Surface texturization of Transparent Conductive Oxides (TCOs) is a well-known strategy to enhance the light-trapping capabilities of thin-film solar cells and thus, to increase their power conversion efficiency. Herein, the surface modification of fluorine-doped tin oxide (FTO) using picosecond infrared direct laser interference patterning (DLIP) is presented. The surface characterization exhibits periodic microchannels, which act as diffraction gratings yielding an increase in the average diffuse transmittance up to 870% in the spectral range of 400–1000 nm. Despite the one dimensionality of the microstructures, the films did not acquire a significant anisotropic electrical behavior, but a partial deterioration of their conductivity is observed as a result of the removal of conductive material. This work proposes the feasibility of trading off a portion of the electrical conductivity to obtain a substantial improvement in the optical performance.

Im ersten Teil wurde Probenvorbereitungs-Methoden und instrumentelle Methoden zur Organofluor-Bestimmung verglichen, um Vor- und Nachteile bei der Summenparameter-Analytik von per- und polyfluorierten Alkylverbindungen (PFAS) zu identifizieren. Daher wurden Oberflächenwasserproben aus der Spree in Berlin und Industrieabwasserproben mit zwei PFAS-Summenparametern analysiert – dem extrahierbaren (EOF) und dem adsorbierbaren organisch gebundenen Fluor (AOF). Beide PFAS-Summenparameter wurden mit zwei fluorsensitiven Detektionssystemen analysiert – Hochauflösender Kontinuumstrahler-Graphitofen Molekülabsorptionsspektrometrie (HR-CS-GFMAS) und combustion Ionenchromatographie (CIC). HR-CS-GFMAS erwies sich im Vergleich zu CIC als der empfindlichere und schnellere Ansatz mit höherer Präzision. Im zweiten Teil wurde eine neue Methode zur PFAS-Summenparameteranalyse und EOF-Bestimmung in Bodenproben auf Basis von HR-CS-GFMAS entwickelt und optimiert. EOF-Massenanteile wurden bei mehrfacher Extraktion und Nutzung der Festphasenextraktion (SPE) zur Entfernung anorganischen Fluors untersucht. Bei einem Vergleich der optimierten Methode mit und ohne SPE zeigte sich eine drastische Diskriminierung von Organofluor-Verbindungen mittels SPE. Im dritten Teil wurden Organofluor-Massenbilanzen in aquatischen Systemen anhand von Oberflächenwasser- und Schwebstoffproben (SPM) untersucht. SPM-Proben wurden mit vier komplementären Analysemethoden analysiert – target und non-target, direct total oxidizable precursor assay (dTOPA) und EOF. Daher wurden drei Organofluor-Massenbilanzansätze für die räumlich und zeitaufgelöste SPM-Probenanalyse verwendet: (I) Identifizierung von oxidierbaren PFAS-Vorläufer, (II) Identifizierung des Anteils der identifizierten und nicht identifiziertes EOF und (III) PFAS-target, PFAS dTOPA, non-target-Screening und EOF-Analyse, um das nicht identifizierte EOF aus Ansatz (II) weiter zu entschlüsseln. / In the first part, a comparison of sample preparation and instrumental methods for organofluorine determination was used to identify advantages and disadvantages in sum parameter analysis of per- and polyfluoroalkyl substances (PFASs). Therefore, surface water samples from the Spree River in Berlin, Germany and industrial effluent samples were analyzed using two PFAS sum parameters – the extractable (EOF) and adsorbable organically bound fluorine (AOF). Both PFAS sum parameters were analyzed using two fluorine sensitive detection systems – high-resolution-continuum source-graphite furnace molecular absorption spectrometry (HR-CS-GFMAS) and combustion ion chromatography (CIC). HR-CS-GFMAS turned out to be the more sensitive and faster approach accompanied with higher precision compared to CIC. In the second part, a new method for PFAS sum parameter analysis and EOF determination in soil samples based on HR-CS-GFMAS was developed and optimized. EOF mass fractions were investigated upon multiple extraction and utilization of solid phase extraction (SPE) for inorganic fluorine removal. In a comparison of the optimized method with and without SPE, a highly biased discrimination of organofluorines using SPE was shown. In the third part, organofluorine mass balances were investigated in aquatic systems using surface water and suspended particulate matter (SPM) samples. SPM samples were analyzed using 4 complementary analytical methods – target and non-target HRMS, direct total oxidizable precursor assay (dTOPA) and EOF. Therefore, 3 organofluorine mass balance approaches were used for SPM sample analysis in spatial and time resolved manner: (I) Identification of oxidizable PFAS precursors, (II) Identification of the proportion of identified and unidentified EOF and (III) PFAS target, PFAS dTOPA, non-target screening and EOF analysis to further unravel the unidentified EOF from approach (II).

Les éléments volatils libérés de la plaque plongeante lors de la subduction jouent un rôle fondamental durant la formation des magmas d'arc dans le coin mantellique. Depuis quelques années, les développements des techniques d'analyse par sonde ionique ont permis l'analyse de ces éléments, en particulier F et Cl, dans les magmas d'arc, et notamment dans les magmas d'arc primaires grâce aux avancées des études sur les inclusions magmatiques. Une récente étude des inclusions magmatiques du Mont Shasta (E. U.) (Le Voyer et al., 2010) a montré que le fractionnement du F et du Cl apportait des informations sur la genèse des magmas d'arc. Afin de caractériser la source de ces magmas, j'ai étudié les coefficients de partage du fluor et du chlore. Dans cette étude, je présente les premiers coefficients de partage du F et du Cl, entre des liquides de fusions silicatés anhydres et hydratés et des minéraux mantelliques tels que olivine, orthopyroxène, clinopyroxène, plagioclase, grenat ainsi que pargasite et phlogopite. Les valeurs sont issues de 300 mesures dans 24 expériences de fusion, réalisées entre 8 et 25 kbars et, 1180 et 1430˚C. Les faibles concentrations en F et Cl dans les minéraux ont été analysées par la sonde ionique Cameca IMF 1280 de WHOI en utilisant le mode d'ions secondaires négatifs. Les résultats montrent que DOpx/meltF varient de 0.123 à 0.021 et DCpx/meltF de 0.153 à 0.083, tandis que DOpx/meltCl varient de 0.002 à 0.069 et DCpx/meltCl de 0.008 à 0.015. De plus, DOl/meltF de 0.116 à 0.005 et DOl/meltCl de 0.001 à 0.004 ; DGrt/meltF de 0.012 à 0.166 et DGrt/meltCl de 0.003 à 0.087 avec l'augmentation de la teneur en eau et la diminution de la température dans les expériences. Je montre aussi que le F est compatible dans la phlogopite (DPhl/meltF >1.2) alors qu'il est incompatible dans la pargasite (DAmp/meltF de 0.36 à 0.63). A l'inverse, Cl est plus incompatible dans la phlogopite (DPhl/meltCl en moyenne 0.09±0.02), que dans la pargasite (DAmp/meltCl de 0.12 à 0.38). Cette étude démontre que F et Cl sont substitués dans des sites spécifiques de l'oxygène, ce qui les rend plus sensibles que les éléments traces aux variations de chimie des cristaux et de la quantité d'eau, et donc aux conditions de fusion. En utilisant ces nouveaux coefficients de partage, j'ai modélisé la fusion de lithologies potentielles du manteau sub-arc permettant de 1) déterminer la quantité de fluide aqueux impliqué dans la fusion, 2) distinguer la fusion induite par apport de fluides de la fusion d'une source à minéraux hydratés et 3) la fusion d'une lithologie à pargasite de celle à phlogopite, et montre que la source de certains magmas primaires d'arc, par exemple d'Italie, contient de la pargasite et de la phlogopite, tandis d'autres magmas primaires d'arc résultent d'une fusion par apport de fluides. / Volatile elements released from the subducting slab play a fundamental role during the formation of arc magmas in the mantle wedge. Advances of melt inclusion studies enlarged the data on volatile abundance in arc magmas, and it is now possible to characterize some volatile contents in arc primary magmas, in particular F and Cl. A recent study of Mt Shasta melt inclusions (LeVoyer et al., 2010) shows that fractionation of F and Cl potentially contains information about arc magma genesis. In order to trace the source of arc magmas, fluorine and chlorine partitioning was investigated. Here, I present new experimental determinations of Cl and F partition coefficients between dry and hydrous silicate melts and mantle minerals: olivine, orthopyroxene, clinopyroxene, plagioclase, garnet and also pargasite and phlogopite. The values were compiled from more than 300 measurements in 24 melting experiments, conducted between 8 and 25 kbars and between 1180 and 1430˚C. The low abundance F, Cl measurements in minerals were done by Cameca IMF 1280 at WHOI using the negative secondary ion mode. The results show that DOpx/meltF ranges from 0.123 to 0.021 and DCpx/meltF ranges from 0.153 to 0.083, while Cl partition coefficient varies from DOpx/meltCl from 0.002 to 0.069 and DCpx/meltCfrom 0.008 to 0.015, as well. Furthermore, DOl/meltF ranges from 0.116 to 0.005 and DOl/meltCl from 0.001 to 0.004; DGrt/meltF ranges from 0.012 to 0.166 and DGrt/meltCl from 0.003 to 0.087 with the increasing water amount and decreasing temperature. I also show that F is compatible in phlogopite DPhl/meltF > 1.2) while DAmp/meltF is incompatible in pargasite DAmp/meltF from 0.36 to 0.63). On the contrary, Cl is more incompatible in phlogopite (DPhl/meltCl > 1.2 on average 0.09 ± 0.02), than in pargasite (DPhl/meltCl from 0.12 to 0.38). This study demonstrates that F and Cl are substituted in specific oxygen site in minerals that lead then to be more sensitive than trace elements to crystal chemistry and water amount variations thus melting conditions. Using those new partition coefficients, I modelled melting of potential sub-arc lithologies with variable quantity aqueous-fluid. This model is able to decipher 1) amount of aqueous-fluid involved in melting, 2) melting induced by fluid or melting of an hydrous mineral-bearing source and 3) melting of either pargasite-bearing lithology or phlogopite-bearing lithology and shows that sources of some primitive melts, for instance from Italy, bear pargasite and phlogopite, while some primitve melts seem to be the results of fluid-induced melts.

La Tomographie par émission de positons (TEP) constitue l’une des techniques d’imagerie médicale les plus novatrices pour la visualisation in vivo des processus biologiques. Elle intervient comme technique de choix pour le diagnostic dans de nombreux domaines notamment, en oncologie, cardiologie ou encore en neurologie. La conception et l’élaboration de nouveaux radiotraceurs sont en perpétuel développement. L’utilisationd’oligonucléotides (ODN) modifiés (aptamères) possédant une grande affinité et spécificité pour une cible (gène,protéine, principe actif), comme radiotraceur pour l’imagerie in vivo apparait comme une alternative intéressante. A ce jour, quelques rares exemples d’oligonucléotides marqués, par un radioisotope, ont été décrits dans la littérature.Dans ce contexte, il a été développé deux méthodologies d’introduction du radioisotope (11C ou 18F) en dernièreétape de synthèse par chimie ‘‘click’’ pour le marquage de nucléosides et d’oligonucléotides envisagés commeradiotraceurs pour la TEP. / Positron Emission Tomography (PET) is a powerful molecular-imaging technique for physiological and biologicalinvestigations in various areas, such as oncology, cardiology, and neurosciences, as well as for drug development.Due to the increasing need of this technique for in vivo applications, there is always a demand for the developmentof new tracers and radiolabeling strategies. Furthermore, because of their excellent targeting capacities and easysynthesis along with a high level of diversity, oligonucleotides are already extensively used in vitro as ligands fornucleic acids (antisense oligonucleotides), proteins, and small related molecules (aptamer oligonucleotides). Theuse of aptamers for in vivo imaging appears especially promising, because of the wide range of possibilitiesavailable to introduce variations in their structure through defined chemical modifications. However, only fewexamples of oligonucleotide labeling for PET have been reported. In this context, we have developed twomethodological ways to introduce the radioisotope (11C, 18F), by ‘‘click’’ chemistry, at the last radiosynthesis stepin order to label nucleoside and oligonucleotide as potential radiotracers for PET.

Dans la première partie nous décrivons la synthèse et l'évaluation biologique de nouveaux inhibiteurs de l'agrégation plaquettaire, composés dont la structure a été établie en partant du 12-HETE et du 13-HODE. Dans la seconde partie nous développons de nouvelles méthodologies pour la préparation de molécules contenant des motifs CF₂R. Tout d'abord une stratégie très flexible a été mise au point pour la préparation de composés gem-difluorobisaryliques et de leurs analogues hétéroaromatiques. Elle est basée sur l'emploi d'intermédiaires gem-difluoropropargyliques faciles d'accès. Par une séquence de Diels-alder-aromatisation on obtient les molécules cibles de la première série. Pour la seconde, des réactions de cycloaddition dipolaire 1,3 ont été utilisées. A partir de ces intermédiaires, des chimiothèques ciblées de molécules fluorées ont été préparées. Nous nous sommes intéressés ensuite à la synthèse de composés fluorés fonctionnalisés et chiraux à travers des réactions d'organocatalyse asymétrique. A partir d'énals gem-difluorés des réactions de Diels-Alder et des additions 1,4 asymétriques ont été réalisées avec succès. / The first part of the thesis deals with the synthesis and biological evaluation of new platelets aggregation inhibitors, based on 12-HETE, 13-HODE and their analogues. In the second part we are interested in novel methodologies for the preparation of CF₂-containing molecules : First, a flexible strategy for the synthesis of gem-difluoro-bisarylic derivatives and heteroaromatic analogues was designed based on the easy synthesis and the reactivity of gem-difluoro propargylic intermediates, which by Diels-Alder cycloaddition and 1,3-dipolar cycloadditions afforded respectively the bisarylic and mixed arylic heteroarylic scaffolds. In addition, two small libraries were constructed around a bisarylic scaffold as representative examples. Second, we were interested in the synthesis of optically active functionalized molecules containing a gem-difluoro group, using asymmetric organocatalysis protocols. After preparation of the gem-difluoro enals, from their difluoropropargylic precursors, asymmetric organocalytic Diels-Alder cycloaddition and 1,4-conjugated additions were successfully performed.

Les travaux présentés dans ce manuscrit ont pour objectifs la synthèse chimique de nouveaux ligands de la protéine de translocation 18 kDa (TSPO), leur évaluation in vitro et le radiomarquage isotopique des candidats les plus prometteurs par l’émetteur de positons à vie brève fluor-18 (t1/2 : 109,8 minutes). Ce travail a pour finalité le développement de nouvelles sondes moléculaires ou biomarqueurs pour l’imagerie non-invasive et atraumatique par Tomographie par Emission de Positons (TEP) de la neuroinflammation, processus reconnu dans les maladies neurodégénératives telles la maladie d’Alzheimer, de Parkinson, la sclérose en plaque et certaines maladies psychiatriques.Le radioligand de choix pour l’imagerie de la TSPO est actuellement le [18F]DPA-714, une pyrazolo[1,5-a]pyrimidine marquée au fluor-18 récemment développée au laboratoire. Cependant, cette molécule subit in vivo la perte rapide de l’atome de fluor radioactif par rupture du motif fluoroalkoxy comme démontrée lors de l’étude de son métabolisme. Mon projet de thèse a donc visé à concevoir et développer de nouveaux dérivés structurellement proches de DPA-714 (analogues) pour lesquelles la liaison entre le squelette principal et le fluor-18 serait renforcée. C’est dans ce cadre que dix-neuf composés ont été préparés et évalués pour leur affinité pour la TSPO, et que deux candidats prometteurs, DPA-C5yne et CfO-DPA-714, ont été radiomarqués au fluor-18 avec de bons rendements radiochimiques (20-30 %) et de hautes radioactivités spécifiques (50-90 GBq/µmol). Ces radioligands ont également été évalués in vivo par imagerie TEP et présentent, chez l’animal, des performances équivalentes voire légèrement supérieures à [18F]DPA-714. / The work presented in this manuscript aims to describe the synthesis of new ligands of the translocation protein 18 kDa (TSPO), their in vitro evaluation and, for the most promising candidates, their isotopic radiolabelling with the short-lived positron emitter fluorine-18 (t1/2 : 109.8 minutes). The ultimate goal of this work consists in developing new molecular probes, or biomarkers, for imaging neuroinflammation in a non-invasive and atraumatic manor using Positron Emission Tomography (PET). Neuroinflammatory processes have been identified in Alzheimer and Parkinson diseases, MS and various psychiatric pathologies.The radioligand of choice for imaging TSPO is currently [18F]DPA-714, a pyrazolo[1,5-a]pyrimidine radiolabelled with fluorine-18 which has been recently prepared in our laboratories. However, [18F]DPA-714 undergoes a rapid in vivo loss of the radioactive fluorine by cleavage of the fluoroalkoxy chain as demonstrated in metabolic studies. Therefore, my PhD project aimed to design and develop new structurally related analogues of DPA-714 where the linkage between the main backbone and the fluorine-18 would be reinforced. To this extent, nineteen compounds were prepared and their affinity towards the TSPO was evaluated. Two promising candidates, coded DPA-C5yne and CfO-DPA-714, were radiolabelled with fluorine-18 with good radiochemical yields (20-30 %) and high specific radioactivities (50-90 GBq/µmol). These radioligands were also evaluated by PET imaging at the preclinical stage and displayed equivalent or slightly improved results when compared to [18F]DPA-714.

Introdução - A quantidade de flúor ingerida, proveniente de todas as fontes, durante o período crítico de formação dos dentes, é o principal fator de risco para a fluorose dentária. Dentre estas fontes estão a água fluoretada, o dentifrício fluoretado e os alimentos, bebidas, fórmulas e suplementos infantis. Considerando-se que a fluorose dentária tem aumentado em todas as regiões é importante avaliar, além da água e do dentifrício, também a contribuição diária do consumo alimentar das crianças e a concentração de flúor nesses itens alimentares para a ingestão de flúor. Objetivo - Descrever o consumo alimentar de crianças de 2 a 6 anos, com relação ao flúor. Métodos - Foram avaliadas 379 crianças, de 2 a 6 anos, faixa etária de risco para fluorose, residentes em Bauru - São Paulo, município com fluoretação artificial da água de abastecimento público. A amostragem foi estratificada por setor, baseando-se no Plano Diretor do Município. O consumo alimentar foi avaliado pelo Questionário de Freqüência Alimentar Semiquantitativo, aplicado aos pais ou responsáveis, e a concentração de flúor nos itens alimentares a partir de análises laboratoriais. As crianças foram classificadas quanto à ingestão diária de f1úor de acordo com a Dietary Reference Intakes. Resultados - Dentre os 70 itens alimentares, o arroz, a água de abastecimento público e o leite foram os mais consumidos; o chá preto, o leite em pó de soja diluído com água de abastecimento público e o biscoito Danyt\'s® apresentaram maior concentração de flúor; a água de abastecimento público, o refrigerante Coca-Cola® e a batata frita representaram maior contribuição diária para ingestão de flúor. Os itens alimentares mais consumidos apresentaram, em média (±DP), concentração de flúor (0,015 ± 0,028 mgF/porção) significantemente menor (p = 0,03) que os menos consumidos (0,107 ± 0,162 mgF/porção). Os itens alimentares com maior concentração de flúor contribuíram significantemente (p < 0,001) para a ingestão do halogênio (0,018 ± 0,037 mgF/dia). A média da ingestão de flúor por meio dos alimentos sólidos e líquidos, da água e da escovação foi de 0,017 ± 0,016; 0,011 ± 0,004 e 0,036 ± 0,028 mgF/kg peso/dia, respectivamente, totalizando 0,064 ± 0,035 mgF/kg peso/dia. Das 379 crianças, 31,2% apresentaram risco de fluorose. O dentifrício e os itens alimentares (sólidos, água e outros líquidos) contribuíram com 57% e 43%, respectivamente, para a ingestão de flúor. Conclusão - O dentifrício foi a principal fonte para a ingestão de f1úor pelas crianças, porém, a concentração desse halogênio nos itens alimentares contribuiu significantemente para a ingestão, representando risco para f1uorose dentária. / The quantity of fluoride ingested, deriving from all sources, during the critical period of formation of the teeth, is the main factor of risk for the dental fluorosis. Among this sources, we have the fluoridated water, the fluoridated dentifrice and the food, drinks, chemical formula and the infant supplements. Taking into consideration that the dental fluorosis has increased in all regions, it is important to evaluate it, besides the water and the dentifrice, the daily contribution of children\'s food consumption and the concentration of fluoride in these food items for the ingestion of fluoride. Objective - Describe the food consumption of children from 2 to 6 years old, relationg to fluoride. Methods - 379 children were evaluated at risking ages for fluorosis, residents in Bauru - São Paulo, district with artificial f1uoridation. The sampling was stratified by sector, based on the Director\'s Plan of the District. The food intake was evaluated by the Food Frequency Semiquantitative Questionnaire, applied on parents or responsable one, and the concentration of fluoride on the food items from analyses in laboraties. The children were classified based on theis daily ingestion of fluoride according to the Dietary Reference Intakes. Results - Among the 70 food items, rice, public water supply and the milk were the most consumed ones; the black tea, the soybean powdered milk diluted in public water and the biscuit Danyt\'s® presented the gratest daily contribution for the ingestion of fluoride. The most consumed food items present, in average (± DP), concentration of fluoride (0,015 ± 0,028 mg F / portion), significantly lower (p = 0,03) that the less consumed (0,107 ± 0,162 mgF/portion). The food items with the greatest concentration of fluoride contributed significantly (p < 0,001) for the ingestion of the mineral (0,018 ± 0,037 mgF/day). The average amount of fluoride ingestion taken from the solid food and the liquid ones (except water) coming from the water and the teeth brushing was 0,017 ± 0,016; 0,011 ± 0,004 and 0,036 ± 0,028 mgF/kg weight/day, respectively, totalizing 0,064 ± 0,035 mgF/kg weight/dia. 31,2% of the 379 children presented risk of fluorosis. The dentifrice and the food items (solid, water and other liquids) contributed with 57% and 43%, respectively, for the ingestion of fluoride. Conclusion - The dentifrice was the main source for the ingestion of fluoride, by the children, however, the concentration of this mineral in food items contributed significantly for the ingestion by the children, representing risk for dental fluorosis.

Introdução - A quantidade de flúor ingerida, proveniente de todas as fontes, durante o período crítico de formação dos dentes, é o principal fator de risco para a fluorose dentária. Dentre estas fontes estão a água fluoretada, o dentifrício fluoretado e os alimentos, bebidas, fórmulas e suplementos infantis. Considerando-se que a fluorose dentária tem aumentado em todas as regiões é importante avaliar, além da água e do dentifrício, também a contribuição diária do consumo alimentar das crianças e a concentração de flúor nesses itens alimentares para a ingestão de flúor. Objetivo - Descrever o consumo alimentar de crianças de 2 a 6 anos, com relação ao flúor. Métodos - Foram avaliadas 379 crianças, de 2 a 6 anos, faixa etária de risco para fluorose, residentes em Bauru - São Paulo, município com fluoretação artificial da água de abastecimento público. A amostragem foi estratificada por setor, baseando-se no Plano Diretor do Município. O consumo alimentar foi avaliado pelo Questionário de Freqüência Alimentar Semiquantitativo, aplicado aos pais ou responsáveis, e a concentração de flúor nos itens alimentares a partir de análises laboratoriais. As crianças foram classificadas quanto à ingestão diária de f1úor de acordo com a Dietary Reference Intakes. Resultados - Dentre os 70 itens alimentares, o arroz, a água de abastecimento público e o leite foram os mais consumidos; o chá preto, o leite em pó de soja diluído com água de abastecimento público e o biscoito Danyt\'s® apresentaram maior concentração de flúor; a água de abastecimento público, o refrigerante Coca-Cola® e a batata frita representaram maior contribuição diária para ingestão de flúor. Os itens alimentares mais consumidos apresentaram, em média (±DP), concentração de flúor (0,015 ± 0,028 mgF/porção) significantemente menor (p = 0,03) que os menos consumidos (0,107 ± 0,162 mgF/porção). Os itens alimentares com maior concentração de flúor contribuíram significantemente (p < 0,001) para a ingestão do halogênio (0,018 ± 0,037 mgF/dia). A média da ingestão de flúor por meio dos alimentos sólidos e líquidos, da água e da escovação foi de 0,017 ± 0,016; 0,011 ± 0,004 e 0,036 ± 0,028 mgF/kg peso/dia, respectivamente, totalizando 0,064 ± 0,035 mgF/kg peso/dia. Das 379 crianças, 31,2% apresentaram risco de fluorose. O dentifrício e os itens alimentares (sólidos, água e outros líquidos) contribuíram com 57% e 43%, respectivamente, para a ingestão de flúor. Conclusão - O dentifrício foi a principal fonte para a ingestão de f1úor pelas crianças, porém, a concentração desse halogênio nos itens alimentares contribuiu significantemente para a ingestão, representando risco para f1uorose dentária. / The quantity of fluoride ingested, deriving from all sources, during the critical period of formation of the teeth, is the main factor of risk for the dental fluorosis. Among this sources, we have the fluoridated water, the fluoridated dentifrice and the food, drinks, chemical formula and the infant supplements. Taking into consideration that the dental fluorosis has increased in all regions, it is important to evaluate it, besides the water and the dentifrice, the daily contribution of children\'s food consumption and the concentration of fluoride in these food items for the ingestion of fluoride. Objective - Describe the food consumption of children from 2 to 6 years old, relationg to fluoride. Methods - 379 children were evaluated at risking ages for fluorosis, residents in Bauru - São Paulo, district with artificial f1uoridation. The sampling was stratified by sector, based on the Director\'s Plan of the District. The food intake was evaluated by the Food Frequency Semiquantitative Questionnaire, applied on parents or responsable one, and the concentration of fluoride on the food items from analyses in laboraties. The children were classified based on theis daily ingestion of fluoride according to the Dietary Reference Intakes. Results - Among the 70 food items, rice, public water supply and the milk were the most consumed ones; the black tea, the soybean powdered milk diluted in public water and the biscuit Danyt\'s® presented the gratest daily contribution for the ingestion of fluoride. The most consumed food items present, in average (± DP), concentration of fluoride (0,015 ± 0,028 mg F / portion), significantly lower (p = 0,03) that the less consumed (0,107 ± 0,162 mgF/portion). The food items with the greatest concentration of fluoride contributed significantly (p < 0,001) for the ingestion of the mineral (0,018 ± 0,037 mgF/day). The average amount of fluoride ingestion taken from the solid food and the liquid ones (except water) coming from the water and the teeth brushing was 0,017 ± 0,016; 0,011 ± 0,004 and 0,036 ± 0,028 mgF/kg weight/day, respectively, totalizing 0,064 ± 0,035 mgF/kg weight/dia. 31,2% of the 379 children presented risk of fluorosis. The dentifrice and the food items (solid, water and other liquids) contributed with 57% and 43%, respectively, for the ingestion of fluoride. Conclusion - The dentifrice was the main source for the ingestion of fluoride, by the children, however, the concentration of this mineral in food items contributed significantly for the ingestion by the children, representing risk for dental fluorosis.

L’objectif ici était de développer une méthode de détection des tumeurs cérébrales via des agents de contraste pour l’IRM du 19F à 7 teslas. Nous évaluons en particulier le potentiel de cette méthode à mettre en évidence l’angiogenèse tumorale à l’aide d’agents de contraste fonctionnalisés avec le peptide RGD et ciblant l’intégrine ανβ3, biomarqueur surexprimé à la surface des néo-vaisseaux irriguant la tumeur. Du fait des basses concentrations locales en agent de contraste, les efforts portent dans un premier temps sur l’optimisation d’une séquence multi échos de spin dédiée à l’imagerie du PFOB (perfluorooctyl bromure), perfluorocarbure biocompatible choisi pour constituer la base de nos agents de contraste. Nous montrons qu’un paramétrage minutieux de cette séquence permet la suppression de la J-modulation et un rehaussement du T2, conduisant à une excellente sensibilité in vitro. La séquence est ensuite testée pour des mesures d’oxygénation dans le foie et la rate chez la souris, après injection d’une émulsion de PFOB. Les résultats indiquent une très bonne précision des mesures après injection d’une seule dose d’émulsion. Notre séquence est également utilisée pour réaliser une étude de biodistribution dynamique, permettant de suivre l’accumulation des nanoparticules d’émulsion dans le foie et la rate juste après injection. Nous montrons par ailleurs qu’il est possible d’évaluer la furtivité d’émulsions contenant différentes quantités de PEG (Poly Ethylène Glycol) en ajustant les données expérimentales sur un modèle pharmacocinétique empirique. La séquence est enfin utilisée pour détecter des nanoparticules d’émulsions fonctionnalisées pour cibler l’intégrine ανβ3 dans un modèle souris U87 de glioblastome. Nous comparons les concentrations en agent de contraste obtenues dans la tumeur avec une émulsion contenant le peptide RGD, et une émulsion contrôle. Les résultats indiquent des concentrations significativement plus élevées avec l’émulsion RGD qu’avec l’émulsion contrôle, supposant un ciblage spécifique d’ανβ3 par les nanoparticules fonctionnalisées. Un dernier chapitre est dédié à une nouvelle méthode de spectroscopie de diffusion en 19F, dont le but est d’éliminer le signal vasculaire provenant des nanoparticules de PFOB circulantes afin d’évaluer le signal ne provenant que des particules liées. / This study aimed at developing a method for detection of brain tumors at 7 teslas thanks to 19F MRI contrast agents. We particularly assessed the potential of this method to highlight tumor angiogenesis with RGD-functionalized contrast agents targeting ανβ3 integrin, a biomarker over-expressed at the surface of new capillary blood vessels. Owing to low local concentrations in contrast agent, the first step consisted in optimizing a multi spin echo sequence dedicated to a well-known biocompatible perfluorocarbon, perfluorooctylbromide (PFOB). We show that careful adjustment of sequence parameters allows cancellation of J-modulation and T2 enhancement, and yields an excellent sensitivity in vitro. Our sequence was then tested for oxygenation measurements in the mouse liver and spleen after injection of a PFOB emulsion. The results demonstrate very good accuracy of the measurements after one single infusion of emulsion. We also perform a dynamic biodistribution study in order to monitor emulsion nanoparticle uptake in the liver and spleen. Moreover, we show that stealth of emulsions grafted with different quantities of polyethylene glycol (PEG) can be assessed by fitting experimental data with a pharmacokinetic empirical model. Our sequence was finally used to visualize ανβ3-targeted nanoparticles in a U87 glioblastoma mouse model. Concentrations found in tumors after injection of an RGD-functionalized emulsion and a control emulsion are compared. Concentrations are found to be significantly higher with the RGD emulsion than with the control emulsion, suggesting specific binding of functionalized nanoparticles with ανβ3 integrin. The last part is dedicated to a new diffusion-weighted 19F NMR spectroscopy sequence. This method aims at suppressing vascular signal coming from circulating PFOB nanoparticles in order to evaluate signal coming from bound nanoparticles only.

Les travaux décrits dans ce manuscrit utilisent les principes de la tectonique moléculaire pour générer des polymères de coordination hautement fluorés et /ou chiraux pour une application potentielle en séparation chirale. La synthèse de 13 porphyrines de type A2B2 substituées en position méso par deux pyridines et par deux chaines fluorées et/ou alkyles a été mise au point. Des réseaux de coordination ont été obtenus en présence de Zn(II) et de Cd(II) et caractérisés par diffraction des RX sur monocristal (DRX). Une analyse systématique des interactions supramoléculaires et notamment de interactions F---F présentes à l’état solide a été conduite. Des réseaux à base de liaisons halogènes ont également été obtenus en présence de di- et tri-iodoarènes et caractérisés par DRX.Le premier chapitre est une introduction générale sur la tectonique moléculaire, le deuxième chapitre décrit les voies des synthèses utilisées pour générer les ligands chiraux et fluorés et leur caractérisation à l’état solide. Le troisième chapitre présente la structure des réseaux mono, bi, et tridimensionnels formés en présence de Zn(II) ou de Cd(II), l’analyse structurale met en évidence un nombre croissant d’interaction F---F en fonction du nombre de fluors présents à la périphérie du macrocycle porphyrinique. Le dernier chapitre se concentre sur l’utilisation des liaisons halogènes de type N---I impliquant des porphyrines ou des tectons de type bipyridine et une série d’ iodofluoroarenes. / This manuscript focuses on the use of molecular tectonics to generate chiral and / or fluorinated coordination polymers based on porphyrin building blocks for potential application in chiral separation. Synthesis of novel A2B2 fluorinated porphyrin tectons is described and their combinations with metal ions and haloarenes molecules are characterized by X-Ray diffraction.The first chapter gives a general introduction on molecular tectonics; the second chapter focuses on the synthetic routes used for the synthesis of highly fluorinated and/or chiral porphyrins and their solid state characterization by X-Ray diffraction analysis, highlighting the importance of the number of fluorine atoms present at the periphery of the tecton on the crystal packing. The third chapter presents the mono-, bi- and three dimensional networks formed by a combination of the porphyrins with Zn(II) or Cd(II). In the solid state, short F---F contacts were observed depending on the number of fluorine atoms present on the porphyrin backbone. The last chapter focuses on the use of halogen bonds, by merging the neutral porphyrin or bipyridine tectons with a series of iodofluoroarenes. The crystalline materials described in this work can be used as potential candidates for the separation of chiral and fluorinated molecules.