Chapter 1 includes a review on dendrimers, their synthesis and applications, with a particular focus on urea-linked dendritic species. The synthetic strategy utilised in this body of work was based on the preparation of a number of branched synthetic building blocks possessing differing terminal functionality. These branched dendrons, bearing three terminal residues and based on the cheap starting material tris(hydroxymethyl)aminomethane (TRIS) 23, involved the coupling of 3.3 equivalents of an appropriately para-substituted benzoic acid chloride with BOC protected TRIS 24 in DCM in the presence of triethylamine. The p-nitro, p-methoxy and p-methyl benzoyl chloride starting materials were obtained commercially, whilst N-(4-carboxyphenyl)maleimide was synthesised according to literature procedures. The BOC protected dendrons (25–27, 34) were synthesized in yields ranging from 50–92%. Deprotection of the BOC protected dendrons 25 and 26 in DCM with TFA, followed by the addition of 1M Na2CO3 afforded the TFA salts 35 and 36, respectively. The corresponding free base amines 37 and 38 were obtained on further treatment of the TFA salts with sodium carbonate. Deprotection of the BOC protected dendrons 27 and 34 afforded the free amines 39 and 48 directly after treatment with sodium carbonate. Synthesis of functionalised branched molecules containing 6- and 9-peripheral functionalities was achieved by refluxing 2 or 3 equivalents of the free amine dendrons with the bi- or tri- functional isocyanate cores, 15 and 45, in refluxing DCM, in most cases the products precipitated from the reaction mixture after 18 h and were isolated simply by filtration, otherwise the removal of the solvent from the reaction mixture afforded the spectroscopically pure product. Conversion of the peripheral nitro functionalised species 14 and 21 to the corresponding amines occurred smoothly via hydrogenation using 5% Pd/C under elevated temperature and pressure (DMF, 55 ºC, 600 psi) and afforded the polyamine 6-mer 51 in 92% yield and the 9-mer 50 in 90% yield, respectively. Similarly, conversion of the methoxy coated 9-mer 42, to the corresponding phenolic compound (AlBr3, dodecane thiol, DCM) afforded the 9-mer polyphenol 52 in an 87% yield. All compounds prepared were fully characterised and crystal structures were obtained for 26 and 35. Chapter 2 includes a review on self-assembled monolayers of organosulfur compounds on gold, applications, patterning techniques and techniques for the characterisation of these surfaces. A number of surface monomers were successfully synthesized, to be used for various surface functionalisations, including the formation of an amine reactive N-hydroxysuccinimide (NHS) disulfide 53, via the DCC coupling of 11,11’-dithiobisundecanoic acid 54 with N-hydroxysuccinimide with an isolated yield of 30%. A novel protein-resistant monomer 58 was also synthesized from 11-undecanoic acid 55 via an acid chloride coupling with triethylene glycol monomethyl ether 58, and isolated in a 72% yield. A number of attempts were made to produce an acyl azide SAM monomer 59, with success finally achieved via the acid chloride coupling of 11,11’-dithiobisundecanoic acid 54 with 5-amino-1,3-benzenedicarbonyl diazide 62 to produce 59 with an isolated yield of ~ 30%. Gold surfaces were prepared on atomically flat silicon wafers using an argon-ion sputterer. SAM films were formed on the gold surfaces via traditional solution based self-assembly methodology. A UV patterning protocol was developed, and a successful patterning trial using the NHS terminated monomer to backfill the UV exposed areas of a dodecane thiol monolayer was achieved and visualized using AFM and fluorescence microscopy after treating the surface with aminofluorescein. The covalent attachment of green fluorescent protein to the monolayer surface via reaction with the NHS terminated monolayer was demonstrated. The fluorescence of the biomolecule was preserved. The formation of a monolayer using the acyl azide monomer 59, was characterised by contact angle and XPS analysis. However, preliminary studies into the activation of the acyl azide surface into the reactive isocyanate were unsuccessful. There is however, significant scope for further investigations into this interesting surface technology. Chapter 3 includes a review on heterobifunctional linker technology with a particular focus on amine and thiol reactive moieties and literature examples of heterobifunctional linkers of this type. Synthesis of heterobifunctional reagents such as 71 and 74 via a two step synthetic methodology involving the coupling of maleic anhydride with the parent amino-acids in acetic acid, followed by a one pot cyclisation and NHS esterification using DCC in DMF were successful, with overall yields of 9% and 32% respectively for the two reaction steps. The one pot extension of 74 with 6-aminohexanoic acid, followed by DCC, facilitated NHS esterification was achieved successfully in a yield of 30%. Attempts to extend 74 with the synthesised amino acid 88 were unsuccessful due to the insolubility of 88 in organic solvents. A different synthetic strategy was devised towards the synthesis of 85 with the coupling of 74 and mono BOC protected ethylene diamine 91 in DCM to give 93 in an isolated yield of 60%. Deprotection of the terminal amine was achieved via reaction with TFA in DCM however all attempts to prepare the free amine were unsuccessful. Subsequent attempts to couple 94 with both succinic anhydride and 92 were unsuccessful. A maleimide functionalized crown ether was synthesised as a molecule for protein modification via the reaction of 74 with 4’-aminobenzo-15-crown-5 97 to produce 98 in an 80% yield. All compounds were fully characterised with crystal structures obtained for 74, 79 and 89.

Thesis (Ph. D.)--State University of New York at Binghamton, Department of Chemistry, 2009. / Includes bibliographical references.

Neste trabalho promovemos a síntese de sulfóxidos vinílicos ?-substituídos através da reação de acoplamento cruzado de Suzuki-Miyaura. Também foi feita a síntese de sulfóxidos enínicos inéditos, pela adição do nucleófilo no carbono β-sulfóxido. Esses compostos eram passíveis de serem submetidos a reação de rearranjo de Pummerer aditivo e assim gerarem uma pequena biblioteca de compostos α-tioaldeídos. Um desses aldeídos sintetizados foi empregado na reação de formação de uma imina propargílica, com consequente reação de CuAAC formando iminas triazólicas. Outras iminas arílicas foram sintetizadas, passando por uma etapa de redução, com intuito de se obter a amina livre, para que fosse feita a reação de ciclização com auxílio de um agente eletrofílico. Outra classe de composto organoenxofre foi sintetizada, as N-sulfinil imina, que após a reação de acoplamento cruzado de Sonogashira, com consequente remoção de um grupo protetor e a formação do anel heterocíclico, foram obtidos compostos triazólicos N-sulfinil imínicos. / In this work we promote the synthesis of α-substituted vinylic sulfoxides through the Suzuki-Miyaura cross coupling reaction. Also the synthesis of unpublished enynic sulfoxides was made, by the addition of the nucleophile in the β-sulfoxide carbon. These compounds were susceptible to additive Pummerer rearragement reaction and thus generated a small library of compounds. One of these aldehydes synthesized was used in the formation reaction of a propargyl imine, with consequent CuAAC reaction, forming triazol imines. Other aryl imines were synthesized, undergoing a reduction step, in order to obtain the free amine, so that the cyclization reaction was carried out with the aid of an electrophilic agent. Another class of organosulfur compound was synthesized, the N-sulfinyl imine, which after the Sonogashira cross-coupling reaction, with consequent removal of a protecting group and formation of the heterocyclic ring, N-sulfinyl imine triazolic compounds were obtained.

Tertiary thiols are a synthetically challenging class of compounds to prepare asymmetrically. The few reported methods for preparing these species require restrictive functionality to be incorporated into the products or are limited to employing simple carbon electrophiles. This thesis details investigations into the lithiation of N-aryl thiocarbamates. A stereoselective intramolecular arylation within lithiated thiocarbamates has been developed allowing the construction of quaternary stereocentres next to sulfur. Simple deprotection allows the isolation of enantiomerically pure tertiary thiols. A procedure for aryl migration within benzylic thiocarbamates has been developed and optimised. Rearrangement occurs in good yield and excellent stereoselectivity in a wide range of thiocarbamate substrates. Various substitution patterns are tolerated on the migrating aryl ring, the benzylic aryl ring and on the benzylic carbon centre. Extension of this methodology has incorporated an asymmetric alkylation of achiral benzylic thiocarbamates as a method of preparing aryl migration substrates. This allows the asymmetric synthesis of tertiary thiols in 2 steps from simple achiral precursors. Aryl migration has also been found to occur in lithiated allylic thiocarbamates with high stereospecificity, allowing preparation of a wider range of tertiary thiols.

New Zealand Black/White F₁ hybrid (NZB/W) and MRL/Mp-lpr/lpr (MRL/lpr) mice spontaneously develop a Systemic Lupus Erythematosus-like autoimmune disease. While the primary immunologic defect in the NZB/W is due to B cells, in the MRL/lpr it is a result of T cell abnormalities. Diethyldithiocarbamate (DTC), an agent suggested to enhance T cell function, was used to treat both strains. Weekly treatment of NZB/W mice with 25 mg/kg DTC had no significant effect upon survival or autoantibody levels but did induce changes in cell surface antigen expression. MRL/lpr mice treated with DTC displayed normalization of cell surface antigen expression (particularly increased expression of Lyt-2, macrophage markers and Lyt-2⁺/L3T4⁺ thymocytes), decreased lymphoproliferation and thymic atrophy, decreased serum autoantibody levels and kidney deposition of C3 and IgM, restored responses to mitogens and significantly prolonged survival. To determine both the influence of MRL background and lpr genes and to better understand on what cell populations DTC effects, changes in cell surface antigen expression were examined in DTC treated MRL-+/+, Balb/c, and Balb/lpr strains. The only consistent similarities observed between all strains tested were DTC induced changes in Mac-1 splenocyte surface antigen expression. In vitro studies showed DTC to have variable effects upon the mitogenic responses of lymphoid cells to phytohemagluttinin, but DTC alone stimulated both MRL/lpr and Balb/lpr lymphocytes. DTC stimulated the null cell population that predominates in lpr gene-bearing mice, but all observed in vitro effects of DTC were dependent upon the adherent cell population included in culture. DTC had no apparent direct effects upon adherent cells alone however. These studies have shown that DTC is capable of positive effects upon one autoimmune murine strain, the MRL/lpr, but not the NZB/W. DTC appears to affect macrophages, but other cell populations are required to obtain full activity of this compound. The variable effects of DTC emphasize the need to define the immunopathology of individual patients with autoimmune disease before initiating treatment with immunomodulative therapy.

Organosulfur compounds have been used by humans for centuries and played a pivotal role in shaping our history. The chemistry presented herein deals primarily with three distinct organic transformations involving organosulfur species. The three transformations are used in tandem to complete the synthesis of natural products. The first chapter examines a new diastereoselective alkylation reaction of sulfenate anions with stereoinduction provided by chiral amino iodides. A series of β-amino sulfoxides are accessed in good yields and selectivities from alkylations with the corresponding lithium arene- and E-1-alkenesulfenate anions. The relative reactivity of different electrophiles towards a selection of lithium sulfenate anions was also evaluated by performing competition experiments. In the second chapter 1,2-dibromotetrachloroethane (C2Br2Cl4) was evaluated as a more economical halogenating agent for the in-situ Ramberg-Bäcklund rearrangement (RBR). A series of trans-stilbenoids were successfully synthesized using this protocol in excellent yields. The new RBR system also worked well for dialkyl and cyclic substrates, but the reaction was plagued by polyhalogenation for hexyl benzyl sulfone. The methodology was extended to the formal total synthesis of natural polyphenol E-resveratrol. Chapter three investigates asymmetric aza-Michael reactions of chiral β-amino sulfoxides/sulfones to synthesize thiomorpholine S-oxides and S,S-dioxides, respectively. Remarkably, cyclizations of the β-amino sulfoxides provide the trans- 3,5-substituted heterocycles, while the β-amino sulfones provide the complementary cis-3,5-substituted heterocycles. The aza-Michael chemistry was exploited along with the sulfenate and RBR protocols to access two ant venom alkaloids. / NSERC

La dégradation accélérée des membranes conductrices protoniques en pile est en partie due à une oxydation induite par la production d'H2O2. Cette étude présente une stratégie originale de stabilisation chimique d'une matrice de sPEEK par l'inclusion de nano-charges stabilisantes. Quatre nano-charges ont été préparées par fonctionnalisation de nanoparticules de silice avec des fonctions chimiques organosoufrées (disulfure, tétrasulfure et thiourée). Un protocole spécifique de mise en forme des membranes hybrides a permis d'obtenir des composites présentant des propriétés mécaniques et une conductivité protonique compatibles avec l'application pile. Les fonctions polysulfures permettent de ralentir la dégradation de la matrice de sPEEK durant l'étape de mise en œuvre et d'augmenter sa conductivité au cours d'un vieillissement ex-situ (H2O2). En présence de fonctions tétrasulfures, la membrane sPEEK ne se dégrade pas durant un test de 1200h en OCV à 70°C et 100%HR. / One of the origins of the accelerated aging of proton exchange membranes used in Fuel Cells is the oxidation induced by H2O2 formation. This work concerns the development of a new way to chemically stabilize a sPEEK membrane by the addition of stabilizing nano-fillers. Four fillers were synthesized by grafting organosulfur functions (disulfide, tetrasulfide and thiourea) onto silica nanoparticles. A specific protocol to prepare hybrid membranes led to materials with suitable mechanical properties and proton conductivity for fuel cells application. Polysulfides allow a significant decrease of the matrix degradation occurring during membrane processing and also a large increase of the proton conductivity of this matrix during ex-situ aging tests (H2O2). A membrane containing tetrasulfide nano-fillers could withstand 1200h in OCV condition at 70°C and 100%RH, without showing any sign of degradation.

No description available.

The techniques of surface deformation and mapping are useful tools for the visualization of medical surfaces, especially for highly undulated or branched surfaces. In this thesis, two algorithms are presented for flattened visualizations of multi-branched medical surfaces, such as vessels. The first algorithm is an angle preserving approach, which is based on conformal analysis. The mapping function is obtained by minimizing two Dirichlet functionals. On a triangulated representation of vessel surfaces, this algorithm can be implemented efficiently using a finite element method. The second algorithm adjusts the result from conformal mapping to produce a flattened representation of the original surface while preserving areas. It employs the theory of optimal mass transport via a gradient descent approach. A new class of image morphing algorithms is also considered based on the theory of optimal mass transport. The mass moving energy functional is revised by adding an intensity penalizing term, in order to reduce the undesired "fading" effects. It is a parameter free approach. This technique has been applied on several natural and medical images to generate in-between image sequences.

Aufgrund seines Nährstoffaneignungsvermögens und Stimulierung des Pflanzenmetabolismus kann der Arbuskuläre Mykorrhiza (AM) Pilz im Gartenbau nutzbringend eingesetzt werden. Der Fokus der Arbeit liegt auf den Möglichkeiten des AM Pilzes a) pflanzenernährerische Probleme zu lösen, b) die Blütenbildung bei Zierpflanzen zu steigern und c) das Gesundheitspotential von Gemüse für den Menschen zu erhöhen (sekundäre Pflanzenmetaboliten). Zur Lösung pflanzenernährerischer Probleme wurden Porree, Pelargonie und Poinsettie auf Torf-Substraten mit 20% und 40% Kompostzusatz untersucht. Ferner wurde Salat auf Torf-Substrat mit drei P Behandlungen getestet: substrateigenes P, Rohphosphat und lösliches P. Frühlingszwiebeln und Schnittknoblauch wurden in Nährlösungen auf Perlit mit niedrigem, mittlerem und hohem NH4+/NO3- Verhältnis ernährt. Gemessen wurde die AM Kolonisation, die Trockenmasse und die N, P, K, S, NO3-, Mg und Zn Konzentrationen im Spross. Die Blütenbildung von Pelargonien und Poinsettien wurde auf Torf-Kompost-Substraten untersucht. Der Einfluss auf die sekundäre Metaboliten von Frühlingszwiebeln und Schnittknoblauch wurde zusammen mit drei NH4+/NO3- Verhältnissen geprüft (s.o.). Untersucht wurden Glukose, Fruktose, Saccharose, lösliche Feststoffe und organische Schwefelverbindungen (gemessen als Pyruvat). Eine AM Kolonisation konnte die Nährstoffversorgung der Pflanze verbessern und die Blütenbildung erhöhen. Jedoch profitierten die Pflanzen unter den beschriebenen experimentellen Bedingungen nicht durchgängig in ihrem Wachstum und Metaboliten vom AM Pilz. Die Zugaben von Kompost ermöglichte die Verbesserung der Substratqualität für die Nährstoffversorgung und das Pflanzenwachstum unter ökologischen Gartenbaubedingungen. Der Ertrag von gesundheitsfördernden organischen Schwefelverbindungen konnte in Abhängigkeit von der jeweiligen Allium Spezies, durch eine Variation des Ammonium/Nitrat Verhältnissen und/oder durch einen AM Effekt auf das Wachstum gesteigert werden. / Arbuscular mycorrhizal (AM) fungi can be beneficial for horticultural crops due to their nutrient acquisition properties and stimulation of the plant metabolism. The present work focuses on the prospects of AM fungi a) to solve plant nutritional problems, b) to induce flower development of ornamental plants, and c) to improve the health potential of crop plants for humans. Contribution of AM fungi to plant nutritional problems were investigated with leek, pelargonium and poinsettia plants on peat-based substrates with 20% and 40% compost additions. Moreover, lettuce plants were supplied on peat-based substrates with substrate own P, rock phosphate, or highly soluble P. Bunching onion and chinese chive were propagated on perlite in nutrient solution with low, medium and high NH4+:NO3- ratios. Mycorrhizal colonization, dry weight, and N, P, K, S, NO3-, Mg and Zn concentrations in plants were measured. Mycorrhizal effects on bud and flower development of pelargonium and poinsettia plants were investigated on peat-based compost substrates. Treatment effects on secondary metabolites in bunching onion and chinese chive were determined by exposing mycorrhizal and non mycorrhizal plants to three NH4+:NO3- supply ratios. The metabolites measured were glucose, fructose, and sucrose, total soluble solids, and organosulfur compounds (measured as pyruvic acid). Colonization improved plant nutrient status and flower development. Under the described experimental conditions, however, plants did not consistently benefit in growth or plant composition from the mycorrhizal symbiosis. Additions of compost were a means of improving the substrate quality for an increased plant nutrient acquisition and plant growth in organic horticulture. The plant quality of Allium species in respect to organosulfur compounds was increased by taking the individual Allium species into consideration, their specific requirements for an optimal NH4+:NO3- supply ratio, and a possible AM effect on plant growth.