 1931. / Biographical. Bibliography: p. 45.

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

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No description available.

Distillation technology involves capital- and energy-intensive processes for light olefin/paraffin separation. Global demand for propylene has already exceeded 110 million tons per year. Therefore, distillation processes used for the separation of C3H6/C3H8 should be replaced or debottlenecked with more efficient and cost-effective technology. In the last three decades, membrane-based gas separation processes have successfully emerged, thus competing with conventional separation processes. Membranes potentially offer lower capital investment and operation cost than distillation columns. In this study, the use of advanced membrane materials for C3H6/C3H8 separation was investigated. Three novel triptycene-based polyimides were synthesized by Dr. Bader Ghanem from one diamine monomer, namely 2,6-dihydroxy-3,7-diaminotriptycene (DTA1-OH), and three dianhydride monomers, (i) non-substituted triptycene tetracarboxylic dianhydride (TDA), (ii) 9,10-dimethyltriptycene tetracarboxylic dianhydride (TDA1) and (iii) 9,10-iso-propyltriptycene tetracarboxylic dianhydride (TDAi3). It is important to note that polyimide membranes based on triptycene dianhydrides and triptycene diamines have never been reported in the literature before. Pure-gas permeability coefficients of He, H2, N2, O2, CO2, CH4, C3H6, and C3H8 were determined at 2 bar and 35 °C. Furthermore, C3H6 and C3H8 gas sorption isotherms were measured by gravimetric techniques, and experimental data were collected up to 7 bar at 35 °C. TDA-DAT1-OH, TDA1-DAT1-OH, TDAi3-DAT1-OH exhibited C3H6 permeability of 12.1, 16.6, and 5.64 Barrer with pure-gas C3H6/C3H8 selectivity of 35.7, 29.6, and 32.8 respectively. These properties exceeded the 2003 pure-gas upper bound for C3H6/C3H8. The BET surface area increased in the order of TDA-DAT1-OH (437 m2/g) < TDAi3-DAT1-OH (467 m2/g) < TDA1-DAT1-OH (557 m2/g). The frecational free volume (FFV) increased in the order of TDAi3-DAT1-OH (0.25) < TDA-DAT1-OH (0.28) < TDA1-DAT1-OH (0.30). TDA1-DAT1-OH (109 μm) showed less and slower physical aging than TDA-DAT1-OH (94 μm) after 60 days, where the O2 and CO2 permeability of both polyimides decreased by about 40% and 69%, respectively. After 30 days, TDAi3-DAT1-OH displayed the highest selectivity gain relative to its counterparts and exceeded the 2008 upper bound for CO2/CH4. TDA1-DAT1-OH exhibited 7-fold higher C3H6 permeability coupled with almost 3-fold higher C3H6/C3H8 selectivity relative to a previously reported commercial polyphenylene oxide (PPO) membrane.

The chenistry of diamino dicarboxylic acids together with that of monoamino dicarboxylie and monocarboxylic acids in of great importance to the chemist because of the rolation- ship of these compounds to the biochemistry of cancer. Diamino dicarboxylic acids in general, contain two asymmetric carbon atoms and may exist in one optically inactive and two optically active forma. Alpha-omoga diamino pinolic acid is the only member of the alpha-omoga diamino dicarboxylic acids thus far known to occur naturally.

Many previous studies have demonstrated that gold compounds possess successful results in catalysis and in medicinal chemistry. The central aim of this dissertation is the design and synthesis of novel gold (I) acyclic diamino carbene complexes as a chemotherapeutic agent for triple-negative breast cancer (TNBC) and for catalysis. In this study, a series of chiral neutral and cationic gold (I) acyclic diamino carbene (ADC) complexes and neutral gold (I) bis- ADC complexes have been synthesized. As the chiral neutral gold (I) ADCs, four diastereomers of S binaphthyl L proline tertiary butyl ester gold (I) chloride, S binaphthyl D proline tertiary butyl ester gold (I) chloride, R binaphthyl L proline tertiary butyl ester gold (I) chloride, and R binaphthyl D proline tertiary butyl ester gold (I) chloride have been synthesized and characterized. Different chiral gold (I) ADC complexes with bulky chiral binaphthyl group and with different amine groups of morpholine, chiral proline methyl ester, and benzyl ester have been synthesized and characterized. After that four diastereomers of the nitrile adduct of cationic binaphthyl proline tertiary butyl ester nitrile and four diastereomers of the isonitrile versions of it have been synthesized and characterized. A series of gold (I) cationic bis ADC complexes have been synthesized and characterized. All these novel gold ADC complexes were tested for biological activity against TNBC cell line MDA-MB-231 and cationic S binaphthyl D proline ester isonitrile adduct, S binaphthyl D proline ester isonitrile adduct and R binaphthyl D proline ester isonitrile adduct gave promising inhibition rates. According to Lipinski's rule, lipophilicity determines the effectiveness of the drug absorption to the body through the lipid membrane. To determine the drug-likeness of the gold ADC complexes, log P values were calculated for some of the synthesized complexes using a modified shake flask method. Gold (I) ADC complexes have been renowned for their ability in catalysis, but enantioselective catalysis is not that well studied. A3 coupling reaction is a well-known reaction for the synthesis of propargyl amines. Here, A3 coupling reaction with a chiral amine has been performed using the previously synthesized four diastereomers of binaphthyl proline tertial butyl ester gold (I) ADCs (SL, RD, RL, SD) as the catalyst expecting four different diastereomers of the product. The reaction exhibited reasonable yields but with a low enantiomeric excess (ee%). However, it gave proof of the principle that asymmetric induction is possible with the synthesized novel chiral gold (I) ADC complexes.

The objective of this research was to development new methodologies for the asymmetric syntheses of amine and natural products from enantiopure sulfinimines (N-sulfinyl imines). In this context, new methods was devised for the asymmetric synthesis of 2,5-cis and trans-disubstituted pyrrolidines from 3-oxo pyrrolidine 2-phosphonates, prepared by an intramolecular metal carbenoid N-H insertion from a sulfinimine derived delta-amino-alpha-diazo- beta-ketophosphonate. Horner-Wadsworth-Emmos reaction of the 3-oxo pyrrolidine 2-phosphonates and aldehydes provided pyrrolidine enones. Hydrogenation (Pd/H2) of the pyrrolidine enones gave cis-2,5-disubstituted pyrrolidines. Luche reduction the pyrrolidine enones followed by a TFA-NaBH3CN mediated hydroxy directed reduction provided the 2,5-trans products. (+)-Preussin, a potent antiviral and antitumor agent was prepared in 9 steps in 28% overall yield from the sulfinimine. An acid catalyzed intramolecular Mannich cyclization of a sulfinimine-derived N-sulfinyl syn-alpha-methyl-beta-amino ketones was employed for the asymmetric synthesis of 2,3,5,6-tetrasubstituted piperidinones. The beta-amino ketones were prepare by treatment of prochiral lithium Weinreb amide enolates with enantiopure (E)-N-(4-(benzyloxy)butylidene)-2,4,6-triisopropylbenzenesulfinamide. This new methodology was highlighted in the first asymmetric synthesis of the poison frog alkaloid (-)-indolizidine 221T. By manipulation of water concentration in tetrahydrofuran, syn- and anti-2,3-diamino esters were prepared by treatment of the lithium enolate of N-(diphenylmethylene) glycine ethyl ester with sulfinimines. Anhydrous THF afforded enantiopure syn-2,3-diamino esters with a syn/anti selectivity of better than 25:1. In a THF-H2O the anti-2,3-diamino esters were formed. The mechanism involves the generation of H2O-LDA species in the formation of enolate which inhibited the retro-Mannich fragmentation in the diamino ester species. (SR,2S,3R)-(-)-Ethyl-2-(N,N-dibenzylamino)-3-N-(p-toluenesulfinyl)amino-pent-4-enoate was employed in an improved total synthesis of the anti-tumor antibiotic (-)-agelastatin A. A series of N-sulfinyl aza-Morita-Baylis-Hillman products were prepared by addition of vinylaluminum and N-methylmorpholine-N-oxide reagents to enantiopure N-(p-toluenesufinyl)- and N-(2-methypropanesulfinyl)-derived sulfinimines from the least hindered direction via a non-chelation control mechanism. Hydrogenation of the these acrylates with a rhodium(I) catalyst afforded anti-alpha-substituted-beta-amino esters with a anti/syn selectivity of better than 17:1. This new methodology is useful for the asymmetric synthesis of anti-alpha-alkyl-beta-amino esters, which are valuable chiral building blocks for the preparation of biologically active nitrogen-containing natural products. / Chemistry

Les oxydations sur les bases nucléiques constituent l’une des sources principale d’apparition de lésions sur l’ADN, qui peuvent être mutagènes ou létales pour les cellules en l’absence de réparation de l’ADN. La Formamidopyrimidine-ADN glycosylase (Fpg), une enzyme procaryote du système de réparation de l’ADN par excision de base (BER), initie la réparation d’un large panel de lésions de ce type via ses activités ADN glycosylase (excision de la base oxydée) et AP lyase (clivage du site abasique par ß,d-élimination). Nous avons réalisé des études fonctionnelles par des techniques biochimiques et structurales par cristallographie des rayons X afin de préciser la spécificité de substrat et le mécanisme catalytique de Fpg. Ainsi, nous avons pu mettre en évidence des déterminants structuraux permettant à cette enzyme d’accommoder des lésions de tailles très différentes dans son site actif, en l’occurrence des résidus 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) substitués ou non en N7 par des adduits encombrants. D’autre part, nous avons caractérisé structuralement et fonctionnellement la reconnaissance et l’excision par Fpg d’une lésion pyrimidique, la 5-hydroxy-5-méthyle-hydantoïne (Hyd). Ainsi, nous avons montré que cette lésion appariée à une cytosine était un bon substrat pour l’enzyme, et nous avons précisé structuralement le mode de reconnaissance de l’Hyd par Fpg. D’autre part, nous avons mis en évidence un comportement inattendu de l’enzyme sur ce substrat. En l’occurrence, nous avons montré biochimiquement et structuralement qu’un pontage covalent se formait en quantités non négligeables entre Fpg et l’Hyd dans des conditions physiologiques. / Oxidations on nucleic bases constitute one of the major sources of DNA lesions appearance, which can be mutagenic or lethal for cells in the absence of DNA repair. The prokaryotic Formamidopyrimidine-DNA glycosylase (Fpg), a base excision DNA repair (BER) enzyme, initiate the repair of a wide range of such lesions via its DNA glycosylase (excision of the oxidized base) and AP lyase (cleavage of the AP site by ß,d-elimination) activities. We carried out functional studies by biochemical techniques and structural studies by X-ray crystallography so as to state Fpg’s substrate specificity and catalytic mechanism. Thus, we have been able to underline the structural determinants enabling this enzyme to accommodate lesions of very different sizes in its active site, in this case 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) residues N7-substituted or not by bulky adducts. On the other hand, we structurally and functionally characterized the recognition and excision by Fpg of a pyrimidic lesion, the 5-hydroxy-5-methyl-hydantoin (Hyd). Thus, we have shown that this lesion paired with a cytosine was a good substrate for the enzyme, and stated structurally the recognition mode of Hyd by Fpg. On the other hand, we have underlined an unexpected behaviour of the enzyme on this substrate. In this case, we have biochemically and structurally shown that a covalent link was formed in sizeable quantities between Fpg and Hyd in physiological conditions.