Depuis la découverte par le Pr. Kagan en 1977 de conditions douces de synthèse du diiodure de samarium (SmI2), ce réactif est rapidement devenu un des meilleurs réducteurs chimiques utilisé en synthèse organique. Cependant, en tant que réducteur mono-électronique, il est souvent employé en quantité sur-stœchiométrique ce qui impose l’utilisation de quantité importante de réactif qui possède par ailleurs une faible solubilité dans le THF (solvant de choix pour ce réactif) ce qui impose également de trop importantes quantités de solvant. Dans ce travail de thèse, nous nous sommes intéressés à l’utilisation de l’électrochimie comme alternative de synthèse de SmI2 pour apporter un certain nombre de solutions aux limitations manifestes de l’utilisation de ce réactif.Dans un premier temps nous avons mis en œuvre une méthode de synthèse du SmI2 grâce à l’utilisation originale d’une anode "sacrificielle" de samarium. Le SmI2 électrogénéré, dosé et parfaitement caractérisé nous a permis de réaliser différentes réactions de formation de liaisons carbone-carbone médiées par ce réactif. Le SmI2 est produit et consommé en continu ce qui réduit considérablement les quantités de solvant habituellement exigées. Cette approche a également permis de préparer et de caractériser d’autres dérivés divalents de samarium souvent plus difficiles à synthétiser. Nous avons ensuite exploré la possibilité d’exploiter cette approche électrochimique pour la mise en place d’une nouvelle procédure catalytique en SmI2. Après avoir mis en évidence l’efficacité de la réduction électrochimique de sels trivalents de samarium en dérivés divalents grâce à l’emploi d’une cathode de samarium, nous avons établi les conditions opératoires d’une nouvelle procédure catalytique en SmI2 assistée par électrochimie évitant ainsi tout additif métallique. Cette approche catalytique a été appliqué avec succès dans différentes réactions de couplage. / Since the seminal reports of Kagan, dedicated to the preparation of samarium diiodides and its usefulness in organic synthesis, SmI2 became one of the most important reducing agents available to the synthetic organic chemist, promoting a multitude of radical and anionic reactions. However, the major limitations according to its preparation remains the concentration of SmI2 in THF (around 0.1M) and the inert atmosphere needed during its manipulation. Therefore, the majority of organic reactions mediated by SmI2 as reductive reagent require a stoichiometric amount or even a large excess.We report herein a new electrochemical method to prepare solutions of samarium diiodide in THF. The simple electrolysis of a samarium rod provides a rapid and straightforward in situ synthesis of SmI2. The electrogenerated complex catalyzes various C-C bond formations. The reagent is produced continuously and leads to efficient organic electrosynthesis with significantly smaller amounts of solvent than usually required. Moreover, samarium metal has been then used for the first time as electrode material to perform an efficient and versatile SmI2 catalytic system assisted by electrochemistry. The established electrocatalytic procedure that excludes any metal additives was successfully applied in various transformations mediated by this useful reagent.

The N=88 isotones lie on the onset of nuclear deformation and have a complicated nuclear structure. To better understand this region, the nuclear levels of ��������Sm were studied in three different �� decay experiments. De-populating ��-rays were measured using the 8�� spectrometer, an array of 20 Compton suppressed Ge detectors. Levels of ��������Sm were populated in varying degrees by three radioactive sources: ��������Pm (J=1���, Q=3454 keV), ��������[superscript m]Eu (J=0���, Q=2303 keV), and ��������[superscipt g]Eu (J=5���, Q=2261 keV), which were all produced at the 88" cyclotron located at LBNL. Among several changes to the existing level structure were the addition of a 0��� level identified at 1603.24 keV, as well as confirming another questioned 0��� assignment of the 1786.47 keV level. Angular correlation analysis was carried out on many different transitions, allowing for spin assignments and the determination of mixing ratios. The results from these three experiments provide extensive new data, and give a fairly complete picture of nuclear levels below about 2 MeV and J���6. The theoretical interpretation of this particular nucleus is still open to question. The data from these experiments, used in conjunction with other studies of nuclei in this same mass region (which are currently underway), may provide further insight into this transition region. / Graduation date: 2003

M.Sc. / Please refer to full text to view abstract

The use of H2O as an additive in SmI2-mediated reductive processes provides access to new transformations and previously inaccessible chemical space. The cyclisation of radicals derived from the selective mono-reduction of Meldrum’s acid derivatives was further investigated and the scope of the methodology expanded to cyclisation cascades. The first general methodology for the reduction of amide-type carbonyls under single electron transfer conditions was developed and applied to the mono-reduction of barbituric acid derivatives, providing an unprecedented direct access to the corresponding hemiaminals with a good degree of stereocontrol. The intermediate acyl-type radicals were in addition successfully exploited in stereoselective radical cyclisations. The hemiaminals derived from mono-reduction and cyclisation of barbituric acid derivatives have been exploited as N-acyliminium equivalents, affording hydrouracils with an excellent degree of regio- and stereoselectivity. Efforts towards the synthesis of the azulene framework of pseudolaric acid B using a model substrate are also described.

Orientador: Celso Dario Ramos / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T18:27:04Z (GMT). No. of bitstreams: 1 Takahashi_MariaEmiliaSeren_M.pdf: 16141939 bytes, checksum: 42dea31b2ec345da45284f3ac4086cfc (MD5) Previous issue date: 2015 / Resumo: Contexto: Apesar do importante potencial dos cálculos dosimétricos para uso clínico em radiosinoviortese (RSV), há poucos dados na literatura sobre este assunto. Neste trabalho, é proposta uma metodologia para dosimetria beta paciente-específica utilizando imagens SPECT/CT para avaliar a dose absorvida por RSV em articulações tratadas com hidroxiapatita marcada com samário-153 (HA-153Sm) e hidroxiapatita marcada com ítrio-90 (HA-90Y). Metodologia: Uma análise voxel-por-voxel foi realizada para construir um mapa de dose absorvida tridimensional para três pacientes tratados com HA-90Y (185MBq) ou HA-153Sm (740MBq). Uma equação genérica de dose absorvida foi utilizada para calcular a dose absorvida no voxel, a partir da atividade intra-voxel obtida da quantificação da imagem SPECT e a sua massa correspondente obtida a partir da imagem CT. Considerando o tamanho do voxel (7.79mmX7.79mmX7.79mm), a energia média e o alcance terapêutico das partículas beta emitidas do 90Y e 153Sm, é assumido que a dose em cada voxel não é afetada pela atividade dos voxels vizinhos. Dados sobre a razão de dose entre HA-90Y e HA-153Sm foram comparados. Resultados: Foram obtidas distribuição espacial da dose absorvida, dose absorvida total e dose absorvida por atividade injetada para cada paciente. A dose absorvida relativa entre HA-90Y e HA- 153Sm foi cerca de 5.5:1. Conclusão: Dosimetria paciente-específica em RSV pode ser uma poderosa ferramenta, especialmente em distribuições heterogêneas de radiotraçadores intra-articulares, quando doses terapêuticas complementares podem ser necessárias. Usando esta metodologia, foi possível demonstrar que podem ser obtidos efeitos terapêuticos comparáveis entre as RSVs realizadas com HA-90Y e HA-153Sm se for utilizada uma atividade cerca 5.5 vezes maior de HA-153Sm / Abstract: Background: Despite the potential clinical importance of dosimetric calculations in radiosynovectomy (RSV), there are very few data in the literature about this topic. In this study, we propose a patient-specific methodology for beta dosimetry using SPECT/CT images to evaluate the absorbed dose of RSV in human joints treated with HA-90Y and HA-153Sm. Methods: A voxel-by-voxel analysis was performed to build a 3D absorbed dose map for three patients treated with HA-90Y (185MBq) or HA-153Sm (740MBq). A generic absorbed dose equation was used to calculate the voxel dose, supported by the voxel activity obtained from quantified SPECT image and the corresponding voxel mass obtained from CT image. Considering the voxel size (7.79mmX7.79mmX7.79mm), the average energy and the therapeutic range of emitted beta particles from 90Y and 153Sm, we assumed that the dose in each voxel is not affected by the activity of neighboring voxels. Data about ratio of absorbed dose between HA-90Y and HA-153Sm were compared. Results: Spatial distribution of absorbed dose, total absorbed dose and absorbed dose per injected activity were obtained for each patient. The calculated relative absorbed dose between HA-90Y to HA-153Sm was about 5.5:1. Conclusions: Patient-specific dosimetry in RSV can be a powerful tool, especially in heterogeneous intra-articular distributions of radiotracer when additional therapeutic doses can be administered. Using this methodology we estimated that it is possible to achieve comparable therapeutic effects for RSV using HA-90Y if one uses activities about 5.5 times greater of HA-153Sm / Mestrado / Clinica Medica / Mestra em Clínica Médica

<p> The energy levels of Sm151 populated in the beta decay of Pm151 have been studied with the aid of magnetic spectrometers. The internal and external conversion spectra were examined with a π√2 spectrometer of 50 cm radius. A Gerholm-type double lens coincidence spectrometer was used to perform electron-beta, electron-electron, electron-gamma and gamma-beta coincidence experiments. In addition, precise measurements of the transition energies obtained by Geiger and Graham (1962) with the Chalk River π√2 iron-free spectrometer are included. A decay scheme based on these results is proposed and speculations are made concerning the possible interpretation of the levels on the basis of the Nilsson model. The results are also compared with other recently published data on this decay.</p> / Thesis / Doctor of Philosophy (PhD)

<p> The alpha-activity of natural samarium has been studied using an ionization chamber. A gridless ionization chamber has been developed in order to obtain high resolution and high sensitivity. The half lives and the energies of the alpha decay of Sm147 and Sm148 were measured where as the alpha-activity of Sm149 and Sm146 could not be detected.</p> <p> Experiments were carried out in order to search for the existence of Particle stable neutron clusters in the range of Mass 6-10 as a component of a nuclear reactor flux and as the product of high energy proton spallation of heavy nuclei.</p> / Thesis / Doctor of Philosophy (PhD)

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Earth and Planetary Sciences, 1982. / Microfiche copy available in Archives and Science / Bibliography: leaves 226-235. / by Mark Albert Sneeringer. / Ph.D.

Developing nanoparticulate delivery systems that will allow easy movement and localisation of a drug to the target tissue and provide more controlled release of the drug in vivo is a challenge for researchers in nanomedicine. The aim of this study was to evaluate the biodistribution of two nano-delivery systems namely, poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing samarium-153 oxide ([153Sm]Sm2O3) as radiotracer and solid lipid nanoparticles (SLNs) containing technetium-99m-methylene diphosphonate (99mTc-MDP), after oral and intravenous administration to rats to prove that orally administered nanoparticles indeed alter the biodistribution of a drug as compared to the drug on its own. Stable samarium-152 oxide ([152Sm]Sm2O3) was encapsulated in polymeric PLGA nanoparticles. These were then activated in a nuclear reactor to produce radioactive [153Sm]Sm2O3 loaded-PLGA nanoparticles. Both the stable nanoparticles as well as the fully decayed activated nanoparticles, were characterized for size, Zeta potential and morphology using dynamic light scattering and scanning electron microscopy (SEM) or transmission electron microscopy (TEM), respectively. SLNs were a form of delivery system which was used to encapsulate the radiotracer, 99mTc-MDP. 99mTc-MDP SLNs were characterized before and after encapsulation for size and Zeta potential. Both nanoparticle compounds were orally and intravenously (IV) administered to rats in order to trace their uptake and biodistribution through imaging and ex vivo biodistribution studies. The PLGA nanoparticles containing [153Sm]Sm2O3 were spherical in morphology and smaller than 500 nm, therefore meeting the objective of producing radiolabelled nanoparticles smaller than 500 nm. Various parameters were optimized to obtain an average particle size ranging between 250 and 300 nm, with an average polydispersity index (PDI) ≤ 0.3 after spray drying. The particles had a Zeta potential ranging between 5 and 20 mV. The Sm2O3-PLGA nanoparticles had an average size of 281 ± 6.3 nm and a PDI average of 0.22. The orally administered [153Sm]Sm2O3-PLGA nanoparticles were deposited in various organs which includes bone with a total of 0.3% of the Injected Dose (ID) per gram vs the control of [153Sm]Sm2O3which showed no uptake in any organs except the GI-tract. The IV injected [153Sm]Sm2O3-PLGA nanoparticles exhibit the highest localisation of nanoparticles in the spleen (8.63%ID/g) and liver (3.07%ID/g). The 99mTc-MDP-labelled SLN were spherical and smaller than 500 nm. Optimization of the MDP-loaded SLN emulsions yielded a slightly higher PDI of ≥0.5 and a size range between 150 and 450 nm. The Zeta potential was between -30 and -2 mV. The MDP-loaded SLN had an average size of 256 ± 5.27 and an average PDI of 0.245.The orally administered 99mTc-MDP SLN had the highest localisation of nanoparticles in the kidneys (8.50%ID/g) and stomach (8.04%ID/g) while the control, 99mTc-MDP had no uptake in any organs except the GI-tract. The IV injected 99mTc-MDP SLN also exhibited a high localisation of particles in the kidneys (3.87%ID/g) followed by bone (2.66%ID/g). Both the IV and oral 99mTc-MDP SLN reported significantly low deposition values in the heart, liver and spleen. Based on the imaging and the biodistribution studies, it can be concluded that there was a significant transfer of the orally administrated radiolabelled nanoparticles from the stomach to other organs vs the controls. Furthermore, this biodistribution of the nano carriers warrants surface modification and optimisation of the nanoparticles to avoid higher particle localisation in the stomach. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Developing nanoparticulate delivery systems that will allow easy movement and localisation of a drug to the target tissue and provide more controlled release of the drug in vivo is a challenge for researchers in nanomedicine. The aim of this study was to evaluate the biodistribution of two nano-delivery systems namely, poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing samarium-153 oxide ([153Sm]Sm2O3) as radiotracer and solid lipid nanoparticles (SLNs) containing technetium-99m-methylene diphosphonate (99mTc-MDP), after oral and intravenous administration to rats to prove that orally administered nanoparticles indeed alter the biodistribution of a drug as compared to the drug on its own. Stable samarium-152 oxide ([152Sm]Sm2O3) was encapsulated in polymeric PLGA nanoparticles. These were then activated in a nuclear reactor to produce radioactive [153Sm]Sm2O3 loaded-PLGA nanoparticles. Both the stable nanoparticles as well as the fully decayed activated nanoparticles, were characterized for size, Zeta potential and morphology using dynamic light scattering and scanning electron microscopy (SEM) or transmission electron microscopy (TEM), respectively. SLNs were a form of delivery system which was used to encapsulate the radiotracer, 99mTc-MDP. 99mTc-MDP SLNs were characterized before and after encapsulation for size and Zeta potential. Both nanoparticle compounds were orally and intravenously (IV) administered to rats in order to trace their uptake and biodistribution through imaging and ex vivo biodistribution studies. The PLGA nanoparticles containing [153Sm]Sm2O3 were spherical in morphology and smaller than 500 nm, therefore meeting the objective of producing radiolabelled nanoparticles smaller than 500 nm. Various parameters were optimized to obtain an average particle size ranging between 250 and 300 nm, with an average polydispersity index (PDI) ≤ 0.3 after spray drying. The particles had a Zeta potential ranging between 5 and 20 mV. The Sm2O3-PLGA nanoparticles had an average size of 281 ± 6.3 nm and a PDI average of 0.22. The orally administered [153Sm]Sm2O3-PLGA nanoparticles were deposited in various organs which includes bone with a total of 0.3% of the Injected Dose (ID) per gram vs the control of [153Sm]Sm2O3which showed no uptake in any organs except the GI-tract. The IV injected [153Sm]Sm2O3-PLGA nanoparticles exhibit the highest localisation of nanoparticles in the spleen (8.63%ID/g) and liver (3.07%ID/g). The 99mTc-MDP-labelled SLN were spherical and smaller than 500 nm. Optimization of the MDP-loaded SLN emulsions yielded a slightly higher PDI of ≥0.5 and a size range between 150 and 450 nm. The Zeta potential was between -30 and -2 mV. The MDP-loaded SLN had an average size of 256 ± 5.27 and an average PDI of 0.245.The orally administered 99mTc-MDP SLN had the highest localisation of nanoparticles in the kidneys (8.50%ID/g) and stomach (8.04%ID/g) while the control, 99mTc-MDP had no uptake in any organs except the GI-tract. The IV injected 99mTc-MDP SLN also exhibited a high localisation of particles in the kidneys (3.87%ID/g) followed by bone (2.66%ID/g). Both the IV and oral 99mTc-MDP SLN reported significantly low deposition values in the heart, liver and spleen. Based on the imaging and the biodistribution studies, it can be concluded that there was a significant transfer of the orally administrated radiolabelled nanoparticles from the stomach to other organs vs the controls. Furthermore, this biodistribution of the nano carriers warrants surface modification and optimisation of the nanoparticles to avoid higher particle localisation in the stomach. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014