INTRODUÇÃO: O câncer de pulmão é a principal causa de morte por câncer em todo o mundo e muitos pacientes apresentam derrame pleural em um estágio avançado da doença, com alta morbidade e mortalidade. Entretanto, a patogênese do derrame maligno é ainda pouco compreendida e as opções terapêuticas são limitadas. OBJETIVO: 1) Estudar a fisiopatologia do derrame pleural maligno em modelo animal com células de Lewis em diferentes concentrações; 2) Avaliar os efeitos da terapia intrapleural com anti-VEGF e anti-EGFR e a frequência de mutações de EGFR e KRAS neste modelo. MÉTODOS: Foi utilizado modelo de neoplasia pleural com camundongos C57BL/6 e células de Lewis (LLC) dividido em duas etapas: estudo com diferentes concentrações de células LLC (0,1, 0,5 e 1,5x105) e avaliação de terapias-alvo. Após a padronização do modelo, quatro grupos de camundongos receberam tratamento intrapleural com anti-VEGF, anti-EGFR, anti-VEGF+anti-EGFR ou solução fisiológica (não tratados) 3, 7, 10 e 14 dias após a indução da neoplasia pleural com 0,5x105 células LLC. Em vinte animais de cada grupo foi avaliada a curva de sobrevida. 160 animais foram submetidos à eutanásia 7, 10, 14 ou 21 dias após e avaliados peso, mobilidade, volume de líquido pleural, marcadores inflamatórios, imunológicos e bioquímicos no líquido, presença de tumores e alterações histológicas em pleura, pulmão, rim, fígado e baço. Através de imunohistoquimica avaliou-se apoptose, proliferação tumoral, VEGF e EGFR. Analisou-se a expressão gênica do EGFR, VEGF, KRAS e ALK e a frequência de mutações do EGFR e KRAS. Análise estatística: One Way ANOVA, Kaplan-Meier, p < 0,05. RESULTADOS: Na etapa de padronização do modelo observamos que a concentração que manteve os parâmetros de neoplasia pleural com maior sobrevida foi de 0,5x105 células LLC. Na segunda etapa do estudo, a carcinomatose pleural foi letal com sobrevida máxima de 25 dias, sem diferença entre os grupos. Redução de peso foi observada em todos os grupos após 21 dias. A mobilidade foi melhor nos grupos que receberam anti-EGFR. O volume de líquido pleural foi maior no grupo não tratado durante todo o estudo. Parâmetros imunológicos e bioquímicos aumentaram temporalmente sendo mais evidentes no grupo sem tratamento. Implantes tumorais na pleura foram mais evidentes no grupo não tratado após 14 dias. A inflamação pulmonar foi mínima em todos os grupos. No grupo não tratado observou-se implantes tumorais no pericárdio e músculo cardíaco após 21 dias, esteatose hepática e renal após 14 dias e hiperplasia de polpa branca do baço no 21º dia. Altos índices de apoptose e menores índices de proliferação tumoral foram observados nos grupos que receberam tratamento com anti-EGFR e anti-VEGF+anti-EGFR. Houve mutação do gene KRAS e superexpressão gênica tumoral do EGFR e do KRAS. CONCLUSÃO: As terapias-alvo reduziram significativamente o derrame pleural, morbidade e parâmetros histológicos, embora sem impacto na sobrevida dos animais neste modelo experimental. Nossos dados indicam que a linhagem tumoral LLC possui um fenótipo tumoral agressivo demonstrado através da mutação do KRAS e superexpressão do EGFR, o que pode estar associado ao pior prognóstico e menor resposta aos inibidores do EGFR / INTRODUCTION: Lung cancer is the leading cause of death by cancer in the world. Many patients have pleural effusion in an advanced stage of the disease, with high morbidity and mortality. However, the pathogenesis of malignant pleural effusion is still poorly understood and the treatment options are limited. OBJECTIVE: 1) To study the pathophysiology of malignant pleural effusion in animal model with Lewis cells in different concentrations; 2) Evaluate the effects of the intrapleural therapy with anti-VEGF and anti-EGFR and the frequency of EGFR and KRAS mutations in this model. METHODS: We used pleural neoplasm experimental model with mice C57BL/6 and Lewis cells (LLC) divided into two steps: study with different concentrations of LLC cells (0.1, 0.5 and 1.5x105) and evaluation of targeted therapies. After the standardization of the model, four groups of mice received intrapleural treatment with anti-VEGF, anti-EGFR, anti-VEGF+anti-EGFR or saline (untreated) 3, 7, 10 and 14 days after induction of pleural neoplasm with injection of 0.5x105 LLC cells. In 20 animals of each group was evaluated the survival curve. 160 animals underwent euthanasia 7, 10, 14 or 21 days after and assessed weight, mobility, volume of pleural fluid, inflammatory, immunological and biochemical markers in the liquid, presence of tumor and histological changes in pleura, lung, kidney, liver and spleen. It was evaluated, through immunohistochemistry, tumor apoptosis and proliferation, VEGF and EGFR. Gene expression of EGFR, VEGF, KRAS and ALK and frequency of mutations of EGFR and KRAS were also evaluated. Statistical analysis: One Way ANOVA, Kaplan-Meier, p < 0.05. RESULTS: In the standardization of the model we observed that the concentration that kept parameters of pleural neoplasm with higher survival rate was 0.5x105 LLC cells. In the second stage, target-therapies, pleural carcinomatosis was lethal with maximum survival of 25 days, with no difference between the groups. Weight decrease was observed in all groups after 21 days. Mobility was better in groups that receiving anti-EGFR. Pleural fluid volume was greater in the untreated group throughout the study. Immunological and biochemical parameters have increased temporarily being most evident in the untreated group. Tumor implants in pleura were more apparent in the untreated group after 14 days. The lung inflammation was minimal in all groups. The untreated group showed tumor implants in the pericardium and heart muscle after 21 days, hepatic and renal steatosis after 14 days and spleen white pulp hyperplasia in 21 day. High rates of apoptosis and smaller tumor proliferation indices were observed in groups that received treatment with anti-VEGF and anti-EGFR+anti-EGFR. We also found gene KRAS mutation and tumoral gene overexpression of EGFR and KRAS. CONCLUSION: Targeted therapies reduced significantly the pleural effusion, morbidity and histological parameters, although without an impact on survival rate in this experimental model. Our data indicate that the tumor lineage LLC has an aggressive tumor phenotype shown by KRAS mutation and overexpression of EGFR, which can be associated with a worse prognosis and a lower response to EGFR inhibitors

Submitted by Fabíola Silva (fabiola.silva@famerp.br) on 2018-02-07T18:29:25Z No. of bitstreams: 1 ulissescamargo_tese.pdf: 700757 bytes, checksum: 68231dab9197a8717320c0e887f2b2f6 (MD5) / Made available in DSpace on 2018-02-07T18:29:25Z (GMT). No. of bitstreams: 1 ulissescamargo_tese.pdf: 700757 bytes, checksum: 68231dab9197a8717320c0e887f2b2f6 (MD5) Previous issue date: 2016-09-22 / Introduction. The spondyloarthritis encomprises a group of diseases strongly associated with HLA-B*27 gene. It has been proposed that genes not belonging to the major histocompatibility complex human influence the genesis of these diseases especially in patients HLA-B*27 negative. Objectives. The aim of this study was to test the hypothesis that the antigens of the ABO, Secretor and Lewis histo-blood systems are associated with spondyloarthritis, especially ankylosing spondylitis (AS). Material and methods. Three hundred and ninety-four patients with clinical suspicion of spondyloarthritis sent for identification of HLA-B*27 gene were analyzed. One hundred and nineteen (30.2%) had confirmed the diagnosis of spondyloarthritis according to the ASAS criteria. The remaining 275 (69.8%) were used as controls. The identification of HLA-B*27 gene was performed using the PCR-SSOP method. The identification of the antigens of the ABO, Secretor and Lewis histo-blood systems was performed using hemagglutination and PCR-RFLP methods. The exact Fisher's test, the chi-square, and the values of Odds Ratio (OR) and Confidence Interval set at 95% were calculated using the GraphPad INSTAT software, accepting the error of 5%. Results. No statistically significant differences were observed in the frequency of antigenic profiles of ABO (χ2: 1.152; p = 0.764; GL: 3), Secreto (χ2: 0.779; p = 0.377; GL: 1) and Lewis (χ2: 1.853; p = 0.396; GL: 2) histo-blood groups between patients and controls. The Lea antigen was more frequent in patients with AS compared to controls (OR: 1.833; 95% CI: 1025- 3284, p = 0.053). This antigen was strongly associated with AS in HLA-B*27 negative patients compared to controls (OR: 4.469; 95% CI: 1931-10342; p = 0.0007). This association remained only in males in the absence of HLA-B*27 gene (OR: 6.880; 95% CI: 1852-25564; p = 0.004). Conclusions. AS is associated to the Lea antigen in HLAB* 27 negative male patients. / Introdução. As espondiloartrites compreendem um grupo de doenças fortemente associadas ao gene HLA-B*27. Tem sido proposto que genes não pertencentes ao complexo principal de histocompatibilidade humano influenciam a gênese destas doenças especialmente nos pacientes HLA-B*27 negativos. Objetivos. O objetivo deste estudo foi testar a hipótese de que os antígenos dos sistemas histo-sanguíneos ABO, Secretor e Lewis estão associados à espondiloartrites, especialmente a espondilite anquilosante (EA). Material e método. Foram analisados 394 pacientes com suspeita clínica de espondiloartrites encaminhados para identificação do gene HLA-B*27. Cento e dezenove (30,2%) tiveram o diagnóstico de espondiloartrite confirmado de acordo com os critérios ASAS. Os 275 (69,8%) restantes compuseram o grupo controle. A identificação do gene HLA-B*27 foi realizada com o uso do método PCR-SSOP. A caracterização dos antígenos dos sistemas histo-sanguíneos ABO, Secretor e Lewis foi realizada com o uso dos métodos hemaglutinação e PCR-RFLP. O teste exato de Fisher, o qui-quadrado, os valores de Odds Ratio (OR) e do intervalo de confiança a 95% foram calculados com o uso do software GraphPad Instat, aceitando o erro de 5%. Resultados. Não foram observadas diferenças estatisticamente significantes nas frequências dos perfis antigênicos dos sistemas histo-sanguíneos ABO (χ2: 1.152; p=0,764; GL: 3), Secretor (χ2: 0.779; p=0,377; GL: 1) e Lewis (χ2: 1.853; p=0,396; GL: 2) de pacientes e controles. Foi observada maior frequência do antígeno Lea em pacientes com EA, comparados aos controles (OR: 1.833; IC 95%: 1.025 – 3.284; p=0,053). Este antígeno mostrou-se fortemente associado à EA em pacientes HLA-B*27 negativos comparados aos controles (OR: 4.469; IC 95%: 1.931 – 10.342; p=0,0007). Esta associação se manteve apenas no gênero masculino na ausência do gene HLA-B*27 (OR: 6.880; IC 95%: 1.852 – 25.564; p = 0,004). Conclusões. A EA está associada ao antígeno Lea nos pacientes masculinos HLA-B*27 negativos.

Made available in DSpace on 2014-12-17T15:42:00Z (GMT). No. of bitstreams: 1 JulioCOS_DISSERT.pdf: 1559177 bytes, checksum: 5d76456c4b64130c51ab0adec9c84e15 (MD5) Previous issue date: 2010-08-16 / This research aims at identifying the learning problems in newly undergraduate students at university, interpreting the nature and causes of these problems, offering subsidies to overcome these difficulties and enabling a meaningful learning through which students give meaning to their learning. As an object for this work was chosen the theme Chemical Bonds - where were studied the forces between atoms to form molecules, compound ions and ionic crystalline structures - and is characterized as one of the most important subjects of Chemistry. In research, it was used a questionnaire with five open questions, answered by 147 students from the early periods of degrees in Chemistry at Universidade Federal do f Rio Grande do Norte. The answers revealed uncertainty on the part of students, both conceptual and representation, with superficial justifications, always using the octet rule to describe models of chemical bonds. Results suggest that these students had inadequate training in high school and that the examinations for entrance into the ranks were made according to flexible criteria less demanding in terms of knowledge. These observations have led to the conclusion that for future changes, it is necessary for high schools and in the early periods in universities favoring the adoption of pedagogical approaches in context and applying strategies to overcome the teaching of superficial memorization on Chemical Bonds, which probably have applied to the teaching of other subjects of chemistry / Este trabalho teve o objetivo de identificar problemas de aprendizagem em alunos de gradua??o rec?m ingressante na universidade, interpretar a natureza e as causas desses problemas, oferecendo subs?dios para supera??o de tais dificuldades e possibilitando uma aprendizagem significava atrav?s da qual o aluno atribua sentido em seu aprendizado. Para o desenvolvimento desse trabalho foi escolhido o tema Liga??es Qu?micas - onde se estudam as for?as que agem entre os ?tomos para formar mol?culas, ?ons compostos ou estruturas cristalinas i?nicas -, que se caracteriza como um dos mais importantes assuntos da Qu?mica. Para isso, utilizou-se um question?rio com cinco perguntas abertas, respondidas por 147 estudantes dos per?odos iniciais das gradua??es em Qu?mica da Universidade Federal do Rio Grande do Norte. As respostas obtidas revelaram inseguran?a dos estudantes, tanto em termos conceituais quanto de representa??o, com justificativas superficiais, recorrendo sempre ? regra do octeto para descrever modelos de liga??es qu?micas. Os resultados sugerem que esses estudantes tiveram uma forma??o inadequada, no ensino m?dio e que os exames para ingresso nas gradua??es se fizeram segundo crit?rios pouco exigentes em termos de conhecimentos. As observa??es feitas levam ? conclus?o de que, para mudan?as futuras, ? necess?rio que escolas de ensino m?dio e dos per?odos iniciais nas universidades privilegiem a ado??o de m?todos pedag?gicos contextualizados, aplicando estrat?gias para superar o ensino memor?stico e superficial sobre Liga??es Qu?micas, o que, provavelmente, se aplica ao ensino de outros temas da Qu?mica

INTRODUÇÃO: O câncer de pulmão é a principal causa de morte por câncer em todo o mundo e muitos pacientes apresentam derrame pleural em um estágio avançado da doença, com alta morbidade e mortalidade. Entretanto, a patogênese do derrame maligno é ainda pouco compreendida e as opções terapêuticas são limitadas. OBJETIVO: 1) Estudar a fisiopatologia do derrame pleural maligno em modelo animal com células de Lewis em diferentes concentrações; 2) Avaliar os efeitos da terapia intrapleural com anti-VEGF e anti-EGFR e a frequência de mutações de EGFR e KRAS neste modelo. MÉTODOS: Foi utilizado modelo de neoplasia pleural com camundongos C57BL/6 e células de Lewis (LLC) dividido em duas etapas: estudo com diferentes concentrações de células LLC (0,1, 0,5 e 1,5x105) e avaliação de terapias-alvo. Após a padronização do modelo, quatro grupos de camundongos receberam tratamento intrapleural com anti-VEGF, anti-EGFR, anti-VEGF+anti-EGFR ou solução fisiológica (não tratados) 3, 7, 10 e 14 dias após a indução da neoplasia pleural com 0,5x105 células LLC. Em vinte animais de cada grupo foi avaliada a curva de sobrevida. 160 animais foram submetidos à eutanásia 7, 10, 14 ou 21 dias após e avaliados peso, mobilidade, volume de líquido pleural, marcadores inflamatórios, imunológicos e bioquímicos no líquido, presença de tumores e alterações histológicas em pleura, pulmão, rim, fígado e baço. Através de imunohistoquimica avaliou-se apoptose, proliferação tumoral, VEGF e EGFR. Analisou-se a expressão gênica do EGFR, VEGF, KRAS e ALK e a frequência de mutações do EGFR e KRAS. Análise estatística: One Way ANOVA, Kaplan-Meier, p < 0,05. RESULTADOS: Na etapa de padronização do modelo observamos que a concentração que manteve os parâmetros de neoplasia pleural com maior sobrevida foi de 0,5x105 células LLC. Na segunda etapa do estudo, a carcinomatose pleural foi letal com sobrevida máxima de 25 dias, sem diferença entre os grupos. Redução de peso foi observada em todos os grupos após 21 dias. A mobilidade foi melhor nos grupos que receberam anti-EGFR. O volume de líquido pleural foi maior no grupo não tratado durante todo o estudo. Parâmetros imunológicos e bioquímicos aumentaram temporalmente sendo mais evidentes no grupo sem tratamento. Implantes tumorais na pleura foram mais evidentes no grupo não tratado após 14 dias. A inflamação pulmonar foi mínima em todos os grupos. No grupo não tratado observou-se implantes tumorais no pericárdio e músculo cardíaco após 21 dias, esteatose hepática e renal após 14 dias e hiperplasia de polpa branca do baço no 21º dia. Altos índices de apoptose e menores índices de proliferação tumoral foram observados nos grupos que receberam tratamento com anti-EGFR e anti-VEGF+anti-EGFR. Houve mutação do gene KRAS e superexpressão gênica tumoral do EGFR e do KRAS. CONCLUSÃO: As terapias-alvo reduziram significativamente o derrame pleural, morbidade e parâmetros histológicos, embora sem impacto na sobrevida dos animais neste modelo experimental. Nossos dados indicam que a linhagem tumoral LLC possui um fenótipo tumoral agressivo demonstrado através da mutação do KRAS e superexpressão do EGFR, o que pode estar associado ao pior prognóstico e menor resposta aos inibidores do EGFR / INTRODUCTION: Lung cancer is the leading cause of death by cancer in the world. Many patients have pleural effusion in an advanced stage of the disease, with high morbidity and mortality. However, the pathogenesis of malignant pleural effusion is still poorly understood and the treatment options are limited. OBJECTIVE: 1) To study the pathophysiology of malignant pleural effusion in animal model with Lewis cells in different concentrations; 2) Evaluate the effects of the intrapleural therapy with anti-VEGF and anti-EGFR and the frequency of EGFR and KRAS mutations in this model. METHODS: We used pleural neoplasm experimental model with mice C57BL/6 and Lewis cells (LLC) divided into two steps: study with different concentrations of LLC cells (0.1, 0.5 and 1.5x105) and evaluation of targeted therapies. After the standardization of the model, four groups of mice received intrapleural treatment with anti-VEGF, anti-EGFR, anti-VEGF+anti-EGFR or saline (untreated) 3, 7, 10 and 14 days after induction of pleural neoplasm with injection of 0.5x105 LLC cells. In 20 animals of each group was evaluated the survival curve. 160 animals underwent euthanasia 7, 10, 14 or 21 days after and assessed weight, mobility, volume of pleural fluid, inflammatory, immunological and biochemical markers in the liquid, presence of tumor and histological changes in pleura, lung, kidney, liver and spleen. It was evaluated, through immunohistochemistry, tumor apoptosis and proliferation, VEGF and EGFR. Gene expression of EGFR, VEGF, KRAS and ALK and frequency of mutations of EGFR and KRAS were also evaluated. Statistical analysis: One Way ANOVA, Kaplan-Meier, p < 0.05. RESULTS: In the standardization of the model we observed that the concentration that kept parameters of pleural neoplasm with higher survival rate was 0.5x105 LLC cells. In the second stage, target-therapies, pleural carcinomatosis was lethal with maximum survival of 25 days, with no difference between the groups. Weight decrease was observed in all groups after 21 days. Mobility was better in groups that receiving anti-EGFR. Pleural fluid volume was greater in the untreated group throughout the study. Immunological and biochemical parameters have increased temporarily being most evident in the untreated group. Tumor implants in pleura were more apparent in the untreated group after 14 days. The lung inflammation was minimal in all groups. The untreated group showed tumor implants in the pericardium and heart muscle after 21 days, hepatic and renal steatosis after 14 days and spleen white pulp hyperplasia in 21 day. High rates of apoptosis and smaller tumor proliferation indices were observed in groups that received treatment with anti-VEGF and anti-EGFR+anti-EGFR. We also found gene KRAS mutation and tumoral gene overexpression of EGFR and KRAS. CONCLUSION: Targeted therapies reduced significantly the pleural effusion, morbidity and histological parameters, although without an impact on survival rate in this experimental model. Our data indicate that the tumor lineage LLC has an aggressive tumor phenotype shown by KRAS mutation and overexpression of EGFR, which can be associated with a worse prognosis and a lower response to EGFR inhibitors

Ces travaux de thèse portent sur l’élaboration et l’étude des propriétés thermomécaniques de polymères dynamiques incorporant des dérivés borés. Tout en appliquant ce concept sur une variété d’architectures macromoléculaires : copolymères fonctionnels, briques di- et tri-fonctionelles, deux réactivités distinctes du bore ont été étudiées et exploitées. Une large gamme de méthodes de caractérisation a été utilisée pour mener à bien ce projet : spectroscopies FTIR et RMN sous différents stimuli, ainsi que de nombreuses analyses thermiques et mécaniques. Dans un premier temps, nous avons considéré la formation de paires de Lewis frustrées entre des acides de Lewis (organoboranes) et des bases de Lewis (amines et phosphines) stériquement encombrés, cette interaction pouvant être fortement modulée par la participation d’un troisième composé tels que des molécules de gaz. Ainsi, nous avons été capables de former des réseaux dynamiques réticulables de façon réversible avec le dioxyde de carbone. Dans un second temps, nous avons mis en évidence une nouvelle réactivité dans les esters boroniques cycliques impliquant une ouverture de cycle à haute température, assistée par la présence de nucléophiles. Cette réaction a été mise à profit pour former des polymères réticulés dynamiquement, pouvant atteindre des températures de transition vitreuse jusqu’à 220°C et dé-réticulables par dilution avec un bon solvant du polymère (apolaire). Cette réactivité a été appliquée à une variété de polymères accessibles par copolymérisation radicalaire (styrène, éthylène, acétate de vinyle, acrylate de butyle) ou par post-fonctionnalisation de polymères commerciaux (polybutadiène) / This thesis focuses on the development and study of thermomechanical properties of dynamic polymers incorporating borylated derivatives. While applying this concept to a variety of macromolecular architectures: functional copolymers, di- and tri-functional bricks, two distinct reactivities of boron have been explored. A wide range of characterization methods has been used to carry out this project: FTIR and NMR spectroscopies under numerous stimuli, as well as many thermal and mechanical analyses. In a first step, we considered the formation of Frustrated Lewis Pairs between Lewis acids (organoboranes) and Lewis bases (amines and phosphines) sterically hindered, as this interaction can be strongly modulated by the participation of a third compound such as gas molecules. Thus, we have been able to form dynamic networks reversibly crosslinkable with carbon dioxide. In a second step, we demonstrated a new reactivity in cyclic boronic esters involving a ring-opening at high temperature, assisted by the presence of nucleophiles. This reaction has been used to form dynamically crosslinked polymers, which can reach glass transition temperatures up to 220°C and de-crosslinkable by dilution in a good (apolar) polymer solvent. This reactivity has been applied to a variety of polymers accessible by radical copolymerization (styrene, ethylene, vinyl acetate, butyl acrylate) or by post-functionalization of commercial polymers (polybutadiene)

Die feste nichtkristalline Lewis-Säure Aluminiumchlorofluorid (ACF, AlCl(x)F(3-x), x = 0.05 .. 0.3) hat die höchste bisher bekannte Lewis-Acidität aller heterogenen Katalysatoren. Sie erreicht die Stärke von Antimonpentafluorid SbF5 und übertrifft sie in manchen Fällen sogar. In dieser Arbeit wurden die Bulk-Struktur des ACF und der sehr ähnlichen Verbindung Aluminiumbromofluorid (ABF) mittels IR-, ESR-, NMR- und Röntgenabsorptionsspektroskopie studiert. Die Oberfläche der Verbindungen wurde durch die Adsorption von Gasen bei niedrigen Temperaturen untersucht, sowie durch IR- und ESR-Spektroskopie adsorbierter Sondenmoleküle. Das thermische Verhalten dieser nichtkristallinen Verbindungen wurde mittels DTA verfolgt. Die Lewis-Acidität kleiner Modellverbindungen wurde NMR-spektroskopisch und mit ab initio Methoden untersucht. Alle Daten wurden mit denen der gut charakterisierten und bekannten Modifikationen des Aluminiumfluorids (AlF3) verglichen. Die kombinierten Ergebnisse der Messungen an beiden festen Phasen erlauben die Entwicklung eines Strukturmodells für diese Verbindungen, das die meisten spektroskopischen Daten und die außergewöhnlich hohe Lewis-Acidität erklären kann. Beide Phasen sind sehr ähnlich zueinander. Das Vorhandensein des schwereren Halogens (Cl, Br) erzeugt eine Störung des Netzwerkes und verhindert die Ausbildung geordneter Strukturen. Der Grad der Unordnung in diesen Phasen ist höher als bei allen anderen Verbindungen des Aluminiumfluorids. Daraus resultiert eine gestörte Oberfläche, was wiederum zu koordinativ ungesättigtem Aluminium an der Oberfläche führt. Die sauren Zentren in ACF und ABF sind stärker als in anderen aluminiumhaltigen Lewis-Säuren. / The solid non-crystalline Lewis acid aluminum chlorofluoride (ACF, AlCl(x)F(3-x), x = 0.05 .. 0.3) has the highest Lewis acidity of any heterogeneous catalyst known so far. It reaches the acidity of antimony pentafluoride (SbF5) and in some cases even exceeds it. In this work the bulk structure of ACF and of the very similar compound aluminium bromofluoride (ABF) was studied by IR, ESR, NMR, and X-ray absorption spectroscopy. The surface of the compounds was investigated by adsorption of gases at low temperatures, as well as by IR and ESR spectroscopy of adsorbed probe molecules. The thermal behavior of these non-crystalline compounds was followed by DTA. The Lewis acidity of small model compounds was studied by NMR spectroscopy and ab initio calculations. All data were compared to those of well characterized known samples of the different modifications of aluminum fluoride (AlF3). The combined results of the measurements of both solid phases allow to set up a structure model for these compounds which can explain most of the spectrocopic data and the extraordinary high Lewis acidity. Both phases are very similar to each other. The occurrence of the heavier halogen (Cl, Br) causes a perturbation of the network and prevents it from forming ordered structures. The degree of disorder of these phases is higher than for any other known compounds of aluminum fluoride. This results in an disordered surface which leads to coordinatively unsaturated aluminum at the surface. The acidic centers of ACF and ABF are stronger than in any other aluminum containing Lewis acid.

Thesis (M.A.)--University of Puerto Rico, Mayagüez Campus, 2004. / Printout. Includes bibliographical references (leaves 192-202).

This thesis deals with secondary interactions in asymmetric catalysis and their impact on the outcome of catalytic reactions. The first part revolves around the metal-catalyzed asymmetric allylic alkylation reaction and how interactions within the catalyst affect the stereochemistry. An OH–Pd hydrogen bond in Pd(0)–π-olefin complexes of hydroxy-containing oxazoline ligands was identified by density functional theory computations and helped to rationalize the contrasting results obtained employing hydroxy- and methoxy-containing ligands in the catalytic reaction. This type of hydrogen bond was further studied in phenanthroline metal complexes. As expected for a hydrogen bond, the strength of the bond was found to increase with increased electron density at the metal and with increased acidity of the hydroxy protons. The second part deals with the use of hydroxy- and methoxy-containing phosphinooxazoline ligands in the rhodium- and iridium-catalyzed asymmetric hydrosilylation reaction. The enantioselectivities obtained were profoundly enhanced upon the addition of silver salts. This phenomenon was explained by an oxygen–metal coordination in the catalytic complexes, which was confirmed by NMR studies of an iridium complex. Interestingly, the rhodium and iridium catalysts nearly serve as pseudo-enantiomers giving products with different absolute configurations. The final part deals with ditopic pyridinobisoxazoline ligands and the application of their metal complexes in asymmetric cyanation reactions. Upon complexation, these ligands provide catalysts with both Lewis acidic and Lewis basic sites, capable of activating both the substrate and the cyanation reagent. Lanthanide and aluminum complexes of these ligands were found to catalyze the addition of the fairly unreactive cyanation reagents ethyl cyanoformate and acetyl cyanide to benzaldehyde, whereas complexes of ligands lacking the Lewis basic coordination sites failed to do so. / QC 20100709

This thesis deals with method development in asymmetric catalysis and specifically syntheses of enantioenriched O-functionalized cyanohydrins. The first part describes the development of a method for the synthesis of O‑alkoxycarbonylated and O-acylated cyanohydrins. Ethyl cyanoformate and acyl cyanides were added to aldehydes in a reaction catalyzed by a chiral dimeric Ti-salen complex together with a tertiary amine. High yields and enantioselectivities were in most cases obtained. Mechanistic studies were performed and a reaction mechanism was proposed. ­ The second part describes a method in which the undesired minor enantiomer in a Lewis acid–Lewis base-catalyzed acylcyanation is continuously recycled into prochiral starting material. Close to enantiopure O‑acylated cyanohydrins were obtained in high yields. The third part deals with asymmetric acylcyanations of ketones. Acetyl cyanide was found to add to α‑ketoesters in a reaction catalyzed by a chiral Lewis base. Yields up to 77% and 82% ee were obtained. The final part describes an enzymatic method for high-throughput analysis of O‑acylated cyanohydrins. The enantiomeric excess and conversion were determined for products obtained from a number of aromatic and aliphatic aldehydes. / QC 20100818

Introduction: Alice in Wonderland is perhaps the most renowned fantasy book for children. Over and above this though, it has relevance for adults. People too often dismiss it as purely escapist reading, a means to escape from the monotony of everyday realism by delving into the realms of fantasy. Many critics propose that it operates on more than one level and I would have to agree - it is a pioneer of children's literature as well as a product and critique of the Victorian age. It is a story that has captured the world's imagination, with vivid characters and exciting adventures. The sequel, Through the Looking-Glass, although not as well known, equally offers an insight into the late nineteenth-century. I intend to explore the many layers found in these stories, and hope to expose them as being more than mere narratives, but as pieces of literature that thrive because they are so cleverly constructed Perhaps also their success lies in that they deal with the universal theme (for children and adults alike) of making sense of the seemingly nonsensical aspects of life and society. The stories, as well as the strange characters and happenings, are reminiscent of the Absurdist genre in drama, in which the objective is to turn the world upside down, so to speak, in order to understand people and society. My dissertation will begin by exploring the literary trends of children's books prior to 1865, in other words, before Alice in Wonderland was published. I intend to present an overview of Victorian and pre-Victorian children's fiction, tracing the development of the story for teaching and religious instruction, up until the time when the story was liberated to be simply the vehicle for pleasurable recreational purposes. Thus my opening chapter is an exploration of the didactic children's literature that dominated the early nineteenth century, examining the educationalists that helped expand the genre of children's literature. Next, I will include a brief biography of Lewis Carroll. It is important to my overall theme in that a biography sums up, in one human centre, the forces at play in Victorian sensibility. As a modern audience, we seem to seize upon the idea of his 'character', desperately attempting to understand what motivated him to write such tour de force stories. The interest for me at this point is to examine how academics have portrayed Carroll's 'character'. The motive behind this section is to beg the question of whether his complex personality affects our reading of the texts, or whether they can be seen as entirely separate from a life to which some scandal has been attributed. In the remainder of my dissertation, I shall focus on how the texts are a reflection of a typical Victorian child's experiences, and discuss how Alice 'grows' as a character, and what she reveals about her society in the process of discovering how she should define herself. Alice is the vehicle for Carroll's subversive commentary about his society, and her experiences in Wonderland and Looking-Glass land are often rooted in the undermining of conventional behaviour and traditions. Lastly, I will examine Carroll's stylistic organization of the narratives, paying particular attention to his treatment of time, dreams and language in the texts. I will discuss what his intentions are in creating 'nonsense that makes sense', as well as what this 'nonsense' discloses about the society he lived in and the values he seems to object to. / Thesis (M.A.)-University of KwaZulu-Natal, Pietermaritzburg, 2004.