Made available in DSpace on 2014-10-09T12:49:34Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:02:34Z (GMT). No. of bitstreams: 1 09995.pdf: 3401015 bytes, checksum: aced83202c3f7ecb0a8933fda0aed0aa (MD5) / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Made available in DSpace on 2014-10-09T12:27:22Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:06:35Z (GMT). No. of bitstreams: 0 / A Medicina Nuclear é uma modalidade de particular importância em oncologia e a investigação de novos radiofármacos direcionados a tumores, seja para diagnóstico e/ou terapia, é uma área de interesse para os pesquisadores. Rituximab (RTX) é um anticorpo monoclonal (AcM) quimérico (IgG 1) que se liga especificamente ao antígeno CD20 com alta afinidade e tem sido usado com sucesso para tratar Linfoma Não-Hodgkin (LNH) de células-B. O antígeno CD20 é expresso sobre mais de 90% dos LNH de células-B. Tecnécio-99m (99mTc) e rênio-188 (188Re) representam um atrativo par de radionuclídeos para uso médico devido as favoráveis propriedades de decaimento para diagnóstico (99mTc: T1/2 = 6 h, radiação γ = 140 keV) e terapia (188Re: T1/2 = 17 h, radiação máxima = 2,12 MeV) e por causa de sua disponibilidade graças aos sistemas de geradores correspondentes 99Mo/99mTc e 188W/188Re. Estes dois radionuclídeos podem ser conjugados aos anticorpos usando métodos químicos similares. O objetivo geral deste trabalho foi estudar a marcação do AcM anti-CD20 (Rituximab) com o radioisótopo 188Re usando duas técnicas: método direto de marcação [188Re(V)] e método de marcação via núcleo carbonila [188Re(I)]. Além do controle de qualidade, o anticorpo radiomarcado foi submetido a estudo biológico in vivo, in vitro e ex vivo. Para a marcação direta, o RTX foi reduzido pela incubação com o agente redutor 2-mercaptoetanol para a geração de grupos sulfidrilas (-SH) e posteriormente marcado com 188Re(V), fazendo-se um amplo estudo de variáveis para se chegar a uma formulação otimizada. Para a marcação usando o núcleo carbonila foram usados os radioisótopos 99mTc e 188Re e dois procedimentos de radiomarcação: (1) RTX nativo marcado com 99mTc(I) e (2) RTX reduzido (RTXred) marcado com 99mTc(I)/188Re(I). Também foi feito um estudo de variáveis para se chegar a formulação otimizada. O método de controle de qualidade para avaliação da pureza radioquímica mostrou um bom rendimento de marcação (93%) para o método direto. Na marcação com o núcleo carbonila, os resultados mostraram que os grupos -SH do anticorpo reduzido são uma possível via de ligação. A formação do composto 99mTc(I)-RTXred foi mais rápida do que 188Re(I)- RTXred, que por sua vez mostrou melhor estabilidade em plasma humano e nenhuma transquelação no desafio a histidina ou cisteína. Os dois compostos mostraram boa afinidade de ligação e uma biodistribuição em camundongos portadores de tumor coerente com a biodistribuição normal do anticorpo e razoável captação no tumor provando a eficiência do método de marcação e potencial uso clínico. / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

No description available.

The dissertation details the experimental work on the attempt to develop rhenium(V)phthalocyanine complexes directly from its +7 oxidation state (perrhenate). Different reducing agents (PPh3, Na2S2O5 and NaBH4) were employed and consequently, different results were acquired, such as rhenium(V)-mediated oxidative hydrolysis of the phthalocyanines (Pcs), the formation of a rhenium-phthalocyanine complex and phthalocyanine-capped nanoparticles. The rhenium nanoparticles that were formed were optimized from a synthesis point of view and, cancer localizing ability of the rhenium nanoparticles was investigated. The complexes were synthesized through direct metalation of pre-formed metal-free phthalocyanines using the “cold isotopes” of the rhenium metal. Rhenium nanoparticles (Re NPs) were synthesized in aqueous saline medium so as to imitate the environment on which Re is produced from its reactor. The nanoparticles (NPs) were capped with phthalocyanines which were covalently biofunctionalized with a folic acid moiety to enhance the targeting ability of the Re NPs. These NP systems were characterised with techniques such as ultraviolet-visible UV-Vis spectroscopy and transmission electron microscopy TEM. Cytotoxicity of the NPs was tested against four different cell lines and subsequently their cytotoxicity profiles were elucidated, and the profiles shown a dose-dependent responsealthough the results in some cell lines were unclear. Their fluorescence properties were also studied to provide photophysical information for investigation of their tumor localization using human cancer cells lines via confocal fluorescence microscopy studies. Particle size effect on localization of NPs was also investigated using confocal fluorescence and TEM. Two sizes were chosen (10 and 50 nm), and the smaller NPs (10 nm) were found to exhibit stronger fluorescence properties than the 50 nm NPs, and they were also found to have a better localization ability than the 50 nm NPs. Finally, their tumor and organ biodistribution studies will be carried out using micro-SPECT kits and model mice (using the “hot” isotopes in a radiopharmacy laboratory).

The development of Rhenium I photocatalysts has been pursued since Lehn first showed the excellent performance of the ReI bipyridine tricarbonyl catalyst. Since then, devel- opment has modified the organic ligand to demonstrate continued or improved activity with other α-diimine bidentate geometries. Geometry has been limited to bidentate motifs, with fac-(CO)3 and axial halides. This work will demonstrate the synthesis, characterization, and testing of a new terdentate, κ3(L3)−Re1(CO)2X (X = Cl, Br, CN, OTf) family of compounds for CO2 reduction, as well as computational investigations into the mechanism of the reduction of CO2 to CO and other species. Development of computational aides will be described as well.

The reaction of 2-[(diphenylphosphino)methyl]-6-methylpyridine (PN) with Os3(CO)12-n(MeCN)n [where n = 0 (1), 1 (2), 2 (3)] has been investigated. Os3(CO)12 reacts with PN in the presence of Me3NO to afford the clusters Os3(CO)11(1-PN) (4) and 1,2-Os3(CO)10(1-PN)2 (5). X-ray diffraction analyses confirm the equatorial coordination of the phosphine(s) in 4 and 5, with the two phosphines in the latter cluster exhibiting a 1,2-trans orientation about the Os-Os vector that contains the two ligands. Treatment of the MeCN-substituted cluster Os3(CO)11(MeCN) and PN (1:1 ratio) in CH2Cl2 gives clusters 4 and 5, in addition to HOs3(η1-Cl)(CO)10(1-PN) (6) as a result of competitive activation of the reaction solvent. Cluster 6 contains 48e- and the diffraction structure reveals the presence of axial chloride and equatorial phosphine ligands which are located on adjacent osmium atoms. The bridging hydride ligand in 6 spans the Cl,P-substituted Os-Os vector. The reaction of Os3(CO)10(MeCN)2 with PN furnishes 5, 6, and 1,1-Os3(CO)10(2-PN) (7) in yields that are dependent on the reagent stoichiometry and reaction solvent. The solid-state structure of 7 confirms the chelation of the PN ligand to a single osmium atom via the pyridine and phosphine moieties at axial and equatorial sites, respectively. The bonding in 7 relative to other possible stereoisomers has been explored by DFT calculations, and the diffraction structure is computed as the thermodynamically most stable form of this cluster. Cluster 4 is photosensitive and CO loss gives 7, in addition to the formation of the dihydride H2Os3(CO)8[µ-CH(NC5H3)CH2PPh2] (8), whose origin derives from the double metalation of the C-6 methyl group of the PN ligand in 7. Photolysis of 7 yields 8 without detectable observation of the expected intermediate hydride HOs3(CO)9[µ-CH2(NC5H3)CH2PPh2]. The PN ligand in 7 undergoes P-C bond activation in toluene at 110 °C to afford the 50e cluster Os3(CO)9(µ-C6H4)(µ-PPh), which contains face-capping benzyne and phosphinidene moieties. The bonding between the benzyne moiety and the opened Os3 frame in 9 has been examined computationally, and these data are discussed relative to and π bonding contributions from the metalated aryl ring to the cluster polyhedron. Thermolysis of BrRe(CO)5 with 4-(2,2-dimethylhydrazino)dimethylhydrazone-3(Z)-penten-2-one in toluene at 70 °C furnishes the new β-diketimine-substituted complex fac-BrRe(CO)3[(Me2NNCMe)2CH2] (1) in 50-70 isolated yield. Product 1 is also obtained in comparable yield when the same reactants are irradiated at 366 nm at room temperature in fluid solution. Treatment of the parent ligand with the "lightly stabilized" rhenium compound fac-BrRe(CO)3(THF)2 affords 1 as the sole observable rhenium product. Complex 1 has been characterized in solution by IR and 1H NMR spectroscopy, and the molecular structure has been determined by single-crystal X-ray diffraction analysis.

This work discusses the C-H bond activation by transition metal complexes using various computational methods. First, we performed a DFT study of oxidative addition of methane to Ta(OC2H4)3A (where A may act as an ancillary ligand) to understand how A may affect the propensity of the complex to undergo oxidative addition. Among the A groups studied, they can be a Lewis acid (B or Al), a saturated, electron-precise moiety (CH or SiH), a σ-donor (N), or a σ-donor/π-acid (P). By varying A, we seek to understand how changing the electronic properties of A can affect the kinetics and thermodynamics of methane C–H activation by these complexes. For all A, the TS with H trans to A is favored kinetically over TS with CH3 trans to A. Upon moving from electron-deficient to electron-rich moieties (P and N), the computed C–H activation barrier for the kinetic product decreases significantly. Thus, changing A greatly influences the barrier for methane C–H oxidative addition by these complexes. Secondly, a computational study of oxidative addition (OA) of methane to M(OC2H4)3A (M = Ta, Re and A = ancillary ligand) was carried out using various computational methods. The purpose of this study was to understand how variation in A and M affects the kinetics and thermodynamics of OA. Results obtained from MP2 calculations revealed that for OA of CH4 to Re(OC2H4)3A, the order of ΔG‡ for a choice of ancillary ligand is B > Al > SiH > CH > N > P. Single point calculations for ΔG‡ obtained with CCSD(T) showed excellent agreement with those computed with MP2 methods. MCSCF calculations indicated that oxidative addition transition states are well described by a single electronic configuration, giving further confidence in the MP2 approach used for geometry optimization and ΔG‡ determination, and that the transition states are more electronically similar to the reactant than the product. Thirdly, a computational study of olefin polymerization has been performed on 51 zirconocene catalysts. The catalysts can be categorized into three classes according to the supporting ligand framework: Class I - Cp2ZrCl2 (ten catalysts), Class II - CpIndZrCl2 (thirty-eight catalysts), and Class III - Ind2ZrCl2 (three catalysts), Cp = η5-cyclopentaidenyl, Ind = η5-indenyl. Detailed reaction pathways, including chain propagation and chain termination steps, are modeled for ethylene polymerization using Class II catalysts. Optimized structures for reaction coordinates indicated the presence of α-agostic interactions in the transition states (TSs) for both the 1st and 2nd ethylene insertions as well as in the ethylene π-complex of the Zr-nPr cation. However, β-agostic interactions predominate in the cationic n-propyl and n-pentyl intermediates. The calculated relative Gibbs free energies show that the TS for insertion of ethylene into the Zr-CH3+ bond is the highest point on the computed reaction coordinates. This study, in concert with previous work, suggests that the type of ring attached to Zr (Cp vs. Ind) affects the reaction kinetics and thermodynamics less significantly than the type of substituents attached to the Cp and indenyl rings, and that substituent effects are even greater than those arising from changing the metal (Zr vs. Hf)

Hard and ultra-incompressible materials are of great interest due to their important applications in industry. A common route to design hard materials is combining transition metals with light and small covalent elements. Light elements such as carbon, oxygen, nitrogen and boron have been considered as good candidates. This study includes the synthesis of ReB2, OsB2 and another higher boride AlMgB14. Most of the techniques used for ReB2 synthesis reported 1:2.5 Re to B ratio because of the loss of the B during high temperature synthesis. However, as a result of B excess, the amorphous boron, located along the grain boundaries of polycrystalline ReB2, would degrade the ReB2 properties. Therefore, techniques which could allow synthesizing the stoichiometric ReB2 preferably at room temperature are in high demand. This thesis reported the synthesis of ReB2 powders using mechanochemical route by milling elemental crystalline Re and amorphous B powders in the SPEX 8000 high energy ball mill for 80 hours. The formation of boron and perrhenic acids are also reported after ReB2 powder was exposed to the moist air environment for a twelve months period of time. The synthesized ReB2 powder was characterized by X-ray diffraction, scanning electron microscope, transmission electron microscope, secondary ion mass spectrometry and Raman spectroscopy. OsB2 also shows its attractive properties. The hardness of orthorhombic OsB2 was reported to be 37 GPa, when the applied load is lowered to 0.245N. However, only one of the three predicted phases has been synthesized. In this study, the hexagonal OsB2 has been synthesized by the mechanochemical method. The lattice parameters of the Hex-OsB2 are iv α=β=90°, γ=120°; a=b=2.9047 Å, c=7.4500 Å. The synthesized OsB2 powder was annealed at 1050°C for 6 days, but no phase change was found. This shows that the Hex-OsB2 is very stable. Another promising hard material, AlMgB14, was also studied in this thesis. The AlMgB14 was synthesized at 1050 °C under normal pressure. Several different routes were tried and compared. It shows AlMgB14 cannot be synthesized merely by ball milling, which can bring the risk of oxidization. Magnesium metal is preferred to use as one of the raw materials.

No description available.

Les synthèses par sol-gel non-hydrolytique (SGNH) d'oxydes mixtes Re-Si-Al et Mo-Si-Al sont présentées comme une voie innovante pour la préparation en une étape de catalyseurs hétérogènes de métathèse. Les catalyseurs supportés à base d'oxyde de molybdène sont intéressants du fait de leur faible coût d'achat, de leur résistance mécanique et de leur bonne activité à température modérée. Les catalyseurs supportés à base d'oxyde de rhénium sont connus pour être très actifs et sélectifs même à température ambiante. Cependant ils sont chers et la sublimation de l'oxyde de rhénium pose problème lors de leur synthèse. La synthèse utilisée est basée sur la réaction en une étape des précurseurs chlorés (ReCl5 ou MoCl3, SiCl4, AlCl3) avec du diisopropyléther (iPr2O) à 110 °C dans le dichloromethane. Le faible coût des précurseurs, l'absence de modificateurs de réactivité et de templates ainsi que la simplicité de synthèse rendent le procédé SGNH particulièrement attractif. Les catalyseurs oxydes mixtes obtenus présentent des compositions bien contrôlées, des textures mésoporeuses et avec des densités en sites acides élevées. La caractérisation par DRX, XPS et ToF-SIMS montre que les catalyseurs peuvent être décrits comme une matrice silice-alumine amorphe avec des espèces de surface Mo et Re bien dispersées. Pour les catalyseurs à base de Re, dans les compositions riches en silice, des pertes de rhénium ont été observées durant la calcination. Cette perte de rhenium peut être évitée en augmentant le taux d'alumine dans la composition. De plus, nous avons montré que la sublimation de Re, au cours de la calcination dans les compositions riches en silice, n'a pas lieu quand toutes les étapes du procédé (synthèse, lavage, séchage et calcination) sont réalisées en l'absence d'humidité. Nous avons étudié l'influence de la composition sur la texture, la structure, l'acidité et les propriétés de surface, qui sont corrélées aux performances catalytiques. Les performances des catalyseurs Re-Si-Al et Mo-Si-Al ont été évaluées en métathèse du propène et en métathèse croisée de l'éthène et du trans-2-butène. Les catalyseurs SGNH sont comparés à des catalyseurs avec des compositions similaires préparés par d'autres méthodes (imprégnation, thermal spreading, flame spray pyrolysis). Les catalyseurs préparés par SGNH présentent une très bonne activité spécifique en métathèse. / The non-hydrolytic sol-gel synthesis (NHSG) of Re-Si-Al and Mo-Si-Al mixed oxides was proposed as an innovative one step route to heterogeneous olefin metathesis catalysts. Supported molybdenum oxide catalysts are receiving much attention as a result of their relatively low price, robustness and good activity at low temperature. Supported rhenium oxide catalysts are known to be highly active and selective even at room temperature. However, they are expensive and moderately stable because of the sublimation of the rhenium oxide. The NHSG synthesis used in this work is based on the one pot reaction of chloride precursors (ReCl5 or MoCl3, SiCl4, AlCl3) with diisopropylether (iPr2O) at 110 °C in dichloromethane. The simplicity of NHSG makes it attractive: multi-step procedures, expensive precursors, or reactivity modifiers are not needed. The mixed oxide catalysts exhibited well-controlled compositions and mesoporous textures, with high acid site densities. XRD, XPS and ToF-SIMS showed that the catalysts could be described as an amorphous silica-alumina matrix with well-dispersed Re or Mo surface species. In the case of Re-based catalysts, rhenium losses by sublimation during calcination were observed for the silica-rich formulations. The loss of rhenium could however be avoided by increasing the Al content. More importantly we demonstrate that Re sublimation during calcination of silica-rich formulations is suppressed when the whole preparation procedure (synthesis, washing, drying and calcination) is carried out in the absence of water. Particular attention was devoted to the study of the influence of the composition on texture, structure, acidity and surface properties, which were correlated with the catalytic performances. The performance of selected Re-Si-Al and Mo-Si-Al catalysts was evaluated in the metathesis of propene and in the cross-metathesis of ethene and trans-2-butene. The NHSG catalysts were compared to catalysts of similar compositions prepared by other more methods (impregnation, thermal spreading, flame spray pyrolysis). The catalysts prepared by NHSG have a high specific activity in the metathesis reaction.