2-D numerical computer models based on thermodynamic and kinematic principles have become invaluable tools for simulating geodynamic processes at these systems. Numerical models have proven effective for allowing the examination and computation of multiple factors simultaneously, providing scientists with an important resource with which to study complex systems. Previously, for instance, numerical models have been used for examining different factors involved in magma production at subduction zones and mid ocean ridges by modelling the influence and interplay of factors such as the effect of hydration and the influence of the depth of the fault between the two plates on the melting (van Keken, 2003; van Keken 2008). Additional models have explored the thermal structure of subduction zones and its relationship to the processes involved at convergent boundaries, including magma production (van Keken, 2023a). Syracuse et al. (2010) used numerical models for subduction zones, creating thermal models that examined dehydration and melting in subduction zones with a variety of slab geometries, convergence velocities, ages and structures. Still others have shown that thermal structure affects melt production, formation of arc volcanoes, dehydration, and seismicity, modelling the effects of varying slab dip, plate convergence velocity, plate age, etc. (Syracuse et al., 2010; Hayes et al, 2018). However, none have yet utilized models to systematically investigate magma production at either subduction zones or mid-ocean ridges to specifically examine both batch and fractional melting with the combination of multiple controlling factors including slab dip, convergence rate, hydration, minerology, and slab age. This project investigated the processes surrounding magma production at subduction and mid-ocean ridge systems through the creation of a numerical model and utilization of the developed model to explore the effects of a multitude of parameters on fractional and batch melting, as well as investigated the incorporation of incompatible elements, and other processes of interest in subduction and mid ocean ridge systems.

Este trabalho visou obter extratos secos padronizados de Curcuma longa L., e sua otimização visando o aumento da solubilidade dos curcuminóides e melhoria nas suas atividades biológicas. No estudo de extração, os curcuminóides foram extraídas utilizando dois solventes, etanol e solução etanólica alcalina e dois processos microondas e ultrassom seguindo planejamentos fatoriais completos 24, e com pH do solvente, teor de etanol, tempo de extração, potência do microondas ou temperatura no ultrassom, e proporção massa da droga pela massa do solvente como variáveis independentes. Os extratos foram caracterizados quanto ao rendimento de sólidos totais, teor de curcuminóides totais, rendimento de curcuminóides totais, teor de curcumina, rendimento de curcumina e atividade antioxidante por difenil-picril-hidrazila. A condição de extração com melhor resultado foi o ultrassom a 20 ºC, solvente etanol 96 ºGL, 1 parte de planta para 7 de solvente, pH 10 e duração de 5 min., pois, nesta condição, obteve-se maior teor de curcumina e maior atividade antioxidante. O estudo visando aumento da solubilidade da curcumina constou da preparação de dispersões sólidas pelos métodos de spray drying e hot melt coating. Ambos os métodos foram estudados com os polímeros hidrofílicos Gelucire® 44:14 e 50:13, e aplicando-se planejamento fatorial tipo Box-Behnken. As dispersões sólidas particuladas foram avaliadas pela morfologia, densidade aparente e de compactação, fator de Hausner, índice de Carr, ângulo de repouso, umidade residual, atividade de água, calorimetria diferencial de varredura, termogravimetria, difração de raio-X, espectrometria de infravermelho, solubilidade em água e teste de dissolução. A maior solubilidade foi obtida com secagem no spray drying a 40 ºC, proporção Gelucire®44/14:curcumina 1:1 e proporção 1:5 de Aerosil:dispersão (DS16). No hot melt coating, a melhor solubilidade foi obtida com maior quantidade de Gelucire 50/13 e menor de Lactose (DS 3). Dispersões sólidas particuladas foram preparadas também com o Gelucire® 50/13 por spray drying (DS 17). Considerando-se os fatores solubilidade e teor de curcumina nas partículas, a dispersão DS 17 foi escolhida como a mais adequada para os ensaios biológicos posteriores. A mesma condição de preparo da DS17 foi usada para produzir dispersões sólidas com o extrato obtido por ultrassom (DSE). Nesta dispersão a solubilidade dos curcuminóides demonstrou ser 330 vezes maior do que o extrato seco nas mesmas condições porém sem a adição de carreador. No ensaio de avaliação da atividade antitumoral in vitro, foram avaliadas a citotoxicidade da curcumina pura, DS 17, DS 3 e a DSE, em diferentes linhagens tumorais, leucemia T (jurkat), melanona (C8161), adenocarcinoma coloretal (HT29), carcinoma hepatocelular (HepG2) e de célula não tumoral (PBMC). A curcumina apresentou atividade citotóxica para células tumorais e esta não foi afetada pelo processo de produção da dispersão sólida. Além disso, a DS do extrato apresentou maior citotoxicidade, o que pode ser devido ao sinergismo de outros compostos. O extrato também foi mais seletivo para células tumorais que a curcumina e as dispersões. O estudo de atividade anti-inflamatória in vivo usando o modelo de edema de pata, demonstrou que a dispersão DS 17 apresentou maior atividade do que a curcumina na mesma dose, indicando que o aumento da solubilidade possibilita uma maior absorção e consequentemente maior biodisponibilidade. / The aim of this work was to obtain standardized dried extracts of Curcuma longa L. and to develop pre-formulations and capsules with improved curcuminoids solubility and higher biological activities. In the extraction study, the powdered roots of Curcuma longa L. were extracted using ethanol and an aqueous alkaline ethanol solution by microwave and ultrasound assisted methods, together with the application of 24 full factorial designs of experiments to better understand the effects of solvent pH, ethanol concentration, microwave power, ultrasound temperature and ratio of drug to solvent (w/w) on the extract. The extracts were characterized by solids yield, curcuminoid content and yield, curcumin content and yield and antioxidant activity by the diphenylpycril hydrazil method. The best extraction resulted from the ultrasound assisted using ethanol 96 oGL at pH 10, 20oC, 1:7 drug to solvent ratio (w/w), during 5 minutes. This condition was chosen because it resulted in the best yields and antioxidant activities. The work developed to improve curcumin and curcuminoid solubilities was based on the preparation of solid dispersions by spray drying and hot melt coating using the hydrophilic carriers Gelucire® 44:14 and 50:13. Applying Box-Behnken designs the effect of process conditions on microparticulate solid dispersions properties, like morphology, bulk and tapped densities, Hausner factor, Carr index, angle of repose, moisture content, water activity, differential scanning calorimetry, thermogravimetric analysis, X-ray powder diffraction, infrared spectrometry, curcuminoid solubility in water and dissolution rate. The highest improvement in drug solubility was obtained by dispersion prepared by spray drying at 40oC, Gelucire® 44:14/curcumin 1:1 ratio, and adding 16,7% Aerosil (DS16). On the other hand, the hot melt granules with best solubility were prepared with higher Gelucire® 50:13 and lower substrate (lactose) contents (DS3). Additional solid dispersion, DS17, was prepared by spray-drying in the same conditions applied to DS16 but using Gelucire® 50:13 as carrier. Considering the aspects drug solubility and content in solid dispersions, DS17 showed the best performance and the same set of conditions used for its preparation was also applied to produce a solid dispersion containing the raw extract obtained by ultrasound extraction. This solid dispersion increased curcumin solubility by a 330-fold factor. In the in vitro antitumor assays pure curcumin, DS3, DS17 and DSE cytotoxicities were evaluated in several tumor cell lines, leukemia T (jurkat), melanona (C8161), adenocarcinoma coloretal (HT29), hepatic carcinoma (HepG2) and in one non tumor (PBMC). The antitumor activities were not influenced by the thermal processes and the extract presented higher cytotoxicity and better selectivity to tumor cells. The in vivo antinflammatory study was performed by the rat paw edema method and showed that solid dispersion DS17 resulted in antinflammatory effect higher than pure curcumin and indomethacin at some doses. The results are an indicative that the increase in drug solubility may incur in an increase oral bioavailability and that the process proposed herein are adequate for preparation of pre-formulations containing less soluble herbal drugs.

No Brasil a esquistossomose é causada pela espécie Schistosoma mansoni e leva principalmente à formação de granulomas e fibroses, hipertensão portal e hepatoesplenomegalia. O praziquantel (PZQ) é o fármaco de primeira escolha para o tratamento e possui baixa solubilidade aquosa, sendo necessárias altas doses para ação terapêutica. A taxa de dissolução do PZQ é fator limitante para a sua biodisponibilidade, portanto, melhorar sua solubilidade é fundamental. O objetivo deste trabalho foi aumentar a solubilidade do PZQ pela obtenção de grânulos contendo dispersões sólidas deste fármaco pelo processo hot melt em leito fluidizado. Além disto, buscou-se estudar a fluidodinâmica e as variáveis do processo de granulação. Inicialmente, dispersões sólidas foram preparadas por simples fusão em polietilenoglicol (PEG) 4000 e PEG 6000 nas proporções 2:1; 1:1; 1:2; 1:5 e 1:10 e estas foram caracterizadas por teste de solubilidade, difração de raios-X, espectroscopia em infravermelho e análises térmicas (DSC e TG). Foram obtidas dispersões sólidas com uma solubilidade duas vezes maior do PZQ, uma menor cristalinidade, uma possível interação fármaco-carreador e sem degradação ou alteração nos principais grupos funcionais. Com estes resultados, a dispersão sólida 1:10 PZQ:PEG 6000 foi escolhida para a etapa da granulação. Os granulados foram obtidos utilizando o planejamento fatorial Box Behnken com as seguintes variáveis: % de dispersão sólida, proporção PZQ:PEG das dispersões e carga de lactose spray-dried (SD) (g). A caracterização dos grânulos foi realizada pelos testes: granulometria, densidade aparente, densidade compactada, fator de Hausner, índice de Carr, ângulo de repouso e doseamento do fármaco, sendo todas estas propriedades avaliadas pela técnica de superfície de resposta (ANOVA). A análise estatística demonstrou que as características dos granulados são, na maioria dos casos, dependentes da % de dispersão sólida e da proporção de PZQ:PEG, sendo satisfatórios e toleráveis os resultados do fluxo dos granulados. Os três melhores granulados foram escolhidos para as análises de microscopia eletrônica de varredura, espectroscopia em infravermelho, difração de raios-X, análise térmica e perfil de dissolução. Estas análises mostraram que nos grânulos houve diminuição da cristalinidade, possíveis interações entre PZQ, PEG e lactose, além do grande aumento no perfil de dissolução. Com estes resultados, confirmam-se as vantagens da granulação por hot melt em leito fluidizado e a importância do estudo de suas variáveis. / In Brazil, schistossomiasis is mainly attributed to the species Schistosoma mansoni, which causes granulomas and fibrosis, portal hypertension and hepatosplenomegaly. Praziquantel (PZQ) is the first choice in the treatment; however, it has low water solubility, thus requiring high doses for a proper therapeutical result. The PZQ dissolution rate is the limiting factor for its bioavailability; therefore, it is fundamental to improve of this drug solubility. The objective of this work was to increase the PZQ solubility with the production of granules containing its solid dispersions, prepared by hot melt process in fluidized bed. Moreover, the fluid dynamic and several variables of the process were studied. First, solid dispersions were prepared by mixing with melted polyethylene glycol (PEG) 4000 and PEG 6000 at the ratios of 2:1; 1:1; 1:2; 1:5 and 1:10. These were characterized by solubility test, x-ray powder diffraction, fourier transform infrared spectroscopy and thermal analyses (DSC and TG). Solid dispersions were obtained with PZQ solubility two times higher than the pure drug, lower crystallinity and without degradation or alteration in the main functional groups. With these results, the solid dispersion 1:10 PZQ:PEG 6000 was chosen for the studies of granulation. The granulates were obtained using the Box Behnken factorial design with the following independent variables: % of solid dispersion, ratio PZQ:PEG in the dispersions and amount of spray-dried lactose (g). The granules characterization was made by the tests of granulometry, bulk density, tapped density, Hausner ratio, Carr index, angle of repose and PZQ assay. In addition, all these properties were evaluated by response surface technique (ANOVA). The statistical analysis, in most cases, showed that the granules characteristics depend significantly on the % of solid dispersion and on the ratio PZQ:PEG. The results on the granules flow properties are satisfactory and acceptable for tableting. The three granulates with best properties were submitted to scanning electron microscopy, fourier transform infrared spectroscopy, x-ray powder diffraction, thermal analysis and dissolution test. These analyses showed that there were, in the granules, decrease of crystallinity, possible interaction among PZQ, PEG and lactose, and also, greater increase in the dissolution test. The advantages of fluid bed hot melt granulation and the importance of studying the process variables are confirmed by the results in this work.

Este trabalho visou obter extratos secos padronizados de Curcuma longa L., e sua otimização visando o aumento da solubilidade dos curcuminóides e melhoria nas suas atividades biológicas. No estudo de extração, os curcuminóides foram extraídas utilizando dois solventes, etanol e solução etanólica alcalina e dois processos microondas e ultrassom seguindo planejamentos fatoriais completos 24, e com pH do solvente, teor de etanol, tempo de extração, potência do microondas ou temperatura no ultrassom, e proporção massa da droga pela massa do solvente como variáveis independentes. Os extratos foram caracterizados quanto ao rendimento de sólidos totais, teor de curcuminóides totais, rendimento de curcuminóides totais, teor de curcumina, rendimento de curcumina e atividade antioxidante por difenil-picril-hidrazila. A condição de extração com melhor resultado foi o ultrassom a 20 ºC, solvente etanol 96 ºGL, 1 parte de planta para 7 de solvente, pH 10 e duração de 5 min., pois, nesta condição, obteve-se maior teor de curcumina e maior atividade antioxidante. O estudo visando aumento da solubilidade da curcumina constou da preparação de dispersões sólidas pelos métodos de spray drying e hot melt coating. Ambos os métodos foram estudados com os polímeros hidrofílicos Gelucire® 44:14 e 50:13, e aplicando-se planejamento fatorial tipo Box-Behnken. As dispersões sólidas particuladas foram avaliadas pela morfologia, densidade aparente e de compactação, fator de Hausner, índice de Carr, ângulo de repouso, umidade residual, atividade de água, calorimetria diferencial de varredura, termogravimetria, difração de raio-X, espectrometria de infravermelho, solubilidade em água e teste de dissolução. A maior solubilidade foi obtida com secagem no spray drying a 40 ºC, proporção Gelucire®44/14:curcumina 1:1 e proporção 1:5 de Aerosil:dispersão (DS16). No hot melt coating, a melhor solubilidade foi obtida com maior quantidade de Gelucire 50/13 e menor de Lactose (DS 3). Dispersões sólidas particuladas foram preparadas também com o Gelucire® 50/13 por spray drying (DS 17). Considerando-se os fatores solubilidade e teor de curcumina nas partículas, a dispersão DS 17 foi escolhida como a mais adequada para os ensaios biológicos posteriores. A mesma condição de preparo da DS17 foi usada para produzir dispersões sólidas com o extrato obtido por ultrassom (DSE). Nesta dispersão a solubilidade dos curcuminóides demonstrou ser 330 vezes maior do que o extrato seco nas mesmas condições porém sem a adição de carreador. No ensaio de avaliação da atividade antitumoral in vitro, foram avaliadas a citotoxicidade da curcumina pura, DS 17, DS 3 e a DSE, em diferentes linhagens tumorais, leucemia T (jurkat), melanona (C8161), adenocarcinoma coloretal (HT29), carcinoma hepatocelular (HepG2) e de célula não tumoral (PBMC). A curcumina apresentou atividade citotóxica para células tumorais e esta não foi afetada pelo processo de produção da dispersão sólida. Além disso, a DS do extrato apresentou maior citotoxicidade, o que pode ser devido ao sinergismo de outros compostos. O extrato também foi mais seletivo para células tumorais que a curcumina e as dispersões. O estudo de atividade anti-inflamatória in vivo usando o modelo de edema de pata, demonstrou que a dispersão DS 17 apresentou maior atividade do que a curcumina na mesma dose, indicando que o aumento da solubilidade possibilita uma maior absorção e consequentemente maior biodisponibilidade. / The aim of this work was to obtain standardized dried extracts of Curcuma longa L. and to develop pre-formulations and capsules with improved curcuminoids solubility and higher biological activities. In the extraction study, the powdered roots of Curcuma longa L. were extracted using ethanol and an aqueous alkaline ethanol solution by microwave and ultrasound assisted methods, together with the application of 24 full factorial designs of experiments to better understand the effects of solvent pH, ethanol concentration, microwave power, ultrasound temperature and ratio of drug to solvent (w/w) on the extract. The extracts were characterized by solids yield, curcuminoid content and yield, curcumin content and yield and antioxidant activity by the diphenylpycril hydrazil method. The best extraction resulted from the ultrasound assisted using ethanol 96 oGL at pH 10, 20oC, 1:7 drug to solvent ratio (w/w), during 5 minutes. This condition was chosen because it resulted in the best yields and antioxidant activities. The work developed to improve curcumin and curcuminoid solubilities was based on the preparation of solid dispersions by spray drying and hot melt coating using the hydrophilic carriers Gelucire® 44:14 and 50:13. Applying Box-Behnken designs the effect of process conditions on microparticulate solid dispersions properties, like morphology, bulk and tapped densities, Hausner factor, Carr index, angle of repose, moisture content, water activity, differential scanning calorimetry, thermogravimetric analysis, X-ray powder diffraction, infrared spectrometry, curcuminoid solubility in water and dissolution rate. The highest improvement in drug solubility was obtained by dispersion prepared by spray drying at 40oC, Gelucire® 44:14/curcumin 1:1 ratio, and adding 16,7% Aerosil (DS16). On the other hand, the hot melt granules with best solubility were prepared with higher Gelucire® 50:13 and lower substrate (lactose) contents (DS3). Additional solid dispersion, DS17, was prepared by spray-drying in the same conditions applied to DS16 but using Gelucire® 50:13 as carrier. Considering the aspects drug solubility and content in solid dispersions, DS17 showed the best performance and the same set of conditions used for its preparation was also applied to produce a solid dispersion containing the raw extract obtained by ultrasound extraction. This solid dispersion increased curcumin solubility by a 330-fold factor. In the in vitro antitumor assays pure curcumin, DS3, DS17 and DSE cytotoxicities were evaluated in several tumor cell lines, leukemia T (jurkat), melanona (C8161), adenocarcinoma coloretal (HT29), hepatic carcinoma (HepG2) and in one non tumor (PBMC). The antitumor activities were not influenced by the thermal processes and the extract presented higher cytotoxicity and better selectivity to tumor cells. The in vivo antinflammatory study was performed by the rat paw edema method and showed that solid dispersion DS17 resulted in antinflammatory effect higher than pure curcumin and indomethacin at some doses. The results are an indicative that the increase in drug solubility may incur in an increase oral bioavailability and that the process proposed herein are adequate for preparation of pre-formulations containing less soluble herbal drugs.

No Brasil a esquistossomose é causada pela espécie Schistosoma mansoni e leva principalmente à formação de granulomas e fibroses, hipertensão portal e hepatoesplenomegalia. O praziquantel (PZQ) é o fármaco de primeira escolha para o tratamento e possui baixa solubilidade aquosa, sendo necessárias altas doses para ação terapêutica. A taxa de dissolução do PZQ é fator limitante para a sua biodisponibilidade, portanto, melhorar sua solubilidade é fundamental. O objetivo deste trabalho foi aumentar a solubilidade do PZQ pela obtenção de grânulos contendo dispersões sólidas deste fármaco pelo processo hot melt em leito fluidizado. Além disto, buscou-se estudar a fluidodinâmica e as variáveis do processo de granulação. Inicialmente, dispersões sólidas foram preparadas por simples fusão em polietilenoglicol (PEG) 4000 e PEG 6000 nas proporções 2:1; 1:1; 1:2; 1:5 e 1:10 e estas foram caracterizadas por teste de solubilidade, difração de raios-X, espectroscopia em infravermelho e análises térmicas (DSC e TG). Foram obtidas dispersões sólidas com uma solubilidade duas vezes maior do PZQ, uma menor cristalinidade, uma possível interação fármaco-carreador e sem degradação ou alteração nos principais grupos funcionais. Com estes resultados, a dispersão sólida 1:10 PZQ:PEG 6000 foi escolhida para a etapa da granulação. Os granulados foram obtidos utilizando o planejamento fatorial Box Behnken com as seguintes variáveis: % de dispersão sólida, proporção PZQ:PEG das dispersões e carga de lactose spray-dried (SD) (g). A caracterização dos grânulos foi realizada pelos testes: granulometria, densidade aparente, densidade compactada, fator de Hausner, índice de Carr, ângulo de repouso e doseamento do fármaco, sendo todas estas propriedades avaliadas pela técnica de superfície de resposta (ANOVA). A análise estatística demonstrou que as características dos granulados são, na maioria dos casos, dependentes da % de dispersão sólida e da proporção de PZQ:PEG, sendo satisfatórios e toleráveis os resultados do fluxo dos granulados. Os três melhores granulados foram escolhidos para as análises de microscopia eletrônica de varredura, espectroscopia em infravermelho, difração de raios-X, análise térmica e perfil de dissolução. Estas análises mostraram que nos grânulos houve diminuição da cristalinidade, possíveis interações entre PZQ, PEG e lactose, além do grande aumento no perfil de dissolução. Com estes resultados, confirmam-se as vantagens da granulação por hot melt em leito fluidizado e a importância do estudo de suas variáveis. / In Brazil, schistossomiasis is mainly attributed to the species Schistosoma mansoni, which causes granulomas and fibrosis, portal hypertension and hepatosplenomegaly. Praziquantel (PZQ) is the first choice in the treatment; however, it has low water solubility, thus requiring high doses for a proper therapeutical result. The PZQ dissolution rate is the limiting factor for its bioavailability; therefore, it is fundamental to improve of this drug solubility. The objective of this work was to increase the PZQ solubility with the production of granules containing its solid dispersions, prepared by hot melt process in fluidized bed. Moreover, the fluid dynamic and several variables of the process were studied. First, solid dispersions were prepared by mixing with melted polyethylene glycol (PEG) 4000 and PEG 6000 at the ratios of 2:1; 1:1; 1:2; 1:5 and 1:10. These were characterized by solubility test, x-ray powder diffraction, fourier transform infrared spectroscopy and thermal analyses (DSC and TG). Solid dispersions were obtained with PZQ solubility two times higher than the pure drug, lower crystallinity and without degradation or alteration in the main functional groups. With these results, the solid dispersion 1:10 PZQ:PEG 6000 was chosen for the studies of granulation. The granulates were obtained using the Box Behnken factorial design with the following independent variables: % of solid dispersion, ratio PZQ:PEG in the dispersions and amount of spray-dried lactose (g). The granules characterization was made by the tests of granulometry, bulk density, tapped density, Hausner ratio, Carr index, angle of repose and PZQ assay. In addition, all these properties were evaluated by response surface technique (ANOVA). The statistical analysis, in most cases, showed that the granules characteristics depend significantly on the % of solid dispersion and on the ratio PZQ:PEG. The results on the granules flow properties are satisfactory and acceptable for tableting. The three granulates with best properties were submitted to scanning electron microscopy, fourier transform infrared spectroscopy, x-ray powder diffraction, thermal analysis and dissolution test. These analyses showed that there were, in the granules, decrease of crystallinity, possible interaction among PZQ, PEG and lactose, and also, greater increase in the dissolution test. The advantages of fluid bed hot melt granulation and the importance of studying the process variables are confirmed by the results in this work.

Dendrimers are a class of perfectly branched symmetric monodisperse macromolecules, which are synthesized using a stepwise procedure. Due to their highly symmetric structure, they possess a definite core, discrete generations and a large number of terminal units. The large number of terminal units and its compact globular conformation endow this class of macromolecules with several unique properties. Over the past two decades, a number of researchers have synthesized a variety of dendrimers and explored their potential applications in various fields ranging from drug delivery, energy harvesting to catalysis. However, dendrimers require tedious stepwise synthesis and purification which limits their scalability. Hyperbranched polymers (HBPs) are a related class of macromolecules having similar highly branched structure but with large number of linear defects and, therefore, they may be considered as unsymmetrical analogues of dendrimers. Despite of having a large number of defects, HBPs display majority of the properties which dendrimers possess such as, high solubility, low chain entanglement, low solution and melt viscosity, encapsulation of guest molecules, conformational adaptability etc. The origin of these defects lies in the single-step statistical random growth process. Although, hyperbranched polymers possess a randomly branched structure, they also carry a large number of peripheral units, like dendrimers. Since, hyperbranched polymers are prepared in a single step, they can be readily scaled up which make them commercially attractive. One of the most widely used methods to prepare hyperbranched polymers is by polycondensation of a AB2 monomer. In our laboratory, during past decade a novel melt trans-etherification methodology was developed to prepare hyperbranched polyethers. For this method, a AB2 monomer was designed having two methoxy benzyl units and one aliphatic hydroxyl group, which in presence of a mild organic acid at 150°C undergoes melt polymerization under continuous removal of methanol. Although, this method allows one to prepare a variety of high molecular weight hyperbranched polyethers structures, it suffers from one serious limitation associated with the monomer structure; the aromatic ring in the monomer should be either electronically deactivated or per-substituted to preclude a side reaction due to electrophilic aromatic substitution, which could result in the formation of insoluble cross-linked product. Polyacetals are a class of polymers which readily degrades under mildly acidic conditions. One of the primary objectives of this thesis was to develop a simple strategy to prepare hyperbranched polyacetal, which would be a new class of highly branched acid-labile scaffold. To achieve this, we used a relatively under-explored chemistry based on trans¬acetalization. Solvent-free melt polymerization via trans-acetalization exhibited some advantages over the trans-esterification or trans-etherification processes; for instance, it required substantially low temperatures, afforded faster reaction rates and absence of side reactions that could lead to crosslinked products. In the 2nd chapter, the first synthesis of hyperbranched polyacetals via this novel melt trans-acetalization polymerization process has been described. The process proceeds via the self-condensation of an AB2 type monomer carrying a hydroxyl group and a dimethylacetal unit (see Figure 1); the continuous removal of low boiling methanol drives the equilibrium towards polymer formation. Here, since the incipient carbocation is stabilized by a neighbouring oxygen atom, it has a substantially lower reactivity and hence does not take part in the electrophilic aromatic substitution; therefore, per-alkylation of the monomer was not required to prevent crosslinking, unlike in the case of the melt trans-etherification process developed earlier. Figure1. Synthesis of hyperbranched polyacetals via trans-acetalization polymerization; different types of units, namely dendtritic (D), linear (L) and terminal (T) units are shown. We studied the degradation behaviour of the solid polymer in an aqueous buffer solution having a pH of 4. Due to the susceptibility of the acetal linkages to hydrolysis, the polymer degrades readily under these mildly acidic conditions to yield 4-hydroxymethyl benzaldehyde as the primary product. After observing the fast degradation kinetics of the hyperbranched polyacetal, we developed approaches to control the rate of degradation. Interestingly, because of the unique topology of hyperbranched structures, the rate of polymer degradation was readily tuned by changing just the nature monomer; longer chain dialkylacetals, such as dibutyl- and dihexylacetals based monomers yielded hyperbranched polymers bearing longer alkyl groups at their molecular periphery. The highly branched topology and the relatively high volume-fraction of the terminal alkyl groups resulted in a significant lowering of the ingress rates of the aqueous reagents to the loci of degradation and, consequently, the degradation rates of the polymers were dramatically influenced by the hydrophobic nature of the terminal alkyl substituents. In an effort to understand this, we performed the degradation studies in solution state, where all three polymers showed almost same rate of degradation. The simple synthesis and easy tuneability of the degradation rates make these materials fairly attractive candidates for use as degradable scaffolds. As already mentioned, the main difference between dendrimers and hyperbranched polymers is that HBPs carry a large number of statistically distributed linear defects. The origin of these linear segments is single step statistically random growth process. There are three kinds of linkages present in the HB structure. For a HB polymer generated from condensation polymerization of an AB2 monomer, these three kinds of linkages are: (i) the linkages where both the B groups have reacted is called a dendritic (D) unit, (ii) linkages where one of the B group has reacted is called a linear (L) unit, and (iii) linkages where both the B groups remain unreacted is called a terminal (T) unit. The defect levels in hyperbranched polymers is quantified by a parameter called degree of branching (DB), which is mole-fraction of dendritic and terminal units with respect to all types of repeat units. In a typical single step AB2 polycondensation process the DB value usually is around 0.5. The strategy most commonly used to achieve high DB values, specifically while using AB2 type self-condensations, is to design an AB2 monomer wherein the reaction of the first B-group leads to an enhancement of the reactivity of the second one. In the 3rd chapter the challenge of synthesizing defect-free hyperbranched polythioacetal has been addressed. In this study, it was shown that an AB2 monomer carrying a dimethylacetal unit and a benzyl thiol group undergoes a rapid self-condensation in the melt under acid-catalysis to yield a hyperbranched polydithioacetal (Figure 2a). By analyzing 1H, 13C, hetero-correlation NMR spectra and by comparison of the NMR spectrum of the polymer with those of model compounds, it was established that the HB polydithioacetals do not contain any linear defects. Furthermore, to understand the origin of defect-free structure, model reactions between dimethylacetal of tolualdehyde and benzyl mercaptan (Figure 2b) were carried out. NMR studies using of these model reactions reveal that the intermediate monothioacetal is relatively unstable under the polymerization conditions and transforms rapidly to the dithioacetal (Figure 2c); since this second step occurs irreversibly towards polymer formation, it leads to a defect-free hyperbranched dithioacetal. Isothermal TGA analysis proved to be an effective tool for monitoring the kinetics of the melt polymerization; these studies revealed that the formation of the polydithioacetal is significantly faster than previously studied polyacetal polymerization, and in the former case two distinct kinetic steps are clearly evident. Figure 2. (a) Synthesis of defect-free hyperbranched polythioacetal; chemical structure of monomer and hyperbranched polydithioacetal; (b) model reaction to probe the unstable intermediate, and (c) variation of the concentration of different species during the model reaction as a function of time showing the appearance and disappearance of unstable intermediate. One of the major differences between linear and hyperbranched polymers is the availability of large number of accessible terminal groups in the latter. Several properties of the hyperbranched polymers are known to be influenced by the nature of the peripheral groups. Of the many methods that have been designed to functionalize the periphery of HBPs, AB2 + A type copolymerization is one of the most readily implementable. Figure 3. (a) Peripheral modification of hyperbranched polydithioacetal using trans-thiocetalization; (b) schematic representation of the sulphur rich hyperbranched polythioacetal having C-22 alkyl chains on its periphery and (c) TEM images of gold nanoparticle synthesized and stabilized via C-22 functionalized hyperbranched polythioacetal. In chapter 3, the synthesis of a defect-free hypebranched polymer via trans-thiocetalization method was described; these polymers possessed only two kinds of units, namely terminal dimethylacetal groups and dendritic dithioacetal units. Because of the difference in reactivity between the dendritic (D) and terminal (T) units, the terminal groups alone was completely transformed, under acid-catalyzed conditions, to a dithioacetal unit by reaction with a variety of thiols, (Figure 3a) such as dodecanethiol, benzyl mercaptan, ethyl, 3-mercaptopropionate etc.; this transformation of the periphery was shown to be quantitative. One unique feature of this hyperbranched polydithioacetal is the high sulfur content; in order to exploit this aspect, the periphery was selectively transformed with docosyl (C-22) segments, and these sulfur-rich hydrophobically capped hyperscaffolds were utilized to stabilize gold nanoparticles in non-polar solvents (Figure 3b and 3c.) The Au-NPs, thus prepared, were characterized by UV-Visible spectroscopy and transmission electron microscopy; it was shown that, typically particles of about 4-5 nm were produced and they could be dried and readily re-dispersed in organic solvents. In the final chapter of the thesis, the first synthesis of photodegradable hyperbranched polyacetals via a melt trans-acetalization polymerization method is described. The AB2 monomer was designed to carry a dimethyl acetal unit, and a nitro group placed ortho to a hydroxymethyl group (Figure 4a). Self-condensation of this AB2 monomer under melt polymerization conditions gives rise to a hyperbranched polyacetal wherein each repeat unit contains a 2-nitrobenzyl linkage which is susceptible to photolytic degradation upon exposure to 365 nm light. Figure 4. (a) Synthesis of photodegradable hyperbranched nitro polyacetal; (b) scanning electron micrograph of the positive pattern obtained from hyperbranched nitro-polyacetal; (c) synthesis of alkyne-azide clickable hyperbranched nitro polyacetal; and (d) clicking onto the reactive micropatterns. Irradiation with UV light causes the photodegradation of the polymer leading to the formation of 2-nitroso terephthalaldehyde and other low molecular weight oligomeric species. Exploiting this photodegradability, the use of this HBP as a positive photoresist to generate micron-size patterns has been demonstrated (Figure 4b); furthermore, changing the terminal groups from dimethyl acetal to dipropargyl acetal (Figure 4c), permitted the generation of patterned substrates that can be clicked with any desired functionality using the azide-yne click reaction. This last feature is unprecedented and provides a potentially quick handle to create functionalizable patterned surfaces.

Es wurde das Verzinkungsverhalten von Baustahl beim Stückverzinken im technisch nutzbaren Bereich untersucht. Dazu wurde das Schichtwachstum der Zinküberzüge bei Verwendung konventioneller ZnPb-Schmelze anhand von Schichtdicken und Gefügeausbildungen in Ab-hängigkeit von den relevanten Parametern ermittelt. Weiterhin wurde der Einfluss des Was-serstoffs im Stahl auf die Schichtbildung beim Feuerverzinken eingeschätzt. Das Resultat ist eine umfassende Modellvorstellung der Schichtbildungsvorgänge beim Feuerverzinken von 435°C bis 620°C. Sie erklärt das Verzinkungsverhalten von Baustahl und trägt zum Verständnis vieler Phänomene beim Feuerverzinken bei. Weiterhin wurden Überzüge aus legierten Zinkschmelzen untersucht. Die Ergebnisse wurden hinsichtlich der Wirkung der einzelnen Legierungselemente in der Zinkschmelze interpretiert. Dem Anwender wird ein Leitfaden zur Verfügung gestellt, der Vor- und Nachteile der in der Praxis verfügbaren Zinkschmelzen beschreibt.

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Ku-band dual-polarization radar backscatter measurements from the SeaWinds on QuikScat (QuikScat) and SeaWinds on ADEOS-2 (SeaWinds) scatterometers are used to classify the melt state and estimate melt severity in Greenland. Backscatter measurements are organized into high temporal and high spatial resolution images created using the Scatterometer Image Reconstruction (SIR) algorithm and a new temporal data segmentation technique. Melt detection is performed using a layered electromagnetic model combined with a Markov chain model. The new melt detection method allows classification of the snow-pack into three states: melt, refreeze, and frozen. Melt severity and refreeze severity indexes are also developed. The melt detection methods developed in this thesis are verified by using a one-dimensional geophysical/electromagnetic model simulation of the snow-pack under melting conditions and by comparison with in situ weather station data at the ETH Camp in western Greenland. The diurnal cycle of backscatter measurements is also analyzed at this location. The melt detection and estimation method is applied to the entire Greenland ice-sheet. The resulting melt classifications and melt severity indexes are used to generate a number of maps outlining the features of the 2003 melt season. Good agreement of the melt severity and a 1978 SASS Greenland ice facies map is observed.

Yes / Several contributions in answering granulation challenges including the use of computer simulation and well thought out experimental analyses are being researched. Using a twin screw granulator (TSG) by design of experiments (DoE), comparisons on 1) equipment similarities i.e., continuous and 2) shear forces, are made to previous literature on continuous equipment and a Cyclomix. This study proposes that equipment specific DoE, better explains the contribution of parameters than investigating an identified parameter from the experimental findings from a specific equipment. Granule strength and structure are presented together with the contribution of process parameters, speed, temperature, and binder content. Seeded structures are present in all but the Extrudomix. Longer residence times within the Cyclomix facilitates seeded structures. Granule crushing strengths are higher in TSG than all other continuous equipment. Optimum condition for the formation of stronger granules with least variation is around 65.4 °C. / The authors would like to acknowledge the support from the CCIP grant (Collaboration, Capacity and IP Development) fund from the University of Bradford for ordering cunsumables and equipment.