L'enjeu de cette thèse est d'identifier des systèmes catalytiques, actifs, sélectifs et stables pour la transformation de l'acide lévulinique (LevA) en 1,4-pentanediol (1,4-PDO) en phase aqueuse. Dans un premier temps, des catalyseurs monométalliques à base de ruthénium (Ru), palladium (Pd), platine (Pt) supportés sur charbon (C) ou sur oxyde de titane (TiO2) sont préparés et testés. Ces premiers résultats ont montré l'importance de certains paramètres sur les performances catalytiques observées. Les catalyseurs à base de Ru se sont révélés les plus actifs et sélectifs en 1,4-PDO (rendement maximal de 50%). L'utilisation de ces catalyseurs monométalliques favorise la formation importante de sous-produits et de réactions de craquage d'où des pertes de carbone transférées en phase gaz. Par imprégnation de différentes teneurs de rhénium (Re) ou de molybdène (Mo) sur ces catalyseurs monométalliques, des catalyseurs bimétalliques Re-Ru et Mo-Ru ont été préparés. L'ajout d'un promoteur permet d'augmenter la vitesse de la réaction de transformation du LevA et améliore significativement la sélectivité en 1,4-PDO (90%). Les mécanismes réactionnels mis en jeu ont été étudiés notamment en s'appuyant sur une modélisation cinétique et sur des tests de réactivité de molécules modèles identifiées comme intermédiaires réactionnels ou produits de la conversion du LevA en 1,4-PDO / The aim of our research project is the hydrogenation of the levulinic acid in aqueous phase into 1,4-pentadeniol using noble metal catalysts (Ru, Pd, Pt) supported on C or TiO2. First results have shown the effect of the metal, the method of preparation or the supports on catalytic performances. Monometallic Ru catalysts are active and selective into 1,4-PDO (maximum yield 50%). By using monometallic catalysts, an important formation of by-products and loss of carbon by cracking reactions was observed. By impregnating various amount of Re or Mo, bimetallic catalysts were prepared. Adding promoter both allows enhancing the reaction rate of LevA hydrogenation and improved the selectivity to 1,4-PDO up to 90%. In order to understand the mechanism, a kinetic modeling and stability test on intermediates or products of the reaction were realized

L'imagerie a pris une importance croissante dans l'étude des processus biologiques. L'utilisation de la microscopie de fluorescence a notamment favorisé le développement de nombreuses molécules sondes pour le marquage et la visualisation de biomolécules en milieu biologique complexe. D'autre part, des techniques d'imagerie complémentaires émergent, comme la microspectroscopie infrarouge. Les complexes organométalliques ont un potentiel important comme outils pour l'imagerie biologique, car ils peuvent combiner sur un même cœur moléculaire des propriétés permettant leur détection par différents types d'imagerie. En particulier, des complexes rhénium tricarbonyl ont été utilisés comme sondes pour l'imagerie multimodale. Ces " SCoMPIs " (Single Core Multimodal Probes for the Imaging) sont luminescents et présentent des signaux infrarouge et de fluorescence X intenses et qui permettent leur détection spécifique en milieu biologique. Dans cette étude, nous nous sommes intéressés aux possibilités d'imagerie multimodale de peptides et de protéines exogènes ou endogènes. Différents SCoMPIs ont été préparés et caractérisés, permettant le marquage N-terminal de peptides, le marquage d'une protéine exogène (homéodomaine) via une réaction thiol-maléimide ou le marquage par affinité d'une protéine endogène (anhydrase carbonique). L'évolution des propriétés de luminescence de SCoMPIs en fonction de l'environnement a été étudiée. Les imageries de luminescence et infrarouge ont permis la détection des peptides en contexte cellulaire, mais pas des protéines marquées avec des SCoMPIs. En revanche, il a été possible de détecter ces faibles quantités par microspectroscopie de fluorescence X. / Bioimaging is now widely used for the study of biological processes. The expansion of fluorescence microscopy has led to the development of small chemical probes for the labelling and imaging of biomolecules in complex biological environments. Alternative imaging techniques, such as infrared microspectroscopy, are also emerging. Organometallic complexes have a great potential as tools for bioimaging, since they can combine on a single molecular core properties enabling their detection by various imaging techniques. In particular, rhenium tricarbonyl complexes have been used for multimodal imaging. These “SCoMPIs” (Single Core Multimodal Probes for the Imaging) are luminescent and exhibit intense, specific infrared and X-ray fluorescence signals, which make possible their multimodal detection in biological media. In this study, we focused on the possibility to perform the multimodal imaging of SCoMPI-labelled peptides and proteins in cells. Various SCoMPIs were prepared and characterized, that were suitable for N-terminal labelling of peptides, labelling of an exogenous protein (homeodomain) through thiol-maleimide labelling, or the affinity-guided labelling of endogenous proteins (carbonic anhydrases). Dependance on the luminescence properties of SCoMPIs with their environment was investigated. SCoMPI-labelled peptides could be easily detected by luminescence and infrared imaging, which was not the case for SCoMPI-labelled proteins. However, it was possible to detect these small amounts of proteins by X-ray fluorescence microspectroscopy.

This dissertation attempts to extend the classes of halogen-containing systems which may be studied using solid-state nuclear magnetic resonance (SSNMR). As line shape broadening due to the quadrupolar interaction (QI) scales inversely with the applied field, high-field magnet technology is indispensable for this research. Combining advanced radiofrequency pulse sequences with high-field wideline data acquisition allowed for the collection of very broad SSNMR signals of all quadrupolar halogen nuclei (i.e., 35/37Cl, 79/81Br and 127I) within a reasonable amount of experimental time. The initial systems for study were of the MX2 variety (M = Mg, Ca, Sr, Ba; X = Cl, Br, I). In total, 9 anhydrous compounds were tested. The effects of hydrate formation were tested on 7 additional compounds. Systematic trends in the observed δiso values (and to a lesser extent, Ω and CQ) were found to be diagnostic of the extent of hydration in these materials. Resolving power was successfully tested using SrBr2, which possesses 4 magnetically unique sites. The composition of CaBr2•xH2O was convincingly determined using SSNMR data and the hydration trends noted above. The sensitivity of the QI to the local bonding environment (e.g., bond distance changes of less than 0.05 Å) was used to refine (when coupled with gauge-including projector augmented-wave density functional theory (GIPAW DFT) quantum chemical computations) the structure of MgBr2, and was used to correct prior NMR data for CaCl2 (earlier accounts had been performed upon a CaCl2 hydrate). During NMR data analysis of certain iodine-containing materials, it was found that standard fitting software (which uses perturbation theory) could not reproduce the observations. Proper analysis required the use of exact simulation software and allowed for the observation of high-order quadrupole-induced effects (HOQIE). This motivated further studies using rhenium-185/187 nuclei, where it was expected that HOQIE would be more dramatic. The observed rhenium SSNMR spectra possessed additional fine structure that had never been observed before experimentally, nor would be expected from currently-available perturbation theory analysis software. Lastly, preliminary results are shown where 127I SSNMR is used to study important supramolecular systems, and the composition of the popular synthetic reagent ‘GaI’ is elucidated.

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No description available.

Mass spectrometry with electrospray ionization is an excellent method for structural analysis of coordination compounds with outstanding sensitivity and selectivity. However, it fails to detect some low-polar rhenium complexes. This master thesis describes derivatization method of non-ionizable rhenium complexes with 1,2-dihydroxybenzene and 2,3- dihydroxytoluenene. Fragmentation mechanisms and structure of prepared complexes was studied using high resolution mass spectrometry and collision-induced dissociation (CID). Furthermore, density functional theory (DFT) computational method was used for prediction of bond cleavage based on bond lengthening.

Investigations in the 99mTc chemistry are stimulated by the search for new radiopharmaceuticals for nuclear medical applications. To understand the coordination mode of Tc with various complexing agents, macroscopic studies of technetium coordination chemistry are often performed using the low energy ß-emitting radionuclide 99Tc, which has a much longer half life (t1/2 = 2.12 x 105 years) than 99mTc, in the mg level. Investigations of Re coordination chemistry are done in conjunction with Tc studies because Re possesses chemical properties similar to those of Tc. For some chemical tasks, Re provides a non-radioactive alternative to work with Tc radioisotopes. In addition, 186Re and 188Re are of great interest to nuclear medicine as they possess nuclear properties favorable for use in therapeutic radiopharmaceuticals. Our investigations of Tc and Re coordination chemistry are toward this goal. A large series of technetium and rhenium complexes resulted from this studies have been characterized by X-ray crystal structure determinations. This survey covers the structural investigations performed by P.Leibnitz and G.Reck (BAM) from 1992 till now. It summarizes results obtained in the Rossendorf technetium group and is not intended to compete with the well-written reviews published so far.

No description available.

Dans cette thèse, des complexes [Re(N^N)(CO)3X]n+ ont été conçus pour différentes applications. Dans le premier chapitre, l’impact de différentes modifications sur le ligand N^N ou le ligand X sur les propriétés photophysiques des complexes a été étudié. Dans le second chapitre, une série de nouveaux complexes a été conçue et étudiée comme catalyseurs homogènes/hétérogènes pour l’électroréduction du CO2. Dans le dernier chapitre, nous avons introduit un ligand diimine pour la coordination au Re en tant que lien dans la macrocyclisation de peptidomimétiques pour la modulation d’interaction protéine-protéine. / In this thesis, [Re(N^N)(CO)3X]n+ complexes were designed towards different applications. In the first chapter, the impact of different modifications on either the N^N ligand or the X ligand on the photophysical properties were studied experimentally and computationally. In the second chapter, we designed and studied a series of new Re complexes as homogeneous/heterogeneous catalysts for CO2 electroreduction and their catalytic abilities were evaluated. In the last chapter, the introduction of a Re complex as macrocyclic linker in macrocyclic peptidomimetics is used to both stabilize the active secondary structure and introduce imaging modalities towards modulation of protein-protein interactions.

Nas últimas décadas a medicina nuclear tornou-se uma grande aliada no auxílio ao diagnóstico de doenças e também para o tratamento do câncer. Parte deste sucesso está relacionada à constante pesquisa e desenvolvimento de novos radiofármacos. Uma classe de molécula que vem se mostrando promissora para o tratamento de tumores, tanto na sua forma orgânica quanto na forma de complexos organo-metálicos, é a tiossemicarbazona e seus derivados, os quais também podem formar complexos com radioisótopos metálicos dando origem a radiofármacos para diagnóstico e terapia. Neste trabalho foram preparados complexos com o ligante benzil-5-hidroxi-3-metil-5-fenil-4,5-diidro-1H-pirazol-1-carboditionato (H2bdtc) com os radioisótopos [99mTc]tecnécio, (67/68Ga)gálio e (111In)índio, e foram avaliados a pureza radioquímica, Log P e a estabilidade na presença de L-cisteína, L-histidina, soro albumina humana (SAH) e plasma de sangue humano; também foram avaliadas a taxa de captação dos radiofármacos in vitro em células de melanoma murino B16F10 e TM1M, além da avaliação da captação ex vivo e in vivo utilizando camundongos C57B/6 inoculados com as duas linhagens tumorais. Com o [99mT]tecnécio foram obtidos dois complexos diferentes, dependendo da concentração do PBS na solução, sendo que em um deles foi possível confirmar sua estrutura como [[99mTc]O(bdtc)(Hbdtc)] a partir do complexo de rênio [ReO(bdtc)(Hbdtc)], o outro complexo de [99mTc]tecnécio, bem como de (67/68Ga)gálio e (111In)índio não tiveram a estrutura caracterizada. A eficiência de marcação dos complexos foi superior a 90 %, com Log P maior que 1 para os complexos [[99mTc]O(bdtc)(Hbdtc)], [[99mTc]-bdtc] e [67/68Ga-bdtc] e 0,9 para [111In-bdtc]. Todos os complexos se mostraram com boa estabilidade na presença de L-cisteína e L-histidina, principalmente na primeira hora de incubação, mas não o foram na presença de SAH e plasma. A captação in vitro dos complexos em células B16F10 e TM1M variou entre 0,6 % e 1,8 %, e nos estudos de biodistribuição ex vivo foi obesrvada intensa e persistente captação hepática e no baço, superando 90 %, e captação no tumor variando de 0,2 % a 3 %, enquanto que nas imagens in vivo não foi possível observar de forma uma adequada captação nos tumores a ponto de permitir o uso como agente de diagnóstico. Os resultados permitem concluir que os complexos de derivados tiossemicarbazonas podem formar complexos com diferentes metais, mas novos derivados devem ser preparados para tentar melhorar o desempenho nos sistemas biológicos. Os experimentos com animais foram aprovados pela Comissão de Ética em Pesquisa da Faculdade de Medicina - USP, processo 372/12 / In recent decades, nuclear medicine has been used as diagnostic agent for disease and for the treatment of cancer. Part of this success is related to the constant research and development of new radiopharmaceuticals. Thiosemicarbazone and their derivatives have proven to be promising agent for the treatment of tumors, both in its organic form or as organo-metallic complexes. Also, they can to form complexes with metal radioisotopes giving radiopharmaceuticals for diagnosis and therapy. In this work we prepared complex of benzyl-5-hydroxy-3-methyl-5-phenyl-4,5-dihydro-1H-pyrazol-1-carboditionato (H2bdtc) with radioisotopes [99mTc]technetium (67/68Ga)gallium and (111In)indium and the radiochemical purity, Log P and stability in the presence of L-cysteine, L-histidine, human serum albumin (HSA) and human blood plasma were assessed; also were assessed the in vitro uptake rate of radiopharmaceuticals in murine melanoma cells B16F10 and TM1M, besides the evaluation of ex vivo uptake and in vivo using C57Bl/6 mice inoculated with both tumor lines. With [99mT] technetium two different complexes were obtained, depending on the concentration of the PBS in the solution, and one of them was had its structure to confirm as [[99mTc]O(bdtc)(Hbdtc)] from the standard rhenium complex [ReO(bdtc)(Hbdtc)], the other [99mTc] echnetium complex as well as (67/68Ga)gallium and (111In)indium not have characterized the structure. The labeling efficiency of compleos was higher than 90%, with log P higher than 1 for the complexes [[99mTc]O(bdtc)(Hbdtc)], [[99mTc]-bdtc] and [(67/68Ga)-bdtc] and 0.9 to [111In-bdtc]. All the complexes showed good stability in the presence of L-cysteine and L-histidine, especially in the first hour of incubation, but not in the presence of HSA and plasma. The uptake in vitro complexes in B16F10 and TM1M cells varied between 0.6% and 1.8%, and in ex vivo biodistribution studies was obesrvada intense and persistent liver uptake and spleen, exceeding 90%, and tumor uptake in changing from 0.2% to 3%, while in vivo imaging was not possible to observe a properly uptake in tumors, not allowing to use these molecules as a diagnostic agent. The results indicate that the thiosemicarbazone derivative complex can give complexes with different metals, but new derivatives should be prepared to try to improve performance in biological systems. The animal experimentation was approved by Comissão de Ética em Pesquisa da Faculdade de Medicina - USP, proccess 372/12