CAPES; Fundação Araucária / A análise conformacional abrange os aspectos da determinação de estruturas geométricas moleculares, energias relativas de confôrmeros e das interações que controlam as estabilidades estruturais. Neste sentido, as preferências conformacionais dos compostos 3-aminopropanol (1), 3-N-metilaminopropanol (2), 3-N,N-dimetilaminopropanol (3), 3-aminobutanol (4), 3-Nmetilaminobutanol (5) e 3-N,N-dimetilaminobutanol (6) foram avaliadas experimentalmente através de espectroscopias de Infravermelho (IV) e Ressonância Magnética Nuclear (RMN), e teoricamente por cálculos usando a Teoria do Funcional de Densidade (DFT). O estudo destes compostos foi importante porque irá melhorar a compreensão das interações que ocorrem nestas moléculas em diferentes ambientes químicos, uma vez que existe uma ampla gama de amino álcoois com aplicações biológicas e sintéticas. Diante disso, os cálculos teóricos mostraram que a ligação de hidrogênio intramolecular (LHI) O-H ...N governa a estabilidade e a preferência conformacional dos compostos 1-6. A LHI favorece uma conformação do tipo pseudo-cadeira de seis membros com substituintes em posições pseudo-equatoriais e pseudo-axiais, os quais apresentam interações repulsivas que também contribuem expressivamente para a estabilidade conformacional, principalmente dos compostos 4-6. Os resultados experimentais obtidos através do IV mostraram que os deslocamentos para o vermelho da banda da ligação OH foram de 193, 225 e 256 cm-1 para os compostos 1, 2 e 3, respectivamente. Estes resultados foram surpreendentes e indicaram que a força da LHI aumenta nesta ordem apesar do efeito estérico também aumentar. Uma primeira metodologia, para calcular a fração molar experimental de confôrmeros com LHI (XLHI) para compostos acíclicos 1,3-dissubstituídos por RMN de 1H, foi proposta neste trabalho. Os resultados de XLHI foram muito interessantes e mostraram que em solventes apolares tais como CCl4 os confôrmeros com LHI são predominantes no equilíbrio conformacional (XLHI = 0,70, 0,69 e 0,78 para os compostos 1-3). Já em solventes polares como DMSO-d6, os valores de XLHI foram bem menores (0,10, 0,08 e 0,08 para os compostos 1-3), indicando uma mudança no equilíbrio conformacional de confôrmeros que faziam LHI para confôrmeros que não tinham este tipo de interação. As análises por Teoria Quântica de Átomos em Moléculas e Interações Não Covalentes evidenciaram, caracterizaram e quantificaram a intensidade da LHI nos compostos 1-6. Estes resultados foram concordantes com os dados experimentais e indicaram que tanto as LHI quanto as interações estéricas influenciam de forma significativa na estabilidade conformacional de todos os compostos estudados. / The conformational analysis covers aspects of the determination of molecular geometric structures, relative energies of conformers and interactions that control structural stabilities. In this sense, the conformational preferences of the compounds (1), 3-N-methylaminopropanol (2), 3-N,N-dimethylaminopropanol (3), 3-aminobutanol (4), 3-N-methylaminobutanol (5) and 3-N,N-dimethylaminobutanol (6) are evaluated experimentally through Infrared (IR) and Nuclear Magnetic Resonance (NMR) spectroscopies and theoretically by calculations using the Density Functional Theory (DFT). The study of these compounds was important because it will improve the understanding of the interactions that occur in these molecules in different chemical environments, since there is a wide range of amino alcohols with biological and synthetic applications. In view of this, theoretical calculations showed that the O-H···N intramolecular hydrogen bonding (IHB) governs the stability and the conformational preference of compounds 1-6. The IHB favors the formation of a chair like six member ring with substituents at pseudo-equatorial-axial positions, which exhibit repulsive interactions that also contribute significantly to the conformational stability, especially of compounds 4-6. The IR experimental results showed a OH band red shift of 193, 225, and 256 cm-1 for compounds 1, 2 and 3, respectively. These results were surprising and indicated that the strength of IHB increases in this order although the steric effect also increases. A first methodology for calculating the experimental molar fraction of hydrogen-bonded conformers (XIHB), in any solvent by 1H NMR, was proposed to attend 1,3-disubstituted acyclic compounds. The XIHB results showed that in non-polar solvents, such as CCl4 solvent, the hydrogen-bonded conformers predominate in the conformational equilibria (XIHB = 0.70, 0.69 and 0.78 for compounds 1-3). In polar solvents, such as DMSO-d6, the XIHB values decrease (0.10, 0.08 and 0.08 in compounds 1-3) indicating a change in conformational equilibria from hydrogenbonded conformers to non-hydrogen-bonded conformers. Quantum Theory of Atoms in Molecules and Non-Covalent Interactions analysis evidences, characterizes and quantifies the strength of IHB in compounds 1-6. These results agreed with the experimental data and indicated that both IHB and steric interactions significantly influence the conformational stability of all compounds studied.

Este trabalho teve como objetivo realizar o processamento do gel polimérico MAGICf, irradiá-lo e caracterizá-lo com quatro métodos de leitura, uma vez que a dosimetria com gel polimérico é uma área promissora no âmbito de controle de qualidade dos tratamentos radioterápicos, pois permite a avaliação de dose tridimensionalmente. Os métodos para caracterização do gel MAGIC-f foram: Tomografia Computadorizada (TC), espectroscopia de Ressonância Magnética Nuclear (RMN), Ressonância Paramagnética Eletrônica (EPR) e espectrofotometria UV/Vis. Para a caracterização por esse último método, foi feita uma nova formulação do gel MAGIC-f adicionando fluoresceína. Os resultados da caracterização desse gel dosimétrico com tomografia computadorizada e EPR não foram satisfatórios, porém com a espectroscopia de RMN obteve-se bons resultados, assim como com a espectrofotometria UV/Vis. A nova formulação do gel para a caracterização com espectrofotometria mostrou-se ser um método inovador e bastante promissor para essa área. / This work aimed to perform the processing of the MAGIC-f polymeric gel, to irradiate it and to characterize it with four methods of reading, since the dosimetry with polymeric gel is a promising area within the scope of quality control of the radiotherapeutic treatments, because it allows dose evaluation three-dimensional. The methods for characterization of the MAGIC-f gel were: Computed Tomography (CT), Nuclear Resonance Magnetic (NMR) and Electron Paramagnetic Resonance (EPR) spectroscopy, and UV/Vis spectrophotometry. For characterization with this last method, a new MAGIC-f gel formulation was made adding fluorescein. The results of the characterization of this dosimetric gel with computed tomography and EPR were not satisfactory, but with NMR spectroscopy satisfactory results were obtained as well as UV / Vis spectrophotometry. The new gel formulation for characterization with UV / Vis spectrophotometry has proved to be an innovative and very promising method for this area.

CAPES; Fundação Araucária / A análise conformacional abrange os aspectos da determinação de estruturas geométricas moleculares, energias relativas de confôrmeros e das interações que controlam as estabilidades estruturais. Neste sentido, as preferências conformacionais dos compostos 3-aminopropanol (1), 3-N-metilaminopropanol (2), 3-N,N-dimetilaminopropanol (3), 3-aminobutanol (4), 3-Nmetilaminobutanol (5) e 3-N,N-dimetilaminobutanol (6) foram avaliadas experimentalmente através de espectroscopias de Infravermelho (IV) e Ressonância Magnética Nuclear (RMN), e teoricamente por cálculos usando a Teoria do Funcional de Densidade (DFT). O estudo destes compostos foi importante porque irá melhorar a compreensão das interações que ocorrem nestas moléculas em diferentes ambientes químicos, uma vez que existe uma ampla gama de amino álcoois com aplicações biológicas e sintéticas. Diante disso, os cálculos teóricos mostraram que a ligação de hidrogênio intramolecular (LHI) O-H ...N governa a estabilidade e a preferência conformacional dos compostos 1-6. A LHI favorece uma conformação do tipo pseudo-cadeira de seis membros com substituintes em posições pseudo-equatoriais e pseudo-axiais, os quais apresentam interações repulsivas que também contribuem expressivamente para a estabilidade conformacional, principalmente dos compostos 4-6. Os resultados experimentais obtidos através do IV mostraram que os deslocamentos para o vermelho da banda da ligação OH foram de 193, 225 e 256 cm-1 para os compostos 1, 2 e 3, respectivamente. Estes resultados foram surpreendentes e indicaram que a força da LHI aumenta nesta ordem apesar do efeito estérico também aumentar. Uma primeira metodologia, para calcular a fração molar experimental de confôrmeros com LHI (XLHI) para compostos acíclicos 1,3-dissubstituídos por RMN de 1H, foi proposta neste trabalho. Os resultados de XLHI foram muito interessantes e mostraram que em solventes apolares tais como CCl4 os confôrmeros com LHI são predominantes no equilíbrio conformacional (XLHI = 0,70, 0,69 e 0,78 para os compostos 1-3). Já em solventes polares como DMSO-d6, os valores de XLHI foram bem menores (0,10, 0,08 e 0,08 para os compostos 1-3), indicando uma mudança no equilíbrio conformacional de confôrmeros que faziam LHI para confôrmeros que não tinham este tipo de interação. As análises por Teoria Quântica de Átomos em Moléculas e Interações Não Covalentes evidenciaram, caracterizaram e quantificaram a intensidade da LHI nos compostos 1-6. Estes resultados foram concordantes com os dados experimentais e indicaram que tanto as LHI quanto as interações estéricas influenciam de forma significativa na estabilidade conformacional de todos os compostos estudados. / The conformational analysis covers aspects of the determination of molecular geometric structures, relative energies of conformers and interactions that control structural stabilities. In this sense, the conformational preferences of the compounds (1), 3-N-methylaminopropanol (2), 3-N,N-dimethylaminopropanol (3), 3-aminobutanol (4), 3-N-methylaminobutanol (5) and 3-N,N-dimethylaminobutanol (6) are evaluated experimentally through Infrared (IR) and Nuclear Magnetic Resonance (NMR) spectroscopies and theoretically by calculations using the Density Functional Theory (DFT). The study of these compounds was important because it will improve the understanding of the interactions that occur in these molecules in different chemical environments, since there is a wide range of amino alcohols with biological and synthetic applications. In view of this, theoretical calculations showed that the O-H···N intramolecular hydrogen bonding (IHB) governs the stability and the conformational preference of compounds 1-6. The IHB favors the formation of a chair like six member ring with substituents at pseudo-equatorial-axial positions, which exhibit repulsive interactions that also contribute significantly to the conformational stability, especially of compounds 4-6. The IR experimental results showed a OH band red shift of 193, 225, and 256 cm-1 for compounds 1, 2 and 3, respectively. These results were surprising and indicated that the strength of IHB increases in this order although the steric effect also increases. A first methodology for calculating the experimental molar fraction of hydrogen-bonded conformers (XIHB), in any solvent by 1H NMR, was proposed to attend 1,3-disubstituted acyclic compounds. The XIHB results showed that in non-polar solvents, such as CCl4 solvent, the hydrogen-bonded conformers predominate in the conformational equilibria (XIHB = 0.70, 0.69 and 0.78 for compounds 1-3). In polar solvents, such as DMSO-d6, the XIHB values decrease (0.10, 0.08 and 0.08 in compounds 1-3) indicating a change in conformational equilibria from hydrogenbonded conformers to non-hydrogen-bonded conformers. Quantum Theory of Atoms in Molecules and Non-Covalent Interactions analysis evidences, characterizes and quantifies the strength of IHB in compounds 1-6. These results agreed with the experimental data and indicated that both IHB and steric interactions significantly influence the conformational stability of all compounds studied.

Este trabalho teve como objetivo realizar o processamento do gel polimérico MAGICf, irradiá-lo e caracterizá-lo com quatro métodos de leitura, uma vez que a dosimetria com gel polimérico é uma área promissora no âmbito de controle de qualidade dos tratamentos radioterápicos, pois permite a avaliação de dose tridimensionalmente. Os métodos para caracterização do gel MAGIC-f foram: Tomografia Computadorizada (TC), espectroscopia de Ressonância Magnética Nuclear (RMN), Ressonância Paramagnética Eletrônica (EPR) e espectrofotometria UV/Vis. Para a caracterização por esse último método, foi feita uma nova formulação do gel MAGIC-f adicionando fluoresceína. Os resultados da caracterização desse gel dosimétrico com tomografia computadorizada e EPR não foram satisfatórios, porém com a espectroscopia de RMN obteve-se bons resultados, assim como com a espectrofotometria UV/Vis. A nova formulação do gel para a caracterização com espectrofotometria mostrou-se ser um método inovador e bastante promissor para essa área. / This work aimed to perform the processing of the MAGIC-f polymeric gel, to irradiate it and to characterize it with four methods of reading, since the dosimetry with polymeric gel is a promising area within the scope of quality control of the radiotherapeutic treatments, because it allows dose evaluation three-dimensional. The methods for characterization of the MAGIC-f gel were: Computed Tomography (CT), Nuclear Resonance Magnetic (NMR) and Electron Paramagnetic Resonance (EPR) spectroscopy, and UV/Vis spectrophotometry. For characterization with this last method, a new MAGIC-f gel formulation was made adding fluorescein. The results of the characterization of this dosimetric gel with computed tomography and EPR were not satisfactory, but with NMR spectroscopy satisfactory results were obtained as well as UV / Vis spectrophotometry. The new gel formulation for characterization with UV / Vis spectrophotometry has proved to be an innovative and very promising method for this area.

Obtaining enantio pure drug molecules is a long standing challenge in asymmetric synthesis implying that the identification of enantiomers and the determination of enantiomeric purity from a racemic mixture are of profound importance. In achieving this target NMR spectroscopy has proven to be an excellent analytical tool. It is well known that normal achiral NMR solvents do not distinguish the spectra of enantiomers. On the other hand, the conversion of substrates to diastereomers using one of the enantiopure chiral auxiliaries, such as, chiral solvating agent, chiral derivatizing agent and chiral lanthanide shift reagent, circumvents this problem. The imposition of diasteomeric interactions circumvents this problem. There is a pool of chiral auxiliaries available in the literature, each of which is specific to molecules of certain functionalities and has its own advantages and limitations. These classical methods have two limitations as they demand the presence of a targeted functional group in the chiral molecule and utilize only chemical shifts to visualize enantiomers. On the other hand in chiral anisotropic medium, due to differential ordering effect, the order-sensitive NMR observables, viz. chemical shift anisotropies (∆σi), dipolar couplings (Dij) and for nuclei with spin >1/2 the quadrupolar couplings (Qi) have enormous power of exhibiting different spectrum for each enantiomer permitting their discrimination. Numerous weakly ordered chiral aligning media have been reported in the literature. Nevertheless there is a scarcity of water compatible medium. Research work presented in this thesis is focused on various aspects, such as, the discovery of new chiral aligning medium for the enantiodiscrimination of water soluble chiral molecules, potential utility of DNA liquid crystal for discrimination of amino acids, on-the-fly monitoring of enzyme kinetics and the preparation of novel composite liquid crystals, hydrogels and thin films. The derived results are discussed in different chapters. Chapter 1 provides a brief introduction to NMR spectroscopy with special emphasis on the conceptual understanding of the tensorial interaction parameters, such as chemical shifts, scalar and dipolar couplings, quadrupolar couplings, effect of r.f pulses, basic introduction to 2D NMR experiments. Subsequently, a broad overview of the enantiomers, specification of their configurations, chirality without stereogenic carbon, chirality in molecules containing different atoms, are discussed. Following this a brief introduction to liquid crystals and their properties, their classification, their orientation in the magnetic field, order parameter are also discussed. The description on the chiral liquid crystals, the differential ordering effect, employment of the orientation dependent NMR interactions, utility of 2H NMR experiments for the visualization of enantiomers and the measurement of enantiomeric composition has been set out in brief. Chapter 2: As far as the organo soluble chiral molecules is concerned (in solvents such as, chloroform, dioxane, tetrahydrofuran and dimethylformamide), it has been well established that an ideal choice of chiral liquid crystal for enantiodiscrimination is poly-�-benzyl-L-glutamate (PBLG). Nevertheless, there is a scarcity of weak aligning medium for water soluble chiral molecules. This chapter introduces the chiral liquid crystal derived from the polysaccharide xanthan, which has numerous applications. The detailed discussion on the preparation of polysaccharide xanthan mesophase is given. The appearance of the mesophse is established by detecting the quadrupole split doublet of dissolved water. Subsequently enantiodiscrimination power of this new medium has been investigated on deuterated D/L-Alanine and (R/S)-β-butyrolactone. For such a purpose the selective 2D-SERF (SElective ReFocussing) experiment has been employed. It has been convincingly demonstrated that the medium has wide applicability for the discrimination of enantiomers, enantiotopic directions in prochiral molecules, measurement of enantiomeric excess and the RDCs in medium sized molecules. The new medium is sustainable over a wide range of temperature and concentration of ingredients, the mesophase is reversible, reproducible, easy to prepare besides being cost effective. It is possible to have the controlled tuning of the degree of order for specific application. Chapter 3: In this chapter the real discriminatory potential of DNA liquid crystalline phase has been explored. It is unambiguously established that; i) the fragmented DNA liquid crystal is able to differentiate between enantiomers of structurally different chiral amino acids; ii) the T1 (2H) values for L/D (alanine) is nearly equal indicating the similar dynamics for both the enantiomers, thus permitting the measurement of ee from the integral areas of the peaks of the contours of 2D spectrum; iii) the enantiotopic discrimination in prochiral compounds has also been successfully explored. Furthermore the analyses of NMR results yielded fruitful information on the analytical potential of DNA chiral liquid crystal, such as, (a) the chiral discrimination is effective on a large range of amino acids with spectral differences ΔΔʋQ‘s and ΔʋQ‘s varying from 80 to 338 Hz, and 50 to 900 Hz respectively; (b) the discrimination phenomenon remain active irrespective of the structure and the electronic nature (polarity) of the fourth substituent around the stereogenic center; (c) compared to an alkyl moiety, the presence of a terminal –OH or –SH group seems to slightly increase both the degree of alignment of the solute and the enantiodiscrimination efficiency compared to alanine; (d) The enantiodiscrimination can be detected easily not only on CD3 and CD groups, but also on CD2 sites exhibiting inequivalent diastereotopic directions; (e) discriminations with rather large differential ordering effect were obtained even for the sites that are situated far away from the asymmetric center; (f) The relative position of quadrupolar doublets from one 2H site to another can be reversed with regard to the absolute configuration (L/D). Chapter 4: Racemases recognize a chiral substrate such as (L-Alanine) and convert it into its enantiomer, i.e., (D-Alanine) and vice versa. Alanine racemase plays a vital role for certain bacteria, providing D-Alanine for peptidoglycan cell-wall biosynthesis. Elucidating the mechanism of enzymatic racemization is crucial for designing new inhibitors that may be useful as a novel class of antibiotics. This requires techniques to discriminate L-and D-Alanine and follow their concentrations as a function of time, so that one can determine the kinetic parameters and study the effect of inhibitors. In this chapter the utility of DNA liquid crystal media for in situ and real-time monitoring of the interconversion of L-and D-alanine-d3 by alanine racemase from Bacillus stearothermophilus has been demonstrated. The enantiomeric excess has been measured at different time intervals to monitor the enzymatic racemization at different time intervals in pseudo 2D NMR. The study unambiguously ascertains the reliability and robustness of utility of NMR in chiral anisotropic phase for monitoring the enzymatic racemization. The method thus provides new mechanistic insight and a better understanding of enzymatic reactions, in particular for alanine racemase. Chapter 5: In continuation with the development of weakly ordered liquid crystals, this chapter reports the spontaneous formation of composite graphene oxide (GO)/double stranded DNA (dsDNA) liquid crystals at higher concentrations of ingredients, and hydrogels at lower concentrations of ingredients, the process of which involves simple mixing in an aqueous phase has been demonstrated. The liquid crystalline phases and hydrogels have been characterized using optical polarized microscopy (OPM), scanning electron microscopy (SEM), Raman spectroscopy and 2H NMR spectroscopy. The observation of strong birefringence in the optical polarized microscope gives evidence for the formation of GO/dsDNA liquid crystals. The strong interaction between the dsDNA and GO was confirmed using Raman spectroscopic analysis. Furthermore, GO/dsDNA thin films have also been prepared and characterized using SEM and OPM. The GO/dsDNA thin film was prepared and its liquid crystal nature was established using OPM and 2H NMR. Importantly, the GO/dsDNA hydrogels were formed without any heat treatment to unwind dsDNA molecules and the porosity of hydrogels can be controlled by changing concentration of the dsDNA. This novel multifunctional composite liquid crystals and hydrogels of GO/dsDNA thus opens up new avenues for many applications like security papers, optical devices such as circular polarizers, reflective displays and drug delivery as well as tissue engineering using GO composite hydrogels.

La métabolomique a pour objet l’identification et la quantification de métabolites dans un échantillon biologique. Cette discipline s’inscrit dans une approche du vivant connue sous le terme de « biologie des systèmes ». La spectroscopie par résonance magnétique nucléaire haute résolution à l’angle magique (RMN HRMAS) est une méthode de choix pour l’obtention de ce type de profilage métabolique. L’épilepsie du lobe temporal (ELT) est une épilepsie focale fréquente associée le plus souvent à des pertes neuronales sélectives, une gliose réactionnelle et une plasticité cellulaire spécifique. Bien que restant débattue, une origine neurométabolique reste un axe de recherche majeur. A ce jour une caractérisation métabolomique des tissus épileptogènes par RMN HRMAS reste à effectuer. Notre travail a consisté dans un premier temps à caractériser, chez le rat, les effets des méthodes de prélèvement et de fixation sur le métabolome cérébral dans le cadre des acquisitions RMN HRMAS. Dans un second temps, nous avons travaillé sur le modèle animal lithium-pilocarpine d’ELT. Nous avons pu décrire le métabolome issu des données RMN 1H HRMAS de différentes structures cérébrales impliquéesdans l’épileptogénèse. Des analyses multivariées de type PLS-DA ont pu mettre en évidence des profils métaboliques pathologiques au sein du cortex entorhinal et de l’hippocampe. A l’aide de substrats marqués au carbone 13 ([1-13C]glucose et de [1,2-13C]acétate) nous avons étudié les voies métaboliques neuronales et gliales. Nos résultats suggèrent l’absence d’anomalies métaboliques au sein des astrocytes. Enfin dans un dernier temps, nous avons effectué des analyses RMN 1H HRMAS sur près de 200 échantillons cérébraux de patients atteints d’ELT. Une analyse multivariée a permis de distinguer les profils métaboliques des hippocampes sclérosés et non sclérosés. En revanche la construction de modèles sur la base d’hypothèses clinico métaboliques (durée de la maladie, fréquence de crises, antécédents de convulsions fébriles) n’a pas permis d’identifier de profils métaboliques spécifiques. L’ensemble de ces données suggère l’existence de profils métabolomiques distincts en fonction des caractéristiques neuropathologiques des patients atteints d’ELT. Notre travail confirme la nécessité d’une approche intégrée de type « biologie des systèmes » pour l’étude de l’ELT aussi bien chez l’homme que dans des modèles animaux. / Metabolomics relates to the identification and quantification of metabolites in biological samples. This discipline is part of an approach known under the term of "systems biology". High Resolution Nuclear Magnetic Resonance Spectroscopy at Magic Angle Spinning (HRMAS NMR) is a method for obtaining metabolic profiling in such sample. Temporal Lobe Epilepsy (TLE ) is a common focal epilepsy often associated with selective neuronal loss, reactive gliosis and specific cellular plasticity. A neurometabolic origin of this epilepsy is a major area of research. To date no characterization of human cerebral biopsy from TLE patients has been conducted using HRMAS NMR. In the present work we aimed first at characterizing, in rats, the effects of sampling methods and fixation on brain metabolome under HRMAS NMR acquisitions. In a second step, we studied the lithium-pilocarpine model of TLE. In this model, we could describe the metabolome from HRMAS 1H NMR data of different brain structures involved in epileptogenesis. Multivariate analysis could highlight pathological metabolic profiles in the entorhinal cortex and hippocampus. Using substrates labeled with carbon 13 ( [1 -13C ]-glucose and [1,2-13C ]-acetate) we studied neuronal and glial metabolic pathways. Our results suggest the absence of metabolic abnormalities in astrocytes metabolism as previously reported. Finally, we conducted HRMAS 1H NMR analysis in nearly 200 brain samples from TLEpatients. Multivariate analysis was able to distinguish metabolic profiles between sclerotic and non sclerotic hippocampi. However mutlivariate models based on clinico- metabolic assumptions (disease duration, frequency of seizures, history of febrile seizures ) did not identify specific metabolic profile. All these data suggest the existence of distinct metabolomic profile based on neuropathological features of patients with TLE. Our work confirm the need of an integrated approach such as " systems biology" for the study of TLE in humans as long as in animal models.

Ressonância magnética nuclear é particularmente útil na caracterização de síntese molecular. Quase todos os compostos moleculares de interesse contêm átomos de nitrogênio e oxigênio em sua estrutura. Como esses elementos químicos costumam desempenhar funções estratégicas em reações e interações intra e intermoleculares, seus espectros NMR têm particular interesse. Com foco na blindagem magnética nuclear e no acoplamento entre spins nucleares, investigamos a dependência dessas constantes magnéticas com relação ao meio. A polarização eletrônica e relaxação geométrica do soluto, devido à presença do solvente, foram sistematicamente consideradas utilizando um tratamento sequencial QM/MM. Nossas observações gerais mostram que efeitos de relaxação de geometria mediados pelo meio têm pouca influência sobre o mecanismo da blindagem magnética nuclear, pelo menos quanto aos sistemas aqui investigados. Em contrapartida, os efeitos da polarização eletrônica são cruciais sobre essa propriedade molecular. Para o nitrogênio em piridina, amônia e formamida, por exemplo, as contribuições isoladas provenientes da relaxação geométrica são da ordem de 1,2 ppm. Note-se que este efeito é muito pequeno se considerarmos que com frequência são observados desvios gás-líquido da ordem de -26 ppm para o nitrogênio. Sobre o oxigênio, esses efeitos podem chegar até 100 ppm. Assim, é crucial entender as origens desses efeitos se desejamos utilizar corretamente espectroscopia RMN em caracterização molecular. Relevantes contribuições para a blindagem magnética têm origens em interações específicas entre soluto e solvente, como ligações de hidrogênio, as quais apenas podem ser isoladas e quantificadas através de modelagem molecular. Sistematicamente constatamos que a blindagem magnética é drasticamente afetada pelo caráter doador ou aceitador do sítio atômico envolvido em ligações de hidrogênio. Com respeito ao nitrogênio, nossos resultados indicam que o comportamento aceitador de hidrogênio de um elemento é responsável por um desvio gás-líquido positivo, enquanto que o caráter doador causa um desvio negativo. Nossas investigações também mostram que a blindagem magnética nuclear é independente com relação à hibridização do nitrogênio e oxigênio, indicando que as contribuições principais têm origens em interações específicas soluto-solvente, as quais devem ser corretamente modeladas. Investigamos sistematicamente os efeitos do solvente sobre o acoplamento indireto entre spins nucleares em amônia líquida. Embora a polarização do soluto seja realmente importante, para essa propriedade há outras contribuições fundamentais. Sem considerar efeitos de geometria, calculamos o acoplamento ANTPOT. 1 J(N-H) como -67,8 Hz. Após incluir esses efeitos, conseguimos uma descrição teórica mais apurada, obtendo um acoplamento de -63,9 Hz. Esses resultados mostram que efeitos de relaxação geométrica mediado pelo meio têm grande influência sobre o acoplamento indireto entre spins nucleares. / Nuclear magnetic resonance is helpful on molecular characterization. Most organic molecular compounds of interest contain nitrogen or oxygen atoms which play strategic functions in chemical reactions and molecular interactions. The NMR technique provides local atomic scale information on molecular properties, thus the study of nuclear magnetic properties of these elements in molecules is of particular interest. Focusing on nuclear magnetic shielding and spin-spin coupling constants we investigated the dependence of these magnetic constants with respect to the medium. Electronic polarization and geometry relaxation effects due to solvent were systematically studied. Our general findings indicate that geometry contributions are negligible in understanding the variation of shielding constants of the investigated systems, but polarization effects are crucial for this molecular property. On nitrogen in pyridine, ammonia and formamide, for instance, isolated contributions from geometry relaxation to shielding constants are around 1,2 ppm. Nitrogen shielding constants are very sensitive to the medium, where solvent effects around -26 ppm are often observed. On oxygen-17 magnetic shielding, the solvent effects can easily reach 100 ppm. It is crucial to understand the origins of these effects if one desires to correctly use NMR spectroscopy for molecular characterization. Our investigations also show that magnetic shielding constants are totally independent of the nitrogen or oxygen hybridization, which indicated that the main contributions arise from solute-solvent interactions. Relevant contributions to shielding constants come from specific solute-solvent interactions like hydrogen-bonds, which can only be quantified by explicit molecular modeling, and we observed that this property has a very strong dependence on the donor or acceptor character of the atomic site involved in hydrogen-bonding interactions. On nitrogen, the acceptor behavior is responsible by the positive gas-liquid shift in shielding constants, while the donor character causes positive shift. We systematically investigated the solvent effects on indirect spin-spin coupling constants of liquid ammonia. Solute polarization is very important, but there are other fundamental contributions to this property. Without including geometry effects we calculated the 1J (N-H) coupling to be -67,8 Hz. After accounting for the solute geometry relaxation we improved the theoretical prediction obtaining the coupling constant value of -63,9 Hz. These results show that geometry relaxation has drastic influence on indirect spin-spin coupling constants.

A aplicação de uma sequência de pulsos com tempo de repetição muito menor que os tempos de relaxação Tp << T2; T1, faz com que a magnetização atinja um estado estacionário descrito por H.Y. Carr como Estado Estacionário em Precessão Livre, Steady State Free Precession (SSFP). Nessa condição, o sinal é composto pela complexa sobreposição das componentes FID e eco. Sequências tipo SSFP são utilizadas na aquisição rápida de sinais, resultando em uma boa razão sinal ruído (s/r) em curto intervalo de tempo, porém introduzem fortes anomalias de fase e amplitude devido a complexa interação das componentes que formam o estado estacionário. Neste trabalho, desenvolvemos sequências de pulsos tipo SSFP para RMN em alta e baixa resolução com alternância e incremento de fase. Em alta resolução desenvolvemos as sequências SSFPdx e SSFPdxdt com incremento de fase linear e quadrático respectivamente. Os resultados mostram que espectros de núcleos com baixa sensibilidade podem ser obtidos com mesma razão s/r em menor tempo experimental e as sequências desenvolvidas removem as anomalias espectrais. Em baixa resolução, os resultados mostram que a introdução de alternâncias de fase na Continuous Wave Free Precession (CWFP) possibilita a remoção da dependência da sequência com o offset de frequência e com o tempo entre pulsos. Além disso, mostramos que a sequência CP-CWFPx-x com ângulo de refocalização pequeno (5&deg; a 10&deg;) possibilita a estimativa rápida do tempos de relaxação longitudinal. Apresentamos também resultados dos estudos e desenvolvidos no estágio de pesquisa no exterior, onde as sequências de pulsos no estado estacionário &ndash; DECPMG e Split 180&deg; &ndash; foram estudas numericamente e implementadas nos sistemas magnéticos compactos: mini-Halbach e MOUSE-NMR. Por fim, são apresentados resultados com os métodos de processamento de dados Krylov Basis Diagonalization Method (KBDM) e a Transformada Inversa de Laplace aplicados na análise de sinais SSFP. Resultados mostram que KBDM é uma ferramenta útil no processamento de dados em alta e baixa resolução, tanto na obtenção de espectros como na determinação da distribuição dos tempos de relaxação. / The application of a pulse sequence with repetition time much smaller than the relaxation times, Tp << T2; T1, causes the magnetization to reach a steady state, described by H. Y. Carr as a Steady State Free Precession (SSFP). In this condition, the signal is composed of the complex overlapping of the FID and eco components. SSFP type sequences are used in fast acquisition of NMR signals, resulting in a good signal to noise ratio (s/r) in a short time interval, however, they introduce phase and amplitude anomalies due to the complex interaction between the components of the steady state. In this work, we develop SSFP type pulse sequences for NMR in high and low resolution, with alternation and increment of phase. In high resolution, we develop SSFPdx and SSFPdxdt sequences, with linear and quadratic phase increment respectively. Results show that the low sensitivity nuclei spectra can be obtained with the same s/r ratio in smaller experimental time, about an order of magnitude, and the developed sequences can remove the spectral anomalies. In low resolution, the results show that the introduction of a phase alternation in the Continuous Wave Free Precession (CWFP) allows the elimination of the dependence of the sequence with the offset frequency and the time between pulses. Besides, we show that the CP-CWFPx-x sequence with a small refocalization angle (5° to 10°) allows the fast estimative of the longitudinal relaxation time in a single experiment. The results of the studies conducted during an international research internship are also presented. Steady state pulse sequences &ndash; DECPMG and Split 180° &ndash; were studied and implemented in compact magnetic systems: mini-Halbach and MOUSE-NMR. Finally, the results of the application of the Krylov Basis Diagonalization Method (KBDM) and the Inverse Laplace Transform for the analysis of SSFP signals are presented. The results show that KBDM is a useful tool in data processing for low and high resolution, both for obtaining spectra and determining the relaxation times distribution.

A cinza obtida da queima controlada da casca de arroz é um material que apresenta propriedades pozzolânicas: reage na presença de água e dióxido de cálcio produzindo silicato de cálcio hidratado (C-S-H), o material que confere a resistência mecânica aos cimentos. Portanto, a cinza de casca de arroz é um material de potencial interesse para o desenvolvimento de cimentos não convencionais, baseados em subprodutos industriais ou agrícolas. Neste trabalho, os compostos presentes em cinzas de alta reatividade pozzolânica e os produtos obtidos de sua reação pozzolânica foram estudados através da Ressonância Magnética Nuclear (RMN) de alta resolução de 13C e 29Si. Na cinza não hidratada foram detectados domínios de sílica amorfa, o componente principal, e quantidades menores de sílica cristalina (cristobalita e quartzo), carbono amorfo e cadeias de siloxanos. Foi estudada a evolução da reação em pastas obtidas da hidratação da cinza na proporção água: cal: cinza O,47H20+O,53(O,1CCA+O,9Cal)=1 (entre 8 e 134 dias de idade). Mediante a RMN de 29Si foi possível caracterizar a formação de C-S-H e disposição dos grupos silicatos na estrutura. A estrutura do C-S-H obtido é comparável à observada em cimentos convencionais e cimentos de escoria de alto forno, e é compatível com os modelos propostos. A quantidade de C-S-H produzido e a velocidade da reação são menores quando comparadas com os outros cimentos. Efeitos da carbonatação de C-S-H foram observáveis em atmosfera ambiente. Foi detectado também o efeito da hidratação sobre os componentes minoritários da cinza. / The ashes obtained from burning rice husks have pozzolanic properties: in the presence of water and calcium dioxide the ashes react to produce calcium silicate hydrate (C-SH), the main binding agent in cementitiuos materials. Therefore, rice husk ashes are interesting materials in order to produce non-conventional cement, based in industrial or agricultural byproducts. The compounds present in a sample of rice husk ashes of high pozzolanic activity, and the products of hydration, were characterized using high resolution solid-state Nuclear Magnetic Resonance (NMR) of 13C and 29Si. Several compounds were detected in anhydrous ashes: amorphous silica (the main component), and minor quantities of crystalline silica (cristobalite and quartz), amorphous carbon and siloxane polymeric chains. Hardened pastes were prepared with a ratio water:calcium dioxide:ash O,47H20+O,53(O,1dioxide ash+O,9calcio)=1. The evolution of the hydration reaction was monitored at several ages between 8 to 134 days. The formation of C-S-H was detected by 29Si-NMR and the arrangement of the silicate groups was characterized. The structure of the C-S-H formed in these pastes agrees with the one observed in conventional cements and also b1ast furnace slag cements. Also, it is in agreement with the accepted structural models of C-S-H. The amount of C-S-H produced and the velocity of the reaction are minor than those observed in blast furnace slag cements. Carbonation effects were detected in ambient atmospheric conditions. Also, the effect of the hydration on the minority compounds was also detected.

A radioterapia de intensidade modulada (IMRT) é uma das mais modernas técnicas radioterapêuticas que permite a entrega de elevadas e complexas distribuição de doses ao volume tumoral, que necessita de novos métodos para o controle de qualidade dos procedimentos efetuados. Nos serviços de radioterapia costuma-se usar para o controle de qualidade do sistema de planejamento, a câmara de ionização para verificação pontual da dose e um dispositivo com diodos semicondutores (MapCHECK2) para a verificação bidimensional em um plano da fluência planejada, entretanto, para a verificação tridimensional dessas distribuições de doses ainda não há um dosímetro consolidado na rotina clínica. Nesse contexto, para a dosimetria tridimensional se destacam os géis poliméricos. Neste trabalho foram feitas a dosimetria convencional, pontual e bidimensional como se faz na rotina clínica e a dosimetria tridimensional utilizando o gel polimérico Magic-f, que apresenta a distribuição de dose volumétrica. Para este trabalho foi escolhido o tratamento de câncer de próstata, pois na atualidade é um dos tipos de cânceres mais comuns entre os homens. No contexto da dosimetria gel, para se obter a informação volumétrica é necessária uma técnica de imagem, no presente caso foram utilizadas imagens por ressonância magnética (magnetic resonance imaging, MRI). A partir dessas imagens é possível determinar as distribuições de doses processando-as em um software desenvolvido pelo grupo que determina as taxas de relaxação R2 associada à dose absorvida e posteriormente comparar as imagens obtidas com as imagens do sistema de planejamento. Para isso, se obteve dez cortes ao longo de cada simulador físico ou fantom em que sua comparação foi feita com a respectiva fatia do sistema de planejamento, na posição correspondente. Para uma avaliação quantitativa foi utilizado o conceito de índice gama, no critério padrão da radioterapia, 3% da dose e 3mm de distância de concordância. Os resultados obtidos com a dosimetria gel se mostram de acordo com os controles de qualidade convencionais e oferecem uma visão global da distribuição de dose no volume alvo. / The intensity modulated radiotherapy (IMRT) is one of the most modern radiotherapeutic technique that enables the delivery of high and complexes conformational doses to the tumor volume, that requires new methods for the quality assurance of the procedures performed. Radiotherapy services usually perform quality assurance of the planning system with the ionization chamber for spot-checking and an array of semiconductor diodes (MapCHECK2) to check on a two-dimensional plane, however for tridimensional dose verification does not exist an established dosimeter in the clinical routine. In this context, for three-dimensional dosimetry the polymeric gels were used. In This work the conventional one and two-dimensional dosimetry as employed in the clinical routine, and the three-dimensional dosimetry using polymer gel MAGIC- f, which provide the volumetric dose distribution. Prostate cancer clinical cases were chosen for this work because this kind of tumor is one of the most common cases in male individuals. In the context of dosimetry gel to obtain volumetric information an imaging technique is necessary, in this case the magnetic resonance imaging (MRI), was used to measure the dose. From these images it is possible to determine the distributions of doses processing them in a software developed by our research group that determines R2 relaxation rates associated with the absorbed dose and subsequently compare the images obtained with the images of the planning system. For this, ten slices were obtained along each phantom, and comparisons were made with the respective slice of the treatment planning system, in the corresponding position. For a quantitative evaluation of the gamma index , in the standard criterion in radiotherapy, 3 % dose and 3 mm distance to agreement was used. The results obtained shown that gel dosimetry agrees with the conventional quality controls and provide an overview of dose distribution in the target volume.