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Cette thèse a porté sur l'étude des propriétés structurales et électroniques d'une série de complexes cubiques A-FeCo représentant des modèles moléculaires des CoFe-PBA. Ces cubes hétérobimétalliques neutres de formule A{Fe4Co4(CN)12} reproduisent une série d'unités cubiques uniques excisées du composé inorganique de type " bleu de prusse ". Le composé moléculaire octamétallique est composé de 4 ions FeIIBS, 3 ions CoIIIBS et 1 ion CoIIHS reliés par des ponts cyanures. Un monocation est hébergée à l'intérieur du cube. Les ions métalliques situés au coin du cube sont liés par des ligand tridentés de type scorpionate (Tp pour Fe et pzTp pour Co). La présence d'un ion Co (II) non équivalent induit un abaissement de la symétrie du Td à C3v. La DRX sur monocristaux a permis de déterminer avec précision l'emplacement du cation inséré dans le cube. En raison de la présence d'une charge négative formelle dans l'un des coins de la cage (celle accueillant l'ion Co (II)), deux types d'interactions entre le cation et le cube ont été postulés. L'une est une interaction électrostatique, et l'autre est l'interaction entre le cation (acide de Lewis) et les systèmes de cyanure (base de Lewis). Au sein de la famille des cubes contenant des ions alcalins, le Cs + interagit avec les 12 ponts cyanures alors que le K + n'interagit qu'avec trois d'entre eux. La spectroscopie RMN 133Cs a permis de confirmer une interaction chimique entre le césium (invité) et la cage (hôte). Ces cubes ont montré une remarquable capacité d'encapsuler différentes monocations de tailles et de nature différentes. / This thesis has focused on the investigation of the structural and electronic properties of a series of A-FeCo cubic complexes representing molecular models of the CoFe-PBAs. These neutral heterobimetallic cubes of abbreviated formula A-{Fe4Co4(CN)12} reproduce a series of single cubic units excised from the Prussian Blue type framework. The octametallic anionic core is composed by 4xFeIILS, 3xCoIIILS and 1xCoIIHS connected via bridging cyanides. A monocation is encapsulated inside the cube. The metal ions situated at the corner of the cube are facially capped by tridentate “scorpionate ligand” (Tp for Fe and pzTp for Co). The occurrence of one non-equivalent Co(II) ion induces a lowering of the symmetry from Td to C3v. Single crystal XRD allowed determining precisely the location of the inserted cation in the cube. Because of the presence of a formal negative charge in one of the corner of the cage (that accommodating the Co(II) ion), two types of interactions between the cation and the cube have been postulated. One is an electrostatic interaction, and the other one is the interaction between the cation (Lewis acid) and the cyanide systems (Lewis base). Within the family of alkali ion containing cubes, the Cs+ interacts with the 12 cyanide bridges whereas the K+ interacts with only three of them. The 133Cs-NMR spectroscopy allowed confirming a through bond interaction between the guest caesium and the host cage.

abstract: The study of subwavelength behavior of light and nanoscale lasing has broad potential applications in various forms of computation i.e. optical and quantum, as well as in energy engineering. Although this field has been under active research, there has been little work done on describing the behaviors of threshold and saturation. Particularly, how the gain-molecule behavior affects the lasing behavior has yet to be investigated. In this work, the interaction of surface-plasmon-polaritons (SPPs) and molecules is observed in lasing. Various phenomenologies are observed related to the appearance of the threshold and saturation regions. The lasing profile, as a visual delimiter of lasing threshold and saturation, is introduced and used to study various parametrical dependencies of lasing, including the number-density of molecules, the molecular thickness and the frequency detuning between the molecular transition frequency and the SPP resonant frequency. The molecular population distributions are studied in terminal and dynamical methods and are found to contain unexpected and theoretically challenging properties. Using an average dynamical analysis, the simulated spontaneous emission cascade can be clearly seen. Finally, theoretical derivations of simple 1D strands of dipoles are presented in both the exact and mean-field approximation, within the density matrix formalism. Some preliminary findings are presented, detailing the observed behaviors of some simple systems. / Dissertation/Thesis / Masters Thesis Chemical Engineering 2017

The present dissertation aims to shed light on the molecular machinery involved in the process of shell formation (thecagenesis) in Arcella (Arcellinida : Amoebozoa). Arcellinida are single-celled testate amoebae organisms, characterized by the presence of an outer shell (test or carapace); it is a monophyletic lineage of Amoebozoa, sister group to a naked amoeboid lineage. No homologous structure to shell is present in the sister group of Arcellinida, thus it is considered an evolutionary novelty. The origin and evolution of the shell in Arcellinida are currently open questions; deciphering its formation process is a key step to address these questions. During each reproductive process by budding division, these organisms build a new shell. In the span of more than a century, several authors have described the thecagenesis process on Arcellinida, primarily focusing on the genus \\textit, based on cyto-morphological evidence. Conversely, the absence of molecular data has impaired advances on describing the molecular aspects of shell formation. In this study, we designed and applied a molecular framework to identify candidate genes and develop a molecular model for the shell formation process in Arcella; we based this framework on single-cell RNA-sequencing, gene expression profiling, Gene Ontology analysis, and comparative analysis of cyto-morphological with newly generated molecular data. We identify and propose a set of 539 genes as the candidate genes for shell formation, based on expression profiling and biological process assignment. We propose a model for the the shell formation process, which describes the mechanistic aspect of this process, hypothetically based on a molecular machinery conserved in Eukaryotes. Additionally, we identified a massive expansion of the Rab GTPase family, a protein likely to be involved on the process of shell formation. In the lights of the present study, we briefly discuss possible evolutionary scenarios involved on the origin and evolution of the shell and present future perspectives; we propose the shell of Arcellinida as a prosperous model to study the origin and evolution of evolutionary novelties, as well as other evolutionary questions / A presente dissertação tem como objetivo lançar luz sobre a maquinaria molecular envolvida no processo de formação de teca (tecagênese) em \\textit (Arcellinida: Amoebozoa). Arcellinida são amebas tecadas unicelulares, caracterizadas pela presença de uma teca (carapaça ou concha) externa; é uma linhagem monofilética de Amoebozoa, grupo irmão de alguns organismos amebóides nus. Nenhuma estrutura homóloga à carapaça está presente no grupo irmão de Arcellinida, sendo considerada como uma novidade evolutiva. A origem e evolução da carapaça em Arcellinida são questões em aberto; Decifrar seu processo de formação é um passo fundamental para abordar essas questões. Durante todo processo reprodutivo, por divisão por brotamento, estes organismo constroem uma nova concha. No decorrer de mais de um século, vários autores descreveram o processo de tecagênese nestes organismos, focando principalmente no gênero \\textit, baseados em evidências cito-morfológicas. Enquanto isso, a ausência de dados moleculares impede avanços na descrição dos aspectos moleculares da formação de conchas. Neste estudo, projetamos e aplicamos uma \\textit molecular para identificar genes candidatos e desenvolver um modelo molecular para o processo de formação de teca em \\textit; Baseamos este \\textit em sequenciamento de RNA \\textit, perfil de expressão gênica, análise de \\textit{Gene Ontology} e análise comparativa de dados cito-morfológicos e moleculares. Nós identificamos e propomos um conjunto de 539 genes como genes candidatos para a formação de carapaça, com base no perfil de expressão e na atribuição de processos biológica. Propomos um modelo para o processo de formação de carapaça, que descreve o aspecto mecanicista deste processo, hipoteticamente baseado em um mecanismo molecular conservado em Eucariotos. Além disso, identificamos uma expansão maciça da família gênica das Rab GTPase, gene provavelmente envolvida no processo de formação de carapaça. À luz do presente estudo, discutimos brevemente possíveis cenários evolutivos envolvidos na origem e evolução da teca e apresentamos perspectivas futuras; propomos a teca dos Arcellinida como próspero modelo para estudar a origem e evolução das novidades evolutivas, bem como outras questões evolutivas

In the present paper, we propose the construction of a physical molecular model through the reuse of recyclable polymeric material, selected in units of selective garbage collect and in the school environment itself. This didactic intervention, especially in the Organic Chemistry classes, greatly helps the students have a threedimensional visualization of the molecules, averting itself, thus, the two-dimensional classicism of the whiteboard and the book. The construction of this handmade learning object has some extremely important characteristics both from an operational point of view of its elaboration as to the didactic point of view. Among them, we can quote: a very low cost; simplicity in the making and enforcement; a good approximation in the representation of the geometries of the molecules and the bond angles to the experimental values. The proposed model could substitute the ones sold on the market without any loss of information, moreover it adds some information that only this model is able to highlight, like the different size of the atoms. None of the representational physical models (either a model sold on the market or a handmade one) provides the discussion about the strength of the link. The model proposed here, however, has sticks with different length purposely, inducing the student to think about and verify the reason of this differentiation. Still regarding the process of learning, we can observe, in an workshop, that the involvement of the students in the making of the molecular kit favors their effective participation as an strategy and a way of a meaningful learning, functioning as a very efficient subsumptive. We still evidence the potential of this project in make the students sensible to the environmental consciousness, in view of the characteristics of the utilized material, indiscriminately discarded in the trash. Furthermore, some workshops were developed with teachers and students of the Public Educational System in the town of Arapiraca-AL. In the occasion, some quizzes were applied about the perception of the students and we observed, in most answers, that the use of the recycled material led to some discussions about what really trash is, this way what we’re going to do to minimize the problems caused by its consume and posterior discard and how to be rightly reused. / No presente trabalho, propomos a construção de um modelo molecular físico por meio do reuso de material polimérico reciclável, selecionados em unidades de coleta seletiva de lixo e no próprio ambiente escolar. Essa intervenção didática, especialmente nas aulas de Química Orgânica, vem auxiliar sobremaneira o aluno a ter uma visualização tridimensional das moléculas, distanciando-se, assim, do classicismo bidimensional da lousa e do livro. A construção desse objeto de aprendizagem possui algumas características extremamente importantes tanto do ponto de vista operacional de sua elaboração, quanto do ponto de vista didático. Dentre elas, podemos citar: o baixíssimo custo; simplicidade de confecção e aplicação; uma boa aproximação na representação das geometrias das moléculas e dos ângulos de ligações aos valores experimentais. O modelo proposto pôde substituir os modelos comerciais sem qualquer perda de informação, inclusive acrescenta informações que somente esse modelo consegue dar destaque, como o tamanho diferenciado dos átomos. Nenhum dos modelos representacionais físicos, seja comercial ou artesanal, traz a discussão sobre a força de ligação. Entretanto, o modelo aqui proposto possui, propositalmente, varetas de diferentes comprimentos, induzindo o aluno a refletir e verificar o porquê dessa diferenciação. Ainda no que diz respeito ao processo de aprendizagem, pudemos observar que o envolvimento dos alunos e do professor na confecção do kit molecular propiciou a participação efetiva dos mesmos como estratégia e forma de aprendizagem significativa, funcionando como um subsunsor bastante eficaz. Ressaltamos ainda, o potencial desse projeto em sensibilizar uma conscientização ambiental, dado às características dos materiais utilizados, descartados no lixo indiscriminadamente. Além disso, foram desenvolvidas oficinas com professores e alunos da rede pública de ensino no município de Arapiraca-AL. Na ocasião, foram aplicados questionários sobre a percepção dos alunos e se observou, na grande maioria das respostas, que o uso de material reciclado levou a discussões sobre o que realmente é lixo, por conseguinte o que faremos para minimizar os problemas causados por seu consumo, posterior descarte e como ser adequadamente reaproveitados.

Although nonflexible, scaled molecular models like Pauling-Corey's and its descendants have made significant contributions in structural biology research and pedagogy, recent technical advances in 3D printing and electronics make it possible to go one step further in designing physical models of biomacromolecules: to make them conformationally dynamic. We report the design, construction, and validation of a flexible, scaled, physical model of the polypeptide chain, which accurately reproduces the bond rotational degrees-of-freedom in the peptide backbone. The coarse-grained backbone model consists of repeating amide and alpha-carbon units, connected by mechanical bonds (corresponding to phi and psi angles) that include realistic barriers to rotation that closely approximate those found at the molecular scale. Longer-range hydrogen-bonding interactions are also incorporated, allowing the chain to easily fold into stable secondary structures. This physical model can serve as the basis for linking tangible bio-macromolecular models directly to the vast array of existing computational tools to provide an enhanced and interactive human-computer interface. We have explored the boundaries of this direction at the interface of computational tools and physical models of biological macromolecules at the nano-scale. Using a CAD-biocomputational framework, we have provided a methodology to design and build physical protein models focusing on shape and dynamics. We have also developed a workflow and an interface implemented for such bio-modeling tools. This physical-digital interface paradigm, at the intersection of native state proteins (P), computational models (C) and physical models (P), provides new opportunities for building an interactive computational modeling tool for protein folding and drug design. Furthermore, this model is easily constructed with readily obtainable parts and promises to be a tremendous educational aid to the intuitive understanding of chain folding as the basis for macromolecular structure. / Ph. D.

Structural studies of peptides has relevance for various applications, like, in de novo design of proteins, in designing better catalysts for organic synthesis, in structure based drug design, in the design and construction of synthetic protein mimics and in building novel materials via supramolecular self assembly. Crystal structure determination of peptides is expected to provide information about their static structure, mode of aggregation, solvation and hydrogen bond interactions of the sequences in the solid state. Comparison and analysis of the related structures from the database analysis could provide information about sequence dependent conformational features, which eventually would act as precursor for de novo protein design. Self assembling processes are common throughout nature and technology. Living cells self assemble, and understanding life will therefore require an understanding of self assembly. Supramolecular chemistry has become an area of intense research, partly inspired by biological ensembles in nature, such as collagen and enzymes or protein assemblies in general. Understanding, inducing, and directing such self assembling processes are key to unraveling the progressive emergence of complex matter. Most of the drugs available today have a broad spectrum of action in that they can act on more than one receptor and the mechanism of action of these drugs are poorly understood. Homology modeling of receptors and docking studies with drug molecules (both peptides and non-peptides) would result in a better understanding of the mechanism of drug-receptor binding thus resulting in the design of more specific and effective drugs. This thesis reports the results of X-ray crystallographic studies of ten molecules listed below (Ter: terephthalic acid) and the molecular model of cholecystokinin type 1 receptor (CCK1R). The abbreviations used for the sequences are given in parenthesis. Boc-Gly-Dpg-Gly-Leu-OMe (GDGL), C24H44N4O7 Boc-Val-Ala-Leu-Dpg-Val-Ala-Leu-Val-Ala-Leu-Dpg-Val-Ala-Leu-OMe (VAL14), C78H14 2N14O17 MeO-Leu-Ter-Leu-OMe (LTeL), C22H32N2O6 MeO-DLeu-Ter-DLeu-OMe (DLTeDL), C22H32N2O6 MeO-Ile-Ter-Ile-OMe (ITeI), C22H32N2O6 MeO-Aib-Ter-Aib-OMe (UTeU), C18H24N2O6 Tyr-Aib-Tyr-Val (YUYV), C27H36N4O7 Tyr-Aib-Ala (YUA), C16H23N3O5 Z-Gly-Gly-Val (ZGGV), C17 H23 N3 O6 DL-4-benzamido-N, N-dipropylglutaramic acid (proglumide), C18 H26 N2 O4 Results from the Dpg containing peptide sequences helped to further the understanding of conformational preferences of this residue. The crystallographic studies on the peptide sequence, which forms a supramolecular triple helix and four pseudopeptide sequences, which adopt supramolecular ladder conformations has provided substantial information on the role of non covalent interactions in supramolecular self assembly. Crystal structure of a Gly-Gly containing tripeptide and database analysis has provided insights into the conformations adopted by this segment in peptides and proteins. The docking of the crystal structure of proglumide, an antagonist of CCK1R has led to the understanding of the mechanism of its interaction with CCK1R.

Le kérogène, fraction insoluble de la matière organique sédimentaire, est un mélange complexe et hétérogène de macromolécules organiques. Ces structures évoluent, essentiellement sous l’effet de la température, au cours des temps géologiques et génèrent les hydrocarbures présents dans les bassins sédimentaires. Comprendre et quantifier les mécanismes physicochimiques associés à ce processus est important pour l’estimation des réserves pétrolières. Au cours de cette étude, deux géopolymères ont été sélectionnés pour représenter la décomposition thermique de structures typiques des kérogènes naturels. Dans un premier temps, une étude expérimentale nous a permis (1) de proposer des structures moléculaires des géopolymères et (2) de décrire les mécanismes primaires de décomposition des géopolymères. Les échantillons ont été analysés au moyen d’expériences de pyrolyse en milieu confiné à cinq températures de référence comprises entre 200 à 300°C. Un schéma cinétique correspondant aux processus précoces de décomposition a été établi à partir des observations expérimentales pour chacun des deux géopolymères. Dans un deuxième temps, les modèles moléculaires élaborés dans l'étape précédente ont été soumis à des simulations moléculaires dynamiques utilisant un champ de forces réactif (ReaxFF). Ces simulations ReaxFF ont apporté une interprétation théorique aux processus-clés observés expérimentalement. L’ensemble des résultats de cette étude suggère que les modèles cinétiques, en une étape implémentés dans les simulateurs de bassin standard ne reproduisent pas correctement la physicochimie des processus de décomposition de la matière organique dans les roches mères naturelles / Kerogen, the insoluble fraction of sedimentary organic matter, is a complex mixing of organic macromolecules, the structure of which evolves during geological times as a function of temperature mainly. The thermal evolution of kerogen is at the origin of hydrocarbon deposits in sedimentary basins. Understanding and quantifying the physicochemical processes associated to this transformation is therefore important to improve the evaluation of petroleum systems. During this study, two geopolymers were selected in order to represent the thermal decomposition of typical structures in natural kerogen. Firstly, an experimental protocol was set up (1) to define molecular structures of the geopolymers, and (2) to describe primary mechanisms of decomposition of both geopolymers. The two samples were analysed using off-line pyrolysis experiments, at five reference temperatures comprised between 200 to 300°C. A kinetic scheme accounting for early decomposition processes was derived from these experimental observations for each geopolymer. Secondly, molecular models were submitted to molecular dynamic simulations using a reactive force field (ReaxFF). ReaxFF simulations provided theoretical supports to the key-processes derived from laboratory experiments. On the overall, results of this study suggested that kinetic models in one step (= parallels reactions implemented in standard (commercial) basin simulators do not adequately reproduce the physicochemistry of organic matter decomposition processes in natural source rocks

La régulation de l’apoptose fait partie des nouvelles cibles thérapeutiques dans la lutte contre le cancer. L’apoptose est l’autodestruction programmée des cellules qui, suite à un besoin physiologique, permet de réguler le développement des cellules. Dans de nombreux cancers, ce mécanisme est inhibé par une surexpression des protéines anti-apoptotiques de la famille Bcl-2 comme Bcl-xL et Mcl-1. Ce phénomène entraîne le développement des cellules tumorales et des résistances aux chimiothérapies. Dans cette optique, notre équipe à l’Institut de Chimie des Substances Naturelles a développé un criblage de plantes tropicales sur ces cibles. Des écorces d’une annonacée de Malaisie, Meiogyne Cylindrocarpa, a été isolé un sesquiterpène dimère, la meiogynine A, présentant une bonne affinité vis-à-vis de Bcl-xL (Ki = 10.7 M). Sa synthèse totale a été réalisée au laboratoire afin de déterminer sa configuration absolue et d’étudier les premières relations structure activité. Un de ses diastéréoisomères a également présenté une bonne affinité vis-à-vis de la protéine Bcl-xL.Afin d’étudier et d’approfondir les premières relations structure activité, la modulation de la meiogynine A a été réalisée. La synthèse des diénophiles acides a été optimisée afin de conduire majoritairement aux diénophiles précurseurs des composés actifs. Différents triènes ont également été synthétisés au laboratoire en vue de modifier la partie Sud de la meiogynine A. Plusieurs analogues ont ainsi pu être obtenus et ont été évalués biologiquement sur des tests in vitro et ex vivo. Des études de modélisation moléculaire et de RMN structurale ont également été réalisées. / The control of the apoptosis is one of the new modern key to fight against the cancer. The apoptosis is the self destruction of cells, part of the homeostasis, which regulates the cell developement. In several cancers, the over-expression of anti-apoptotic proteins, as Bcl-xL and Mcl-1 parts of the Bcl-2 proteins family, inhibate this naturel process. This phenomenum induce the tumoral cells developement and the chemotherapy’s resistance. In order to find new compounds which can regulate the apoptosis, our group in the Institut de Chimie des Substances Naturelles has screened different tropical plants on these targets. A Malaysian plant, Meiogynine Cylindrocarpa, was selected and the phyotchemist work on this plant gave us a new sesquiterpen , the meiogynin A (Ki = 10.7 M on Bcl-xL). Its total synthesis was realised in our laboratory in order to determine its absolute configuration and find the first structure activity relation. One of the synthetised diastereoisomers has presented a better affinity toward the protein. In order to precise these first structure activity relations, the modulation of the meiogynin A was initiated. The synthesis of the acid dienophiles was optimised, the main compounds are the precursors of the active decalins. New triene was also obtained in order to modulate the South Part of the meiogynin A. Thanks to a Diels-Alder reaction, these precursors were combined in order to form new analogues of the meiogynin A. All these compounds were biologically tested (in vitro et ex vivo). Experiments of molecular docking and 2D NMR were also realised.