La formation de métastases est la cause majeure des décès par cancer. Le développement de métastases est consécutif à une série d‟événements complexes tels que la migration, l‟invasion et la prolifération cellulaire. Le canal potassique SK3 (membre de la famille des SKCa) régule la migration des cellules cancéreuses du sein et favorise le développement de métastases osseuses. Le but du projet était d‟identifier et de caractériser les voies d‟entrées calciques associées à la migration cellulaire dépendante du canal SK3 dans différents cancers (sein, colon et prostate). Nous avons pu mettre en évidence que les canaux Ca2+qui étaient associés au canal SK3 variaient en fonction du cancer et régulaient la migration cellulaire dépendante du canal SK3. De plus, nous avons montré que la localisation de ces complexes KCa/Ca2+ dans les radeaux lipidiques était importante pour leur régulation et leur fonction. Ainsi, la délocalisation de ces complexes hors des radeaux lipidiques par des alkyl-phospholipides est un moyen permettant de moduler la migration des cellules exprimant le canal SK3 et le développement de métastases. / In most cases of cancer, metastasis and not the primary tumor per se is the main cause of mortality. To establish secondary growth in distant organs cancer cells must develop an enhanced propensity to migrate. The key objective of this thesis proposes that some actors of Ca2+ signaling (Orai, and TRPC, STIM) coupled to SK3 channel would form complexes that play a critical role in cell migration of various cancers (breast, colon and prostate). Furthermore we showed that the localization of these channels complexes in lipid-rafts is essential to their regulation and function. Thus, the delocalization of these complexes of lipid-raft outside by alkyl-phospholipids could be a new way to modulate the SK3/Ca2+ dependent cell migration and metastasis development.

La valorisation non alimentaire de la biomasse végétale représente un enjeu actuel majeur dans le contexte du développement de la bioraffinerie végétale. En Champagne-Ardenne, la transformation des co-produits d'origine agricole fait l'objet d'études importantes. Le son et la paille, co-produits abondants de la filière blé, sont riches en hémicelluloses, polysaccharides constitués essentiellement de pentoses, majoritairement de D-xylose. La principale voie de valorisation des pentoses tels que le xylose est leur fonctionnalisation par voie chimique, mais l'utilisation d'enzymes telles que des xylanases et des β-xylosidases représente une voie de synthèse plus respectueuse de l'environnement et permettant, en outre, d'accéder à de nouvelles molécules inaccessibles par la voie chimique classique (DP plus importants). L'étude conduite dans le cadre de la thèse a concerné l'évaluation et l'amélioration de la synthèse enzymatique par transglycosylation d'alkyl xylosides et oligoxylosides catalysée par une β-xylosidase et deux xylanases. Une seconde voie de valorisation enzymatique a été étudiée, à savoir la synthèse de xylosides et oligoxylosides présentant des propriétés biologiques pouvant notamment être exploitées pour des applications cosmétiques. A travers la mutagénèse dirigée au niveau du sous-site aglycone d'une β-xylosidase de Bacillus halodurans, nous avons montré l'importance de résidus aromatiques de ce sous-site sur les capacités d'hydrolyse et de transglycosylation de l'enzyme. Les résultats obtenus nous ont permis de dégager quelques pistes d'ingénierie du sous-site aglycone de la xylosidase pour optimiser les rendements de transglycosylation en présence d'alcools à longues chaînes carbonées. L'étude de l'effet des conditions réactionnelles sur la synthèse d'alkyl oligoxylosides catalysée par deux xylanases (l'une de Thermobacillus xylanilyticus, l'autre commerciale) a montré la possibilité de produire les alkyl oligoxylosides par voie enzymatique avec des rendements satisfaisants, notamment en réduisant les problèmes physiques d'accessibilité de l'alcool au site actif de l'enzyme. Nous avons également mis en évidence des profils de synthèse différents d'une enzyme à l'autre mais également en fonction des conditions réactionnelles, notamment en ce qui concerne le DP moyen. Notre étude montre également que la synthèse d'alkyl oligoxylosides est possible directement à partir de son de blé prétraité par voie hydrothermale. En ce qui concerne les propriétés physico-chimiques des produits de transglycosylation, nous avons montré que, tout en étant non purifiés, les pentyl et octyl β-D-oligoxylosides obtenus par synthèse enzymatique présentent des propriétés comparables à celles de produits commerciaux utilisés pour leurs propriétés tensio-actives. L'étude de méthodes de synthèse enzymatiques et chimio-enzymatique de xylosides et d'oligoxylosides ciblés pour certaines propriétés biologiques a montré que les deux xylanases étudiées précédemment pouvaient utiliser en tant qu'accepteur, en plus des alcools linéaires, des alcools aromatiques, des diols ou encore un ester ou un alcyne, ce qui a permis d'accéder à des produits originaux. Des tests biologiques réalisés sur des fibroblastes humains, ont montré que les xylosides et oligoxylosides ainsi produits ne sont pas cytotoxiques. Des tests sur l'initiation de la biosynthèse de glycosaminoglycanes, menés avec certains produits, ont conduit à des résultats positifs pour la biosynthèse d'acide hyaluronique. / Non-food valorization of plant biomass currently represents a major challenge in the context of plant biorefinery. In Champagne-Ardenne, the processing of agricultural by-products is the subject of numerous studies. Wheat bran and straw are abundant agricultural by-products and are rich in hemicelluloses, which are polysaccharides essentially constituted by pentoses, mainly D-xylose. The major route for the valorization of pentoses such as xylose is their functionalization by chemical means. Nevertheless, the use of enzymes, such as xylanases and β-xylosidases, represents a more environmentally friendly way and can also lead to the synthesis of new molecules inaccessible through conventional chemistry. The study conducted during the PhD concerned the evaluation and the improvement of the enzymatic synthesis by transglycosylation of alkyl xylosides and oligoxylosides catalyzed by a β-xylosidase and two xylanases. The second pathway for enzymatic valorization investigated was the synthesis of xylosides and oligoxylosides with biological properties that could be applied for cosmetic use.By site-directed mutagenesis in the aglycone subsite of a β-xylosidase from Bacillus halodurans, we have shown the role of aromatic residues on the hydrolysis and transglycosylation capabilities of the enzyme. The results obtained allowed us to identify some engineering of the aglycone subsite of the β-xylosidase to optimize the transglycosylation yields in the presence of alcohols with long carbon chains.The study of the effect of the reaction conditions on the synthesis of alkyl oligoxylosides catalyzed by two xylanases (one from Thermobacillus xylanilyticus and other is commercially available) has shown the ability to produce alkyl oligoxylosides by enzymatic synthesis with acceptable yields. We also pointed out that, depending on the reaction conditions, the products obtained were different particularly as regards the average DP. Our study has also shown that the synthesis of alkyl oligoxylosides is possible directly from hydrothermally pretreated wheat bran. Concerning the physico-chemical properties of transglycosylation products, we have demonstrated that non purified pentyl and octyl β-D-oligoxylosides obtained by enzymatic transglycosylation exhibit similar properties than commercial products used for their surface-active properties. The study of enzymatic an chemo-enzymatic methods for the synthesis of xylosides and oligoxylosides targeted for their biological properties showed that both xylanases previously studied could use linear alcohols but also aromatic alcohols, diols, ester or alkyne alcohols as acceptors for the preparation of original compounds. Biological tests performed on human fibroblasts pointed out that the xylosides and oligoxylosides produced are not cytotoxic. Initiation of the biosynthesis of glycosaminoglycans tested with some of the products has led to positive results for the synthesis of hyaluronic acid by the fibroblasts.

Chez les plantes, la subérine est un biopolymère constitué de composés aliphatiques etaromatiques déposés au niveau de la paroi des cellules de plusieurs tissus comme l’endodermeet le périderme des racines ou encore le manteau des graines. La subérine forme une barrièrehydrophobe permettant entre autres de contrôler les flux d’eau et de solutés, et de protéger laplante de stress environnementaux comme la sécheresse ou les pathogènes. Grâce à desanalyses en LC-MS/MS et en GC-MS, nous avons pu montrer que la majorité des alcools grasprésents dans la fraction soluble de racines d’Arabidopsis thaliana est sous forme d’alkylcaféates et d’alkyl coumarates. De plus, nous avons montré que ces cires associées aupolymère de subérine sont présentes dès les premiers stades du développement de la racine.Une étude de la distribution des chaînes acyles des racines nous a permis de mettre enévidence la contribution majeure des alcools gras dans la composition de la subérine ainsi quel’importance de la subérine dans le métabolisme lipidique des racines. Afin d’identifier desacteurs impliqués dans l’export des précurseurs de la subérine vers l’espace extracellulaire,nous avons mené une approche de génétique inverse en utilisant des lignées mutées pour desgènes codant notamment pour des ABCG transporteurs co-exprimés avec des gènes connuspour participer à la biosynthèse de la subérine. Les résultats de ces analyses ont confirmé quele processus d’export fait intervenir plusieurs protéines pouvant avoir des fonctionsredondantes et ont suggéré l’implication d’un nouveau transporteur dans l’export desprécurseurs de subérine. / In plants, suberin is a complex biopolymer made of aliphatic and aromatic compounds.It is deposited in the cell wall of tissues such as the endoderm and the periderm of roots or thecoat of the seeds. Suberin forms a hydrophobic barrier controlling the flow of water andsolutes, and protecting the plant from environmental stresses such as drought or pathogens.Through LC-MS/MS and GC-MS analyses, we have shown that the majority of the fattyalcohols present in the soluble fraction of Arabidopsis roots is in the form of alkyl caffeatesand alkyl coumarates. Such waxes, most probably associated with the suberin polymer, arealready detected at early stages of root development. A study of the distribution of all acylchains present in roots allowed us to highlight the major contribution of fatty alcohols in thecomposition of suberin and the importance of suberin in the global lipid metabolism of theroots. To identify proteins involved in the export of suberin precursors to the extracellularspace, we conducted a reverse genetic approach using lines mutated in genes coding forseveral ABCG transporters which were co-expressed with genes known to participate in thebiosynthesis of suberin. The results of these analyses confirmed that the export processinvolves several proteins that can have redundant functions, and supported the involvement ofa new transporter in the export of the suberin precursors.

Photo-initiated reactions involve the use of ultraviolet (UV) or visible light radiation to effect chemical transformations. Some of the advantages of photo-initiated reactions over thermal or high pressure reactions include mild reaction conditions like ambient temperature and pressure, good control over the reaction by the simple switching on/off the light source, and faster reaction kinetics. Usually, semiconductor photocatalysts or oxidizing agents are used to enhance the rate of photo reactions. “Photocatalysis” involves the generation of valence band holes and conduction band electrons by the band gap excitation of a semiconductor photocatalyst. These charge carriers produce reactive hydroxyl and superoxide radicals, which mediate oxidation and reduction reactions. However, the oxidizing agents are decomposed by the incident radiation to generate reactive radicals, which accelerate the photo reaction. Today, photocatalysis and photo-oxidative reactions are widely being practiced for environmental pollution abatement, synthesis of fine chemicals, synthesis of polymers, generation of hydrogen as a clean energy carrier, and in anti-fogging and self-cleaning surface treatments. The present investigation focuses on elucidating the mechanism and kinetics of environmentally and synthetically relevant photo-initiated reactions for a better understanding of the fundamental aspects of the photo processes. The different photo-initiated reactions studied in this dissertation can be grouped under the broad categories of (i) photocatalytic degradation of organic compounds like dyes and phenols, and reduction of metal ions, (ii) photocatalytic degradation of polymers, (iii) selective photocatalytic oxidation of cyclohexane, (iv) sonophotocatalytic degradation of dyes, (v) photopolymerization, and (vi) sonophotooxidative degradation of polymers. Nano-sized TiO2, synthesized by solution combustion technique (henceforth denoted as CS TiO2), was used as the photocatalyst for most of the above reactions, except for the last two polymer reactions, where organic initiators were used. Invariably, the photocatalytic activity of CS TiO2 was compared with the commercially available Degussa P-25 TiO2 (DP25). Based on the experimental results, detailed mechanisms were proposed for the different reactions, kinetic models were derived, and the rate coefficients signifying the importance of the underlying reaction steps were evaluated. Pd2+ substituted and Pd0 impregnated TiO2 were synthesized by solution combustion and reduction techniques, respectively, and characterized by powder XRD, XPS, TEM, BET surface area, UV/visible, TGA, FT-IR and photoluminescence measurements. While the above catalysts are known to be more active compared to CS TiO2 for the gas phase NO reduction and NO decomposition reactions, it was found in this study, that these catalysts exhibit lower activity for the degradation of organic compounds like dyes, phenol and 4-chlorophenol, in the aqueous phase. The decrease in activity was correlated with a reduction in surface area and photoluminescence intensity of these catalysts, compared to CS TiO2. Ag+ substituted (Ag sub) and Ag0 impregnated (Ag imp) nano-TiO2 were synthesized by solution combustion and reduction techniques, respectively, and characterized by the above standard measurements. These catalysts were used for the photodegradation of dyes, and the selective photooxidation of cyclohexane to cyclohexanone. For the photocatalytic degradation of dyes, unsubstituted CS TiO2 exhibited the highest activity, followed by 1% Ag imp and 1% Ag sub. However, for the photooxidation of cyclohexane, the total conversion of cyclohexane and the selectivity of cyclohexanone followed the order: 1% Ag sub > DP-25 > CS TiO2 > 1% Ag imp. The kinetics of photodegradation of the dyes and the photooxidation of cyclohexane was modeled using Langmuir-Hinshelwood rate equation, and a free radical mechanism, respectively. This study proves that the photoactivity of a catalyst is not solely determined by a single physical property, but rather by a number of variables including the surface area, band gap, surface hydroxyl content, oxide ion vacancy and surface charge of the catalyst. The photocatalytic degradation of five anionic, eight cationic and three solvent dyes, containing different functional groups, was evaluated. The degradation of the dyes was quantified using the initial rate of decolorization and overall percent mineralization. The decolorization of the anionic dyes with CS TiO2 followed the order: Indigo Carmine > Eosin Y > Amido Black 10B > Alizarin Cyanine Green > Orange G. The decolorization of the cationic dyes with DP-25 followed the order: Malachite Green > Pyronin Y > Rhodamine 6G > Azure B > Nile Blue Sulfate > Auramine O ≈ Acriflavine ≈ Safranin O. CS TiO2 exhibited higher rates of decolorization and mineralization for all the anionic dyes, while DP-25 was better in terms of decolorization for most of the cationic dyes. The solvent dyes exhibited adsorption dependent decolorization. The observed results were rationalized based on the molecular structure and degradation pathway of the dyes. The simultaneous photocatalytic degradation of phenolic compounds like phenol and 4-nitrophenol, and the reduction of metal ions like copper (Cu2+) and chromium (Cr6+) were studied. It was found that the presence of phenol accelerated the reduction of Cu2+ to Cu+, and the presence of phenol and 4-nitrophenol accelerated the adsorption of Cr6+ onto CS TiO2. A detailed dual-cycle, multi-step reaction mechanism was proposed for the simultaneous degradation and reduction, and a model was developed using the network reduction technique. The kinetic rate constants in the model were evaluated for the systems studied. The simultaneous UV and ultrasound (US) degradation of anionic dyes was carried out in presence of CS TiO2. The rates of degradation and mineralization of the dyes were higher for the sonophotocatalytic process compared to the individual photo-and sonocatalytic processes. The effect of dissolved gases and US intensity on the sonophotocatalytic degradation of the dyes was evaluated. A dual-pathway network mechanism of sonophotocatalytic degradation was proposed for the first time, and the rate equations were modeled using the network reduction technique. The kinetic rate coefficients of the individual steps were evaluated for all the systems by fitting the model with the experimental data. Eosin Y and Fluorescein dye sensitized visible light degradation of phenol, 4chlorophenol, 2,4-dichlorophenol and 2,4,6-trichlorophenol was studied. A detailed mechanism of sensitized degradation was proposed, and a mechanistic model for the rate of degradation of the phenolic compound was derived by using the pyramidal network reduction technique to evaluate the rate coefficients. An important conclusion of this study indicates that at low initial dye concentrations, the rate of degradation of the phenolic compound is first order in the concentration of the dye, while at high initial dye concentrations, the rate is first order in the concentration of the phenolic compound. The different phenolic and dye intermediates that were formed during degradation were identified by mass spectrometry, and a most probable pathway of degradation was proposed. The solution photopolymerization of methyl-, ethyl-, butyl-and hexylmethacrylates in presence of benzoyl peroxide as the initiator was studied. The effect of initiator and monomer concentrations on the time evolution of polymer concentration, number average molecular weight (Mn) and polydispersity (PDI) was examined. The reversible chain addition and β-scission, and primary radical termination steps were included in the mechanism along with the classical initiation, propagation and termination steps. The rate equations were derived using continuous distribution kinetics and solved numerically to fit the experimental data. The model predicted the instantaneous increase of Mn and PDI of the polymers to steady state values. The rate coefficients exhibited a linear increase with the size of the alkyl chain of the alkyl methacrylates. Poly(acrylamide-co-acrylic acid) copolymers of different compositions were synthesized and characterized. The copolymers were statistical with a relatively high percentage of acrylamide units, as determined by 13C-NMR. The aqueous phase photolytic and photocatalytic degradation of the copolymers and the homopolymers was conducted. The degradation was modeled using continuous distribution kinetics. The degradation followed a two step mechanism, wherein the rapid first step comprised of the scission of weak acrylic acid units along the chain, which was followed by the breakage of the relatively strong acrylamide units. The rate constants for the weak and strong links followed a linear trend with the percentage of acrylic acid and acrylamide in the copolymer, respectively. The photocatalytic degradation of the copolymers of methyl methacrylate with butyl methacrylate (MMA-BMA), ethyl acrylate (MMA-EA) and methacrylic acid (MMA-MAA) was carried out in toluene. The copolymers and the corresponding homopolymers degraded randomly along the chain. The degradation rate coefficient was determined using continuous distribution kinetics. The time evolution of the hydroxyl and hydroperoxide stretching vibration in the FT-IR spectra of the copolymers indicated that the degradation rate follows the order: MMA-MAA > MMA-EA > MMA-BMA. The photodegradation rate coefficients were compared with the activation energy of pyrolytic degradation. The observed contrast in the order of thermal stability compared to the photostability of these copolymers was attributed to the two different mechanisms governing the scission of the polymers and the evolution of the products. The mechano-chemical degradation of poly(methyl methacrylate), poly(ethyl methacrylate) and poly(n-butyl methacrylate) using US and UV radiation, in presence of benzoin as the photoinitiator, was carried out. A degradation mechanism that included the decomposition of the initiator, generation of polymer radicals by hydrogen abstraction of the initiator radicals, and reversible chain transfer between the stable polymer and the polymer radicals, was proposed. The mechanism assumed mid-point chain scission due to US and random chain scission due to UV radiation. The steady state evolution of PDI was successfully predicted by the continuous distribution kinetics model. The rate coefficients of polymer scission due to US and UV radiation exhibited a linear increase and decrease with the size of the alkyl group of the poly(alkyl methacrylate)s, respectively.

1 Abstract This doctoral thesis is focused on the synthesis and characterization of novel hybrid polysaccharide-based polymers applicable for biomedicine, specifically for a conceptually new bimodal cancer treatment - immunoradiotherapy. For this purpose, polysaccharides β-glucan from Auricularia auricula-judae and κ-carrageenan from Kappaphycus alvarezii, exhibiting immunostimulatory and anticancer activities, were chosen to be grafted with thermoresponsive poly(2-isopropyl-2-oxazoline-co-2-butyl-2-oxazoline)s (POXs) (with different graft lengths and grafting densities) that induced a lower critical solution temperature of the final polymers. The thermoresponsive behavior of resulting polymers was studied with temperature-dependent light scattering methods, fluorescence measurements and also nuclear magnetic spectroscopy to select a polymer material with the most suitable properties for the intended application, aiming at a polymer depot formation after the injection of a polymer solution into the body. The chosen polymer, β-glucan-graft-POX with graft length of 2500 Da, was then modified to bear 1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid and a fluorescent dye Dyomics-615 at the graft ends and tested first in vitro to investigate its immunostimulatory properties and also the cellular uptake....

No description available.

A great deal of research has been devoted in recent years to the search for new drugs for the treatment of epilepsy and related convulsive disorders. This emphasis is occasioned by the fact that no one drug is effective for all patients, and also by the fact that the toxicity of a drug varies considerably from one patient to another. Among the most effective drugs are certain members of the hydantoin and barbituric acid series. For some time there has been in progress in this laboratory an investigation of members of these two series in which a hetro atom attached directly to the hetrocyclic nucleus is introduced into the side chain at position five of these two series.

Les PolyGlycosides d'Alkyle (APGs) sont des agro-tensioactifs dont les propriétés de surface, la biodégradabilité et l'innocuité vis-à-vis de la peau leur offrent de nombreuses applications dans les domaines de la détergence, de la cosmétique et de l'alimentaire. Les APGs sont synthétisés selon la réaction de glycosidation acido-catalysée de Fischer entre un sucre et un accepteur de glycosyle, tel qu'un alcool gras. A l'échelle industrielle, cette voie de synthèse présente plusieurs contraintes liées à la faible solubilité du sucre dans l'alcool lipophile, l'utilisation de pressions réduites et la manutention de catalyseurs acides toxiques et/ou corrosifs. Ces facteurs imposent un équipement spécifique, augmentent les coûts de production et favorisent la dégradation des APGs. Dans un premier temps, les sulfoxydes et les sulfones ont été utilisés comme solvants dans la synthèse d'APGs sans catalyseur et à pression atmosphérique. Cette méthodologie est transposable à de nombreux donneurs et accepteurs de glycosyle. Notre étude a montré que la réaction de glycosidation est catalysée par les acides organiques produits par caramélisation partielle du sucre. La faible solubilité des solvants soufrés dans les alcools gras à température ambiante a été mise à profit dans la mise au point d'un procédé de synthèse d'APGs permettant la récupération et le recyclage de ces solvants. Un milieu réactionnel biphasique décanol - sulfolane a été décrit pour l'obtention d'un rendement en xylosides de décyle supérieur à 80 % en un temps de réaction remarquablement court. La synthèse d'APGs par conversion directe de la biomasse lignocellulosique a fait l'objet de la seconde partie de ce travail. La réaction de transglycosidation du xylane et des hémicelluloses de peuplier a été réalisée sous activation thermique, sans solvant ou en présence de diméthylsulfoxyde, et sous irradiations micro-ondes. L'efficacité de chaque mode d'activation à promouvoir la réaction de transglycosidation a été discutée en fonction de l'origine botanique et de la composition chimique des matières végétales. / Alkyl PolyGlycosides (APGs) are biobased and biodegradable amphiphilics with good surfactant properties and low skin irritability, which are sought in cosmetics, detergents and food. APGs are synthesized by acid-catalyzed Fischer's glycosidation of a carbohydrate source and a glycosyl acceptor such as a long-tailed alcohol. Industrial APGs production suffers from various drawbacks such as the poor solubility of the carbohydrate in the fatty alcohol, the pressure management and the use of toxic or corrosive acid catalysts. Those issues impose more stringent demand on equipment, increase the production costs and favor APGs degradation reactions.Firstly we have been involved in developing an innovative strategy for the catalyst-free synthesis of APGs under atmospheric pressure. Sulfoxides and sulfones have been efficiently used for the manufacture of APGs starting from various glycosyl donors and acceptors. The reaction was induced by organic acids produced by partial carbohydrate caramelisation. Interestingly some of the sulfur-containing solvents were not soluble in fatty alcohols at room temperature whereas the reaction medium was homogenous at the glycosidation temperature. These solvents have been easily recovered and recycled without decrease of APGs yields. A decanol-sulfolane biphasic reaction medium has been designed for the production of decyl-D-xylosides in short reaction times and yields up to 83 %.The second phase of this work was focused on the direct conversion of lignocellulosic materials into APGs. The transglycosidation reaction of xylan and poplar hemicelluloses has been studied under thermal activation, without solvent or in the presence of dimethylsulfoxide, and under microwave irradiations. The efficiency of each activation mode has been discussed as a function of the botanical origin and the chemical composition of lignocellulosic substrates.

This thesis concerns the development of metal-free applications using diaryliodonium salts. The first project describes an arylation protocol of allylic and benzylic alcohols in aqueous media. The method proceeds under mild conditions and the ether products were obtained in moderate to good yields. The methodology was also expanded to include arylation of phenols, giving diaryl ethers in good to excellent yields. In the second project, an arylation method that included a wider range of aliphatic alcohols was developed. The scope of accessible alkyl aryl ethers was studied and included a comparative study of phenylation and nitrophenylation of various alcohols. Finally, a formal metal-free synthesis of butoxycain was performed, illustrating the applicability of the developed method. The third project focused on the limitations and side reactions occurring in Chapter 2 and 3. First, an approach to access symmetric diaryl ethers via arylation of hydroxide was presented. This reaction gave rise to a number of side products, which we hypothesized to originate from aryne-type intermediates. A mechanism for the formation of these side products was suggested, supported by trapping and deuterium labeling experiments. Oxidation of the alcohol to the corresponding ketone was also observed and the mechanism of this interesting side reaction was investigated. The latter was suggested to proceed via an intramolecular oxidation without the involvement of radicals or arynes. The fourth project covers a method to synthesize highly sterically congested alkyl aryl ethers via arylation of tertiary alcohols using diaryliodonium salts. The method displayed a broad scope of tertiary alcohols and was also suitable for fluorinated alcohols. The final project detailed in this thesis deals with C-arylation with diaryliodonium salts, showcasing nitroalkanes as well as a nitro ester as suitable nucleophiles for metal-free arylation. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.</p>

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1979. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Vita. / Includes bibliographical references. / Ph.D.