O presente trabalho teve como objetivo principal avaliar o efeito dos recobrimentos TiN e TiAlN depositados por PVD a plasma na liga Ti-6Al-4V sob condições de fluência a 600 °C e corrosão em meios contendo cloreto a 25, 60 e 80 °C. O trabalho foi complementado com análises microestruturais e dos revestimentos superficiais utilizando-se as técnicas de difração de raios X, microscopias óptica, eletrônica de varredura e de transmissão, medidas de microdureza e oxidação isotérmica. Os resultados permitiram concluir que a liga Ti-6Al-4V constituída pela configuração de Widmanstätten apresentou dureza média de 343 HV para a condição como recebida. Após os tratamentos por PVD a plasma observou-se um recobrimento à base de TiN de espessura de 2,2 ?m e composição igual a Ti0,7N. O recobrimento a base de TiAlN/TiAlCrN apresentou espessura em torno de 6 ?m e composição igual a (Ti0,38Al0,62)N/(Ti0,31Al0,50Cr0,19)N. As medidas do potencial em circuito aberto e polarização mostraram que a liga Ti-6Al-4V apresentou comportamento ativo com transição ativo-passiva em solução HCl e comportamento passivo em solução NaCl a 25, 60 e 80 °C. As amostras recobertas por TiN e TiAlN/TiAlCrN apresentaram comportamento passivo nas duas soluções corrosivas e em todas as temperaturas estudadas. A amostra revestida por TiN depositado por PVD apresentou os menores valores de taxa secundária em fluência para tensões maiores que 222 MPa, contudo a amostra nitretada a plasma apresentou maiores valores de vida útil e níveis de ductilidade. A análise conjunta dos expoentes de tensão, energia de ativação e estrutura de discordâncias indicaram que o principal mecanismo de deformação por fluência foi controlado por escalagem de discordâncias. O cálculo do parâmetro de tolerância ao dano (W) contribuiu para indicar que os revestimentos TiN e TiAlN/TiAlCrN, apesar de protegerem a superfície da oxidação, diminuíram a capacidade de deformação plástica ao longo do estágio terciário e vida útil da liga Ti-6Al-4V, reduzindo a ductilidade. Finalmente, os tratamentos superficiais utilizados neste trabalho foram eficientes por seu efeito de proteção através da deposição de um elemento cerâmico mais estável na superfície e não por transformações causadas na microestrutura. / This study aimed to evaluate the effect of the plasma-assisted PVD TiN and TiAlN/TiAlCrN coatings in the Ti-6Al-4V alloy under creep conditions at 600 °C and under corrosion conditions in environments containing chloride at 25, 60 and 80 °C. The study was complemented by microstructural and surface coatings analysis using XRD, optical, scanning and transmission electron microscopy, microhardness and isothermal oxidation. The results showed that the Ti-6Al- 4V alloy with Widmanstätten morphology presented an average hardness of 343 HV for as received condition. After treatment by plasma PVD, it was observed a TiN based coating, with 2,2 ?m and composition of Ti0,7N. The TiAlN/TiAlCrN based coating presented 6 ?m of thickness and composition of (Ti0,38Al0,62)N/(Ti0,31Al0,50Cr0,19)N. Anodic polarization and open circuit potential showed that Ti-6Al-4V alloy had active behavior with active - passive transition in HCl solution and passive behavior in NaCl solution at 25, 60 and 80 °C. The TiN and TiAlN/TiAlCrN coated samples showed passive behavior in both corrosive solutions and at all studied temperatures. The TiN coated sample showed the lowest values of secondary creep rate for stresses greater than 222 MPa, however, the plasma nitrided sample showed higher levels of service life and ductility. The analysis of stress exponents, activation energy and dislocations structures indicated that the main mechanism of creep was controlled by climbing dislocations. The damage tolerance parameter (W) calculation contributed to indicate that TiN and TiAlN/TiAlCrN coatings, although protect the surface from oxidation, decreased plastic deformation ability throughout tertiary stage and service life of the Ti-6Al-4V alloy, decreasing ductility. Finally, the surface treatments, used in this study, were efficient for their protective effect by depositing a more stable ceramic compound on surface and not by transformations caused on microstructure.

Orientador: Carlos Henrique Inácio Ramos / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-18T21:37:15Z (GMT). No. of bitstreams: 1 Gava_LisandraMarques_D.pdf: 9573403 bytes, checksum: 4d69a29d08ffc20e4544b876f131fb0d (MD5) Previous issue date: 2011 / Resumo: A função biológica das proteínas está relacionada à sua estrutura tridimensional adquirida pelo processo de enovelamento protéico. Neste contexto, proteínas denominadas, genericamente, de chaperonas moleculares exercem papel fundamental atuando no auxílio do enovelamento correto, no reenovelamento e na dissociação de agregados protéicos. A Hsp90 é uma das chaperonas moleculares mais importantes, é essencial para a viabilidade celular em eucariotos e está normalmente associada a proteínas atuantes no ciclo e sinalização celular, o que torna essa chaperona um alvo bastante interessante para abordagens terapêuticas de diversas doenças. A Hsp90 pode ser modulada por co-chaperonas diversas. Nesse trabalho foram caracterizadas as proteínas CHsp90 (domínio C-terminal da Hsp90 humana), e as co-chaperonas Hop e Tom70, além da interação entre C-Hsp90 e Tom70. Foram aplicadas técnicas de dicroísmo circular e emissão de fluorescência do triptofano; seguidas pela caracterização por ultracentrifugação analítica, gel filtração analítica, espalhamento dinâmico de luz, cromatografia de gel filtração acoplada a espalhamento de luz em multi-ângulos (SEC-MALS) e gel nativo. Para os ensaios de interação foram aplicadas técnicas de pull-down, SEC-MALS e calorimetria de titulação isotérmica. As proteínas foram produzidas puras e enoveladas, com estado oligomérico determinado como dímero para C-Hsp90 e monômero para Hop e Tom70, sendo que essas também foram encontradas como espécies diméricas. A estequiometria de interação entre a C-Hsp90 e Tom70 foi determinada em 1 monômero da Tom70 para 1 dímero da C-Hsp90, com KD de 360 ± 30 nM, ?Happ = -2,6 ± 0,1 kcal/mol e ?S = 21 ± 1 cal/mol.K, sugerindo que a interação é dirigida por entalpia e entropia. Os resultados obtidos nesse trabalho contribuem para uma melhor compreensão do sistema Hsp90, que está envolvido em diversos processos celulares essenciais e patológicos, como doenças neurodegenerativas, processos inflamatórios, infecções e câncer / Abstract: The biological function of proteins is related to its three dimensional structure acquired via protein folding process. In this context, the molecular chaperones play a key role acting as auxiliary protein on protein folding, refolding and dissociation of protein aggregates. Hsp90 is one of the most important molecular chaperones, is essential for cell viability in eukaryotes and is usually associated with proteins involved in cell cycling and cell signaling, which makes these chaperone a very interesting targeting for therapeutic approaches for several diseases. The chaperone activity of Hsp90 can be modulated by other proteins, called co-chaperones. In this work, we characterized the protein C-Hsp90 (Cterminal domain of human Hsp90) and the co-chaperones Hop and Tom70, and also the interaction between C-Hsp90 and Tom70. Circular dichroism and fluorescence emission of tryptophan was first applied for initial characterization of the proteins, followed by analytical ultracentrifugation, analytical gel filtration, dynamic light scattering, size exclusion chromatography - multi angle light scattering (SEC-MALS) and native gel. The interaction between C-Hsp90 and Tom70 were measured by techniques like pull-down, SEC-MALS and isothermal titration calorimetry. The proteins were produced pure and soluble and their oligomeric state were determined as dimer for C-Hsp90, and monomer for Hop and Tom70, these two co-chaperones were also found as dimeric species. The stoichiometry of interaction between C-Hsp90 and Tom70 was determined by SEC-MALS and ITC as been 1 dimer of C-Hsp90 to 1 monomer of Tom70, with a KD of 360 ± 30 nM, ?Happ = -2.6 ± 0.1 kcal/mol and ?S = 21 ± 1 cal/mol.K, suggesting that these interaction is driven by both, enthalpy and entropy. The results contribute to a better understanding of the important Hsp90 machinery, which is involved in many essential cellular and pathological processes, such as neurodegenerative diseases, inflammation, infection and cancer / Doutorado / Bioquimica / Doutor em Biologia Funcional e Molecular

CO2 global emissions exceed 30 Giga tonnes (Gt) per year, and the high atmospheric concentrations are detrimental to the environment. In spite of efforts to decrease emissions by sequestration (carbon capture and storage) and repurposing (use in fine chemicals synthesis and oil extraction), more than 98% of CO2 generated is released to the atmosphere. With emissions expected to increase, transforming CO2 to chemicals of high demand could be an alternative to decrease its atmospheric concentration. Transportation fuels represent 26% of the global energy consumption, making it an ideal end product that could match the scale of CO2 generation. The long-term goal of the study is to transform CO2 to liquid fuels closing a synthetic carbon cycle. Synthetic fuels, such as diesel and gasoline, can be produced from syngas (a combination of CO and H2) by Fischer Tropsch synthesis or methanol synthesis, respectively. Methanol can be turned into gasoline by MTO technologies. Technologies to make renewable hydrogen are already in existence, but CO is almost exclusively generated from methane. Due to the high stability of the CO2 molecule, its transformation is very energy intensive. Therefore, the current challenge is developing technologies for the conversion of CO2 to CO with a low energy requirement. The work in this dissertation describes the development of a recyclable, isothermal, low-temperature process for the conversion of CO2 to CO with high selectivity, called Reverse Water Gas Shift Chemical Looping (RWGS-CL). In this process, H2 is used to generate oxygen vacancies in a metal oxide bed. These vacancies then can be re-filled by one O atom from CO2, producing CO. Perovskites (ABO3) were used as the oxide material due to their high oxygen mobility and stability. They were synthesized by the Pechini sol-gel synthesis, and characterized with X-ray diffraction and surface area measurements. Mass spectrometry was used to evaluate the reducibility and re-oxidation abilities of the materials with temperature-programmed reduction and oxidation experiments. Cycles of RWGS-CL were performed in a packed bed reactor to study CO production rates. Different metal compositions on the A and B site of the oxide were tested. In all the studies, La and Sr were used on the A site because their combination is known to enhance oxygen vacancies formation and CO2 adsorption on the perovskites. The RWGS-CL was first demonstrated in a non-isothermal process at 500 °C for the H2-reduction and 850 °C for the CO2 conversion on a Co-based perovskite. This perovskite was too unstable for the H2 treatment. Addition of Fe to the perovskite enhanced its stability, and allowed for an isothermal and recyclable process at 550 °C with high selectivity towards CO. In an effort to decrease the operating temperature, Cu was incorporated to the structure. It was found that Cu addition inhibited CO formation and formed very unstable oxide materials. Preliminary studies show that application of this technology has the potential to significantly reduce CO2 emissions from captured flue gases (i.e. from power plants) or from concentrated CO2 (adsorbed from the atmosphere), while generating a high value chemical. This technology also has possible applications in space explorations, especially in environments like Mars atmosphere, which has high concentrations of atmospheric carbon dioxide.

In order to characterize mechanical components used in high responsibility applications, the knowledge of chemical composition and results from regular experiments such as traction, impact and hardness tests is important, but not sufficient. They cannot supply the necessary information that permit anticipating, in a reliable way, the components behavior in actual working conditions. As an example, there are engines cylinder head submitted to mechanical and thermal tensions that are relatively high during the in service use, and very high in same very demanding condition. During long run times and any failure in the cooling and/or lubrication the temperature may reach 300ºC. This temperature variation causes thermal shocks which may generate cracks and/or a wide ranging of plastic deformation in regions close to the pistons. Even not considering the thermal shock effects caused by failure, even so, a short number of start-up and shutdown cycles of engine, are considered the main cause of small cracks. This indicates that the generation of cracks in cylinder head may be considered as low cycle thermomechanical fatigue problem. Another problem is the microstructure heterogeneity in the component due to the casting process, leading to different physical and mechanical properties in the same piece. Besides the presence of porosity generated by gas bubbles and voids of solidification, which may be as great as short crack, reducing the nucleation life and changing the problems focus for the fatigue crack growth. The purpose of this study was to determine the isothermal and thermomechanical fatigue property through low cycle fatigue, as well as the fatigue crack growth, relaxation, microestrutural characterization and modeling of mechanical behavior by finite element for the aluminum alloy employed in the manufacture of engine cylinder head by the national automotive industry. Isothermal fatigue experiments were carried out at temperature of 120ºC and 280ºC and the thermomechanical performed in phase between the temperatures of 120ºC and 280ºC. The relaxation experiments were performed at some temperatures with trapezoidal wave loading, whereas the experiments of fatigue crack growth carried out at temperatures of 120ºC, 200ºC and 280ºC for sine and trapezoidal wave loading in displacement and load control. The microstructure analysis was also made in the specimens after the fatigue test by optical microscopy and scanning electron microscopy SEM. The results of these experiments showed that the casting defects and materials inhomogeneities, coupled long run times in high temperatures and loads, are a critical factor in the component performance. These results help us to establish accurate models for life prediction of the engine cylinder head. / Para caracterizar componentes usados em aplicações de alta responsabilidade não basta apenas conhecer a composição química e os resultados de ensaios de tração, impacto e dureza, pois estes podem não fornecer os subsídios necessários que permitam prever, de maneira confiável, o comportamento dos componentes nas condições reais de trabalho. Exemplo disto são os cabeçotes de motor automotivos, submetidos a tensões térmicas e mecânicas relativamente altas durante seu uso normal e altíssimo em condições extremas. Durante longos tempos de funcionamento e eventuais falhas na refrigeração e ou lubrificação a temperatura pode chegar a valores próximos de 300ºC. Esta variação de temperaturas provoca choques térmicos que podem gerar trincas e/ou uma grande quantidade de deformação plástica em regiões próximas aos pistões. Desconsiderando a presença de choques térmicos provocados por falhas, ainda assim, uma pequena quantidade de ciclos de acionamento e parada do motor, é considerada como os principais causadores de pequenas trincas. Isso indica que o surgimento de trincas em cabeçotes de motor deve ser considerado um problema de fadiga termomecânica de baixo ciclo. Outro problema é a heterogeneidade microestrutural no componente devido ao processo de fundição, levando a propriedades mecânicas e físicas diferentes em uma mesma peça. Além da presença de porosidade gerada por bolhas de gás e vazios de solidificação, que podem adquirir tamanho tal que se aproximem de pequenas trincas, diminuindo a vida para a nucleação e assim mudando o foco do problema para o de propagação de trinca por fadiga. A proposta deste trabalho foi a de determinar as propriedades de fadiga isotérmica e termomecânica através de ensaios de fadiga de baixo ciclo, bem como as propriedades de propagação de trinca por fadiga, relaxação, caracterização microestrutural e modelagem do comportamento mecânico por elementos finitos para a liga de alumínio utilizada na fabricação de cabeçotes de motores automotivos pela indústria nacional. Os ensaios de fadiga isotérmica foram realizados nas temperaturas de 120ºC e 280ºC e os ensaios termomecânicos foram realizados em fase entre as temperaturas de 120ºC e 280ºC. Os ensaios de relaxação foram realizados em várias temperaturas com carregamento de onda trapezoidal, enquanto que os ensaios de propagação de trinca por fadiga foram realizados nas temperaturas de 120ºC, 200ºC e 280ºC para carregamentos de onda senoidal e trapezoidal em controle de carga e de deslocamento. Foi feita também análise microestrutural nos corpos de prova, após os ensaios de fadiga, por microscopia óptica e por microscopia eletrônica de varredura MEV. Os resultados destes ensaios mostraram que os defeitos de fundição e a falta de homogeneidade no material, aliados a longos tempos de exposição a carregamentos e em altas temperaturas, constituem um fator crítico no desempenho do componente. Estes resultados ajudarão a estabelecer modelos precisos de previsão de vida para os cabeçotes de motor.

This thesis studies the influence of internal nozzle flow characteristics over a large spectrum of experimental conditions and diagnostics. Experiments were carried out for two nozzle geometries---cylindrical and conical single hole nozzles---and three different fuels. Two of the fuels are pure components---n-heptane and n-dodecane---while the third fuel consists of a three-component surrogate to better represent the physical and chemical properties of diesel fuel. Measurements include a complete hydraulic characterization consisting of instantaneous injection rate and spray momentum flux measurements; a high-speed visualization of isothermal liquid spray; a high-speed visualization of the evaporative inert spray, imaging liquid and vapor phases simultaneously and finally, a high-speed visualization of the high temperature reactive spray, imaging vapor phase and OH* chemiluminescence for each injection event. All high-temperature diagnostics were performed in a continuous flow test chamber that allows an accurate control on a wide range of thermodynamic conditions (up to 1000 K and 15 MPa). The experimental findings from this work, and the large database obtained (available for download at: http://www.cmt.upv.es/DD01.aspx), could be used to validate CFD models that could help the community understand the fundamental driving mechanisms behind these observations. / En esta tesis se estudia la influencia del flujo interno sobre un amplio espectro de condiciones y diagnósticos experimentales. Se realizaron experimentos para dos geometrías de tobera---toberas cilíndrica y cónica de un único orificio---y tres combustibles. Dos de los combustibles son puros---n-heptano y n-dodecano--- mientras el tercero es un combustible sustituto que consiste en una mezcla de tres componentes que busca representar mejor las propiedades físicas y químicas del diesel. Las medidas incluyen una caracterización hidráulica completa, compuesta por tasa de inyección y cantidad de movimiento instantáneas; una visualización de alta velocidad del chorro líquido isotermo; una visualización de alta velocidad del chorro inerte evaporativo, con captura simultánea de las fases líquida y vapor y, finalmente, una visualización del chorro reactivo a alta temperatura, con captura de la fase vapor y la quimioluminiscencia del radical OH* para cada evento de inyección. Todos los diagnósticos en condiciones de alta temperatura fueron realizados en una maqueta de alta presión y temperatura de flujo constante que permite controlar con precisión un rango amplio de condiciones termodinámicas (hasta 1000 K y 15 MPa). Los resultados experimentales y la gran base de datos obtenida en este trabajo (disponible en: http://www.cmt.upv.es/DD01.aspx), podrían ser utilizados para validar modelos CFD detallados que podrían ayudar a la comunidad científica a entender mejor los mecanismos fundamentales que producen los resultados observados. / Aquesta tesi estudia la influència del flux intern sobre un gran espectre de condicions i diagnòstics experimentals. Es van realitzar experiments per a dos geometries de tovera---toveres ci¿líndrica i cónica amb un únic orifici---i tres combustibles. Dos dels combustibles són purs---n-heptà i n-dodecà--- mentre el tercer combustible consisteix en una mescla de tres components que formen un combustible substitut que busca representar millor les propietats físiques i químiques del dièsel. Les mesures inclouen una caracterització hidràulica completa, composta per taxa d'injecció i quantitat de moviment instantanis; visualització d'alta velocitat del doll líquid isoterme; visualització d'alta velocitat del doll inert evaporatiu, capturant simultàniament les fases líquid i vapor i, finalment, una visualització del doll reactiu a alta temperatura, capturant la fase vapor i la quimioluminiscència del radical OH per a cada esdeveniment d'injecció. Tots els diagnòstics en condicions d'alta temperatura van ser realitzats en una insta¿lació d'alta pressió i temperatura amb flux constant que permet controlar amb precisió un ampli rang de condicions termodinàmiques (fins a 1000 K i 15 MPa). Els resultats experimentals i la gran base de dades obtinguda en aquest treball (disponible a la web en: http://www.cmt.upv.es/dd01.aspx), podrien ser utilitzats per tal de validar models CFD detallats que podrien ajudar a la comunitat científica a entendre millor els mecanismes fonamentals que produeixen aquestes observacions. / Viera Sotillo, JP. (2017). Experimental study of the effect of nozzle geometry on the performance of direct-injection diesel sprays for three different fuels [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/81857 / TESIS

The use and knowledge of additive manufacturing technologies are rapidly growing. It is crucial to understand the processing-structure-property relationship, which is highly discussed when trying to understand the science of a material. One commonly used material in aerospace applications is titanium alloy, lately Ti-6Al-2Sn-4Zr-2Mo (Ti-6242). This work is addressed towards a laser metal deposition wire (LMD-w) manufactured Ti-6242 built on a Ti-6Al-4V (Ti-64) base plate.  The microstructure of titanium alloys, like all other alloys, are highly dependent on its thermal history. It is crucial to understand the microstructural change in order to optimize the material properties. The prediction of microstructure through simulation can be improved by obtaining experimental input. Since the microstructure of an LMD-w manufactured component is different from the subtractive manufactured, the change from heat treatments are different considering the different start structures. It is therefore of interest to analyse isothermal heat treatments effect on solution heat treated microstructure of LMD-w Ti-6242, from an industrial application point of view. The objective of this work is to analyse the effect of isothermal heat treatment on microstructural changes for LMD-w Ti-6242 wall.  The as received state was solution heat treated according to GKN standard, isothermal treatments were additionally performed and the change was analysed with microstructural characterization. The prior beta grain size, alpha lath thickness, phase fraction and hardness have been measured. Focus has been on the Ti-6242 wall for the measurements of alpha lath thickness and phase fraction. However, an analysis of the interface and heat affected zone (HAZ) has been made as well. MIPAR, an image analysis program was used for alpha lath thickness and phase distribution measurements. It has been concluded that the hardness of the material increases with increasing isothermal temperature during heat treatment and that the lath thickness increases with longer holding time. An equilibrium diagram has been obtained for Ti-6242 from a solution heat treated microstructure of LMD-w between the temperatures of 700°C and 1000°C and a time-temperature-transformation diagram (TTT-diagram), in the range of 700°C-1000°C and a holding time from 30 seconds to 2 hours. / Efterfrågan av samt kunskapen om additiva tillverkningsmetoder ökar kraftigt. Det är därför av stort intresse att förstå relationen mellan process-struktur-egenskaper, vilket ofta diskuteras för att förstå vetenskapen bakom ett material. Ti-6Al-2Sn-4Zr-2Mo (Ti-6242) har under den senaste tiden väckt stort ett intresse inom flygindustrin. I detta arbete har fokus lagts på laser metal deposition wire (LMD-w) tillverkat material bestående av en Ti-6242 vägg på en Ti-64 basplatta.  Titanlegeringars mikrostruktur är känslig mot den termiska historiken inom materialet. Det är därför av stort intresse att förstå hur mikrostrukturen ändras för att kunna optimera materialet. Förutberäkning genom simulering av mikrostrukturens förändring kan förbättras med hjälp av experimental indata. Eftersom mikrostrukturen av en LMD-w tillverkad komponent är annorlunda från traditionella tillverkningsmetoder, kommer förändringen av mikrostrukturen från värmebehandlingar vara olika, eftersom ursprungsstrukturen inte är densamma. Därför är det av intresse att analysera isotermiska värmebehandlingars påverkan på en upplösningsbehandlad mikrostruktur tillverkad med LMD-w, från en industriell synpunkt. Målet med detta arbete är att analysera effekten av isotermisk värmebehandling på mikrostrukturen av en LMD-w Ti-6242 vägg.  Startmaterialet bestod av ett upplösningsbehandlat tillstånd enligt GKN standard, isotermiska värmebehandlingar gjordes och förändringen analyserades genom mikrostrukturkarakterisering. Primära beta korn, alfaband, fasfraktion och hårdhet har mätts. Fokus har legat i Ti-6242 väggens mätningar av alfaband och fasfraktion, dock har en analys av den värmebehandlade zonen (HAZ) i basplattan gjorts. MIPAR, ett bildanalysprogram, har använts för att mäta alfaband och fasdistribution.  Det kan konstateras att hårdheten av materialet ökar med ökande isotermisk temperatur under värmebehandling, och att alfabandens tjocklek ökar med längre hålltider. Ett jämnviktsdiagram har framtagits för upplösningsbehandlad Ti-6242 LMD-w mellan temperaturerna 700°C och 1000°C. Ett tid-temperatur-transformations diagram (TTT-diagram) inom intervallet av 700°C-1000°C och från 30 sekunder till 2 timmar.

This thesis is focused at possibilities of preparation and characterization of XRD-amorphous delaminated and dehydroxylated talc phase – meta-talc, which can have its potential application and a starter material for a preparation of magnesium-silicate analogues of geopolymers. Changes in structure and morphology of talc ore were observed during this work. For the purposes of this research, two various talc ores – chloritic and dolomitic were examined. Whole process of meta-talc preparation was examined with whole scale of instrumental techniques such as X-ray diffraction, simultaneous thermogravimetric a differential thermal analysis, infrared spectroscopy, scanning electron microscopy or laser analysis of particle size. Meta-talc can be obtained via mechanochemical activation of talc ore with subsequent calcination. Mechanochemical treatment lead to destruction of original crystal structure and breaking of original bonds, i.e. the product of this treatment was almost amorphous and delaminated. Most of hydroxyl groups were converted to molecules of water which remained adsorbed or coordinated in ore structure. These molecules were removed during calcination step.

This master thesis deals with study of chitosan-lignohumate, chitosan-polystyrenesulfonate, chitosan-alginate and chitosan-carrageenan polyelectrolyte complexes. The work was motivated by research of finding suitable alternative substance for lignohumate. The molecular weights of substances were characterized using SEC-MALLS. A degree and a character of the interactions between polyelectrolyte were studied by isothermal titration calorimetry and dynamic light scattering method. The calorimetric experiments proved that decreasing concentration of samples causes decreasing of heat flow. The best calorimetric measurements were provided by adding chitosan into polymer solution. The interactions between chitosan and polyanions and influence of mixing order were proved also by measuring intensity of zeta potential, Z-average of particle size and turbidity. New chitosan-based materials have a big potential in agriculture and medicine.

<div>Drug solubility is a persistent challenge in pharmaceutical product development. The objective of this research is to develop a formulation/processing strategy by means of a biodendrimeric solid dispersion (BDSD) platform, for increasing the solubility and dissolution rate of poorly water-soluble drugs. The BSDS platform combines a novel type of excipient, referred to as DLB, with a new application of the hot melt extrusion (HME) process.</div><div><br></div><div>Four model compounds – phenytoin (PHT), griseofulvin (GSF), ibuprofen (IBU), and loratadine (LOR) – were used to evaluate the solubilization effect of an octenylsuccinate-modified dendrimer-like biopolymer (OS-DLB). Shake-flask solubility measurements show that OS-DLB exerts significant solubilizing effect when present at less than 0.2% in water. The presence of hydrophobic C₈ chains on OS-DLB creates the type of favorable nonpolar microenvironment necessary for producing a parallel liquid phase equilibrium responsible for the increase in the total amount of drug dissolved in aqueous media. The higher the hydrophobicity of the drug, the higher the observed solubilization effect. Isothermal titration calorimetry studies show that drug solubilization by OS-DLB occurs by means of entropy-driven interactions. These studies also show that the intermolecular interaction between IBU and OS-DLB in solution exhibits very small energy change upon mixing but a stronger effect on entropy. In comparison, the intermolecular interaction between the less hydrophobic GSF and OS-DLB have significant effects on both enthalpy and entropy. Consequently, in terms of solubilization enhancement, it was found that the interaction between IBU and OS-DLB is entropy-driven (more favorable), while in the case of GSF, the interacting molecules are arranged to maximize enthalpic interaction.</div><div><br></div><div>Based on the solubility studies, a formulation/processing approach for enhancing the dissolution rate of the model drugs was developed. The biopolymer serving as both carrier and solubilizing agent, was coprocessed with poloxamer, functioning as a processing aid, using hot melt extrusion (HME) as an enabling technology. The result is a non-amorphous solid dispersion, exhibiting high and long-lasting supersaturation upon dissolution. A 3-factor, 3-level Box-Behnken design was implemented to define the optimal design space for the formulation/extrusion process. The results obtained from multivariate data analysis (partial least squares and principal components analysis) and response surface modeling suggest that drug release performance of IBU BDSDs is strongly influenced by the processing variables, while maximum release of GSF from the BDSDs can be attained through selective combination of functional excipients.<br></div>

Der erste Teil dieser Arbeit untersucht die Ladungswechselwirkung zwischen Proteinen und Polyelektrolyten. Dabei wird die Bindung von Polyakrylsäure (PAA) als kurzes Modell-Polyelektrolyt an Humanalbumin (HSA) in einer umfassenden experimentellen und theoretischen Studie untersucht und sehr gute Übereinstimmung der Resultate konnte festgestellt werden. Die Computersimulationen in dieser Arbeit wurden von Xiao Xu im Rahmen seiner Promotion durchgeführt. Thermodynamische Daten wurden mit Hilfe von Isothermer Titrationskalorimetrie (ITC) gesammelt und strukturelle Untersuchungen wurden mit Hilfe von Neutronenkleinwinkelstreuung (SANS) durchgeführt. Die Analyse von Bindungsaffinitäten zeigte eine eins zu eins Bindung von PAA mit HSA, die entropisch getrieben ist und strukturellen Untersuchungen weisen eine stabile Proteilstruktur unabhängig von der Adsorption durch PAA auf. Im zweiten Teil der Arbeit wird die Wechselwirkung zweier uremischer Toxinen, nämlich Phenylessigsäure (PhAA) und Indoxylsulfat (IDS), mit HSA untersucht. Eine wichtige Schlussfolgerung aus der Analyse der ITC Daten ist, dass begünstigende, hydrophobe Wechselwirkungen die treibende Kraft für die Adsorption von Toxinen an HSA sind, und dass hierbei die Enthalpie-Entropie-Kompensation (EEC) zu tragen kommt. Weiterhin zeigen SANS Untersuchungen, dass die Proteinstruktur trotz Adsorption stabil bleibt und konnte außerdem über Interpartikulare Wechselwirkung von HSA-Toxin Komplexen aufklären. Im Allgemeinen ist HSA strukturell unverändert durch die Adsorption von Liganden. Diese Feststellung erlaubt die Interpretation von ITC Daten, da damit gemessene Wärmeprozesse ausschließlich von Bindungsprozessen herrühren. Die vorliegende Arbeit konnte zeigen, dass eine ausführliche thermodynamische Analyse durch Kombination von theoretischer mit experimenteller Arbeit, eine umfassende Einsicht in die Mechanismen von Bindungsprozessen ermöglicht. / The first part of the thesis explores the charge-charge interaction between proteins and polyelectrolytes. Polyacrylic acid (PAA) is used as a short model polyelectrolyte to interact with human serum albumin (HSA) the most abundand protein in blood, in a comprehensive experimental and theoretical study. The results thereby coincide very well. Computer simulation studies were performed by Xiao Xu within the framework of his PhD thesis. Thermodynamic data were collected by means of isothermal titration calorimetry (ITC) and structural analysis performed using small-angle neutron scattering (SANS). The analysis of binding free energies revealed one to one binding that is mainly driven by entropy. Structural investigations give proof of the stability of the protein beside adsorption. In the second part, the interaction of two uremic toxins, namely phenylacetic acid (PhAA) and indoxyl sulfate (IDS), with HSA is studied. Systematic ITC experiments reveal two binding sites for both of the two toxins and show small dependence of binding affinities on ionic strength in contrast to PAA adsorption to HSA. This leads to the key conclusion that the favorable hydrophobic interaction is the driving contribution for adsorption and enthalpy-entropy compensation (EEC) effect comes into play. SANS studies of high concentrated HSA-toxin solutions proofed the stability of the protein structure and shed light on the interparticle interaction of HSA-toxin complexes. In general, HSA is structurally robust regardless of ligand uptake. This finding allows the interpretation of ITC data by confirming that the measured heat signals are purely associated to the binding process. The present thesis has demonstrated that a full thermodynamic analysis in combination with theoretical modelling can provide a comprehensive understanding of binding in terms of identifying driving forces and their contributions to protein ligand interaction.