Le domaine de la physique des plasmas froids a émergé avec les premières découvertes fondamentales en physique atomique et en physique des plasmas il y a plus d’un siècle. Toutefois, ce domaine a été rapidement orienté vers les applications. L’une des plus importantes dans la première moitié du XXème est le "Calutron" (California University Cyclotron), inventé par E. Lawrence à Berkeley, qui faisait partie du projet Manhattan, et utilisé comme un spectromètre de masse pour séparer les isotopes de l’uranium. Dans un rapport du projet Manhattan daté de 1949, D. Bohm fait deux observations qui sont fondamentales pour la physique des plasmas froids :(i) Les ions doivent avoir une énergie cinétique minimales lorsqu’ils entrent dans la gaine du plasma, estimée à Te/2, Te étant la température électronique.(ii) Le transport du plasma à travers un champ magnétique est augmenté par des instabilités.La propulsion électrique par plasma est utilisée pour des satellites militaires et des sondes spatiales depuis les années 1960 et a suscité un intérêt grandissant ces vingt dernières années avec le développement des applications commerciales des technologies spatiales. Néanmoins, les mêmes questions que celles auxquelles D. Bohm était confronté, c’est-à-dire le transport multidimensionnel, l’interaction plasma-gaine, et les instabilités, se posent toujours. La théorie et les simulations sont d’autant plus importantes pour la conception des systèmes de propulsion électrique que les tests en conditions réelles nécessitent le lancement d’un satellite dans l’espace.Dans ce travail, nous établissons les équations du transport multidimensionnel dans un plasma isotherme, nous proposons un critère de gaine qui permet de rendre compte de la saturation du champ magnétique dans un plasma froid et faiblement ionisé, et nous modélisons le refroidissement des électrons à travers le filtre magnétique du propulseur PEGASES (Plasma Propulsion with Electronegative Gases). Toutes les théories sont motivées et validées par un grand nombre de simulations particulaires PIC bi-dimensionnelles, en utilisant le code LPPic qui a été partiellement développé dans le cadre du projet. Enfin, les cas de simulation sont étendus à une décharge inductive à plasma dans l’iode, avec un nouvel ensemble de section efficaces de réaction. / The field of low temperature plasma physics has emerged from the first fundamental discoveries in atom and plasma physics more than a century ago. However, it has soon become very much driven by applications. One of the most important of them in the first half of the XXth century is the "Calutron" (California University Cyclotron) invented by E.~Lawrence in Berkeley, that was part of the Manhattan project, and operated as a mass spectrometer to separate uranium isotopes. In a 1949 report of the Manhattan project, D.~Bohm makes two observations that are fundamental for low-temperature plasma physics.(i) The ions must have minimum kinetic energy when they enter the plasma sheath estimated to T_e/2 , Te being the electron temperature in eV ;(ii) Plasma transport across a magnetic field is enhanced by instabilities.Plasma electric propulsion is used on military satellites and space probes since the 1960s and has gained more and more interest for the last twenty years as space commercial applications were developing. However, the same questions as the ones D.~Bohm was faced with, namely multi-dimensional transport, plasma sheath interaction, and instabilities, arise. Theory and simulation are even more important for electric space propulsion systems design since testing in real conditions involves to launch a satellite into space.In this work, we derive the equations of the multi-dimensional isothermal plasma transport, we establish a sheath criterion that causes the magnetic confinement to saturate in low-temperature, weakly ionized plasmas, and we model the electron cooling through the magnetic filter of the PEGASES (Plasma Propulsion with Electronegative Gases) thruster. All the theories are driven and validated with extensive two-dimensional particle-in-cell (PIC) simulations, using the LPPic code that was partially developed in the frame of this project. Finally, the simulation cases are extended to an iodine inductively coupled plasma (ICP) discharge with a new set of reaction cross sections.

This master´s thesis deals with an examination of different solution types a for the chemical passivation of a silicon surface. Various solutions are tested on silicon wafers for their consequent comparison. The main purpose of this work is to find optimal solution, which suits the requirements of a time stability and start-up velocity of passivation, reproducibility of the measurements and a possibility of a perfect cleaning of a passivating solution remainig from a silicon surface, so that the parameters of a measured silicon wafer will not worsen and there will not be any contamination of the other wafers series in the production after a repetitive return of the measured wafer into the production process. The cleaning process itself is also a subject of a development.

La synthèse de la 5-azagalanthamine, un analogue azoté de galanthamine, utilisée dans le traitement palliatif de la maladie d’Alzheimer, a été envisagée dans le cadre d’une étude de relations structure-activité. Durant cette thèse nous avons examiné quatre voies de synthèse afin d’accéder à la 5-azagalanthamine. La première voie est basée sur la réaction de Pictet-Spengler afin de fermer le dernier cycle de l’azagalanthamine. De nombreuses tentatives ont été effectuées sur différents types de substrats mais cette stratégie s’est révélée inefficace. La deuxième approche consiste en une oxydation d’anilide ortho-substitué par un groupement méthoxy, avec un réactif à base d'iode hypervalent pour accéder à une spirodiènone, un intermédiaire clé de la synthèse. En effectuant cette réaction nous n’avons pas obtenu le produit attendu, mais une 1,2-dispirodiénone, un motif inhabituel, et très rare. Après avoir optimisé les conditions réactionnelles, nous avons étudié la généralité de la réaction avec d'autres substrats. La modélisation moléculaire ainsi que des études de voltammétrie cyclique ont été réalisées (Chabaud, L.; Hromjakova, T.; Rambla, M.; Retailleau, P.; Guillou, C. Chem. Commun. 2013, 49, 11542-11544. Hromjakova, T.; Retailleau, P.; Grimaud, L.; Gandon, V.; Chabaud, L. et Guillou, C. accepté EurJOC, 2015, DOI 10.1002/ejoc.201501160).Ensuite nous avons examiné l’approche basée sur le couplage intramoléculaire pallado-catalysé. Après les premiers résultats encourageant avec le substrat modèle nous avons réalisé une optimisation des conditions réactionnelles. Une étude de généralité de la réaction avec d'autres substrats a été effectuée. Malheureusement, il s’est avéré que la substitution sur le cycle aromatique n’était pas bien tolérée conduisant à de faibles rendements. Par conséquent cette méthodologie n’a pas pu être appliquée à la synthèse de l’azagalanthamine. Dans la dernière voie de synthèse examinée nous avons repris les travaux antérieurs entrepris dans notre laboratoire concernant la réaction de Heck intramoléculaire. La diminution de la longueur de la chaîne liant les deux cycles a permis d’obtenir des résultats très prometteurs. / The synthesis of 5-azagalanthamine, the analogue of galanthamine that is used in Alzheimer treatment, was investigated for structure - activity relationship studies.During this thesis I explored four synthetic approaches with the aim of preparing the 5-azagalanthamine. The first one is based on a Pictet-Spengler reaction used for ring closure of the last cycle of azagalanthamine. We carried out many tests on various types of substrate but this strategy has proved to be ineffective. The second approach consists of an oxidation of ortho-methoxy substituted anilide by hypervalent iodine reagent to access a spirodienone, a key intermediate of the synthesis. Interestingly this reaction did not result in the expected compound but we observed the formation of an unusual motif, the 1,2-dispirodienone. After conditions optimisation we studied the scope and limitations with others substrates. Molecular modelling and cyclic voltammetry studies were also carried out (Chabaud, L.; Hromjakova, T.; Rambla, M.; Retailleau, P.; Guillou, C. Chem. Commun. 2013, 49, 11542-11544. Hromjakova, T.; Retailleau, P.; Grimaud, L.; Gandon, V.; Chabaud, L. and Guillou, C. accepté EurJOC, 2015, DOI 10.1002/ejoc.201501160).Then we investigated an approach based on palladium-catalysed intramolecular coupling. After the first encouraging results with the model substrate, we did optimization of the reaction conditions and the study of substrate scope. Unfortunately we discovered that the substitution was not well tolerated and decreased the yield. Therefore this methodology could not be applied to the synthesis of the azagalanthamine. In the last approach we used previous work of our laboratory on the intramolecular Heck reaction. The reduction of the length of the linker between both cycles showed to be beneficial. We obtained promising results with this approach.

Le développement de méthodes de synthèse asymétrique est très important pour l’accès à des molécules à visées thérapeutiques. Dans ce contexte, nous nous sommes intéressés à l’utilisation d’organocatalyseurs chiraux pour la synthèse de molécules cycliques énantioenrichies. Dans une première partie sont présentées des réactions de cycloadditions formelles (3+2), (4+2) et (4+3) à partir d’ènecarbamates ou de diènecarbamates catalysées par des acides phosphoriques chiraux. Ces derniers étant bifonctionnel, ils permettent l’activation des deux partenaires de cycloaddition menant à la synthèse d’indolines, de 2,3-dihydrobenzofuranes, de benzoquinones carbonannulées, de cyclohepta[b]indoles et de tétrahydroquinolines de façon hautement stéréosélective. Dans une seconde partie, nous nous sommes intéressés à l’utilisation de composés d’iode hypervalent chiraux comme organocatalyseurs. En effet, ces composés présentent une réactivité intéressante tout en étant stable et faiblement toxique. Ainsi, leur utilisation dans une réaction de lactonisation à partir de substrats flexibles a permis l’obtention de divers hétérocycles avec de bons résultats. / The development of new enantioselective methodologies is essential for the synthesis of bioactive compounds. In this context, we were interested in using organocatalysts for the synthesis of enantioenriched cyclic molecules. In a first part will be describe chiral phosphoric acid catalyzed (3+2), (4+2) and (4+3) formal cycloadditions using enecarbamate or dienecarbamate. These catalysts are bifunctional and can interact with both cycloaddition partners leading to the synthesis of 2,3-dihydrobenzofuranes, carboannulated benzoquinones, cyclohepta[b]indoles and tetrahydroquinolines with high stereocontrol. In a second phase, we were interested in using chiral hypervalent iodine as organocatalyst. Theses compounds present interesting reactivity while being stable and not very toxic. Their use permits us to develop a lactonisation starting from flexible substrate and led to the synthesis of various heterocycles with good results.

Background: Although radioactive iodine 131 (RAI) has been successfully used in differentiated thyroid cancer (DTC) patients therapy for more than 70 years, thus far published data regarding RAI- induced salivary glands functional impairment have been inconsistent. Due to the trend towards using lower activities or even RRA omission, the possible RAI untoward effects have been widely discussed. Aim: To evaluate and quantify salivary gland function in thyroidectomised DTC patients before and after RRA using activity of 3.7 GBq and to compare salivary gland functional changes in DTC patients after single or repeated RAI treatment (using activities  5.5 GBq) with their age- and sex-matched RAI-naive counterparts using salivary gland scintigraphy with 99m Tc- pertechnetate. In addition, we performed subjective symptoms evaluation. Patients and Methods: Salivary gland scintigraphy (SGS) was performed in 31 RAI-naive patients (6 men, 25 women, median age 52 years) before and 4.6 months after RRA. Salivary gland function was measured also in 23 patients (7 men, 16 women, median age 60 years) with RAI administration history and compared with their age- and sex-matched counterparts. Non-parametric Wilcoxon and Mann-Whitney tests were used (due to non-normal data distribution) for statistical analysis. A p...

Face aux enjeux environnementaux actuels, la catalyse est devenue un outil majeur pour la synthèse de molécules complexes et à visées thérapeutiques. Dans ce contexte, nous nous sommes intéressés au développement de nouvelles méthodes de synthèses innovantes, efficaces, sans métaux ou activées par la lumière visible. Ainsi, mes travaux de thèse ont fait appel à deux thématiques largement étudiées au sein de notre laboratoire que sont la catalyse photorédox et l'organocatalyse. Dans ce manuscrit, la première partie porta sur la conception de réactions multicomposants photocatalysées pour la synthèse de structures trifluorométhylées avec de bons rendements. La partie suivante a été consacrée au développement et à l’évaluation de nouveaux photocatalyseurs supportés, robustes et recyclables. La troisième partie présenta l’élaboration de réactions de cyloadditions formelles (4+3) et (4+2), catalysées aux acides phosphoriques chiraux pour une synthèse efficace, énantiosélective et diastéréosélective de cyclohepta[b]indoles et de spiroindolines. Dans la quatrième partie, une stratégie combinant l’organocatalyse asymétrique et la photocatalyse pour la synthèse de tryptamines α-substituées β-aminées potentiellement biologiquement actives a été décrite. Enfin, l’élaboration de nouveaux composés d’iode hypervalent chiraux et leur évaluation en tant qu’organocatalyseurs fût rapportées dans la dernière partie de ce manuscrit de thèse. / In front of current environmental challenges, catalysis has become a major tool for the synthesis of complex and therapeutic molecules. In this context, we have focused on the development of new synthesis methods that are innovative, efficient, metal-free or activated by visible light. Thus, my thesis work has involved two themes that have been widely studied in our team: photoredox catalysis and organocatalysis. In this manuscript, the first part focused on the conception of photocatalyzed multicomponent reactions for the synthesis of trifluoromethylated structures with good yields. The following section devoted to the design and evaluation of new supported, robust and recyclable photocatalysts. The third part presented the formulation of formal (4+3) and (4+2) cyloaddition reactions, catalyzed with chiral phosphoric acids for an effective, enantio- and diastereo-selective synthesis of cyclohepta[b]indoles and spiroindolines. In the fourth part, a strategy combining asymmetric organocatalysis and photocatalysis for the synthesis of potentially biologically active α-substituted β-amino tryptamines was described. Finally, the elaboration of new chiral hypervalent iodine compounds and their evaluation as organocatalysts was reported in the last part of this thesis manuscript.

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Background: Boron Neutron Capture Therapy (BNCT) is a binary approach to cancer therapy that requires accumulation of boron atoms preferentially in tumour cells. This can be achieved by using nanoparticles as boron carriers and taking advantage of the enhanced permeability and retention (EPR) effect. Here, we present the preparation and characterization of size and shape-tuned gold NPs (AuNPs) stabilised with polyethylene glycol (PEG) and functionalized with the boron-rich anion cobalt bis(dicarbollide), commonly known as COSAN. The resulting NPs were radiolabelled with 124I both at the core and the shell, and were evaluated in vivo in a mouse model of human fibrosarcoma (HT1080 cells) using positron emission tomography (PET). Methods: The thiolated COSAN derivatives for subsequent attachment to the gold surface were synthesized by reaction of COSAN with tetrahydropyran (THP) followed by ring opening using potassium thioacetate (KSAc). Iodination on one of the boron atoms of the cluster was also carried out to enable subsequent radiolabelling of the boron cage. AuNPs grafted with mPEG-SH (5 Kda) and thiolated COSAN were prepared by ligand displacement. Radiolabelling was carried out both at the shell (isotopic exchange) and at the core (anionic absorption) of the NPs using 124I to enable PET imaging. Results: Stable gold nanoparticles simultaneously functionalised with PEG and COSAN (PEG-AuNPs@[4]) with hydrodynamic diameter of 37.8 0.5 nm, core diameter of 19.2 1.4 nm and -potential of 18.0 0.7 mV were obtained. The presence of the COSAN on the surface of the NPs was confirmed by Raman Spectroscopy and UV-Vis spectrophotometry. PEG-AuNPs@[4] could be efficiently labelled with 124I both at the core and the shell. Biodistribution studies in a xenograft mouse model of human fibrosarcoma showed major accumulation in liver, lungs and spleen, and poor accumulation in the tumour. The dual labelling approach confirmed the in vivo stability of the PEG-AuNPs@[4]. Conclusions: PEG stabilized, COSAN-functionalised AuNPs could be synthesized, radiolabelled and evaluated in vivo using PET. The low tumour accumulation in the animal model assayed points to the need of tuning the size and geometry of the gold core for future studies.

Biological markers (i.e., biomarkers) are essential in clinical and epidemiological studies as they may provide mechanistic insights into the developmental origins of disease, as well as improve diagnostic testing and risk assessment for disease prevention. However, major challenges remain due to the lack of rapid yet selective analytical methods for high throughput screening that are also amenable to volume-restricted specimens. This thesis includes two major research themes that take advantage of capillary electrophoresis (CE) separations, including (1) the targeted analysis of urinary iodide and thiocyanate for assessment of nutritional adequacy and tobacco smoke exposures in the population, and (2) the discovery of new biomarkers in sweat specimens that may improve universal newborn screening programs for cystic fibrosis (CF) infants beyond impaired chloride transport. Chapter II examines the prevalence and risk factors associated with iodine deficiency in 24 h urine samples collected from 800 participants across four clinical sites in Canada as part of the Prospective Urban and Rural Epidemiological (PURE) study when using CE with UV detection in conjunction with sample self-stacking. Importantly, regional variations in iodine status were revealed with participants from Quebec City and Vancouver at greater risk for iodine deficiency than Hamilton and Ottawa. Overall, iodine supplement use, thyroxine prescription, urinary sodium excretion, and self-reported dairy intake were found to be protective factors against iodine deficiency. Chapter III applied a validated CE assay to measure urinary thiocyanate as a biomarker of tobacco smoke and dietary exposures in an international cohort of 1000 participants from the PURE study spanning 14 countries with varied income status, smoking habits, and diet quality. Current smokers residing in high-income countries had the highest extent of cyanide exposure indicative of greater harms from tobacco smoke compared to middle- and low-income countries after adjusting for smoking intensity and other covariates. Chapter IV introduces a rapid CE method with indirect UV detection to simultaneously measure sweat chloride and bicarbonate from presumptive CF infants’ residual sweat samples. Although bicarbonate did not provide clinical value in neonatal CF diagnosis, sweat chloride testing by CE may reduce test failure rates due to insufficient volumes from infants in a clinical setting. Lastly, Chapter V applied an untargeted strategy to characterize the sweat metabolome from presumptive CF infants when using multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). A panel of sweat metabolites were found to discriminate CF from non-CF (i.e., unaffected carriers) infants, including aspartic acid, glutamine, oxoproline, and pilocarpic acid, which also correlated with sweat chloride. The clinical utility of these sweat metabolites to prognosticate late-onset CF infants from indeterminate sweat chloride test results was also explored. In summary, this thesis contributes innovative separation methods for biomarker screening and discovery in clinical and epidemiological studies for the prevention and early treatment of human diseases that benefit from optimal nutrition. / Dissertation / Doctor of Philosophy (PhD)

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