Conselho Nacional de Desenvolvimento Científico e Tecnológico / Epidemiological studies have suggested that intake of fruits and vegetables act in the prevention of several diseases such as cancer and cardiovascular diseases. This can be explained by these bioactive compounds are present in their food nutritional matrix that may have different biological activities, including antioxidant, antitumor, genoprotective and in preventing the oxidation of LDL. However, much of the fruit remains to be studied. This is the case of Solanum sessiliflorum popularly known as mana-cubiu or cubíu fruit coming from the Amazon region of Brazil, considered the "Amazonian apple". This fruit is popularly used as a medicine to control the itching of the skin and reducing cholesterol levels, glucose and uric acid in the blood. Once S. sessiliflorum studies are still incomplete, the aim of this study was to chemically characterize the extract and perform tests to determine their prospecting potential antioxidant, antitumoral and effect in vitro on preventing the oxidation of LDL. For this, the study was conducted in two stages, the first stage was prepared hydroalcoholic extract of the peel and seed and pulp. After preparation of the extract, the chemical characterization was conducted by the same determination of total bioactive compounds (flavonoids, tannins and polyphenols), then the extract was chemically characterized by high performance liquid chromatography (HPLC). In the second step, we evaluated the antioxidant potential and in citoprotetor in and in PBMC (Peripheral Blood Mononuclear Cells) and human plasma exposed to hydrogen peroxide (H2O2). We also evaluated the antitumor activity in lines of breast (MCF7) and colorectal (HT29) cancer cell cancer, assessing cell proliferation and viability. After this, the effect has been evalueted on the oxidation of LDL (isolated from healthy individuals). The results obtained indicate that the extract of Solanum sessiliflorum presents in its composition total bioactive compounds such as flavonoids, tannins and polyphenols. These results corroborate the analysis performed by HPLC which indicated that the extracts present in its composition gallic acid, caffeic acid, quercetin, rutin, β carotene and catechin (the latter except in the pulp and seed extract). When examined the in vitro antioxidant effect was observed that extracts at different concentrations did not show any pro-oxidant potential. However extract the pulp and the seeds had antioxidant and cytoprotective activity. It was also observed that the extract of the pulp and the seeds had antigenotoxic and specific antitumor activity for colorectal cancer cells (in vitro tests performed with strain HT29 cells), and no antitumor activity was observed for breast cancer cells (MCF7), instead of the expected high concentrations in the extract increased the viability and proliferation. Another important finding was that both extracts, seeds and pulp and peel showed potential for inhibiting oxidation of LDL. In synthesis, the in vitro results obtained data indicate that S. sessiliflorum has antioxidant, antitumor and citoprotetor activity and present potential to inhibit the oxidation of LDL. These results should be proof of the presence of bioactive compounds in its composition as flavonoids, polyphenols and catechins. In literature there are several studies that report that eating foods rich in these types of compounds are related to the prevention of several chronic diseases, such as cancer and cardiovascular diseases. / Estudos epidemiológicos têm sugerido que a ingestão de frutas e verduras atuam na prevenção de diversas patologias, tais como o câncer e doenças cardiovasculares. Isto pode ser explicado por estes alimentos apresentarem compostos bioativos na sua matriz nutricional que podem ter diversas atividades biológicas, incluindo atividade antioxidante, antitumoral, genoprotetor e na prevenção da oxidação do LDL. Entretanto, uma grande parte dos frutos ainda precisa ser estudada. Este é o caso do Solanum sessiliflorum popularmente conhecido como mana-cubiu ou cubíu fruto oriundo da região amazônica do Brasil, considerado a maçã amazônica que é popularmente utilizado como medicamento no controle do prurido da pele e na redução dos níveis de colesterol, glicose e ácido úrico no sangue. Uma vez que estudos sobre o S. sessiliflorum são ainda incipientes, o objetivo deste estudo foi caracterizar quimicamente o extrato de S. sessiliflorum e realizar ensaios de prospecção para determinar seu potencial efeito antioxidante, antitumoral e na prevenção da oxidação do colesterol LDL através de ensaios in vitro. Para isto, o estudo foi conduzido em duas etapas, na primeira etapa foram preparados dois extratos hidroalcóolicos 1) da casca e 2) da semente e polpa do S. sessiliflorum. Após preparo do extrato, foi conduzida a caracterização química do mesmo através da determinação de compostos bioativos totais (flavonoides, taninos e polifenóis), em seguida, o extrato foi caracterizado quimicamente por cromatografia líquida de alta eficiência (CLAE). Na segunda etapa, foi avaliado o potencial antioxidante e citoprotetor em plasma humano exposto ao peróxido de hidrogênio (H2O2) e também em PBMCs (Peripheral Blood Mononuclear Cells). Também foi verificada a atividade antitumoral em linhagens de célula de câncer de mama (MCF7) e de câncer de colorretal (HT29), avaliando a proliferação e a viabilidade celular. Após, foi avaliado o efeito na oxidação do LDL (isolado de indivíduos saudáveis). Os resultados obtidos indicam que o extrato de Solanum sessiliflorum apresenta em sua composição compostos bioativos totais como os flavonóides, taninos e polifenóis. Estes resultados corroboram com as análises realizadas por CLAE que indicaram que os extratos apresentam em sua composição ácido gálico, ácido caféico, quercetina, rutina, β-caroteno e catequina (este último exceto no extrato de polpa e semente). Quando analisado o efeito antioxidante in vitro foi observado que os extratos nas concentrações testadas não apresentaram potencial pró-oxidante. No entanto o extrato da polpa e da semente apresentou atividade antioxidante e citoprotetora. Também foi observado que o extrato da polpa e da semente apresentou atividade antigenotóxica e antitumoral específica para células de câncer de colorretal (teste in vitro realizado com linhagem de células HT29), e não foi observado atividade antitumoral em relação à linhagem de células de câncer de mama (MCF7), pelo contrário do esperado, em altas concentrações o extrato aumentou a viabilidade e a proliferação celular. Outro importante achado foi que ambos os extratos, semente e polpa e casca apresentaram potencial de inibição da oxidação do LDL. Em síntese, os dados obtidos nos experimentos in vitro indicam que o S. sessiliflorum apresenta atividade antioxidante, antitumoral, antigenotóxica e potencial de inibir a oxidação do LDL. Estes resultados devem-se a presença de compostos bioativos em sua composição como flavonóides, polifenóis e catequina. Na literatura há diversos estudos que relatam que a ingestão de alimentos ricos nestes tipos de compostos está relacionada à prevenção de diversas doenças crônicas, como o câncer e doenças cardiovasculares.

As estruturas metal-óxido-semicondutor (MOS) são o coração dos transistores de efeito de campo. O estudo e caracterização físico-química desses dispositivos foram a chave para o avanço da tecnologia do Si na indústria microeletrônica. Hoje, a ciência busca novos materiais para a produção de dispositivos de alta mobilidade. Um dos materiais visados é o Ge, pois apresenta mobilidade de cargas superior ao Si (duas vezes para elétrons e quatro vezes para lacunas). Porém, a interface Ge/GeO2 é de natureza reativa, limitando seu uso na construção de tais dispositivos. Muitos esforços têm sido feitos para superar as limitações. Entre eles, encontram-se a passivação da superfície do Ge a partir de solução aquosa de (NH4)2S, previamente a deposição do dielétrico. Outra etapa do processamento desse material na indústria a ser investigada são os tratamentos térmicos posteriores à deposição: a caracterização de estruturas MOS de Pt/HfO2/Ge submetidas a tratamentos térmicos levaram a melhoria das propriedades elétricas. Nesse sentido, o trabalho tem como objetivos investigar o papel da passivação sulfídrica em estruturas dielétrico/Ge e a influência do eletrodo de Pt nas estruturas Pt/HfO2/Ge quando submetidas a tratamentos térmicos. / The heart of field effect transistors is the metal-oxide-semiconductor (MOS) structure. Physico-chemical characterization of the materials employed in such structures enabled the development of Si technology. Nowadays, in order to build high mobility devices, new material are needed. Ge is an alternative material, since its carrier mobilities are higher than those of Si (almost two times for electrons and four times higher for holes). However, the GeO2/Ge interface is not thermally stable, which is a problem for its use on electronic devices. Many attempts to enhance this stability were already investigated. Among them, sulfur passivation of the Ge surface was employed using (NH4)2S aqueous solution prior to the deposition of dielectric layers. Another important step in the fabrication of MOS structures is post-deposition annealing. Pt/HfO2/Ge MOS structures presented improved electrical characteristics following post deposition annealing. The main objectives of this work are to investigate the role of sulfur passivation on dielectric/Ge structures and the influence of Pt electrode in Pt/HfO2/Ge structures submitted to post deposition annealing.

Dans le cadre d’une Convention CIFRE, la thèse est financée par la société Renault, ce travail vise à développer un supercondensateur carbone-carbone dont le coût de fabrication est compatible avec le marché automobile ; c’est en effet leur coût élevé qui constitue encore à l’heure actuelle un frein à leur développement. Dans une première partie de ce travail, il a été montré que l’essentiel du coût repose en grande partie sur la purification de l’électrolyte utilisé mais surtout du carbone activé, qui est le matériau actif d’électrode. Notre travail s’est donc focalisé sur l’étude du vieillissement électrochimique de cellules de supercondensateurs de laboratoire assemblées avec différents carbones, afin d’essayer d’identifier les phénomènes responsables du vieillissement. Un autre objectif a été d’identifier les caractéristiques que doivent présenter les carbones alternatifs candidats au remplacement des carbones commerciaux. L’étude réalisée dans ce travail de thèse a permis de définir deux modes de vieillissement différents suivants les carbones utilisés. Un premier type de vieillissement entraîne l’augmentation conjointe de la résistance série équivalente et de la capacité, dû à une dégradation/oxydation du carbone à l’électrode positive. Un second mode de vieilissement mène à l’augmentation seule de la résistance série équivalente par la formation d’une couche d’interface solide conductrice ionique. Quelque soit le mode vieillissement, aucune corrélation directe n’a pu être établie avec les fonctions de surface des carbones activés. La piste la plus probable repose sur le taux et la nature des impuretés présentes dans le carbone activé, certaines étant électroactives, voire pouvant jouer un rôle catalytique. / In the context of a CIFRE Convention, the thesis is financed by Renault s.a.s., this work aims at developing a carbon-carbon supercapacitor whose manufacturing cost is compatible with the automotive market, which still hinders their development. In a first part of this work, it has been shown that the cost mainly depends on the purity of the materials used: electrolyte but also activated carbon, the electrode active material. Our work has therefore been focused on the study of the electrochemical aging of laboratory supercapacitor cells assembled with different carbons, to identify their ageing mechanisms and to define the key features alternative carbons must achieve to replace commercial carbons. This work has evidenced two different modes of aging, depending on the carbon used. A first ageing mode results in the joint increase of the equivalent series resistance as well as the capacity, due to a degradation / oxidation of the carbon at the positive electrode. A second mode leads to the sole increase in equivalent series resistance by the formation of an ionic conductive solid interface layer. Whatever the aging mode, no clear influence of the surface functions of activated carbons could be evidenced. The most likely assumption is based on the content and the nature of the impurities present in the activated carbon, some of which are electroactive and can even play a catalytic role.

At present, the extraction of biochar and its use is a much-discussed topic in the chemical and research fields. The use of biochar is very often declined in the areas of agriculture, waste management, environmental improvement and the fight against global warming. In addition to these sectors, the topic of biochar is also addressed in the production of bio-diesel and bio-oil. Due to the current use of secondary products during biotechnological processes, the presented theoretical and practical study focused on the issue of obtaining biochar from bran by pyrolysis at different temperatures. Part of the practical part was the extraction of biochar from bran and its subsequent analysis, which could be used to characterize biochar obtained from bran by pyrolysis physically and chemically. The characterization of bran biochar was solved by various analytical methods. These techniques yielded, for example, pH, conductivity, particle distribution, elemental composition of biochar, porosity and content of polycyclic aromatic hydrocarbons. Thanks to this study, the properties of biochar and its possible applications in everyday life were characterized in detail. Given the very promising use of biochar obtained from bran, it can be said that this will be a very desirable topic for the future.

Une enquête ethnobotanique a été menée en Bosomtwi et Sekyere Est Districts de la Région Ashanti, au Ghana, en utilisant des questionnaires validés pour identifier les plantes traditionnellement utilisées pour gérer le paludisme. Cinq plantes avec une utilisation élevée ont été sélectionnés et une extraction préliminaire des matières végétales sélectionnées effectuées avec de l'eau, le methanol, l'acétate d'éthyle et d'éther de pétrole. Les extraits ont été dosés pour l'activité antiplasmodiale utilisant les méthodes antiplasmodiales in vitro. Les deux les plus prometteuses plantes, Phyllanthus fraternus (Phyllanthaceae) et Bambusa vulgaris (Pocea) ont été choisis pour l'isolement bio-guidée de constituants bioactifs en utilisant des méthodes chromatographiques (par exemple TLC, flash chromatographie, HPLC semi-préparative). Élucidation de la structure des composés isolés ont été effectuées en utilisant des méthodes spectroscopiques (par exemple 1D et 2D Magnétique Nucléaires Résonance (MNR), infrarouge et spectrométrie de masse et leur activité antiplasmodiale étudiés. / An ethnobotanical survey was conducted in Bosomtwi and Sekyere East Districts of the Ashanti Region, Ghana, using validated questionnaires to identify plants used traditionally to manage malaria. Five plants with high usage were selected and a preliminary extraction of the selected plant materials done using water, methanol, ethyl acetate and petroleum ether. The extracts were assayed for antiplasmodial activity using in vitro antiplasmodial methods. The two most promising plants, Phyllanthus fraternus (Phyllanthaceae) and Bambusa vulgaris (Pocea) were selected for bio-guided isolation of bioactive constituents using chromatographic methods (e.g. TLC, flash chromatography, semi-preparative HPLC). Structural elucidation of the isolated compounds were done using spectroscopic methods (e.g. 1D and 2D Nuclear Magnetic Resonance, Infrared and mass spectrometry) and their antiplasmodial activity studied.

Cette étude a pour objectif d'apporter des éléments de réponse à la compréhension de la nature et de l'origine des effets biologiques des nanoparticules (NP) de boehmite en réalisant des tests de contacts in vitro sur des macrophages de culture (RAW 264.7), les macrophages étant la cible cellulaire privilégiée au niveau du tractus respiratoire. Différents domaines de la réponse cellulaire en relation avec les propriétés physico-chimiques des particules ont été étudiés. Dans une première partie l’activité biologique a été mesurée sur des NP de boehmite puis après broyage ou dispersion permettant d’observer en particulier l’influence de la taille des particules dans la réponse cellulaire.Les résultats soulignent que les particules industrielles de boehmite sont principalement caractérisées par une activité modérée au niveau de la réponse inflammatoire, mais sans effet cytotoxique ou sans stress oxydant significatif. Des différences en fonction de la taille des particules ont été observées sur les paramètres inflammatoire et cytotoxique.Toutefois, les mesures des biomolécules libérées dans les surnageants de culture cellulaire peuvent être biaisées par l’adsorption de ces biomolécules sur les NP en présence. Ainsi, ce mécanisme d'adsorption doit être pleinement compris pour éviter une interprétation erronée des données obtenues. Dans un second temps l’objectif a donc été d’élaborer une méthodologie afin d’évaluer les interactions organo-minérales en terme d’affinité et de quantité de biomolécules adsorbées sur les nanoparticules à l’équilibre thermodynamique et de déterminer une loi de correction. Dans ce contexte nous nous sommes intéressés en particulier au TNF-α. / This study aimed at a better understanding of the biological effects of boehmite nanoparticles by carrying out in vitro tests using a macrophage-like cell line (RAW 264.7), as macrophages represent the first target cells in the respiratory tract. Different cellular responses: inflammation (evaluated by the release of TNF-α), cell death (assessed by the release of LDH), and oxidative stress (production of ROS) were studied in relation to physico-chemical properties of the particles. In the first part of this work, the biological activity was measured using boehmite nanoparticles obtained either from industrial environment or by hydrothermal synthesis, and after grinding or dispersion that enabled us to observe the influence of particle size on the cellular response.The results point out that industrial boehmite particles are mainly characterized by a moderate pro-inflammatory activity, no cytotoxic effect and no significant oxidative stress. Differences depending on the size of the particles were observed on the inflammatory and cytotoxic parameters.However, the assessment of biomolecules released into cell culture supernatants may be biased by the adsorption of biomolecules on the nanoparticles. Thus, the adsorption mechanism must be fully understood to avoid misinterpretation of the results. Therefore, the second aims of this work were to develop a methodology to assess the organo-mineral interactions in terms of affinity and quantity of biomolecules adsorbed on the nanoparticles at the thermodynamic equilibrium and to determine a correction law. We focused more specifically our study on TNF-α.

Afin de contribuer à la préservation du patrimoine laitier libanais, l'objectif principal de cette étude a été de caractériser le fromage Darfiyeh, une variété traditionnelle fabriquée à partir de lait de chèvre cru et affinée dans une outre en peau de chèvre. Parallèlement à cet objectif, et pour mieux comprendre l'affinage du Darfiyeh, le transfert de composés d’arôme à travers la peau de chèvre a été étudié au moyen d’un dispositif expérimental original. Trois lots indépendants de production de Darfiyeh ont été analysés après 20, 40 et 60 jours d'affinage. Les résultats des analyses physico-chimiques ont montré que le Darfiyeh est un fromage à pâte mi-dure, caractérisé par une protéolyse et une lipolyse modérées. Le 3-méthyl butanal, le 1-phényl éthanol et le 1-octanol contribuent à la fraction aromatique particulière du Darfiyeh. Les analyses microbiologiques ont mis en évidence (Log cfu.g-1 fromage) des lactobacilles mésophiles (7,1-10,4), des bactéries lactiques (BL) thermophiles cocciformes (6,6-8,4) et des lactobacilles thermophiles (5,5-7,2). Afin d'explorer l'écosystème naturel du Darfiyeh, une combinaison d'approches classiques et moléculaires a été appliquée. L'identification classique a révélé des espèces appartenant aux genres Streptococcus, Enterococcus, Lactococcus et Lactobacillus. Les profils de Temporal Temperature Gel Electrophoresis (TTGE) ont révélé des bandes communes avec l'identification classique. Des analyses menées par PCR spécifiques de l'espèce bactérienne ont confirmé la présence of S. thermophilus, E. faecium, E. durans, Lc. lactis subsp. lactis et Lc. lactis subsp. cremoris. La PCR en temps réel a permis la quantification de S. thermophilus et d' E. faecium, avec un seuil de détection respectif de 104 ufc.g-1 de Darfiyeh et une gamme de 107-109 ufc.g-1 de Darfiyeh, respectivement. Pour le transfert d'arômes à travers la peau de chèvre, l'absorption et la perméabilité de trois molécules aromatiques modèles (2-butanone, 2,3-butanedione, 2-butanol) dans un système solution aqueuse/peau de chèvre a été suivi, après 20, 40 et 60 jours d'exposition. Jusqu'à 40 j d'exposition, le transfert des molécules aromatiques était régi par leurs propriétés physico-chimiques et par le temps d'exposition. Après 60 j, le système solution aqueuse/peau s’est traduit par une tendance à la migration des molécules modèles depuis la peau vers la solution simulée de Darfiyeh. Autrement dit, le transfert de ces molécules modèles dans le système simulé paraît s’établir de façon cyclique. Ce travail est une première contribution scientifique et technique au secteur de la valorisation durable de la tradition fromagère libanaise / In order to contribute for the preservation of the Lebanese dairy heritage, the aim of this study was to characterize Darfiyeh cheese, a traditional variety made from raw goats' milk and ripened in goat's skin. Parallel to this objective, and for a better understanding of Darfiyeh ripening, aroma transfer towards goat skin was conducted through an experimental device. Three independent batches of Darfiyeh production were analyzed after 20, 40 and 60 days of ripening. Physico-chemical results showed that Darfiyeh is a semi-hard goat's milk cheese which undergoes a moderate proteolysis and lipolysis. 3-methyl butanal, 1-phenyl ethanol and 1-octanol contribute to the distinctive aromatic fraction of Darfiyeh. As for microbiological results, bacterial counts (Log cfu.g-1 cheese) for mesophilic lactobacilli (7.1-10.4), thermophilic coccal-shaped lactic acid bacteria (LAB) (6.6-8.4) and thermophilic lactobacilli (5.5-7.2) were found. In order to explore Darfiyeh natural ecosystem, a combination of classical and molecular approaches was applied. Classical identification revealed members of the genera Streptococcus, Enterococcus, Lactococcus and Lactobacillus. Temporal Temperature Gel Electrophoresis (TTGE) profiles revealed common bands between the classical identification. Species-specific polymerase chain reactions (PCR) confirmed the presence of S. thermophilus, E. faecium, E. durans, Lc. lactis subsp. lactis and Lc. lactis subsp. cremoris. Real time PCR enabled quantification of S. thermophilus and E. faecium, with a detection threshold of 104 ufc.g-1 of Darfiyeh and a range of 107-109 ufc.g-1 of Darfiyeh, respectively. As for aroma transfer towards goat skin, absorption and permeability of three model aroma molecules (2-butanone, 2,3-butanedione, 2-butanol) in aqueous solution/goat skin system were followed, after 20, 40 and 60 days of exposure. Until 40 days, the transfer of aroma molecules was dependent on their physico-chemical properties and exposure time. After 60 days, the molecules migrate from the skin to the aqueous solution. Therefore, in such a simulated system, aromatic molecules seem to move under a cyclic way. This work is a first scientific and technical contribution to the preservation of traditional Lebanese cheesemaking

La thérapie génique est une forme de médecine moléculaire qui a des potentialités majeures dans le traitement d'un grand nombre de maladies héréditaires ou de cancers. Les acides nucléiques doivent pénétrer à l'intérieur des cellules et interagir avec la machinerie génétique présente. Une des plus grandes limitations dans l'application de ce type de traitement est le développement d'un vecteur sûr et efficace pour transporter ces molécules dans les cellules. Les vecteurs sont classifiés traditionnellement en deux grandes catégories : viral et non-viral. Les vecteurs de type viral sont les plus efficaces et utilisés dans la majorité des tests cliniques, cependant ils peuvent provoquer une forte réponse immunitaire et ils ont des coûts importants de production. Les vecteurs de type non viral peuvent être fabriqués facilement en grande quantité, ne sont pas immunogéniques et possèdent l'avantage de pouvoir être modulés en fonction des applications. Les lipides et les polymères cationiques sont les plus étudiés à cause de leurs propriétés de complexation avec les acides nucléiques. Cependant ces complexes chargés positivement peuvent être toxiques à cause de leur interaction non spécifique avec les membranes cellulaires, ce qui limite leur utilisation in vivo. Cela a conduit à la recherche de nouveaux vecteurs, neutres ou anioniques, pour diminuer les problèmes de cytotoxicité. Les nucléolipides (NL) sont des molécules hybrides bioinspirées amphiphiles formées d’une partie hydrophile nucléotidique et d’une partie hydrophobe lipidique. Ces molécules sont donc capables de s'autoassembler et de former des structures supramoléculaires avec des propriétés physico-chimiques principalement liées à la nature chimique de la tête polaire nucléotidique. L'interaction avec des acides nucléiques est alors possible grâce à des interactions de type Watson-Crick, cependant elles ne sont pas suffisamment élevées pour former un complexe stable pour être utilisées dans les conditions biologiques. La synthèse d’une nouvelle famille de molécules hybrides de type amino-nucléo-lipides (ANL) a été développée dans l'objectif d'améliorer les interactions et donc la complexation grâce à la présence d'un acide aminé sur la partie polaire de l’amphiphile. La synthèse chimique des ANLs avec différents acides aminés (glycine, phénylalanine) en position 5' du sucre et différentes lipides (dimiristoyl, dioleoyl) estérifié au phosphate présent en position 3' a été réalisée. Les études physico-chimiques réalisées par diffusion dynamique de la lumière (DLS), cryo-microscopie électronique (cryo-TEM) et diffusion des rayons X aux petits angles (SAXS) ont permis d'étudier la morphologie et l'organisation structurale des objets supramoléculaires formés par ces molécules. Ces études ont en particulier permis de mettre en évidence la relation entre la structure chimique et les propriétés physico-chimiques. Les NLs forment des vésicules unilamellaires et les ANLs, grâce à la présence de l'acide aminé sur la tête polaire, forment des vésicules de type multilamellaire. L'étude des interactions, réalisée par calorimétrie à titration isotherme (ITC), entre les vésicules et un acide nucléique modèle (poly A) montre qu'il existe une interaction entre les deux partenaires, mais que cette interaction n'est pas suffisamment forte pour envisager des applications biologiques. La stratégie d'utiliser un cation divalent, comme le calcium, pour ponter les charges négatives des nucléolipides et les charges négatives des acides nucléiques a été envisagé et les complexes ont été étudiés par SAXS. Enfin, des transitions de morphologies observées en fonction de la concentration ont été étudiées par DLS et cryo-TEM. Ces transitions de morphologies ont pu être corrélées à des effets de force ionique sur les propriétés de la tête polaire. / Gene therapy is a molecular medicine and a very powerful tool for the treatment of several diseases such as inherited disorder and cancer. Nucleic acids must penetrate into cells in order to interact with their genetic material. Currently the main limitation to the application of this treatment towards clinics is the lack of robust, safe and efficient gene delivery vectors. The two major classes of vectors are those based on recombinant viruses and those based on non-viral systems. Viral vectors are the most efficient and used in several clinical trials, however they can elicit a strong immune reaction and they possess high cost of production. Non-viral vectors are less immunogenic and can be easily produced on a large scale. A large variety of both cationic lipids and polymers have been developed due to their ability to interact spontaneously with negatively charged nucleic acids to form complexes. However these positively charged complexes can present some toxicity due their non-specific interaction with cell membranes and seric proteins. This is the main limitation for their clinical use. For this purpose, new vectors, neutral or anionic, have to be developed in order to diminish the cytotoxicity and increase the circulation time. Nucleotide-lipids (NLs) are bio-inspired amphiphilic hybrid molecules composed of a hydrophilic nucleotidic moiety and a hydrophobic lipophilic moiety. These molecules are able to self-assembly to form supramolecular structures which possess particular physico-chemical properties due to the chemistry of their polar head. These molecules can interact with a nucleic acid by Watson-Crick base pair interactions, however they are not sufficiently strong to form a stable complex that can be used for a biological application. A new chemical family of hybrid amphiphile, amino acid-nucleotide-lipids (ANLs), has been developed in order to increase the interactions and the stability of the complex thank to the presence of the amino acid on the polar head. Herein, we have synthesized novel amino acid-nucleotide-lipids, presenting phenylalanine (or glycine) and thymidine residues and saturated (dimiristoyl) or unsaturated (dioleoyl) diacyl glycerol lipid. The morphology and the structural organization of the supramolecular objects formed by these molecules was studied by dynamic light scattering (DLS), cryo-electron microscopy (cryo-TEM) and small angle X-ray scattering (SAXS). These studies allowed investigating the relation between the chemical structure and the physic-chemical properties. The amino acids, inserted at the 5′ position of the nucleotide-lipids, stabilize multilamellar systems, whereas unilamellar vesicles are formed preferentially in the case of nucleotide-lipids. Both NLs and ANLs exhibit weak interactions with complementary polyA RNA as revealed by isothermal titration calorimetry (ITC) investigations, however they are not sufficiently strong to form a stable complex that can be used for a biological application. The use of multivalent cations, such as Ca2+, which bridge the phosphate groups on the lipid polar heads with those of the backbone of nucleic acids, to form ternary complexes, has been investigated by SAXS. Finally, a structural study, by DLS and cryo-TEM of NLs aggregates in aqueous solutions as a function of ionic strength and surfactant concentration, has been conducted in order to investigate the different morphologies of the systems.

A exposição a fontes naturais de radiação contribui com mais de 98% da dose de radiação normalmente recebida da população; esta dose é principalmente atribuída à incorporação de radionuclídeos naturais das séries de decaimento do 238U e 232Th que possuem meia-vidas relativamente longas. A qualidade da água para consumo humano deve ser constantemente analisada e, um parâmetro muito importante analisado é a radioatividade natural presente. Quando os radionuclídeos naturais estão presentes em águas minerais há uma maior preocupação, pois estas águas podem conter concentrações moderadamente elevadas de 226Ra, 228Ra e 222Rn originalmente dissolvidas e dos radionuclídeos 210Pb e 210Po, que embora apresentem menores concentrações, contribuem para um aumento da irradiação interna e externa dos indivíduos. As áreas de estudo do presente trabalho foram os Parques das Águas de Cambuquira e Marimbeiro e de uma fonte particular de uma fazenda localizados na cidade de Cambuquira, Minas Gerais, onde as águas minerais são frequentemente utilizadas para consumo humano e uso médico. Assim, o objetivo deste trabalho foi determinar as concentrações de atividade dos radionuclídeos 226Ra, 228Ra e 210Pb e 210Po, avaliar as doses efetivas comprometidas devido ao consumo e fazer a caracterização química inorgânica destas águas minerais. Os radionuclídeos foram determinados por medida alfa e beta total e espectrometria alfa, após separação radioquímica em coletas realizadas sazonalmente. Para a caracterização química inorgânica foram determinadas as concentrações dos elementos As, Ag, Ba, Ca, Cd, Co, Cr, Cu Fe, K, Mn, Ni, Se, Ti e V por fluorescência de raios X. As concentrações de atividades dos radionuclídeos variaram de 4 ± 1 mBq/l a 509 ± 32 mBq/l para 226Ra, de 3,7 ± 0,1 mBq/l a 631 ± 27 mBq/l para 228Ra, de 5 ± 1 mBq/l a 60 ± 5 mBq/l para 210Pb e de abaixo do limite de detecção da metodologia a 36 ± 2 mBq/l para o 210Po. A dose efetiva comprometida máxima em adultos foi de 0,12 mSv/a para 226Ra, 0,32 mSv/a para 228Ra, 0,03 mSv/a para 210Pb e para 210Po 0,031 mSv/a. Dentre os elementos analisados por fluorescência de raios X, os elementos Ag, As, Cd, Cr, Cu, Ni, Se e Ti apresentaram valores abaixo do limite mínimo de detecção da metodologia. Os elementos Ba e Co, considerados contaminantes nas águas minerais, apresentaram valores maiores do que estabelecido pela ANVISA e CONAMA para águas minerais, respectivamente. No entanto, trabalhos da literatura brasileira realizados com água mineral de em outros locais apresentaram valores próximos ao do presente estudo, mostrando que concentrações acima do limite podem representar uma anomalia natural do aquífero. / Exposure to natural sources of radiation contributes more than 98% of the radiation dose normally received from the population; this dose is mainly attributed to the incorporation of natural radionuclides from the 238U and 232Th decay series which have relatively long half-lives. The quality of the water for human consumption must be constantly analyzed and, a very important parameter analyzed is the presence of the natural radioactivity. When the natural radionuclides are present in mineral waters there is a greater concern because these waters may contain somewhat high concentrations of 226Ra, 228Ra and 222Rn originally dissolved and the radionuclides 210Pb and 210Po, which, although presenting lower concentrations, contribute to an increase in irradiation both internal and external. The study areas of the present work were the Water Parks of Cambuquira and Marimbeiro and a private spring of a farm located in the city of Cambuquira, Minas Gerais, where the mineral waters are frequently used for human consumption and medical use. Thus, the objective of this work was to determine the activity concentrations of the radionuclides 226Ra, 228Ra and 210Pb and 210Po, to evaluate the committed effective doses and to perform the inorganic chemical characterization of these mineral waters due to their consumption. The natural radionuclides were determined by gross alpha and beta measurement and alpha spectrometry, after radiochemical separation in samplings carried out seasonally; for the inorganic chemical characterization the elements As, Ag, Ba, Ca, Cd, Co, Cr, Cu Fe, K, Mn, Ni, Se, Ti and V concentrations were determined by X-ray fluorescence. The activity concentrations of the radionuclides varied from 4 ± 1 mBq/l to 509 ± 32 mBq/l for 226Ra, from 3.7 ± 0.1 mBq/l to 631 ± 27 mBq/l for 228Ra, 5 ± 1 mBq/(LID) to 36 ± 2 mBq/l for the 210Pb and below the detection limit to 60 ± 5 mBq/l for 210Pb. The maximum committed effective doses in adults for 226Ra was 0,12 mSv/y, 0,32 mSv/y for 228Ra, 0,03 mSv/y for 210Pb and 0,031 mSv/y for 210Po. Among the elements analyzed by X-ray fluorescence, the elements Ag, As, Cd, Cr, Cu, Ni, Se and Ti presented values below the minimum limit of detection. The elements, such as Ba and Co, considered contaminants in mineral waters, presented higher values than established by ANVISA and CONAMA for mineral waters, respectively. However, Brazilian literature studies with mineral water from other sites presented values similar to the present study, showing that concentrations above the limit may represent a natural anomaly of the aquifer.

O Reservatório Taiaçupeba, localizado no estado de São Paulo, na divisa dos municípios Mogi das Cruzes e Suzano, faz parte do Sistema Produtor Alto Tietê SPAT. A água deste reservatório é captada pela ETA da Sabesp para tratamento e distribuição, abastecendo 3,1 milhões de pessoas. Para se avaliar possíveis riscos à qualidade da água deste importante reservatório; foram coletados quatro perfis de solo e quatro testemunhos de sedimento na área de influência do reservatório. Este trabalho teve como objetivo avaliar a concentração de atividade dos radionuclídeos naturais 238U, 226Ra,210Pb, 232Th, 228Ra, 228Th e 40K e realizar a caracterização química inorgânica determinando os elementos As, Ba, Ce, Co, Cr, Cs, Eu, Hf, K, La, Lu, Nd, Rb, Sb, Sc, Se, Sm, Ta, Tb, Th, U, Yb e Zn no solo e sedimento marginal. As técnicas analíticas empregadas foram a espectrometria gama de alta resolução e a análise por ativação com nêutrons instrumental (INAA), repectivamente. Realisou-se a análise do fator de enriquecimento FE para avaliar a contribuição antrópica nas concentrações dos elemento químicos obtidos por INAA, utilizando como referência os valores da Crosta Continental Superior CCS. Analisou-se, também, a composição granulométrica, o conteúdo de água e o teor de matéria orgânica para auxiliar na interpretação dos resultados obtidos. Na análise granulométrica os perfis de solo apresentaram maiores percentuais de fração fina (silte + argila), enquanto que os testemunhos de sedimento apresentaram em sua maioria maiores percentuais de fração grossa (areia). Todos os perfis de solo apresentaram umidade praticamente constante, entre 10% e 20%. O sedimento apresentou variação no conteúdo de água, no geral reduzindo com a profundidade, sendo esta mais acentuada em um dos testemunhos. Em relação à matéria orgânica constatou-se maiores percentuais médios nos testemunhos de sedimento. No estudo das concentrações dos radionuclídeos naturais, verificou-se as maiores concentrações de atividade para os radionuclídeos 40K,232Th e 228Th, no solo, e 232Th e 210Pb, no sedimento. Em relação à caracterização química inorgânica do solo e sedimento foram determinados altos valores para os elementos As e Sb (40 mg.kg-1 e 2,9 mg.kg-1) quando comparados com os valores da CCS (1,5 mg.kg-1 e 0,2 mg.kg-1), respectivamente. Um dos testemunhos apresentou concentração elevadíssima para o elemento Zn (concentração máxima de 38157 mg.kg-1 e média de 6602,6 mg.kg- 1) quando comparada aos valores da crosta continental superior (71 mg.kg-1), indicando forte contribuição antrópica. Na análise do fator de enriquecimento, além dos elementos citados acima, outros elementos como Ce, Co, Cr, Cs, Eu Hf, La, Lu, Nd, Sm, Tb, Th, U e Yb também apresentaram contribuição antrópica. / The Taiaçupeba Reservoir, located in the state of São Paulo, on the border of the municipalities of Mogi das Cruzes and Suzano, is part of the Alto Tietê Producer System - SPAT. The water from this reservoir is captured by Sabesp\'s ETA for treatment and distribution, supplying 3.1 million people. In order to evaluate possible risks to the water quality of this important reservoir, four soil profiles and four sediment cores were collected in the area of influence of the reservoir. The aim of this work was to evaluate the concentration of the natural radionuclides 238U, 226Ra, 210Pb, 232Th, 228Ra, 228Th and 40K and to perform the inorganic chemical characterization determining the elements As, Ba, Ca, Ce, Co, Cr, Cs, Eu, Fe, Hf, K, La, Lu, Na, Nd, Rb, Sb, Sc, Se, Sm, Ta, Tb, Th, U, Yb and Zn in soil profiles and marginal sediment cores. The analytical techniques used were high resolution gamma spectrometry and instrumental neutron activation analysis (INAA), respectively. The analysis of the enrichment factor - EF was performed to evaluate the anthropic contribution in the concentrations of the chemical elements obtained by INAA, using as reference the values of the Upper Continental Crust UCC. The granulometric composition, the water content and the organic matter content were also analyzed to aid in the interpretation of the obtained results. In the particle size analysis, the soil profiles presented higher percentages of fine fraction (silt + clay), while the sediment samples showed in the majority of the cores higher percentages of coarse fraction (sand). The soil samples presented almost constant moisture in all profiles, varying from 10% and 20%. The sediment cores presented variation in the water content, generally reducing with the depth. Regarding organic matter, it was observed a higher mean percentage in the the sediment cores. In the study of the natural radionuclide concentrations the highest values determined were verified for the radionuclides 40K, 232Th and 228Th in the soil samples and 232Th and 210Pb in the sediment samples. In relation to the inorganic chemical characterization of soil and sediment, high values for As and Sb elements (40 mg.kg-1 and 2.9 mg.kg-1) were determined when compared to the values of UCC (1.5 mg. kg-1 and 0.2 mg.kg-1), respectively. One of the sediment cores presented very high concentration for the element Zn (maximum concentration of 38157 mg.kg-1 and mean value of 6602.6 mg.kg-1), higher than the value of UCC (71 mg.kg-1), indicating a strong anthropogenic contribution. In the analysis of the enrichment factor, other elements such as Ce, Co, Cr, Cs, Eu Hf, La, Lu, Nd, Sm, Tb, Th, U and Yb also presented anthropogenic contribution.