Le rayonnement synchrotron est l'un des facteurs clés du grand succès de la cristallographie macromoléculaire au cours des dernières décennies. Plus de 90% de toutes les structures de protéines de la base de données PDB a été résolu par cristallographie en utilisant des sources de rayonnement synchrotron et environ 95% d'entre elles a été déterminé à partir de cristaux congelés.Cependant, les structures déterminées par des techniques de congélation sont limitées par la nature statique des cristaux congelés. Avec le développement récent des sources de RX produites par lasers à électrons libres (XFEL), qui sont en mesure de produire des impulsions femtosecondes très intenses de rayons X, l'ère de la « diffraction avant destruction » et de la cristallographie sérielle femtoseconde utilisant des micro- ou nano- cristaux a commencé (SFX).Au cours du procédé SFX un cristal de protéine n'est exposé qu'une fois au faisceau de rayons X pendant quelques dizaines de femtosecondes avant qu'il ne soit complètement détruit. Les données sont collectées à partir de cristaux orientés de façon aléatoire par rapport au faisceau de rayons X; une seule exposition par cristal est possible. Afin de recevoir un ensemble de données plus complet, de nouvelles techniques d'analyse de données de diffraction ont été développées.La première expérimentation réussie du procédé (SFX) a été réalisée au LCLS à Stanford en décembre 2009 sur des cristaux du photosystème I et de lysozyme. Les experts en cristallographie des installations XFEL peuvent déterminer des structures de protéines à température ambiante presque exemptes de dégâts d'irradiation, en raison des pulses de FEL femtosecondes si brèves, qu'ils passent à travers l'échantillon avant que des dommages de rayonnement importants ne se produisent.Après la présentation des premières expériences SFX réussies, des efforts pour effectuer une cristallographie en série de cristaux de taille de l’ordre des micromètres à température ambiante ont commencé au sein des synchrotrons. Une première tentative de cristallographie synchrotron en série et à température ambiante a été tentée à PETRA III à DESY à Hambourg. Cette méthode a été nommée SMX (synchrotron serial millisecond crystallography), où des milliers d'échantillons sont collectés à partir de cristaux individuels passant par le faisceau à rayons X. Avec le développement des techniques de cristallographie série à température ambiante au sein des synchrotrons, la répartition de la dose sur un grand nombre de cristaux compense l’augmentation des dommages liés à l’irradiation à température ambiante.Bien que les sources de rayonnement synchrotron n'atteindront probablement jamais la même luminosité que les impulsions de rayons X comme dans les XFELs, elles ont un certains nombre d'avantages. L'un d'eux est la flexibilité de configuration grâce au paramétrage de lignes de faisceaux microfocus. Un autre est que plusieurs expositions par cristal sont possibles. En outre, les synchrotrons sont plus répandus dans le monde: la probabilité d'obtenir un temps d'expérimentation dans un synchrotron est plus élevée que pour une installation XFEL. En effet, maintenant deux installations XFEL sont ouvertes pour les utilisateurs .L'objectif de cette thèse est de proposer et de mettre en œuvre des méthodes qui permettront de recueillir des données en utilisant l'approche de la cristallographie série à l'installation synchrotron européen (ESRF, Grenoble, France). Cette thèse présente différentes techniques pour réaliser la cristallographie sérielle sur la ligne ID13 à l’ESRF. L'objectif était de développer la cristallographie sérielle sur synchrotron basée sur la numérisation micro-diffraction pour démontrer que les sources de rayonnement synchrotron peuvent être utilisées comme un instrument de routine pour cette technique avec des protéines globulaires et membranaires. Les aspects de la collecte de données et leur traitement seront également discutés. / Synchrotron radiation is one of the key factors for the tremendous success of macromolecular crystallography during the past decades. More than 90 % of all protein structures in PDB database were solved by crystallography using synchrotron radiation sources and around 95 % of them were determined from cryocooled crystals1,2. A whole data set can be collected from one flash-cooled crystal. Data-collection at cryogenic temperatures drastically reduces radiation damage effects. However, structures determined using cryo freezing techniques are limited by static nature of frozen crystals.With the recent development of X-ray free-electron laser facilities (XFELs), which are able to produce extremely intense femtosecond X-ray pulses, the era of “Diffraction before destruction” and serial femtosecond crystallography (SFX) for micro-/nano-sized crystals has begun3. In the SFX technique a protein crystal is only exposed once to the X-ray beam for tens of femtoseconds before it is completely destroyed. The data is collected from randomly oriented crystals that are exposed to the X-ray beam; only one shot per crystal is possible. In order to receive a complete data set, new data analysis techniques that are capable of dealing with large quantities of diffraction data have been developed. First experiment where serial femtosecond crystallography (SFX) approach was first carried out was performed at the Linac Coherent Light Source (LCLS, Stanford, USA) in December 2009 on photosystem I and lysozyme crystals4,5,6. At XFELs facilities crystallographers can perform room temperature structure determination of proteins almost free of radiation damage, due to the fact that femtosecond flashes of FEL is so brief, that it passes through the sample before the significant radiation damage occurs.After presenting first successful experiments with SFX technique, efforts to perform serial crystallography of micron-sized crystals at room-temperature started at synchrotron sources. First attempt to perform synchrotron room-temperature serial crystallography has been done at PETRA III at DESY in Hamburg using glass capillary based microfluidics7. This method was named synchrotron serial millisecond crystallography (SMX), where thousands of patterns are collected from individual crystals passing through the X-ray beam8. With development of room-temperature serial crystallography techniques at the synchrotrons, the exposure distributed on a large number of crystals in the sample, which helps compensating the effect of increased radiation damage at ambient temperature.Although synchrotron sources most certainly will never reach the same brightness of X-ray pulses like XFELs, they have some advantages. One of them is possibility to perform any set up due to the flexibility of the parameters of microfocus beamlines. Another advantage of SMX is that several shots per crystals are possible. Also should be mentioned that synchrotrons are more widespread all over the world, so possibility to get a beamtime at the synchrotron is much higher than at XFELs, because currently only two XFEL facilities are open for users (LCLS, USA and SACLA, Japan).The aim of this dissertation is to propose and to implement methods that will allow to collect data using the serial crystallography approach at the European synchrotron radiation facility (ESRF, Grenoble, France). This dissertation presents different techniques to perform synchrotron serial crystallography at ID13 beamline. The goal was to develop synchrotron serial crystallography based on scanning micro-diffraction to demonstrate that synchrotron sources can be used as a routine instrument to perform serial crystallography with soluble and membrane proteins. The aspects of the data collection and data processing also will be discussed.

abstract: With the advent of the X-ray free-electron laser (XFEL), an opportunity has arisen to break the nexus between radiation dose and spatial resolution in diffractive imaging, by outrunning radiation damage altogether when using single X-ray pulses so brief that they terminate before atomic motion commences. This dissertation concerns the application of XFELs to biomolecular imaging in an effort to overcome the severe challenges associated with radiation damage and macroscopic protein crystal growth. The method of femtosecond protein nanocrystallography (fsPNX) is investigated, and a new method for extracting crystallographic structure factors is demonstrated on simulated data and on the first experimental fsPNX data obtained at an XFEL. Errors are assessed based on standard metrics familiar to the crystallography community. It is shown that resulting structure factors match the quality of those measured conventionally, at least to 9 angstrom resolution. A new method for ab-initio phasing of coherently-illuminated nanocrystals is then demonstrated on simulated data. The method of correlated fluctuation small-angle X-ray scattering (CFSAXS) is also investigated as an alternative route to biomolecular structure determination, without the use of crystals. It is demonstrated that, for a constrained two-dimensional geometry, a projection image of a single particle can be formed, ab-initio and without modeling parameters, from measured diffracted intensity correlations arising from disordered ensembles of identical particles illuminated simultaneously. The method is demonstrated experimentally, based on soft X-ray diffraction from disordered but identical nanoparticles, providing the first experimental proof-of-principle result. Finally, the fundamental limitations of CFSAXS is investigated through both theory and simulations. It is found that the signal-to-noise ratio (SNR) for CFSAXS data is essentially independent of the number of particles exposed in each diffraction pattern. The dependence of SNR on particle size and resolution is considered, and realistic estimates are made (with the inclusion of solvent scatter) of the SNR for protein solution scattering experiments utilizing an XFEL source. / Dissertation/Thesis / Ph.D. Physics 2011

>Magister Scientiae - MSc / The efficiency of organic photovoltaics is influenced by the structure of the polymer, the morphology of the film, the interfaces between the layers, the choice of electron acceptor material and the ratio between the electron acceptor material and the polymer. In this project, we have used regioregular poly (3-hexylthiophene) (rr-P3HT) as the electron donor material and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), a derivative of the C60 fullerene, as the acceptor material. Different weight-ratios of rr-P3HT to PCBM were prepared by stirring for several hours in a chloroform solution and subsequently spin coated onto crystalline silicon and transparent conductive oxide/glass substrates. The effect of the PCBM concentration on the photo-induced optical emission and absorption properties of rr-P3HT was investigated by photoluminescence and ultraviolet-visible spectroscopy, respectively. Changes in the structural properties, as a function of the weight-ratio, were probed by high-resolution transmission electron microscopy, x-ray diffraction, Fourier transform infrared spectroscopy and Raman spectroscopy. Results show that the structural integrity and crystallinity of rr-P3HT is compromised with the addition of excessive amounts of PCBM, which has a negative impact on the optical absorption of rr-P3HT and the photo-induced charge transfer mechanism between the rr-P3HT and PCBM. This work illustrates that blending rr-P3HT with an equal weight of PCBM results in an optimum configuration for improved performance in organic photovoltaic devices.

Non-crystalline thin solid films are seeing increasing interest for a wide variety of applications. However, understanding structure and compositional variations in these films is an immense challenge. Conventional bulk structural or compositional characterization techniques such as X-ray diffraction often do not provide an adequate amount of information on their own. Electron microscopy is an incredibly powerful technique for structural and compositional film characterization, but is limited to inspection of only a small volume of any given sample. Rather than using one technique alone to gain information about a specimen, the greatest success is realized when these techniques are used in concert. This dissertation illustrates the idea that statistical analysis of electron microscopy data can provide information invaluable to interpreting bulk structural and compositional data from non-crystalline films. The first set of examples include demonstration of a statistical analysis method that can be applied to electron microscopy data to determine the presence of inhomogeneity along one film axis. This analysis method is applied to understanding compositional inhomogeneity that develops during formation of amorphous oxide films from aqueous solutions. Key insights are revealed that aid interpretation of bulk film X-ray characterization and possible processing conditions that lead to the compositional inhomogeneity. The second and third sets of examples describe the importance of electron microscopy analysis for structure determination in rotationally-disordered, non-epitaxial 2D heterostructures prepared from modulated elemental reactants. The second set of examples investigates the effects of nanoarchitecture on interlayer interactions and layer structure in heterostructures with interleaved BiSe and NbSe2 layers. The BiSe layers in these compounds display an interesting structural variation that impacts the overall compound properties. The structural variation is not visible using typical X-ray diffraction experiments, but analysis of electron microscopy images provides key insight into its existence. Finally, the third set of examples investigate several SnSe-containing heterostructures that provide insight into the unusual consequences of their non-epitaxial structure and film formation from modulated elemental reactants. Electron microscopy analysis, in conjunction with other characterization techniques, was invaluable for uncovering structural and compositional details within these compounds. This work contains previously published and unpublished co-authored material. / 10000-01-01

Ensaios cronogalvanométricos, análises por difração de raios -X, microscopia eletrônica de varredura (MEV) e curvas de polarização potenciostáticas foram usadas com o propósito de caracterizar os filmes formados sobre o aço API T95 em soluções alcalinas de sulfeto de sódio (Na2S 0,02M). As características destes filmes foram analisadas em função do pH da solução. O pH usado em cada caso (entre 8 e 11) foi obtido através da injeção de gás sulfídrico (H2S) na solução previamente desarejada. As curvas de polarização potenciostáticas mostram o aparecimento de uma região passiva ou pseudo-passiva para os pHs mais elevados (1 O e 11 ). As curvas cronogalvanométricas permitiram verificar uma queda de densidade de corrente nestes mesmos pHs, evidenciando a melhor proteção contra a corrosão dos filmes de sulfeto formados nestas condições. / Chronogalvanometric electrochemical essays, X - ray diffraction analysis, scanning electron microscopy (SEM) and potentiostatic curves were used with the pourpose of characterizing the sulfide films formed on API T95 steel in alkaline sodium sulfide (Na2S 0,02M) environments. The characterization of these films were followed by pH measurements and the potential at witch they were formed. The pH of the used environments was varied between 8 and 11 through hydrogen sulfide (H2S) injection in the previously deaerated solution. Potentiostatic polarization curves indicate a pseudopassive or passive area in the highest pH values (1 O and 11 ). The chronogalvanometric curves show a decrease of current density, at the same pH, characterizing a better corrosion protection of the films formed in these conditions.

Dentre os principais e mais efetivos tratamentos superficiais para a melhora das propriedades da superfície dos aços, encontra-se a nitretação e a nitrocarbonetação. Os benefícios da nitretação nos aços são o aumento da dureza, resistência ao desgaste, resistência à fadiga e resistência à corrosão. Por possuírem elementos como cromo, molibdênio e manganês, os aços ferramenta e aços baixa liga de ultra alta resistência são beneficiados pela nitretação. Neste trabalho, estudou-se o efeito da nitretação nos aços SAE 4140 e SAE H13 através de análises metalográficas, espectroscopia de emissão óptica, difração de raios-x, microdureza e ensaio pino-sobre-disco. Para efeito de comparação, amostras de aço SAE 1045 e ferro puro foram nitretadas juntamente com amostras dos dois materiais anteriores. Foram executados três tratamentos diferentes em cada um dos aços, nitretação com baixo potencial de nitrogênio, nitretação com alto potencial de nitrogênio e nitrocarbonetação. Os dois primeiros tratamentos foram realizados em três tempos diferentes de duas, quatro e seis horas e a nitrocarbonetação foi realizada em seis horas. Os resultados mostraram a formação de uma camada nitretada com de camada branca seguida de uma camada de difusão com gradiente de propriedades. Um aumento significativo de dureza superficial é observado com a aplicação dos tratamentos. A nitrocarbonetação junto com alto potencial de nitretação se mostrou não sendo benéfica para a formação da camada em relação à nitretação com mesmo potencial. Nos testes tribológicos realizados, a camada nitretada se mostrou eficiente em aumentar a resistência ao desgaste nos aços SAE 4140 e SAE H13. / Among the main and most effective surface treatments for improving the surface properties of steels are nitriding and nitrocarburizing. The benefits of nitriding in steels are the increase in hardness, wear resistance, fatigue resistance and corrosion resistance. Because they have elements such as chromium, molybdenum and manganese, tool steels and low alloy steels of ultra high strength are benefited by nitriding. In this work, the effect of nitriding on SAE 4140 and SAE H13 steels was studied through metallographic analysis, optical emission spectroscopy, x-ray diffraction, microhardness and pin-on-disc test. For comparison purposes, samples of SAE 1045 steel and pure iron were nitrided together with samples of the two former materials. Three different treatments were performed in each of the steels, nitriding with low nitrogen potential, nitriding with high nitrogen potential and nitrocarburizing. The first two treatments were performed at three different times of two, four and six hours and nitrocarburizing was performed in six hours. The results showed the formation of a nitrided layer with a white layer followed by a gradient layer of properties. A significant increase in surface hardness is observed with the application of the treatments. Nitrocarburizing together with high nitriding potential proved to be of no benefit to the formation of the layer in relation to nitriding with the same potential. In the tribological tests carried out, the nitrided layer proved efficient in increasing wear resistance in SAE 4140 and SAE H13 steels.

This work has involved the study of the magnetic behaviour of small magnetic nanoparticle systems. Due to the reduced size of magnetic nanoparticles they present distinctive properties, such as size and surface effects, that have been analysed in this work, as well as the effect of interactions in such systems. The samples chosen for the study were magnetite particles in the form of a ferrofluid and Co nanoclusters in a nonmagnetic matrix of Cu. Both systems present very narrow particle size distributions, which facilitates the interpretation of the data. The samples have been subjected to basic characterisation, which includes the determination of the distribution of magnetic particle sizes using the magnetisation curves at room temperatures, TEM microscopy and X-ray diffraction, in the case of the ferrofluid samples. For the nanoclusters, a time of flight spectrometer has been used to obtain the number of atoms per cluster. Many of the measurements have been performed at low temperatures, where thermal effects are minimised. For such measurements the samples have been frozen in a zero applied field, so that they have a random distribution of magnetic moments prior to the measurement. The energy barrier distributions have been calculated via the temperature decay of remanence (TDR). From this study, an effective anisotropy constant has been calculated. For the study of the interactions, surface and size effects, magnetisation, susceptibility (ZFC), remanence and delta-M curves, as well as the time dependence of magnetisation have been studied. The attempt frequency of the different particle size systems has been calculated using different techniques. The basic magnetic behaviour can be explained on the basis of the Neel blocking model. It has been found that the systems with the smaller particles have significant surface effects, which are enhanced at lower temperatures. Interactions, which are weak due to the low concentration of magnetic material in the samples (<10%), have been found to be overall demagnetising and the evolution of the magnetic properties with dilution has been explained. As is the case for the surface effects, interaction effects are stronger at low temperatures due the reduction of thermal effects. The experimental results have been compared with calculations from a Montecarlo model for fine particles, which includes the effects of concentration, anisotropy, particle size and temperature.

Submitted by LAÉRCIO SANTOS SILVA null (laerciosantos18@gmail.com) on 2016-03-21T21:18:03Z No. of bitstreams: 1 Dissertação_Laercio_Santos_Silva_espelhada_2016.pdf: 1714650 bytes, checksum: 47f05faa577cbb7bf53e0c788cea097a (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-03-22T19:10:43Z (GMT) No. of bitstreams: 1 silva_ls_me_jabo.pdf: 1714650 bytes, checksum: 47f05faa577cbb7bf53e0c788cea097a (MD5) / Made available in DSpace on 2016-03-22T19:10:43Z (GMT). No. of bitstreams: 1 silva_ls_me_jabo.pdf: 1714650 bytes, checksum: 47f05faa577cbb7bf53e0c788cea097a (MD5) Previous issue date: 2016-02-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A diversidade geológica do Planalto condicionou a formação de diversos solos, predominando na fração argila caulinita, óxidos e hidróxidos de ferro e gibbsita. Entre estes, os óxidos e hidróxidos de ferro e a gibbsita são considerados pedoindicadores ambientais na região tropical. Desta forma, os objetivos desta pesquisa foram: i) caracterizar os óxidos de ferro pedogênicos formados a partir de compartimentos geológicos com baixos e altos teores de ferro total do Planalto Ocidental Paulista e associá-los com o grau de dissecação da paisagem; ii) caracterizar os óxidos de ferro dos solos do Planalto Ocidental Paulista por espectroscopia de reflectância difusa. Baseado nas informações geológicas, geomorfológica e na amplitude de variação dos teores de ferro pedogênicos (Fed e Feo). Foram coletadas doze amostras de solo na profundidade de 0,0 – 0,2 m para caracterização mineralógica e espectral. A magnitude dos teores totais obtida pela digestão com ácido sulfúrico evidenciou a diferença do material de origem, geologia, intensidade de pedogênese e geomorfologia. Nos solos da Formação Vale do Rio do Peixe predominaram a mineralogia caulinítica, enquanto na Formação Serra Geral, hematítica. Os atributos granulométricos, químicos e mineralógicos foram influenciados pelo grau de dissecação dos solos do Planalto Ocidental Paulista. O comportamento espectral das regiões em diferentes estágios de dissecação, foram diferentes na faixa espectral dos óxidos (530 a 570 nm) e caulinita (1880 a 2380 nm). A caulinita foi melhor pedoindicador para caracterizar a paisagem em diferentes estágios de dissecação nos solos de arenito, enquanto que a hematita e goethita foram melhores pedoindicadores para caracterizar a paisagem em diferentes estágios de dissecação nos solos basalto. Esse resultado pode auxiliar na compreensão da evolução da paisagem e do solo em outras bacias sedimentares. / The geological diversity of Plateau conditioned the formation of various soils, predominantly kaolinite in the clay fraction, iron oxides and hydroxides and gibbsite. Among these, the oxides and hydroxides of iron and gibbsite are considered environmental pedoindicadores in the tropical region. Thus, aimed to The geological diversity of Plateau conditioned the formation of various soils, predominantly kaolinite in the clay fraction, iron oxides and hydroxides and gibbsite. Among these, the oxides and hydroxides of iron and gibbsite are considered environmental pedoindicadores in the tropical region. Thus, aimed to characterize the oxides and hydroxides of iron (hematite and goethite), kaolinite and gibbsite Western Paulista Plateau and associate them with the landscape of the state of play in different environments with total iron content. Based on geological, geomorphological and amplitude variation of pedogenic iron levels (Fed and Feo). Twelve soil samples were collected at a depth 0.0 to 0.2 m for mineralogical and spectral characterization. The magnitude of the total contents obtained by digestion with sulfuric acid showed the difference in the source material, geology, geomorphology and pedogenesis intensity. In soils Training Fish River Valley predominated kaolinitic mineralogy, while the Serra Geral Formation, hematítica. The granulometric, chemical and mineralogical attributes were influenced by the degree of dissection of the Western Paulista Plateau soil. The spectral behavior of the regions at different stages of dissection were different in the spectral range of oxides (530 to 570 nm) and kaolinite (1880 to 2380 nm). The kaolinite was better environmental indicators to characterize the landscape in different stages of dissection in sandy soils, whereas hematite and goethite were better environmental indicators to characterize the landscape at different stages of dissection in basalt soils. This result may help to understand the evolution of the landscape and soil in other sedimentary basins. the oxides and hydroxides of iron (hematite and goethite), kaolinite and gibbsite Western Paulista Plateau and associate them with the landscape of the state of play in different environments with total iron content. Based on geological, geomorphological and amplitude variation of pedogenic iron levels (Fed and Feo). Twelve soil samples were collected at a depth 0.0 to 0.2 m for mineralogical and spectral characterization. The magnitude of the total contents obtained by digestion with sulfuric acid showed the difference in the source material, geology, geomorphology and pedogenesis intensity. In soils Training Fish River Valley predominated kaolinitic mineralogy, while the Serra Geral Formation, hematítica. The granulometric, chemical and mineralogical attributes were influenced by the degree of dissection of the Western Paulista Plateau soil. The spectral behavior of the regions at different stages of dissection were different in the spectral range of oxides (530 to 570 nm) and kaolinite (1880 to 2380 nm). The kaolinite was better environmental indicators to characterize the landscape in different stages of dissection in sandy soils, whereas hematite and goethite were better environmental indicators to characterize the landscape at different stages of dissection in basalt soils. This result may help to understand the evolution of the landscape and soil in other sedimentary basins.

Made available in DSpace on 2014-06-11T19:25:34Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-06-21Bitstream added on 2014-06-13T18:29:03Z : No. of bitstreams: 1 desalvi_stb_me_araiq.pdf: 2540043 bytes, checksum: eec00d5945f97f02d5462694316da5d8 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O polimorfismo é observado em diversos fármacos, sendo decorrente das condições empregadas na síntese e purificação da substância. Os polimorfos possuem diferentes propriedades físico-químicas, o que pode afetar de maneira significativa a biodisponibilidade e estabilidade do fármaco. A maioria dos fármacos é comercializada na forma sólida, podendo ter estrutura amorfa ou policristalina. As formas policristalinas são facilmente detectadas por difração de raios X por policristais e, conhecendo-se a estrutura cristalina (ou parcial), é possível realizar a quantificação dos polimorfos nos fármacos através da aplicação do método de Rietveld ou PONKCS1. Neste projeto foram analisados, por difração de raios X, vários medicamentos comercializados, assim como foram definidos os procedimentos adequados para essas análises. Dos cinco medicamentos analisados, dois fazem parte da RENAME2 (ácido acetilsalicílico, carbamazepina) e do Programa Farmácia Popular do Brasil3. Os outros três (ácido mefenâmico, mebendazol e norfloxacino) estão sendo analisados por serem consumidos em abundância no Brasil. O mebendazol fazia parte da lista da RENAME quando esse trabalho teve início, porém na lista de 2010 ele foi retirado tendo em vista que o albendazol apresentou maior eficiência. A importância de tal trabalho está ligada à necessidade de oferecer à população economicamente carente, medicamentos de melhor qualidade e, consequentemente, melhor qualidade de vida. Palavras-chave: físico-química; polimorfismo; difração de raios X; Método de Rietveld / Polymorphism has been observed in several drugs. This is due to conditions employed synthesis and purification of the substance. Polymorphs show different physico-chemical properties, which can affect signicantily their stability and biovailability. Most drugs are commercialized as solids and may present amorphous or polycrystalline structures. Polycrystalline forms are easily detectable through X-ray diffraction by polycrystals and when the crystal structure is entirely (or partially) known, quantification of the drug’s polymorphs is possible by means of the Rietveld Method (or PONKCS)4 employment application. In this work commercial tablets were analyzed using X-ray diffraction and suitable methods for these analyses were optimized. From five drugs analyzed, acetylsalicylic acid and carbamazepine are included in RENAME5 and Programa Farmácia Popular do Brasil6. Mefenamic acid, mebendazole and norfloxacin were analyzed once they are greatly consumed in Brazil. The importance of this research lies on the necessity of offering higher quality drugs to poor population and, thus, to provide a better public health. Keyword: chemistry-physics; polymorphism; X-ray diffraction; Rietveld Method

Made available in DSpace on 2014-06-11T19:35:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-26Bitstream added on 2014-06-13T19:24:23Z : No. of bitstreams: 1 antonio_sg_dr_araiq.pdf: 3454612 bytes, checksum: bd4c8a55e48ef284f15b56dd9fe7c3d9 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A maioria dos fármacos é administrada na forma sólida (amorfo ou policristalino). As formas policristalinas são facilmente detectadas por difração de raios X. Estes fármacos podem cristalizar de diversas formas (polimorfo). Os polimorfos podem apresentar diferentes propriedades físico-químicas e assim apresentar alterações na biodisponibilidade. O polimorfismo decorre das condições empregadas na síntese e purificação da substância, dependendo do tipo de solvente utilizado e da temperatura da reação. Utilizando a difração de raios X e conhecendo a estrutura cristalina é possível a quantificação dos polimorfos nos fármacos através do Método de Rietveld. Neste trabalho, através da difração de raios X por pó, foram indexados os difratogramas de três compostos: a Atorvastatina Cálcica Forma I, o Mebendazol Forma A e um isômero da Tibolona (Isotibolona). Estas indexações permitiram a decomposição de seus respectivos padrões de difração e o posterior uso desses padrões decompostos na identificação dos compostos em matérias primas. Também foram estabelecidos os procedimentos adequados para obtenção dos dados de difração dos fármacos estudados nesse trabalho (ácido mefenâmico, atorvastatina, carbamazepina, mebendazol, tibolona), de forma a permitir a quantificação inequívoca dos seus polimorfos presentes em matérias primas. Um dos problemas mais importantes nessas análises está relacionado à resolução do equipamento que pode causar ambiguidade tanto nas intensidades quanto no alargamento dos picos. Difratogramas de raios X de fármacos apresentam (a) alta sobreposição de picos devido à grande cela unitária e baixa simetria, e (b) orientação preferencial devido aos cristalitos anisotrópicos. Assim, em alguns casos, como tibolona e carbamazepina, foi necessário usar a alta resolução para diminuir a sobreposição dos picos e... / The majority of pharmaceuticals are prescribed in solid form (amorphous or polycrystalline). The polycrystalline forms are detected by rays X diffraction. These pharmaceuticals can crystallize in several forms (polymorphs), which present distinct physico-chemical properties and biodisponibility. The polymorphism occurs due to conditions used in the synthesis and purification of the substance, depending on the type of solvent used and the temperature reaction. Utilizing X-Ray powder diffraction and if the crystal structure are known, it is possible, using the Rietveld Method, to quantify the amount of each polymorph in the pharmaceutical. In this work, x-ray diffraction patterns of three compounds were indexed: Atorvastatin calcium form I, mebendazole form A and isotibolone (a tibolone isomer). These indexing allowed pattern decomposition which was used for its identification in raw materials of these drugs. The procedure for the suitable X-ray diffraction data collection was also established for the pharmaceuticals studied in this work (mefenamic acid, atorvastatin, carbamazepine, mebendazole, tibolone), in order to have an unequivocal quantification of their polymorphs in raw materials. One of the most important problem in pharmaceutical analysis is related to the equipment resolution, which can cause ambiguity in the peak intensities and broadening. X-ray diffraction patterns present (a) high peak overlap due to the large unit cell and low symmetry and (b) preferred orientation due to the anisotropic crystallites. Then, in some cases, like tibolone and carbamazepine, it was necessary to use high resolution equipments for decreasing the peak overlap and the suitable correction of the anisotropic peak broadening caused by the crystallite anisotropy. The high resolution also allows the unit cell refinement without ... (Complete abstract click electronic access below)