Base teórica: Artrite reumatoide (AR) é uma doença autoimune que afeta as articulações e progride de maneira simétrica e erosiva. Além dos achados articulares, pode ocorrer de perda muscular e síndrome da caquexia. Atualmente, não existe um marcador que sirva de preditor da síndrome de caquexia reumatoide. Estudos metabolômicos em pacientes com AR demonstram uma complexidade em encontrar um biomarcador para caquexia. Ademais, não há modelo experimental de caquexia descrito na literatura, mas o modelo de artrite induzida por colágeno (CIA) possui potencial de ser modelo de caquexia reumatoide. A partir deste modelo, pode-se fazer a busca por biomarcadores de caquexia reumatoide via metabolômica. Objetivo: Avaliar o modelo de CIA como modelo experimental de caquexia reumatoide. Avaliar o perfil metabólico da urina no modelo de CIA e correlacionar com parâmetros clínicos de caquexia reumatoide em busca de possíveis biomarcadores. Métodos: Camundongos machos DBA/1J foram induzidos (CIA; n=13) no dia zero e receberam reforço 18 dias após, e grupo mantidos saudáveis sem indução (CO; n=11). Nos dias 0, 18, 25, 35, 45, 55 e 65 após a indução, foram realizados: coleta de urinas; teste de desempenho físico; teste de locomoção espontânea; teste de força; medida do volume do edema da pata traseira; avaliação do escore clínico; pesagem; e avaliação da ingestão alimentar. Após os 65 dias, os animais foram eutanasiados e tecidos musculares (gastrocnêmio – GA; e tibial anterior – TA) foram dissecados para pesagem e realização da razão sarcoplasmática. Os dados foram analisados por ANOVA de duas vias, seguido de Bonferroni, ou teste t de Pearson, com significância a partir de um p<0,05. A urina coletada foi submetida à ressonância nuclear magnética (1D e 2D J-res). Os metabolitos foram identificados via Chenomx (1D) e pelo Birmingham Metabolite Library (BML; 2D J-res). Utilizou-se a o modelo estatístico de PCA, PLSDA e PLSR para criar ranqueamento de metabolitos (significância a partir de um p<0,05). Analizou-se as rotas metabólicas via Metaboanalyst a partir do ranqueamento de metabólitos obtidos. Os metabólitos obtidos foram filtrados para rotas metabólicas que ocorrem no músculo para identificação de potenciais biomarcadores de perda muscular. Resultados: O grupo CIA apresentou redução de até 24% na locomoção espontânea, de até 66% na força e de até 24% no teste de desempenho físico após 35 dias da indução, bem como redução no peso do GA (24%) e TA (25%), e relação sarcoplasmática (22 e 23%, respectivamente) em relação ao grupo CO. Os modelos estatísticos de PCA, PLSDA e PLSR, e o filtro pelas rotas metabólicas relacionadas com o músculo geraram uma lista de 28 metabólitos e relacionados com o desenvolvimento da doença, sendo eles: 3-metilhistidina, 4-aminobutirato, acetilcolina, arginina, aspartato, carnosina, creatina, creatinina, glutamina, histamina, histidina, isoleucina, leucina, metionina, lisina, mio-inositol, dimetilglicina, acetilalanina, acetilmetionina, pantotenato, fenilalanina, fosfocolina, fosfocreatina, piridoxina, sarcosina, succinilacetona, tiamina, e urocanato. Conclusão: Em concordância com os resultados de redução nos parâmetros de: massa muscular, locomoção espontânea, força e desempenho físico, somando-se a ausência de anorexia bem como mudança no peso, o modelo animal de CIA representa um modelo experimental próprio para caquexia reumatoide. A análise do perfil metabólico deste modelo permite sugerir 28 metabólitos relacionados ao processo de perda muscular, que podem vir a ser biomarcadores de caquexia reumatoide, objetivando prognóstico, diagnóstico e acompanhamento da síndrome. Destes metabólitos, os principais são pertencentes ao metabolismo de: histidina; arginina e prolina; glicina, serina e treonina; fosfocreatina, bem como outros aminoácidos e vitaminas do complexo B. / Background: Rheumatoid Arthritis (RA) is an autoimmune disease that affects the joints and has a symmetric development and it is erosive. Besides joint damage, it can develop muscle loss progress into cachexia syndrome. Currently, there is no marker that can predict it development in rheumatoid patients. Metabolomics in RA have shown to be complex to find out a biomarker for this syndrome. Also, there is no experimental model of cachexia described in literature yet; however the collageninduced arthritis (CIA) animal model seems to be a feasible model for rheumatoid cachexia. With this model, the research for a biomarker of rheumatoid cachexia can be done by metabolomics. Objectives: It will be evaluated if the CIA animal model can be also an animal model of rheumatoid cachexia. Afterwards, it will be evaluated a metabolic profile from urine of this animal model and correlate with clinical signs of rheumatoid cachexia to find out plausible biomarkers of it. Methods: Male DBA/1J mice were submitted to CIA (n=13), immunization occurred at day zero and a booster was performed 18 days after, and a healthy group with no induction (CO; n=11). At the 0,18, 25, 35, 45, 55 and 65 days after the first injection, it was done: urine collection; physical performance test; free exploratory locomotion test; strength test; hindpaw edema volume measurement; follow up disease development; weighted; and food intake. After the 65 days, animals were euthanized and muscle (gastrocnemious – GA; and tibial anterior – TA) were dissected, and weighted for sarcoplasmic ratio. Data were analyzed by two-way ANOVA followed by Bonferroni post hoc, and t-test of Pearson, and statistical critical limit was set for p<0.05. The collected urine was used for nuclear magnetic resonance (1D and 2D J-res). Metabolites were identified by Chenomx (1D) and by the Birmingham Metabolite Library (BML; 2D J-res). Statistical model were performed using PCA, PLSDA and PLSR to create a ranking list of the metabolites (statistical critical limit was set for p<0.05). It was analyzed the metabolic pathway by Metaboanalyst from the data of metabolite ranking list. Then, the metabolite list was filtered by the metabolic pathways that take place in muscle tissue, in order to identify plausible biomarkers of muscle loss. Results: CIA group has shown reduction in up to 24% of free locomotion fatigue, up to 66% of strength and up to 24% of endurance physical performance after 35 days of the induction, as well as a decrease in GA (24%) and TA (25%) weight, and sarcoplasmic ratio also reduced (22 and 23%, respectivamente) related to CO group. The PCA, PLSDA and PLSR statistical models, and the filter by metabolic pathways related to muscle provided a list of 28 metabolites related to disease development, as can be listed: 3-methylhistidine, 4-aminobutyrate, acetylcholine, arginine, aspartate, carnosine, creatine, creatinine, glutamine, histamine, histidine, isoleucine, leucine, methionine, lysine, myo-inositol, dimethylglycine, acetylalanine, acetylmethionine, pantothenate, phenylalanine, phosphocholine, phosphocreatine, pyridoxine, sarcosine, succinylacetone, thiamine, and urocanate. Conclusions: Accordingly with the data with reduction of: muscle mass, spontaneous locomotion, strength and physical performance, added with absence of anorexia as well as weight change, CIA animal model is a feasible experimental model for rheumatoid cachexia. Concerning the metabolic profile from this model, it can be suggested 28 metabolites related to muscle loss in which can be tested for biomarker of rheumatoid cachexia, targeting prognosis, diagnosis, and syndrome follow up. From those metabolites, the main ones are engaged to metabolism of: histidine; arginine and proline; glycine, serine and threionine; phosphorcreatine, as well as other amino acids and vitamins from B complex.

Os alcaloides têm apresentado diversas atividades biológicas. Entre eles, a montanina vem demonstrando um bom desempenho nesse sentido, como, atividade antioxidante, ação inibitória do crescimento de culturas bacterianas e importante atividade de inibição do crescimento de linhagens tumorais. Atualmente, não existem muitos relatos da sua caracterização ou métodos analíticos quantitativos disponíveis na literatura para atribuir seu teor. Assim, após purificação, a caracterização da montanina foi realizada por calorimetria exploratória diferencial (DSC), espectroscopia na região do ultravioleta (UV), infravermelho (IV), espectrometria de massas (CLAE-EM), ressonância magnética nuclear de hidrogênio (RMN1H), de carbono (RMN13C) e em 2D homo e heteronucleares tais como COSY (nJH-H, escalar), NOESY (nJH-H, dipolar), HSQC (1JH-C, escalar) e HMBC (nJH-C, escalar). Na sequência, foram desenvolvidos métodos empregando a cromatografia líquida de alta eficiência (CLAE) acoplada aos detectores ultravioleta e aerossol carregado (CLAE- UV/DAC) para a quantificação da montanina. Os mesmos foram validados, avaliando-se os parâmetros de especificidade, linearidade, intervalo, limite de detecção, limite de quantificação, precisão, exatidão e robustez. Os resultados obtidos foram avaliados por estatística descritiva e os métodos comparados pelo resultado da análise de variância (ANOVA). Desse modo, foram desenvolvidos procedimentos que podem ser aplicados para aprimorar o controle de qualidade, contribuindo para assegurar a eficácia terapêutica da montanina. / Alkaloids have several biological activities. Among them, montanine have shown antioxidant activity, inhibitory effect on bacterial growth and important activity inhibiting growth of some tumor cell lines. Currently, there are a few reports about its characterization as well as quantitative analytical methods to determine its purity. Thus, after a purification step, montanine will be characterized by its differential scanning calorimetry (DSC), ultraviolet spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (HPLC-MS), nuclear magnetic resonance of proton (NMR1H), carbon (NMR13C) and 2D homo and heteronuclear such as COSY (nJH-H, scalar), NOESY (nJH-H, dipolar), HSQC (1JH-C, scalar) and HMBC (nJH-C, scalar). Further, quantitation methods will be developed employing high-performance liquid chromatography (HPLC) coupled with ultraviolet and charged aerosol detectors (HPLC-UV/CAD). These methods will be validated regarding the parameters specificity, linearity, range, detection limit, quantitation limit, precision, accuracy and robustness. The results will then be evaluated by descriptive statistics and the developed methods will be compared using analysis of variance (ANOVA). Therefore, tests will be developed that can be used to improve quality control, helping to ensure the therapeutic efficacy of montanine.

Abstract This thesis reports simulations of direct observables in electron and nuclear spin relaxation experiments in an example paramagnetic system, as well as polarization transfer occurring in a spin-exchange optical pumping (SEOP) experiment. Studies of paramagnetic relaxation are important, e.g., in the development of agents used for enhanced contrast in magnetic resonance imaging. SEOP is used to produce hyperpolarized noble gases, which are then used to, e.g., enhance sensitivity in structural studies of matter with nuclear magnetic resonance. Presently the theory, available software and hardware for such computational modeling have reached a state in which quantitative reproduction of the experimentally observed magnetization decay is possible from first principles. The present multiscale computations are carried out from first principles combining molecular dynamics simulations of atomistic motion and quantum-chemical electronic structure calculations of the spin interaction parameters that enter the effective spin Hamiltonian. A time series of the spin Hamiltonian is then explicitly used to propagate spin dynamics in the system, and dynamical time constants of the magnetization are obtained through ensemble averaging. The complete decay of electron spin magnetization could be followed directly within the duration of the simulation, whereas the nuclear spin relaxation rates were extracted using Kubo’s theory regarding generalized cumulant expansion and stochastic processes. The extracted electron and nuclear spin relaxation rates for the chosen prototypic system, the aqueous solution of Ni²⁺, are in quantitative and semi-quantitative agreement, respectively, with the available experimental results. The simulations of polarization transfer corroborate the empirical observations on the importance of van der Waals complexes and binary collisions in the spin-exchange process. Long van der Waals complexes represent the overwhelmingly most significant kind of individual events, but the short binary collisions can also give a relatively important contribution due to their vast abundance. This thesis represents a first study in which first principles-calculated trajectories of individual events could be followed. The simulations reported in this thesis were run without any empirical parametrization and thus represent a significant step in first-principles computational modeling of magnetization dynamics.

This thesis combines synthetic studies for isotopic enrichment with solid-state characterisation techniques to investigate two classes of microporous materials: zeolites and metal-organic frameworks (MOFs). These materials have a wide range of successful applications, from industrial catalysis to medicine, resulting in the increasing need for both a complete understanding of their unique structural features and synthetic methods to target new frameworks. Nuclear magnetic resonance (NMR) spectroscopy, thanks to its sensitivity to the local, atomic-scale, environment and its element specificity, is applied, in combination with powder X-ray diffraction (PXRD), electron microscopy, N2 adsorption and mass spectrometry, to the study of these materials. Oxygen atoms play a crucial role in the structure and chemistry of zeolites and MOFs, making 17O NMR an excellent tool for chemical and structural investigations. However, the low natural abundance of this isotope (0.037%) and the cost of 17O-enriched reactants require the development of atom-efficient synthetic processes for isotopic enrichment. In the first part of this work, the unconventional assembly-disassembly-organisation-reassembly (ADOR) method is applied to the Ge-doped UTL framework and optimised in reduced-volume conditions for economic enrichment to obtain 17O- and 29Si-enriched UTL-derived zeolites. In situ and ex situ solid-state characterisation studies show that isotopic enrichment not only enables a more detailed spectroscopic investigation, but also provides new insights into the mechanism of the ADOR process and its sensitivity to experimental conditions. In the second part of this work, dry gel conversion synthesis and a novel steaming procedure are studied as cost-effective 17O-enrichment pathways for Al, Ga and Sc mixed-metal terephthalate MOFs. 17O solid-state NMR spectroscopy, in combination with PXRD and electron microscopy, is employed to investigate cation disorder and 17O NMR spectra are shown to be sensitive to substitution of metal centers and conformational changes upon interaction with guest molecules.

Magister Scientiae - MSc / In this study two medicinal plant species, namely Galenia africana and Elytropapus rhinocerotis, the former belonging to the family Aizoceae and the latter belonging to the family Asteraceae, have been investigated and different compounds isolated and characterized. Both species are important plants used in traditional medicine in Africa and particularly in South Africa. Flavanoids are secondary metabolites found in plants. They have a protective function against UV radiation and have a defence against invading illnesses due to their important antioxidant activity. Much of the food we eat and some beverages we drink contain flavonoids. The aim of this study was to investigate the electrochemistry of flavanoids isolated from these species. / South Africa

Made available in DSpace on 2015-08-19T13:52:53Z (GMT). No. of bitstreams: 2 5.pdf: 3872815 bytes, checksum: 455a971c4daecfecb98403b32be14999 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2012 / Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos/Farmanguinhos. Rio de Janeiro, RJ, Brasil. / O efavirenz (EFA) está classificado como um fármaco de classe II, pois é pouco hidrossolúvel e altamente permeável pelo trato gastrointestinal. Estas duas características básicas são essenciais para sua biodisponibilidade. Assim, a escolha de uma formulação adequada para esse fármaco é essencial no desenvolvimento de comprimidos, para garantir melhor disponibilização no trato gastrointestinal, de forma a alcançar a biodisponibilidade e o efeito terapêutico desejados. Nesse trabalho, oEFA e a mistura EFA:polivinilpirrolidona (PVP), preparados por processos de micronização com intuito de aumentar a dissolução do fármaco, foram espectroscopicamente estudados e caracterizados. No caso do EFA sua estrutura foi modelada usando o método B3LYP com intuito de auxiliar na análise dos resultados experimentais. A caracterização espectroscópica foi realizada utilizando diversas técnicas como infravermelho (IV) e ressonância magnética nuclear (RMN)em solução e de sólidos. A análise térmica por calorimetria diferencial de varredura(DSC) e a análise termogravimétrica (TGA) mostraram que os processos de comicronização não afetaram a estrutura cristalina do fármaco puro e nem a do fármaco nas misturas. A RMN comprovou a integridade dos mesmos, em solução eno estado sólido, indicando que o EFA encontra-se dimerizado. Os estudos de RMN também mostraram que, tanto no estado líquido quanto no sólido, ocorrem interações intermoleculares via ligação de hidrogênio do EFA com a PVP. Os espectros de RMN de sólido indicaram que ocorre dissolução parcial do EFA na matriz polimérica / Efavirenz (EFA) is classified as a class II drug because it is poorly water soluble and highly permeable through the gastrointestinal tract. These two basic characteristics are essential for its bioavailability. Thus, the choice of a suitable formulation for this drug is essential in the development of tablets to ensure better gastrointestinal tract in order to achieve both the bioavailability and the therapeutic effect desired. In this work, EFA and the blends EFA:polyvinylpyrrolidone (PVP) were prepared by spray drying and grinding processes in order to increase the solubility of the drug, were studied and characterized spectroscopically. In the case of EFA its structure was modeled using the B3LYP in order to aid the analysis of the experimental results. The spectroscopic characterization was performed using various techniques such as infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) in solution and solid state. Thermal analysis by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), showed that the micronization process neither affected the crystal structure of the pure drug nor the drug in blends. NMR confirmed the integrity of the solution and the solid form and identified that the EFA is dimerized. The NMR studies also showed that both liquid and solid interactions occur via intermolecular hydrogen bonding of EFA with PVP. The NMR spectra indicated that occurs the solid partial dissolution of the EFA in the polymer matrix.

Base teórica: Artrite reumatoide (AR) é uma doença autoimune que afeta as articulações e progride de maneira simétrica e erosiva. Além dos achados articulares, pode ocorrer de perda muscular e síndrome da caquexia. Atualmente, não existe um marcador que sirva de preditor da síndrome de caquexia reumatoide. Estudos metabolômicos em pacientes com AR demonstram uma complexidade em encontrar um biomarcador para caquexia. Ademais, não há modelo experimental de caquexia descrito na literatura, mas o modelo de artrite induzida por colágeno (CIA) possui potencial de ser modelo de caquexia reumatoide. A partir deste modelo, pode-se fazer a busca por biomarcadores de caquexia reumatoide via metabolômica. Objetivo: Avaliar o modelo de CIA como modelo experimental de caquexia reumatoide. Avaliar o perfil metabólico da urina no modelo de CIA e correlacionar com parâmetros clínicos de caquexia reumatoide em busca de possíveis biomarcadores. Métodos: Camundongos machos DBA/1J foram induzidos (CIA; n=13) no dia zero e receberam reforço 18 dias após, e grupo mantidos saudáveis sem indução (CO; n=11). Nos dias 0, 18, 25, 35, 45, 55 e 65 após a indução, foram realizados: coleta de urinas; teste de desempenho físico; teste de locomoção espontânea; teste de força; medida do volume do edema da pata traseira; avaliação do escore clínico; pesagem; e avaliação da ingestão alimentar. Após os 65 dias, os animais foram eutanasiados e tecidos musculares (gastrocnêmio – GA; e tibial anterior – TA) foram dissecados para pesagem e realização da razão sarcoplasmática. Os dados foram analisados por ANOVA de duas vias, seguido de Bonferroni, ou teste t de Pearson, com significância a partir de um p<0,05. A urina coletada foi submetida à ressonância nuclear magnética (1D e 2D J-res). Os metabolitos foram identificados via Chenomx (1D) e pelo Birmingham Metabolite Library (BML; 2D J-res). Utilizou-se a o modelo estatístico de PCA, PLSDA e PLSR para criar ranqueamento de metabolitos (significância a partir de um p<0,05). Analizou-se as rotas metabólicas via Metaboanalyst a partir do ranqueamento de metabólitos obtidos. Os metabólitos obtidos foram filtrados para rotas metabólicas que ocorrem no músculo para identificação de potenciais biomarcadores de perda muscular. Resultados: O grupo CIA apresentou redução de até 24% na locomoção espontânea, de até 66% na força e de até 24% no teste de desempenho físico após 35 dias da indução, bem como redução no peso do GA (24%) e TA (25%), e relação sarcoplasmática (22 e 23%, respectivamente) em relação ao grupo CO. Os modelos estatísticos de PCA, PLSDA e PLSR, e o filtro pelas rotas metabólicas relacionadas com o músculo geraram uma lista de 28 metabólitos e relacionados com o desenvolvimento da doença, sendo eles: 3-metilhistidina, 4-aminobutirato, acetilcolina, arginina, aspartato, carnosina, creatina, creatinina, glutamina, histamina, histidina, isoleucina, leucina, metionina, lisina, mio-inositol, dimetilglicina, acetilalanina, acetilmetionina, pantotenato, fenilalanina, fosfocolina, fosfocreatina, piridoxina, sarcosina, succinilacetona, tiamina, e urocanato. Conclusão: Em concordância com os resultados de redução nos parâmetros de: massa muscular, locomoção espontânea, força e desempenho físico, somando-se a ausência de anorexia bem como mudança no peso, o modelo animal de CIA representa um modelo experimental próprio para caquexia reumatoide. A análise do perfil metabólico deste modelo permite sugerir 28 metabólitos relacionados ao processo de perda muscular, que podem vir a ser biomarcadores de caquexia reumatoide, objetivando prognóstico, diagnóstico e acompanhamento da síndrome. Destes metabólitos, os principais são pertencentes ao metabolismo de: histidina; arginina e prolina; glicina, serina e treonina; fosfocreatina, bem como outros aminoácidos e vitaminas do complexo B. / Background: Rheumatoid Arthritis (RA) is an autoimmune disease that affects the joints and has a symmetric development and it is erosive. Besides joint damage, it can develop muscle loss progress into cachexia syndrome. Currently, there is no marker that can predict it development in rheumatoid patients. Metabolomics in RA have shown to be complex to find out a biomarker for this syndrome. Also, there is no experimental model of cachexia described in literature yet; however the collageninduced arthritis (CIA) animal model seems to be a feasible model for rheumatoid cachexia. With this model, the research for a biomarker of rheumatoid cachexia can be done by metabolomics. Objectives: It will be evaluated if the CIA animal model can be also an animal model of rheumatoid cachexia. Afterwards, it will be evaluated a metabolic profile from urine of this animal model and correlate with clinical signs of rheumatoid cachexia to find out plausible biomarkers of it. Methods: Male DBA/1J mice were submitted to CIA (n=13), immunization occurred at day zero and a booster was performed 18 days after, and a healthy group with no induction (CO; n=11). At the 0,18, 25, 35, 45, 55 and 65 days after the first injection, it was done: urine collection; physical performance test; free exploratory locomotion test; strength test; hindpaw edema volume measurement; follow up disease development; weighted; and food intake. After the 65 days, animals were euthanized and muscle (gastrocnemious – GA; and tibial anterior – TA) were dissected, and weighted for sarcoplasmic ratio. Data were analyzed by two-way ANOVA followed by Bonferroni post hoc, and t-test of Pearson, and statistical critical limit was set for p<0.05. The collected urine was used for nuclear magnetic resonance (1D and 2D J-res). Metabolites were identified by Chenomx (1D) and by the Birmingham Metabolite Library (BML; 2D J-res). Statistical model were performed using PCA, PLSDA and PLSR to create a ranking list of the metabolites (statistical critical limit was set for p<0.05). It was analyzed the metabolic pathway by Metaboanalyst from the data of metabolite ranking list. Then, the metabolite list was filtered by the metabolic pathways that take place in muscle tissue, in order to identify plausible biomarkers of muscle loss. Results: CIA group has shown reduction in up to 24% of free locomotion fatigue, up to 66% of strength and up to 24% of endurance physical performance after 35 days of the induction, as well as a decrease in GA (24%) and TA (25%) weight, and sarcoplasmic ratio also reduced (22 and 23%, respectivamente) related to CO group. The PCA, PLSDA and PLSR statistical models, and the filter by metabolic pathways related to muscle provided a list of 28 metabolites related to disease development, as can be listed: 3-methylhistidine, 4-aminobutyrate, acetylcholine, arginine, aspartate, carnosine, creatine, creatinine, glutamine, histamine, histidine, isoleucine, leucine, methionine, lysine, myo-inositol, dimethylglycine, acetylalanine, acetylmethionine, pantothenate, phenylalanine, phosphocholine, phosphocreatine, pyridoxine, sarcosine, succinylacetone, thiamine, and urocanate. Conclusions: Accordingly with the data with reduction of: muscle mass, spontaneous locomotion, strength and physical performance, added with absence of anorexia as well as weight change, CIA animal model is a feasible experimental model for rheumatoid cachexia. Concerning the metabolic profile from this model, it can be suggested 28 metabolites related to muscle loss in which can be tested for biomarker of rheumatoid cachexia, targeting prognosis, diagnosis, and syndrome follow up. From those metabolites, the main ones are engaged to metabolism of: histidine; arginine and proline; glycine, serine and threionine; phosphorcreatine, as well as other amino acids and vitamins from B complex.

Orientador: Prof. Dr. Caetano Rodrigues Miranda / Tese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Nanociências e Materiais Avançados, 2015. / A presente Tese baseia-se nas aplicacoes das propriedades de Ressonancia Magnetica Nuclear (RMN) de Liquidos e de Estado Solido para entender alguns processos que ocorrem na dinamica de sistemas de interesse para a Industria do Petroleo via simulacoes computacionais moleculares. Portanto, na primeira parte, utilizou-se metodos de primeiros principios para caracterizar o processo de degradacao da pasta cimenticia e, a adsorcao de hidrocarbonetos em superficies minerais. Dessa forma, foi possivel avaliar sistemas de diferentes dimensoes desde de estruturas 3D ate 0D a partir de simulacoes baseadas na Teoria do Funcional da Densidade, com e sem van der Waals (vdW) para calcular os parametros espectrais de RMN. Por meio de simulacoes de RMN de Estado Solido, investigou-se o processo de degradacao da pasta cimenticia, conhecido como ataque tardio da etringita que ocorre por meio de reacoes do gesso hidratado (CaSO4.2H2O) com o aluminato tricalcico (Ca3Al2O6) formando o composto chamado etringita (Ca6Al2(OH)12.(SO4)3.26H2O). Os resultados para as tres estruturas bulk ou 3D, a partir dos nucleos de 43Ca, 33S, 27Al e 17O, mostraram, em particular, que os nucleos de calcio garantem indicacoes suficientes da estrutura que esta sendo avaliada, principalmente para o caso da etringita. Isso mostra que a coordenacao altera os espectros, uma vez que afeta o ambiente quimico local. Os sistemas de 2D representados pelas superficies de calcita (CaCO3 ) e silica (SiO2 ¿¿-quartzo (0001) hidrofobica e hidrofilica) foram igualmente abordados via simulacoes computacionais de RMN do Estado Solido. A calcita e a silica sao os principais constituintes das rochas sedimentares nos reservatorios de petroleo e uma caracterizacao detalhada da interacao dessas superficies minerais com hidrocarbonetos representativos do oleo e bastante oportuna. Para a primeira superficie, os espectros dos sitios de calcio garantiram informacoes a respeito local e o tipo de adsorbato. Similarmente para a segunda, as assinaturas dos nucleos de 17O permitiram observar a presenca dos adsorbatos na superficie bem como o tipo de superficie analisada. A segunda parte do estudo abrange as estruturas 0D, em que utilizou-se nanoparticulas (NPs) de SiO2 funcionalizadas com etileno glicol (EG) e acido sulfonico (AS) em solucao para obtencao dos tempos de relaxacao de RMN transversal (T2). A partir de simulacoes de Dinamica Molecular Classica pode-se observar que os sinais de T2 das moleculas de agua para o sistema bulk aproximam-se dos valores obtidos experimentalmente, validando o metodo. Com a adicao das NPs, os sinais de T2 sao devido a forte adsorcao da superficie hidrofilica das NPs de SiO2 com as moleculas de agua. Assim, podemos sugerir que a tecnica de RMN simulada pode ser uma ferramenta poderosa na analise de reservatorios, uma vez que perturbacoes no sistema podemser, efetivamente, detectadas. Alem de exercer papel importante na Recuperacao Avancada de Petroleo. / In this Thesis we explore computational applications of Nuclear Magnetic Resonance (NMR) properties to understand some dynamic processes that occur in the oil reservoir systems. Therefore, we used first principles methods to characterize the delayed ettringite attack (DEA) and the adsorption of hydrocarbon molecules in the mineral surfaces. In this way, it was possible to evaluate different system dimensions since 3D to 0D nanostructures by computational simulations based on Density Functional Theory, with or without van der Waals (vdW) dispersion corrections, to achieve the Solid State Nuclear Magnetic Resonance (SSNMR) parameters. Through SSNMR simulations, cement phases: gypsum dihydrate (CaSO4.2H2O), tricalcium aluminate (Ca3Al2O6) and ettringite (Ca6Al2(OH)12.(SO4)3.26H2O), which are directly involved on DEA process were investigated. The results for the three bulk or 3D nanostructures from 43Ca, 33S, 27Al and 17O nuclei, shown in particular that calcium nuclei ensure sufficient guidance of the structure which is being evaluated, especially in the case of ettringite. This study shows that the coordination change the spectra, since it affects local chemical environment. The 2D systems represented by calcite (CaCO3 ) and silica (SiO2 ¿¿-quartzo (0001) hidrofobica e hidrofilica) surfaces were analyzed via ab initio SSNMR. Since calcite and silica is a major constituent of sedimentary rocks in oil reservoir, a more detailed characterization of the interaction between hydrocarbon molecules and mineral surfaces is highly desirable. Our results show a chemical shift differentiation for atoms located on different sites (bulk and surface) for calcite and silicate systems. Interestingly, the presence of hydrocarbon molecules also modifies the chemical shift of adsorbed the Ca and O sites for both surfaces, respectively. The second part concerns the 0D nanostructures, which is represented by SiO2 nanoparticles functionalized with ethylene glycol (EG) and sulfonic acid (SA). These NPs were immersed on water solution to obtain the relaxation time distribution, especially T2, by Molecular Dynamics simulations. It was found that the correlation function of water when the SiO2 is present takes longer because the water molecules can not rotate easily because the hydrophilic silica surface has a strong adsorption property. Therefore, T2 relaxation time is decreased compared to the bulk water and this is probably related to the fact that there is a hydrophilic silica surface in the system. Thus, we suggest that the simulated NMR technique can be a powerful tool in the analysis containers, since disturbances in the system can be effectively detected. In addition to play an important role in Enhanced Oil Recovery (EOR).

Ce travail de thèse s’articule autour de la synthèse et de la caractérisation d’hydroxydes doubles lamellaires (HDLs) par une approche combinant spectroscopie vibrationnelle, RMN du solide et diffraction des rayons X. Les objectifs portent sur la description de la distribution cationique dans les feuillets ainsi que sur l’étude des propriétés structurales et dynamiques des espèces interfoliaires. Les investigations sont principalement menées pour des HDLs de type MgII/AlIII (ratio compris entre 2 et 4) avec une complexification progressive des espèces intercalées : de l’anion carbonate pour lequel les matériaux possèdent une affinité préférentielle, à d’autres anions inorganiques comme les halogénures, le perchlorate et le nitrate, pour finir sur des hybrides organo-minéraux formés par intercalation d’anions organiques/biomolécules (acides aminés et cyclodextrines). Les recherches effectuées ont permis de mettre en évidence un ordre cationique local au sein des feuillets, conservé après échange anionique. Par ailleurs, il a été possible de rationaliser les comportements propres à chaque espèce anionique dans l’espace interfoliaire, qui dépendent fortement de la densité de charge des feuillets, ainsi que du taux d’hydratation des composés. En particulier, la coexistence des anions carbonate et hydrogénocarbonate dans l’espace interfoliaire et leur dynamique d’échange avec le dioxyde de carbone atmosphérique sont révélées. D’autre part, une nouvelle sonde de dynamique interfoliaire par RMN 27Al est proposée. Enfin, l’étude pas à pas des HDLs intercalant tout d’abord l’oxalate puis des acides aminés a permis le transfert des connaissances obtenues pour les HDLs inorganiques aux hybrides organo-minéraux. Le manuscrit se termine sur une application des hybrides contenant des cyclodextrines pour le traitement d’eaux polluées par des composés organiques polycycliques / This thesis work is based on the synthesis and the characterization of layered double hydroxides (LDHs) by an approach combining vibrational spectroscopy, solid-state NMR and X-ray diffraction. The objectives include a description of the cations distribution in the layers, as well as a study of the structural and dynamic properties of the interlayer species. Investigations are mainly carried out for MgII/AlIII LDHs (ratio between 2 and 4) with an increased complexity of the intercalated species: from carbonate for which the materials have a preferential affinity, to other inorganic anions such as halides, perchlorate and nitrate, to finish with organo-mineral hybrids obtained by intercalation of organic anions/biomolecules (amino acids and cyclodextrins).The research carried out highlighted a local cationic order in the layers, preserved after anionic exchange. Furthermore, it has been possible to rationalize the behaviour of each anion in the interlayer space, which strongly depends on the layers charge density, as well as on the hydration state of the compounds. In particular, the coexistence between carbonate and hydrogenocarbonate anions in the interlayer space and their dynamic exchange with atmospheric carbon dioxide are revealed. On the other hand, a new interlayer dynamics probe by 27Al NMR is proposed. Finally, the step-by-step study of LDHs, first intercalating oxalate and then amino acids, allowed the transfer of the knowledge obtained for inorganic LDHs to organo-mineral hybrids. The manuscript ends with an application of cyclodextrins-containing hybrids for the treatment of water polluted with polycyclic organic compounds

Made available in DSpace on 2016-06-02T20:18:09Z (GMT). No. of bitstreams: 1 TeseFVS.pdf: 3401633 bytes, checksum: b22a99a2e3db18dc60852a024a747b7f (MD5) Previous issue date: 2004-02-05 / Universidade Federal de Minas Gerais / studies about muscle regeneration and injury used invasive methods in animals. Although the muscle regeneration process in many mammals is similar to the one found in humans, it is necessary to improve the application of non-invasive procedures used in the evaluation of the muscle regeneration and injury in humans. Non-invasive techniques such as surface electromyography, isokinetic dynamometry and nuclear magnetic resonance (NMR) for imaging have been used in studies in humans for the evaluation of the skeletal muscle. However, studies in which all these procedures are used together, allowing a more detailed evaluation of the muscle morphology and function, are rare.Thus, the aim of this study was to evaluate the behaviour of the medium maximal isometric torque, the electrical activity and the muscle pain before the injury, during the 7 days after the injury and also between the 21st and 30th days after the injury, when the muscle has already regenerated. For this, a injury was induced in the quadriceps femoris muscle through intense eccentric exercise. To confirm if the model utilized was effective to produce the muscle injury, the plasma activity of the creatine kinase (CK) was also evaluated and the NMR for imaging of the quadriceps femoris muscle was realized. Ten university student volunteers (21,9±1,5), sedentary and without musculoskeletal dysfunction in the lower right limb participated in this study. The extensor medium maximal isometric torque was evaluated through maximal isometric contraction with the knee joint at 90º of flexion, in the isokinetic dynamometer (Biodex Multi-joint System 2 da BIODEX MEDICAL SYSTEM Inc). The electrical activity (Root Mean Square-RMS and Median Frequency) of the vastus medialis oblique (VMO), vastus lateralis (VL) and rectus femoris (RF) muscles was analysed simultaneously to mensuration of the isometric torque, utilizing a Digital Analogue Conversor A/D (LYNX) and single differential active electrodes of surface (LYNX). The quantitative and qualitative analysis of the pain were realized by Visual Analogue Scale (VAS) and by Brazilian Version of Short-Form McGill Pain Questionnaire. The activity of CK was measured utilizing the Kit CK-NAC UV unitest (Wiener lab) and the NMR was realized in the ToRM 0.5 equipment. For the induction of quadriceps femoris muscle injury, the volunteers were submitted to 4 series of 15 maximal eccentric isokinetic contractions, at angle velocity 5º.s-1. The results of this study demonstrated that the medium maximal isometric torque reduced significantly until the 4th day after the eccentric exercise (immediately after and 1st - 4th days after, p<0.01; 4th day after, p<0.05). The RMS of the VMO, VL and RF muscles reduced significantly the 2nd day after (p<0.01, p<0.01 e p<0.05, respectively). However, the RMS of the VL and RF muscles between the 21st and 30th days was significantly greater than before the exercise (p<0.01). There wasn t alteration in the median frequency after tthe eccentric exercise (VMO, p= 0.90; VL, p= 0.55 e RF, p= 0.89). The intensity of pain was greater until the 3rd day, and the peak occurred in the 2nd day after (p<0.01). The McGill Pain Questionnaire demonstrated that the word heavy was the most used to describe the pain after the induced injury by eccentric exercise. The peak of activity of the CK occurred in the 2nd day after the eccentric exercise(p<0.05). The evaluation by NMR demonstrated that the greatest extension of injury occurred in the 2nd and 7th days after, and some voluteers still showed injury sign between the 21st and 30th days. In conclusion, the eccentric exercise reduced the medium maximal isometric torque, increased the activity of the CK, changed the RMS and resulted in pain, which were gradually recovered in one week, despite the presence of muscle injury. / A maioria dos estudos sobre a lesão e regeneração muscular utilizou métodos invasivos em animais. Embora o processo de regeneração muscular em muitos mamíferos seja similar ao encontrado em humanos, é necessário melhorar a aplicação de procedimentos não-invasivos usados na avaliação da lesão e regeneração muscular em humanos. Técnicas não-invasivas tais como a eletromiografia de superfície, a dinamometria isocinética e a ressonância magnética nuclear (RMN) por imagem têm sido utilizadas em estudos em humanos para a avaliação do músculo-esquelético. No entanto, raros são os estudos em que todos esses procedimentos são utilizados conjuntamente, permitindo uma avaliação mais detalhada da função e da morfologia muscular. Assim, o objetivo desse estudo foi avaliar o comportamento do torque isométrico máximo médio, a atividade elétrica e a dor muscular antes da lesão, durante os 7 primeiros dias pós-lesão e também entre o 21º e 30º dias pós-lesão, quando o músculo já se regenerou. Para isso, foi induzida lesão no músculo quadríceps femoral através de exercício excêntrico intenso. Para comprovar se o modelo utilizado foi efetivo para produzir a lesão muscular, foi também avaliada a atividade plasmática da creatina-quinase (CK) e foi realizada a RMN por imagem do músculo quadríceps femoral. Participaram deste estudo 10 universitárias voluntárias (21,9±1,5), sedentárias e sem qualquer patologia osteomioarticular no membro inferior direito. O torque isométrico máximo médio extensor foi avaliado através de contrações isométricas máximas com a articulação do joelho à 90º de flexão, num Dinamômetro Isocinético (Biodex Multi-joint System 2). A atividade elétrica (Root Mean Square-RMS - Raiz Quadrada da Média dos Quadrados e a Freqüência Mediana) dos músculos vasto medial oblíquo (VMO), vasto lateral (VL) e reto femoral (RF) foi analisada simultaneamente à mensuração do torque isométrico, utilizando-se um Conversor Analógico Digital A/D (LYNX) e eletrodos ativos diferenciais simples de superfície (LYNX). As análises quantitativas e qualitativas da dor foram realizadas pela Escala Visual Analógica Visual Analog Scales (VAS) e pela Versão Brasileira Resumida do Questionário McGill de Dor. A atividade da CK foi mensurada utilizando-se o Kit CK-NAC UV unitest e a RMN foi realizada no equipamento ToRM 0.5. Para a indução da lesão no músculo quadríceps femoral, as voluntárias foram submetidas a 4 séries de 15 contrações isocinéticas excêntricas máximas, à velocidade angular de movimento de 5º/s. Os resultados deste estudo demonstraram que o torque isométrico máximo médio diminuiu significativamente até o 4º dia após o exercício excêntrico (imediatamente após e do 1º ao 3º dias após, p<0,01; 4º dia após, p<0,05) . O RMS dos músculos VMO, VL e RF diminuiu no 2º dia após o exercício (p<0,01, p<0,01 e p<0,05, respectivamente). Entretanto, o RMS dos músculos VL e RF entre o 21º e 30 º dias foi maior ao antes do exercício (p<0,01). Não houve alteração na freqüência mediana após o exercício excêntrico (VMO, p= 0,90; VL, p= 0,55 e RF, p= 0,89). A intensidade da dor foi maior até o 3º dia após o exercício excêntrico, com o pico ocorrendo no 2º dia após (p<0,01). O questionário McGill demonstrou que a palavra pesada foi a mais utilizada para caracterizar a dor após a lesão induzida pelo exercício excêntrico. O pico da atividade da CK ocorreu no 2º dia após o exercício excêntrico (p<0,05). A avaliação pela RMN demonstrou que a maior extensão da lesão ocorreu no 2º e 7º dias após, com algumas voluntárias ainda apresentando sinais de lesão entre o 21º e 30º dias. Em conclusão, o exercício excêntrico diminuiu o torque isométrico máximo médio, aumentou a atividade da CK, alterou o RMS e resultou em dor, os quais se recuperaram gradualmente na primeira semana, apesar da presença de lesão muscular.