Des liquides riches en K2O ( K2O > 2 pds. % ; K2O/Na2O > 1) sont observés dans la majeure partie des contextes géodynamiques sur Terre. Ces liquides sont principalement caractérisés par leurs teneurs en K2O variant entre 3 et 13 pds. % et des rapports K2O/Na2O de 1 – 40. Les compositions chimiques des différents groupes de liquides riches en K2O observés sont extrêmement variables, depuis des termes très sous-saturés en silice (kamafugites, kimberlites, lamproïtes madupitiques à olivine) à des termes sur-saturés en silice (shoshonites, lamproïtes à phlogopite). Ces fortes teneurs en K2O et les rapports K2O/ Na2O élevés ne peuvent pas être obtenus par la fusion de péridotites fertiles ou réfractaires. Des expériences de fusion partielle en piston-cylindre ont été réalisées sur des péridotites à phlogopite ± amphibole dans les domaines de stabilité du spinelle et du grenat (1 et 3 GPa) afin de déterminer la capacité du manteau lithosphérique à produire des liquides riches en K2O. La présence de faibles teneurs en fluor dans le matériel de départ stabilise le phlogopite à des températures supérieures aux études antérieures. Les faibles degrés de fusion obtenus à 1 GPa sont sur-saturés en silice et leur teneur en K2O est tamponnée à 4 – 6 pds. % par la présence de phlogopite résiduel pour des péridotites fertile et réfractaire, respectivement. Les expériences réalisées à 3 GPa montrent que les premiers degrés de fusion sont sous-saturés en silice mais plus riches en K2O (6 – 8 pds. % pour la lherzolite et la harzburgite, respectivement) que dans le domaine du spinelle, démontrant l’importance de la pression sur la genèse de liquides riches en K2O. Les modélisations réalisées montrent également que l’augmentation de la proportion de phlogopite dans la source ne modifie pas la teneur en K2O des liquides formés mais diminue leurs rapports K2O/Na2O. Par conséquent, la fusion de péridotite à phlogopite dans la gamme de pression étudiée ne permet pas d’obtenir des liquides aussi riches en K2O que certains lamproïtes et kamafugites. Une série d’expériences réalisée sur du phlogopite pur à 1 et 3 GPa montrent que les liquides dérivés de telles sources sont très riches en K2O (12 – 14 pds. %) et comparables aux lamproïtes. Les différentes lithologies dans le manteau ne permettent cependant pas d’expliquer la grande gamme de composition des liquides riches en K2O et nécessitent des conditions riches en éléments volatils (H2O, CO2, F) et des fugacités d’oxygène réductrices. / K2O-rich melts (K2O > 2 wt. %; K2O/Na2O > 1) have been described in all of the major geodynamic settings on Earth. These melts are mainly characterized by their huge K2O content, ranging between 2 – 13 wt. % and K2O/Na 2 O ratios of 1 – 40. The chemical compositions of the different K2O-rich melt groups span a very high variability, from strongly silica undersaturated melts (kamfugites, kimberlites, madupitic lamproites) to silica-rich terms (shoshonites, phlogopite lamproites). These very high K2O contents together with strong K2O/Na2O ratios cannot be derived from partial melting of fertile or depleted peridotites. Partial melting experiments have been conducted in piston cylinder apparatus on phlogopite ± amphibole-peridotite in the spinel and garnet stability fields (1 – 3 GPa) in order to determine the ability of the lithospheric mantle to produce K2O-rich melts. The presence of small amounts of fluorine in the starting material leads to stabilize phlogopite at higher temperatures than previously determined. The first degrees of melting at 1 GPa are silica-rich and their K2O contents are buffered to 4 – 6 wt. % in the presence of residual phlogopite, depending on the source fertility (lherzolite and harzburgite, respectively). In the garnet stability field at 3 GPa, low-degree melts are silica-undersaturated but are enriched in K2O, compared to the garnet stability field: from 6 to 8 wt. % in lherzolite and harzburgite sources, respectively. These results suggest that pressure is a key parameter in the mantle to produce K2O-rich melts. Partition coefficient modelings show that increasing the phlogopite proportion in the mantle source does not modify the K2O content of derived melts, but decreases their K2O/Na2O ratios. Consequently, partial melting of phlogopite-peridotite in this range of pressure cannot accounts for the highest K2O contents observed in natural lamproites and kamafugites. A series of experiments has been realized on pure phlogopite at 1 and 3 GPa, showing that derived melts are strongly enriched in K2O (12 – 14 wt. %) and share chemical affinities with lamproites. Peridotite or pyroxenite melting in the presence of phlogopite, however, do not permit to reproduce the high chemical variability of natural K2O-rich melts requires volatile-rich conditions (H2O, CO2, F) and reduced oxygen fugacities.

Positron emission tomography (PET) is an important and powerful nuclear imaging modality and is essential in a range of medical fields. A suitable radiotracer must be identified in order for PET imaging to provide high quality and quantifiable data about the pathology. This includes the design and implementation of optimal radiochemistry that will reliably deliver the radiotracer that can answer the pertinent biological questions being asked. PET can be used to study the biological processes which are involved in pain perception and inflammatory responses that can occur in a number of chronic and acute conditions. This thesis aims to demonstrate how PET radiochemistry can enhance our knowledge of these biological processes and permits access to the underlying molecular mechanisms behind pain and inflammation. This thesis has been written in an alternative format, comprising the different areas which have been investigated. The work encompasses the study of the endogenous opioid system using the opioid receptor antagonist [11C]diprenorphine. This includes the design and automation of [11C]diprenorphine radiochemistry followed by the development of a method to reliably analyse its metabolism. Finally the application of [11C]diprenorphine in a clinical PET study, investigating opioid receptor occupancy by endogenous opioids as well as up-regulation of opioid receptors in the brain, is described. In the study of inflammation a pro-inflammatory cytokine, recombinant human interleukin-1 receptor antagonist (rhIL-1RA), was radiolabelled with novel 18F radiochemistry permitting pharmacokinetic study in pre-clinical models. This is followed by the design of a new technique to radiolabel white blood cells with 89Zr for quantifiable cell trafficking with PET. For this technique, chitosan nanoparticles are used to deliver the radio-metal cargo into white blood cells with a proposed application in inflammatory models. The process of chitosan nanoparticle construction is described alongside development of a procedure that is optimised for use in the proposed application. This thesis covers a variety of topics illustrating the contribution of PET radiochemistry in the area of pain and inflammation. The synergy between identification of new biological targets and development of radiotracers and radiolabelling strategies ensure PET radiochemistry will continue to contribute to our knowledge of pain and inflammation and aid understanding of its role in countless medical conditions.

L’acide (L)-tartrique, co-produit de l’industrie vinicole, est une petite molécule chirale, polyfonctionnelle et peu coûteuse. L’association de la chiralité de ce synthon aux propriétés physico-chimiques de l’atome de fluor a permis d’accéder à des hétérocycles azotés polyfonctionnels énantiopurs contenant un groupement trifluorométhyle porté par un carbone quaternaire.Les synthons de départ, les hémiaminals cycliques trifluorométhylés dérivés de l’acide (L)-tartrique diversement substitués, ont été obtenus par deux voies de synthèse : l’une basée sur une réaction de cyclisation d’un céto-amide trifluorométhylé en présence d’une amine ; l’autre sur une réaction de trifluorométhylation nucléophile d’un imide cyclique.Les dérivés de ces hémiaminals sont des précurseurs d’ions N-acyliminiums dans diverses réactions d’α-amidolakylations diastéréosélectives. Toutefois, l’addition de nucléophiles carbonés a été réalisée avec une efficacité variable. L’addition hautement diastéréosélective de nitriles selon une variante de la réaction de Ritter sur ces hémiaminals a permis de synthétiser divers oxazolines et (amido)pyrrolidin-2-ones originaux, énantiopurs, porteur d’un carbone chiral trifluorométhylé.Mots-clés : Acide tartrique, Trifluorométhylation nucléophile, Synthèse asymétrique, Hémiaminal, N-acyliminium, Carbinamide, Réaction de Ritter. / (L)-tartaric acid, a by-product of the wine industry, is a small chiral and polyfunctional molecule, affordable at low cost. Its chirality combined with the physical and chemical properties of fluorine enabled to afford original polyfunctional and optically pure nitrogen-containing heterocycles, incorporating a quaternary trifluoromethylated carbon.Our starting materials, the variously substituted trifluoromethylated cyclic hemiaminals derived from the (L)-tartaric acid, have been synthesized using two different methods : one is based on the cyclization of a trifluoromethylated keto amide in the presence of an amine, and the other one consists in a nucleophilic trifluoromethylation of a cyclic imide.These hemiaminal derivatives constitute N-acyliminium precursors in various diastereoselective α-amidoalkylations. However, the addition of C-nucleophiles has shown varying efficacy. The highly diastereoselective addition of nitriles on these hemiaminals, according to a Ritter-type reaction, led to the synthesis of original and optically pure oxazolines and (amido)pyrrolidin-2-ones including a chiral trifluoromethylated carbon.Key-words : Tartaric acid, Nucleophilic trifluoromethylation, Asymmetric synthesis, Hemiaminal, N-acyliminium, Carbinamide, Ritter reaction.

The development of new unconventional routes to small functionalized fluorocarbons (FCs) continues to be an attractive target due to the high utility of FCs in a broad range of applications, including their use as refrigerants, solvents, and surfactants. With the phasing out of hydrofluoroalkanes as refrigerants, there is a growing interest in the synthesis of new hydrofluoroolefins (HFOs), which are known to have significantly reduced global warming potential relative to hydrofluoroalkanes. Currently, energy-intensive conditions and toxic starting materials are typically necessary for their syntheses, making these processes environmentally problematic. The approach we have proposed for alternative ‘greener’ methods for functionalized FC production targets a transition metal-catalyzed synthesis involving the formation of metallacyclic intermediates through the oxidative cycloaddition of simple fluorinated alkenes, e.g., tetrafluoroethylene (TFE) and trifluoroethylene (TrFE), at low-valent nickel centres. There is precedent for the generation of short fluoroalkyl chain (C4-C6) compounds through homogeneous catalysis. For example, Baker et al. showed that you could catalytically hydrodimerize two molecules of tetrafluoroethylene (TFE) or one molecule of TFE with one molecule of ethylene using low valent Ni catalysts and π-acidic monodentate ancillary ligands, affording octafluorobutane and 1,1,2,2-tetrafluorobutane respectively. The objective of this Thesis is to further the state-of-the-art in fluoroorganometallic chemistry by gaining a deeper understanding of transition metal fluoroalkyl complexes as a function of metal-fluoroalkyl and carbon-fluorine bond reactivity. The over-arching goal is to harness said reactivity for the synthesis of new value-added fluorocarbons. Due to the robust nature of carbon-fluorine and metal-fluoroalkyl bonds in transition metal fluoroalkyl complexes, intensive conditions are often necessary to achieve any reactivity. Recently, bifunctional ligands have proven to be useful at effecting challenging transformations through unconventional ligand-assisted substrate activation pathways. Chapters 2 and 3 herein explore the use of a bidentate phosphinothiol ligand in the context of perfluoronickelacyclopentane reactivity. Synthetic approaches for the formation of phosphinothioether- and phosphinothiolate-supported perfluorometallacycles are outlined along with ensuing reactivity studies, including examples of Cα-F, Cβ-F, and Ni-Cα bond activation. Furthermore, a metal-mediated synthesis of functionalized FC, (E)-1,2,3,3,4,4-hexafluoro-1-butene, is provided. Chapter 4 sheds light on the comparatively underdeveloped chemistry of fluorinated nickelacycles generated from TrFE. A systematic study of monodentate phophine and phosphite ligand effects on metallacyclopentane regio-/stereochemistry is presented. The behaviour of the generated hydrofluoronickelacyclopentanes in the presence of acidic additives allows for a direct analogy to be made regarding the effects of the extent of metallacycle fluorination on C-F and Ni-C activation. In search of new approaches to novel functionalized FC synthesis, Chapter 5 will re-visit the use of bifunctional ligands, investigating the formation and reactivity of new perfluoronickelacycles featuring [P,NH] and [P,Nˉ] bidentate ligands. Finally, Chapter 6 summarizes the findings of this Thesis and discusses some of the future opportunities that will build on this work. The increased understanding of the stoichiometric systems presented herein will be directly important to the development of nickel-catalyzed routes to HFOs. As the demand for new “greener” refrigerants and propellants increases, the synthesis of small-molecule functionalized FCs using transition metal catalysis and waste fluorinated feedstocks can offer a mild, atom economical approach to new, unique candidates that will be appealing to industrial partners.

NiSi is an attractive material in the production of CMOS devices. The problem with the utilization of NiSi, is that there is no proper method of cleaning the oxide on the surface. Sputtering is the most common method used for the cleaning, but it has its own complications. Dry cleaning methods include the reactions with radicals and these processes are not well understood and are the focus of the project. Dissociated NF3 and NH3 were used as an alternative and XPS is the technique to analyze the reactions of atomic fluorine and nitrogen with the oxide on the surface. A thermal cracker was used to dissociate the NF3 and NH3 into NFx+F and NHx+H. There was a formation of a NiF2 layer on top of the oxide and there was no evidence of nitrogen on the surface indicating that the fluorine and hydrogen are the reacting species. XPS spectra, however, indicate that the substrate SiO2 layer is not removed by the dissociated NF3 and NiF2 growth process. The NiF2 over layer can be reduced to metallic Ni by reacting with dissociated NH3 at room temperature. The atomic hydrogen from dissociated ammonia reduces the NiF2 but it was determined that the atomic hydrogen from the ammonia does not react with SiO2.

Orientador: Marcelo Giannini / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-22T02:35:57Z (GMT). No. of bitstreams: 1 Ayres_AnaPaulaAlmeida_M.pdf: 3452977 bytes, checksum: c1245f8af84e3e9b42ae18f3eb096ed8 (MD5) Previous issue date: 2013 / Resumo: O objetivo desse estudo foi avaliar a resistência de união à dentina de sistemas restauradores contendo ou não fluoretos em sua composição e o comportamento do esmalte e da dentina adjacentes às restaurações, quando submetidos ao desafio cariogênico in vitro. Adicionalmente, durante o desafio cariogênio foi mensurada a liberação de fluoreto dos adesivos. Para o estudo foram utilizados 64 dentes terceiros molares humanos e quatro sistemas restauradores: FL-Bond II/Beautifil II, Bond Force/Estelite Sigma, GC Fuji II LC e Adper Easy Bond/Filtek Z350 XT. No estudo de resistência da união à dentina, utilizou-se a dentina coronária, onde foram aplicados os materiais restauradores (n=8). Os dentes foram seccionados para obtenção dos espécimes e o teste de microtração foi realizado em dois tempos: imediato e após um ano de armazenamento em saliva artificial. Para o estudo da microdureza longitudinal, foram confeccionadas cavidades na região cervical, as quais foram restauradas com os quatro sistemas propostos, de acordo com as recomendações dos fabricantes (n=8). Os dentes restaurados foram submetidos à ciclagem térmica (3.000 ciclos) e, posteriormente, à ciclagem de pH durante oito dias. A mensuração da microdureza subsuperficial foi realizada em esmalte e em dentina, em três distâncias da parede cavitária e em seis profundidades em relação à superfície submetida à ciclagem de pH. As soluções desmineralizantes e remineralizantes utilizadas nessa ciclagem foram utilizadas para análise de concentração catiônica de flúor. A análise estatística de resistência de união dentinária mostrou que os valores médios não foram afetados após um ano de armazenamento em saliva artificial para nenhum dos sistemas restauradores. Os resultados de microdureza longitudinal em esmalte apresentaram diferença estatística significativa apenas para a distância 50 ?m. Mas os valores médios de microdureza Knoop em esmalte foram semelhantes para os quatro sistemas restauradores quando avaliados nas mesmas distâncias e profundidades. O mesmo padrão de resultado foi encontrado na dentina, mas os valores médios de microdureza não apresentaram diferença estatística entre as distâncias da restauração. A análise catiônica de flúor detectou liberação de fluoreto nos espécimes restaurados com GC Fuji LC II e FL-Bond II/Beautifil II. A partir dos resultados desse estudo in vitro é possível afirmar que os sistemas restauradores avaliados apresentaram estabilidade da união por um ano, porém apresentaram pouca capacidade de inibição de cárie secundária em esmalte e em dentina, independentemente da liberação ou não de fluoretos / Abstract: The aim of this study was to evaluate the bond strength to dentin of restorative systems containing or not fluoride in their compositions and the performance of enamel and dentin around the restorations, when submitted to cariogenic challenge in vitro. Additionally, the fluoride released was measured during the pH cycling. This study used 64 third molars human teeth and four restorative systems were selected: FL-Bond II/Beautifil II, Bond Force/Estelite Sigma, GC Fuji II LC and Adper Easy Bond/Filtek Z350 XT. For the bond strength evaluation, it was used oclusal dentin in which the restorative materials were applied (n=8). The "restored" teeth were sectioned for obtaining bonded beam specimens and the microtensile test was performed in two times: imediate and after one year of storage in artificial saliva. For the cross-sectional microhardness test, cervical cavities were prepared and filled with the restorative systems according to the manufacturer's instructions (n=8). The restored teeth were submitted to thermo cycling (3.000 cycles) and subsequent pH-cycling during eight days. The cross-sectional microhardness analysis was performed in enamel and dentin, at three distances from cavity wall and at six depths regarding the surface submitted to pH-cycling. The desmineralizing and remineralizing solutions of this pH-cycling regimen was used for fluor cationic concentration analysis. The statistical analysis of bond strength to dentin showed that means were not reduced after one year of storage in artificial saliva for no restorative systems. The results of cross-sectional microhardness measurements in enamel presented significant statistical difference only at the distance of 50 ?m. However, means of Knoop microhardness measurements were similar for the four restorative systems when compared to the same distances and depths. The same pattern of results was found in dentin, but the means of microhardness measurements showed no significant statistical differences between the distances from the restorations. Fluor cationic concentration analysis detected fluoride releasing by the specimens restored GC Fuji LC II and FL-Bond II/Beautifil II. The results of this in vitro study suggest that the restorative products tested presented bond stability after one year, but showed little ability to inhibit secondary caries around restoration, independently on fluoride releasing or not / Mestrado / Dentística / Mestra em Clínica Odontológica

No description available.

Ce travail traite de la synthèse énantiosélective de composés trifluorométhylés via l’étude de la réaction d’isomérisation rédox d’alcools allyliques trifluorométhylés catalysée par des complexes de ruthénium. Nous avons mis au point la réaction d’isomérisation rédox d’alcools allyliques secondaires β-trifluorométhylés. Une étude du mécanistique réactionnel a mis en évidence que l’étape cinétiquement déterminante de cette réaction pour les substrats β-trifluorométhylés est différente de celle décrite pour les substrats non fluorés, il s’agit de l’étape d’insertion. Cette observation nous a permis de mettre au point une réaction d’isomérisation rédox énantiospécifique permettant un transfert intramoléculaire de chiralité via un processus suprafacial. Cette méthode a été appliquée à la synthèse du (S)-CF3-citronellol. En parallèle, nous avons étudié la réaction tandem : isomérisation rédox – transfert d’hydrogène en partant d’alcools allyliques ou d’énones β-trifluorométhylées permettant l’accès aux alcools saturés correspondants. / This work deals with the enantioselective synthesis of trifluoromethylated compounds via the study of the ruthenium catalyzed redox isomerization reaction of trifluoromethylated allylic alcohols. We have developed optmized conditions for the redox isomerization of β-trifluoromethylated secondary allylic alcohols. A mechanistic study of the reaction revealed that the rate determining step for β-trifluoromethylated substrates is different from that described for the non-fluorinated substrates. This observation allowed us todevelop an enantiospecific redox isomerization reaction with a total transfer of chirality via a suprafacialintramolecular process. This methodology has been applied to thesynthesis of (S)-CF3-citronellol. In parallel, we have studied the tandem reaction : redox isomerization - transfer hydrogenation starting from β-trifluoromethylated allylic alcohols orenones, allowing access to the corresponding saturated alcohols.

La fluorooléfine (CF=CH), motif isostère et isoélectronique de la liaison amide, peut être utilisé comme mime efficace de la liaison peptidique. De plus, ce motif confère une meilleure résistance à la dégradation enzymatique comparé à la liaison peptidique. Cette thèse s’inscrit dans notre programme de développement de nouvelles méthodologies d’accès aux fluoropseudopeptides. Dans une première partie, nous appliquons diverses stratégies originales du laboratoire vers la synthèse d’un analogue du neuropeptide 26RFa. Dans une seconde partie est présentée une stratégie générale vers l’accès à des pseudopeptides possédant un motif proline, un acide aminé extrêmement important. Ainsi, la synthèse asymétrique d’analogues fluorés de dipeptide incluant l’unité proline (AA-[(Z) ou (E)CF=C]-Pro), de conformation cisoïde ou transoïde, a été développée. Enfin, nous avons étendu cette méthodologie à la synthèse d’un analogue de l’Enalapril®, molécule biologiquement active. / The Fluoroolefin moiety (CF=CH) can be used as an effective peptide bond mimic due to isoelectronic and isosteric properties. Moreover, this moiety provides better resistance to enzymatic degradation compared to native peptide bond. This thesis is part of our program aiming at developing new methodologies towards fluoropseudopeptides. In a first part, we apply various innovative strategies from the laboratory to the synthesis of an analog of neuropeptide 26RFa. In the second part is presented an overall strategy towards fluorinated pseudopeptide including a proline residue, an amino acid extremely important. Thus, the asymmetric synthesis of fluorinated dipeptide analogues AA-[(Z) or (E) CF=C]-Pro, under cisoid or transoid conformation, has been developed. Finally, we extend this methodology to the synthesis of an analogue of biologically active Enalapril®.

L’hypoxie est connue pour être responsable d’une propagation tumorale accrue. En conséquence, les tumeurs hypoxiques nécessitent un diagnostic rapide et précis. L’accès à toutes les localisations tumorales par l’imagerie nucléaire est devenu un intérêt majeur pour l’orientation thérapeutique. Dans la première partie de ce manuscrit, un nouveau traceur de l’hypoxie tumorale marqué au technétium 99m a été développé avec succès. De nouveaux traceurs organosilylés marqués au fluor 18 ont également été étudiés. Un second travail a porté sur le développement d’une nouvelle stratégie de fluoration nucléophile pour la préparation de traceurs TEP. Des essais synthèse du Fluorodésoxyglucose ont été réalisés. L’élaboration de cette stratégie a également conduit au développement d’une nouvelle méthodologie de synthèse de dérivés d’acides sulfoniques par déprotection de thiols au moyen d’hypochlorite de tert-butyle. / It has been recognized that hypoxia plays a major negative role in overall tumor progression. The identification and quantitative estimation of tumor hypoxia by means of nuclear imaging is an important factor in planning the therapeutic strategy for a better clinical outcome. In the present work, a new 99mTc tracer for imaging tumor hypoxia has been successfully developed. New organosilicon fluorinated derivatives were also studied. Every synthesized compounds incorporated a nitroimidazole moiety, which is selectively trapped in hypoxic cells. The second part of this work, led to the development of a new nucleophilic fluorination strategy for the preparation of PET tracers. The new strategy was attempted for the preparation of Fluorodeoxyglucose. In the course of this study, a novel oxidative deprotection method of thiols was developed. Herein was described, the synthesis of sulfonic acid derivatives by oxidative deprotection of thiols using tert-butyl hypochlorite.