Orientadores: Francisco Maugeri Filho, Maria Isabel Rodrigues / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-21T20:28:07Z (GMT). No. of bitstreams: 1 Forte_MarcusBrunoSoares_D.pdf: 4684118 bytes, checksum: 7ad3d65f4a3a6f6e525b286c594a4a22 (MD5) Previous issue date: 2013 / Resumo: A proposta desta tese foi o estudo da adsorção do ácido clavulânico (CA) em hidróxidos duplos lamelares (LDH) e o uso desses adsorventes em colunas de leito fixo na separação entre o CA e aminoácidos. A tese foi desenvolvida em três etapas: na primeira, utilizou-se LDH do tipo hidrotalcitas. Os adsorventes foram avaliados quanto à cinética de adsorção em banho finito. O melhor sistema foi a hidrotalcita com 70 % de magnésio na composição (HT70c) com fração de sólidos (em relação ao volume de líquido) no reator est = 15,0 mg/mL usando água como solvente. O modelo de equilíbrio melhor ajustado foi o linear com os seguintes coeficientes de adsorção: k = 0,404; 0,602; 0,849 e 1,083 L/g para 16,5; 19,0; 21,5 e 24,0°C, respectivamente, evidenciando um aumento da capacidade de adsorção com aumento da temperatura. O sistema foi avaliado termodinamicamente quanto à energia livre de Gibbs (?G°), entalpia (?H°) e entropia (?S°), sendo que os valores calculados foram: ?G° = 2,100; 1,301; 0,503 e -0,295 kJ/mol para 16,5; 19,0; 21,5 e 24,0°C, respectivamente, ?H° = 94,602 kJ/mol e ?S° = 0,319 kJ/mol.K. A segunda etapa foi desenvolvida no Laboratório de Materiais Inorgânicos da Université Blaise Pascal na França, durante Estágio de Doutorado-Sanduíche. LDH com outras composições foram sintetizados, caracterizados e avaliados quanto à adsorção de CA. A difração de raios X indicou a formação de uma estrutura cristalina com uma distância entre as lamelas de aproximadamente 22 Å. Os espectros na região do infravermelho apresentaram sinais característicos da molécula de CA: ligações C=C (720 ¿ 840, 1640 e 1657 cm-1), C-O-C e C-N (1036, 1060 e 1292 cm-1), C-N (1354 cm-1), C-OH (1392 cm-1) e COOH (1551, 1581 cm-1). A análise termogravimétrica indicou a presença de uma molécula interlamelar com peso molecular de aproximadamente 194 g/mol. Essas análises confirmam a presença do CA no espaço interlamelar e, desta forma, a afinidade da molécula de CA pelos sítios dos LDH. A adsorção de CA em diferentes fases de LDH (Zn2Cr-NO3, Zn2Al-NO3 e Mg2Al-NO3) foi avaliada por meio de isotermas de adsorção a 20,0; 30,0 e 35,0°C. O sistema escolhido como mais conveniente foi o Zn2Cr-NO3, cujos parâmetros ajustados para o modelo de Freundlich foram kF = 73,63; 128,76 e 229,62 mg1-nF.LnF/g e nF = 0,35; 0,38 e 0,33 para 20,0; 30,0 e 35,0°C. Na terceira etapa,partículas contendo cristais de Zn2Cr-NO3 encapsulados em microgéis de alginato (LDHME) foram obtidas através de gelificação iônica, a fim de possibilitar o uso desses adsorventes em colunas cromatográficas. Uma coluna foi empacotada com as partículas de LDHME a fim de avaliar a separação de CA em relação aos aminoácidos tirosina (TYR) e prolina (PRO), já que são os principais contaminantes presentes no meio fermentativo, pelo método de pulso cromatográfico. O uso das partículas de LDHME na separação de CA foi considerado satisfatório levando a fatores de purificação de 2,32 vezes o inicial e a um grau de pureza das soluções de 93 %. Um modelo matemático foi desenvolvido para adsorção de ácido clavulânico (CA) em coluna de leito fixo, empacotada com partículas LDHME. Curvas de ruptura foram obtidas experimentalmente e o sistema foi avaliado em relação aos tempos de operação assim como eficiências e produtividades em função de variações simultâneas das condições experimentais, vazão (Q) e altura de leito (L), através de um delineamento composto central rotacional (DCCR). A vazão foi avaliada no intervalo de 0,19 a 0,82 mL/min e a altura do leito de 3,0 a 5,0 cm. O algoritmo particle swarm optimization (PSO) se mostrou eficaz na estimação dos parâmetros do modelo proposto. Depois de validado experimentalmente em condições distintas das usadas na estimação, o modelo foi usado como ferramenta na otimização da adsorção de CA através de um DCCR, cujos resultados foram obtidos com simulações usando níveis superiores para as variáveis de entrada (Q de 0,80 a 1,50 mL/min e L de 7,0 a 10,0 cm) considerando somo respostas o tempo de ruptura (tb), tempo de exaustão (te), eficiência de recuperação (frec), eficiência de utilização da coluna (fcol) e a produtividade (P). Esse procedimento foi considerado satisfatório já que houve diminuições consideráveis nos tempos de operação e aumentos nas respectivas eficiências e produtividades. As melhores condições de operação do sistema estudado para adsorção de CA foram: Q = 1,15 mL/min e L = 10,0 cm, cujas respostas foram: tb = 24 min, te = 110 min, frec = 96 %, fcol = 37 % e P = 117 kg/h / Abstract: The main focus of this thesis was to study the adsorption of clavulanic acid (CA) in layered double hydroxides (LDH) and to use these adsorbents in fixed bed columns for separation of CA from amino acids. The thesis was developed in three steps: first, it was used LDH-type hydrotalcites. Adsorption studies were performed in stirred batch glass reactors. It was shown that distilled water and a solid/liquid ratio of 15.0 mg/L generated the most favourable conditions for adsorption. A calcined hydrotalcite containing 70 % of MgO was selected for further study since it presented the best adsorption performance. Adsorption equilibrium was evaluated from adsorption isotherms determined at different temperatures. The experimental isotherm data were well fitted by a linear equilibrium model with the corresponding adsorption constants being klin = 0.404, 0.602, 0.849 and 1.083 L/g at 16.5, 19.0, 21.5 and 24.0°C, respectively, showing an increased adsorption capacity at higher temperatures. Thermodynamic evaluation of the process allowed the Gibbs¿ free energy (?G°), the standard enthalpy change (?H°) and the standard entropy change (?S°) to be estimated as follows: ?G° = 2.100, 1.301, 0.503 and ¿0.295 kJ/mol at 16.5, 19.0, 21.5 and 24.0°C, respectively; ?H° = 94.602 kJ/mol; and ?S° = 0.319 kJ/(mol.K), respectively. The second step was developed at the Laboratory of Inorganic Materials of the Blaise Pascal University France during a doctoral internship in France. Different LDH compositions have been investigated: Zn2Cr-Cl, Zn2Cr-NO3, Zn2Al-NO3 and Mg2Al-NO3. Zn2Cr-CA hybrid LDH assemblies were prepared through coprecipitation method to evaluate the affinity between the CA molecule and the interlayer sites. Experiments were carried out using two different sources of CA, i.e. the pharmaceutical product Clavulin® and Clavulanate: Avicel (1:1). The resulting inorganic-organic "sandwich" structure was characterized by a combination of techniques showing an expansion of the layered structure from 0.78 nm to values between 2.30 and 2.60 nm upon CA intercalation; a molecular sieve role of LDH host is also pointed out. Isotherms studies were carried out to evaluate the adsorption capacity of LDH towards CA in presence of contaminants such as amino acids. The Freundlich adsorption model was found to fit the data well and indicating relatively large adsorption capacity, as high as 73.63, 128.76 and 229.62 mg1-nFLnFg-1 at 20, 30 and 35°C, respectively. Besides, the adsorption of CA is classified as an endothermic and spontaneous process with the following calculated thermodynamic parameters: ?H° = 20.516 kJ/mol, ?S° = 0.081 kJ/mol.K and ?G° = -3.271, -4.082, -4.488 kJ/mol for 20, 30 and 35°C, respectively. Particularly, the adsorption of CA onto Zn2Cr-NO3 is a favorable process thus allowing us to envisage the use of LDH in CA biomolecule separation. In the third step, microparticles containing crystals of Zn2Cr-NO3 microencapsulated in alginate (LDHME) were obtained by ionic gelation in order to allow the use of these adsorbents in chromatography columns. A column was packed with particles of LDHME to evaluate the separation of CA from mixtures with amino acids such as tyrosine (TYR) and proline (PRO) using the chromatographic pulse methodology. The use of these LDHME microparticles in the CA separation was satisfactory leading to purification factors of 2.32 times the original and a purity of 93% of the solutions. A mathematical model has been developed for adsorption of CA in a fixed bed column packed with LDHME particles. Breakthrough curves were obtained and the system was experimentally assessed in relation to the time of operation as well as efficiencies and yields due to simultaneous variations of experimental conditions, flow rate (Q) and bed height (L) using a central composite rotatable design (CCRD), considering as responses the breakthrough time (tb), the exhaustion time (te), the recovery efficience (frec), the column utilization efficience (fcol) and the process productivity (P). The flow rate was assessed in the range from 0.19 to 0.82 mL/min and the bed height from 3.0 to 5.0 cm. The particle swarm optimization algorithm (PSO) was shown to be effective in the estimation of the parameters of the proposed model. Once validated experimentally under different conditions from those used in the estimation, the model has been used as a tool in optimizing the adsorption of CA by a CCRD, whose results were obtained using simulations with higher levels for the input variables (0.80 < Q < 1.50 mL/min and 7.0 < L < 10.0 cm). This procedure was considered satisfactory since there were significant reductions in operating times and increases in their productivity and efficiencies. The best operating condition of the system studied for CA adsorption were: Q = 1.15 mL/min and L = 10.0 cm, the answers were: tb = 24 min, trec = 96 %, frec = 110 min, frec = 37% and P = 117 kg/h / Doutorado / Engenharia de Alimentos / Doutor em Engenharia de Alimentos

Orientador: Liliane Maria Ferrareso Lona / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Química / Made available in DSpace on 2018-08-24T08:44:00Z (GMT). No. of bitstreams: 1 Botan_Rodrigo_D.pdf: 8541673 bytes, checksum: fc88cab0852acd3cb9bf0b6052e4458d (MD5) Previous issue date: 2014 / Resumo: Ao longo da última década, nanocompósitos poliméricos vêm atraindo grande atenção da comunidade científica e industrial. Este fato se deve à notável melhora em inúmeras propriedades destes novos materiais, proporcionado pelo uso de uma pequena quantidade de nanoreforços. Entre as propriedades melhoradas é possível citar com maior destaque as propriedades mecânicas e térmicas. Buscando alcançar melhores propriedades para o poli(estireno) (PS), o objetivo deste trabalho foi o de sintetizar nanocompósitos in situ de PS com hidróxidos duplos lamelares (HDLs) e hidroxissal lamelar (HSL). Para isto, foram sintetizados dois tipos de HDLs e um tipo de HSL, os HDLs foram modificados com ácido láurico, ácido palmítico e uma mistura destes dois ácidos e o HSL foi modificado com ácido palmítico. Os HDLs e HSL sintetizados foram caracterizados por difração de raios x (DRX), microscopia eletrônica de varredura (MEV), espectroscopia no infravermelho por transformada de Fourier (FTIR) e análise termogravimétrica (TGA). Os nanocompósitos foram sintetizados in situ por polimerização em massa e foram caracterizados por DRX, FTIR, TGA, calorimetria exploratória diferencial (DSC), microscopia eletrônica de transmissão (MET), ensaio de flexão, análise da fratura e teste de flamabilidade. Os resultados obtidos demostram que estes novos nanocompósitos foram sintetizados, apresentando, de uma forma geral, uma boa interação polímero ¿ reforço com morfologia variando da intercalada/esfoliada a esfoliada. A estabilidade térmica e, principalmente, a propriedade mecânica apresentaram ganhos significativos em todos os materiais estudados quando comparadas com o polímero puro, fato que possibilita uma vasta gama de aplicação destes novos materiais em diversos campos da pesquisa e engenharia / Abstract: Over the past decade, polymer nanocomposites have attracted interest, both in the industry and in the academia. They often exhibit remarkable improvement in their properties when compared with neat polymer or conventional micro and macrocomposites using low levels of reinforcements, usually maximum 5% by weight. The improvements mainly include mechanical, thermal, and physical properties. Seeking to achieve better properties for poly(styrene) (PS), the purpose of this work was to in situ synthesize PS with layered double hydroxides (LDHs) and layered hydroxide salt (LHS) nanocomposites. Thus, two types of LDH and a type of LHS was synthesized, the LDHs were modified with lauric acid, palmitic acid and a mixture of both, and LHS was modified with palmitic acid. The LDHs and LHS synthesized were characterized by x-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA). The nanocomposites were synthesized by in situ bulk polymerization and were characterized by XRD, FTIR, TGA, differential scanning calorimetry (DSC), transmission electron microscopy (TEM), bend test, fracture analysis and flammability test. The obtained results show that indeed these new nanocomposites were synthesized. These nanocomposites have in general good interaction polymer ¿ reinforcement with morphology varying from intercalated/exfoliated to exfoliated. The thermal stability and mechanical property mainly, showed significant improvement in all materials studied, when compared with the neat polymer, a fact that enables a wide range of application of these new materials in various fields of research and engineering / Doutorado / Engenharia Química / Doutor em Engenharia Química

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第19740号 / 工博第4195号 / 新制||工||1647(附属図書館) / 32776 / 京都大学大学院工学研究科分子工学専攻 / (主査)教授 田中 庸裕, 教授 阿部 竜, 教授 陰山 洋 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

There has been much interest in the use of therapeutics based on ribonucleic acid interference(RNAi) to inhibit synthesis of mutant proteins ever since Elbashir et al. (Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. and Tuschl, T., 2001. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 411, 494-498.) found that synthetic double stranded small interfering ribonucleic acids (siRNAs) can initiate this evolutionarily conserved process in mammalian cells. Since RNAi is able to target single genes and therefore mitigate the underlying molecular pathology of diseases, RNAi-based therapeutics will most likely benefit monogenic neurodegenerative diseases such as Huntington’s disease. It is however particularly difficult to deliver exogenous materials such as siRNAs into neurons in vivo as the blood-brain barrier (BBB) isolates the brain from the vascular system and prevents permeation of most materials. Neurons also do not take up exogenous materials readily. Therefore, effective delivery of siRNAs into the brain remains one of the biggest challenges impeding their use as a potential neurotherapeutic. Layered double hydroxide (LDH) nanoparticles are a class of anionic clay materials that have demonstrated great potential as a DNA (deoxyribonucleic acid) delivery system for a variety of mammalian cell lines due to their unique physiochemical properties. This thesis examined the feasibility of LDH as a siRNA delivery system for cultured neurons and demonstrated that the delivered siRNAs are able to effectively down-regulate synthesis of a target protein with minimal toxicity. Experiments were conducted using double stranded DNAs (dsDNAs) initially, and siRNAs were then used to verify these results. It was shown that nucleic acids(dsDNAs and siRNAs) could successfully intercalate into pristine LDHs to form nucleic acid-LDH complexes that had properties suitable for use as a delivery system in mammalian cells. These studies established that LDHs and nucleic acid-LDH complexes were biocompatible with neurons isolated from embryonic day 17.5 mouse cerebral cortex, suggesting that LDH can be used for nucleic acid delivery into cultured neurons. LDHs were also shown to successfully deliver nucleic acids into a non-neural mammalian cell line (NIH 3T3 cells). Finally, this thesis demonstrated for the first time that LDHs were able to deliver siRNAs into neurons, providing encouraging preliminary evidence that sequence specific gene silencing of the Mus Musculus Deleted in Colorectal Cancer (DCC) gene had occurred. However, down-regulation of the DCC protein did not occur consistently, suggesting that further optimisation is needed to improve the efficacy of siRNA-LDH complexes to inhibit expression of target protein in neurons. In future, LDHs should be further developed as an efficient siRNA delivery system for therapeutic gene silencing in the central nervous system using a neurodegenerative disease model such as the Huntington’s disease mouse model, which closely phenocopies the human disease. This model will allow the in vivo efficacy of these nanoparticles to be tested and subsequently improved in order to deliver siRNAs locally and systematically into the brain.

There has been much interest in the use of therapeutics based on ribonucleic acid interference(RNAi) to inhibit synthesis of mutant proteins ever since Elbashir et al. (Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. and Tuschl, T., 2001. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 411, 494-498.) found that synthetic double stranded small interfering ribonucleic acids (siRNAs) can initiate this evolutionarily conserved process in mammalian cells. Since RNAi is able to target single genes and therefore mitigate the underlying molecular pathology of diseases, RNAi-based therapeutics will most likely benefit monogenic neurodegenerative diseases such as Huntington’s disease. It is however particularly difficult to deliver exogenous materials such as siRNAs into neurons in vivo as the blood-brain barrier (BBB) isolates the brain from the vascular system and prevents permeation of most materials. Neurons also do not take up exogenous materials readily. Therefore, effective delivery of siRNAs into the brain remains one of the biggest challenges impeding their use as a potential neurotherapeutic. Layered double hydroxide (LDH) nanoparticles are a class of anionic clay materials that have demonstrated great potential as a DNA (deoxyribonucleic acid) delivery system for a variety of mammalian cell lines due to their unique physiochemical properties. This thesis examined the feasibility of LDH as a siRNA delivery system for cultured neurons and demonstrated that the delivered siRNAs are able to effectively down-regulate synthesis of a target protein with minimal toxicity. Experiments were conducted using double stranded DNAs (dsDNAs) initially, and siRNAs were then used to verify these results. It was shown that nucleic acids(dsDNAs and siRNAs) could successfully intercalate into pristine LDHs to form nucleic acid-LDH complexes that had properties suitable for use as a delivery system in mammalian cells. These studies established that LDHs and nucleic acid-LDH complexes were biocompatible with neurons isolated from embryonic day 17.5 mouse cerebral cortex, suggesting that LDH can be used for nucleic acid delivery into cultured neurons. LDHs were also shown to successfully deliver nucleic acids into a non-neural mammalian cell line (NIH 3T3 cells). Finally, this thesis demonstrated for the first time that LDHs were able to deliver siRNAs into neurons, providing encouraging preliminary evidence that sequence specific gene silencing of the Mus Musculus Deleted in Colorectal Cancer (DCC) gene had occurred. However, down-regulation of the DCC protein did not occur consistently, suggesting that further optimisation is needed to improve the efficacy of siRNA-LDH complexes to inhibit expression of target protein in neurons. In future, LDHs should be further developed as an efficient siRNA delivery system for therapeutic gene silencing in the central nervous system using a neurodegenerative disease model such as the Huntington’s disease mouse model, which closely phenocopies the human disease. This model will allow the in vivo efficacy of these nanoparticles to be tested and subsequently improved in order to deliver siRNAs locally and systematically into the brain.

Submitted by Rafael Santana (rafael.silvasantana@ufpe.br) on 2017-05-05T19:46:41Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação - João Pontes.pdf: 4350203 bytes, checksum: f257892b21eaa20d49ac346d6af6568b (MD5) / Made available in DSpace on 2017-05-05T19:46:41Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Dissertação - João Pontes.pdf: 4350203 bytes, checksum: f257892b21eaa20d49ac346d6af6568b (MD5) Previous issue date: 2016-02-26 / CAPES / A indústria farmacêutica ainda tem enfrentado o desafio da baixa biodisponibilidade de fármacos nas últimas décadas, onde os Hidróxidos Duplo Lamelares (HDLs) apresentam-se como alternativa para o incremento de solubilidade. A olanzapina (OLZ), pertencente à classe II do Sistema de Classificação Biofarmacêutica, apresenta baixa solubilidade aquosa, dificultando sua absorção após administração. É utilizada no tratamento agudo e manutenção do transtorno bipolar e esquizofrenia, doenças que apresentam o Estresse Oxidativo na sua fisiopatologia. O presente trabalho teve como objetivo a obtenção, caracterização e avaliação in vitro do potencial antioxidante de sistemas binários entre OLZ e diferentes HDLs, visando incremento de solubilidade do fármaco. Os resultados das caracterizações por difração de raios X, espectroscopia vibracional na região do infravermelho e análise térmica mostraram diferenças favoráveis nos resultados apresentados pelos sistemas binários, quando comparados ao fármaco isolado, indicando redução da cristalinidade do fármaco. Tal fato culminou num incremento acima de 1734% na solubilização do fármaco no estudo de dissolução in vitro. Os experimentos antioxidantes in vitro demonstraram que tanto os sistemas binários quanto a OLZ isolada apresentam capacidade antioxidante e, em certos casos, a interação entre HDL e OLZ promoveu melhorias no desempenho do fármaco. No teste em Artemia salina, os HDLs isolados não mostraram toxicidade e os sistemas binários diminuíram a toxicidade da OLZ, quando comparada ao fármaco isolado. Tais resultados fornecem boas expectativas para futuros testes in vivo e favorecem a proposta de utilização dos HDLs como um excipiente funcional na indústria farmacêutica. / The pharmaceutical industry yet faces the low bioavailability challenge of drugs in the last decades, in this matter, Layered Double Hydroxides (LDH) present themselves as an alternative to solubility enhancement. Olanzapine (OLZ), belonging to class II in the Biopharmaceutical Classification System, has low aqueous solubility, hindering its absorption after administration. It is used in the treatment of bipolar disorder and schizophrenia, diseases that have oxidative stress in its pathophysiology. This dissertation aimed at obtaining, characterization and in vitro evaluation of the antioxidant potential of binary systems of OLZ and LDHs, aiming to increase aqueous solubility of the drug. The characterization by X-ray diffraction, vibrational spectroscopy in the infrared region and thermal analysis showed favorable differences in the results presented by binary systems when compared to the drug alone, indication a reduction of Olanzapine’s crystallinity. This fact resulted in an increase above 1734% on drug solubilization in the in vitro dissolution. The antioxidants in vitro experiments demonstrated that binary systems and isolated OLZ exhibited antioxidant capability and, in certain cases, the interaction between LDH and OLZ promoted improvement in the drug's performance. In the tests on Artemia salina, the LDHs alone showed no toxicity and the binary systems decreased the toxicity of OLZ compared to drug alone. These results provide good expectations for future in vivo testing and favor the proposed use of LDHs as a functional excipient in the pharmaceutical industry.

La présence combinée de différents types de polluants dans les effluents industriels est une problématique assez complexe à résoudre pour les chercheurs dans le domaine de la protection de l'environnement. Dans ce contexte, le principal objectif de ce travail de thèse a été d'améliorer la compréhension des mécanismes de sorption à l'interface solide liquide, processus impliqués dans la rétention compétitive pour une sélection de colorants organiques et d'espèces inorganiques sur des matériaux adsorbants modèles. Ce manuscrit comprend une étude détaillée de l'adsorption combinant différentes approches et techniques expérimentales complémentaires, principalement à partir de mesures de cinétiques et d'isothermes d'adsorption, une étude structurale par diffraction des rayons X, et une approche thermodynamique par calorimétrie isotherme de titrage. Trois colorants azoïques: Méthyl Orange (MO), Orange II (OII) et Orange G (OG) ont été retenus pour ce travail. Ils ont la particularité de présenter différentes tailles de molécules, différentes charges et caractères hydrophile/ hydrophobe, … D'autre part, deux types de matériaux chargés positivement et considérés comme échangeurs anioniques ont été choisis comme solides adsorbants modèles : Mg-Al Hydroxyde Double Lamellaire (HDL) contenant dans son espace interfoliaire soit des contre-ions nitrate (Mg-Al-HDL-NO3) soit des chlorures (Mg-Al-HDL-Cl) et une résine échangeuses d'ions Amberlite® IRN-78. Enfin, l'impact des oxoanions comme les carbonates (IV), les sulfates (VI), les chromates (VI) et phosphates (V) sur les propriétés de rétention des colorants sur ces adsorbants a été évalué. Dans un premier temps, l'adsorption des colorants a été réalisée sur ces trois matériaux dans des systèmes mono-composant afin d'étudier en détail les mécanismes de rétention. L'étude des Mg-Al-HDL échangés par diffraction des rayons X a permis de montrer que l'échange d'anions est accompagné de l'intercalation dans l'espèce interfoliaire de la nouvelle espèce sorbée, générant des modifications structurales. En systèmes mono- et multi-composant, la rétention des MO semble supérieure à la capacité d'échange anionique (CEA) théorique des HDL. Ce comportement a été attribué à l'adsorption du colorant sur les surfaces externes, ainsi qu'à la co-adsorption des cations sodium, contre-ions du colorant. Il a aussi été montré que la capacité d'adsorption dépend fortement du caractère hydrophile-hydrophobe des colorants et de leur capacité à établir des interactions latérales (de pi-stacking) avec les autres espèces voisines directement au sein de l'espace interfoliaire. La calorimétrie de titrage isotherme a mis en évidence des comportements inhabituels dans les thermogrammes décrivant l'évolution de l'enthalpie cumulative de déplacement, en lien avec la formation d'agrégats fibrillaires provenant de l'interaction entre l'OII et les espèces Mg(II), issues de la dissolution partielle des HDL au contact du colorant.Dans un second temps, l'étude de la compétition entre les colorants organiques et des anions inorganiques sur ces matériaux a démontré que l'élimination de colorant est fortement influencée par la présence d'anions phosphate ainsi que d'anions carbonate. L'analyse détaillée des différentes espèces compétitives a permis de proposer une classification sur la base de trois types de schémas de compétitions, en lien avec la forme des isothermes individuelles et les données calorimétriques, comme l'enthalpie cumulative en système mono-composant. L'ensemble de cette description des mécanismes de rétention dans des systèmes mono- ou multi-composants a été complété par des études plus applicatives comme les phénomènes de cinétiques de sorption, de réversibilité. Mots-clés: Hydroxydes double lamellaires, résines échangeuses d'ions, Méthyl Orange, Orange II, Orange G, Cr(VI), anions inorganiques, adsorption en système mono- ou multi-composant, étude structurale par DRX, calorimétrie isotherme de titrage. / The co-occurrence of various pollutants in industrial effluents is one of the most difficult problems the researchers have to face in the field of Environmental Remediation. In this context, the main objective of the present Ph.D. thesis has been to improve the comprehension of the sorption mechanisms involved in the competitive retention of selected organic dyes and inorganic species at the Solid-Liquid interface by using some model sorbents.The manuscript reports the results of advanced sorption studies made by combining several experimental techniques, mainly including kinetic and equilibrium adsorption measurements, XRD diffraction, as well as isothermal titration calorimetry. Three Azo dyes differing in the molecular size, electric charge, and hydrophobic/hydrophilic character, i.e., Methyl Orange (MO), Orange II (OII), and Orange G (OG), were selected for the purpose of this work. Two types of solid materials possessing positively charged surface sites were considered as model sorbents: layered double hydroxide structures based on Mg and Al (molar Mg:Al ratio of 2) with either nitrate (Mg-Al-LDH-NO3) or chloride counter-ions (Mg-Al-LDH-Cl) localized in the interlayer space, on the one hand, and strongly basic anion-exchange resin, Amberlite® IRN-78, on the other hand. The impact of carbonate(IV), sulfate(VI), chromate(VI), and hydrogen phosphate(V) oxyanions on the retention capacity of model sorbents towards the three dyes was also investigated thoroughly.In the first step, the single-component adsorption onto three sorbents was analyzed in regards with the detailed mechanism of retention. In all cases, an ion-exchange pathway between the pristine compensating anions (NO3-, Cl-, OH-) or anions coming from the ambient atmosphere (e.g., carbonates) and the oncoming anionic species was identified as the principal retention mechanism. In the case of LDH sorbents, this anion exchange was accompanied by the intercalation of the adsorbing species within the interlayer space with the concomitant changes in the layered structure, as inferred from the XRD study of the LDH samples loaded with the appropriate solute species. The retention of monovalent MO anions, both from the single-solute and bi-solute solutions, was found to exceed the anionic exchange capacity (AEC) of the LDH samples, which was ascribed to the dye adsorption on the external surface paralleled by the co-adsorption of sodium cations. The adsorption capacity was demonstrated to depend strongly on the hydrophilic-hydrophilic character of the dye units and their capacity of generating lateral interactions (e.g., pi-stacking) with other adsorbed species within the LDH structure. The use of isothermal calorimetry allowed the unusual shape of the curve representing the cumulative enthalpy of displacement to be attributed to the formation of OII aggregates/fibers induced by the presence of Mg and Al cations originating from the partial dissolution of the LDH sample. Competitive adsorption of dye and selected inorganic anions on the three model sorbents was studied in the second step in view of increasing the efficiency of dyes removal by optimizing experimental conditions. One of the main achievements was to categorize the dye uptake schemes in the presence of inorganic anions in regards with the shape of the experimental adsorption isotherms and to correlate them with the individual adsorbate affinities for the LDH sample, as inferred from the calorimetry measurements of the cumulative enthalpy of displacement in single-solute systems. The discussion on the mechanisms of dye retention in the single- and multi-component systems was supplemented by experimental studies of such applicative aspects of sorption phenomena as kinetics, reversibility, and selectivity.Keywords: Layered double hydroxides, anion-exchange resin, Methyl Orange, Orange II, Orange G, Cr(VI), inorganic anions, single-solute and multi-solute adsorption, XRD study, isotherm titration calorimetry.

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No. of bitstreams: 1 innamarthanangoi.pdf: 4605252 bytes, checksum: 945db0de8851ec1b0dc51a32f4ee760e (MD5) Previous issue date: 2015-07-30 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Cálculos de primeiros princípios baseados na Teoria do Funcional da Densidade (DFT) foram utilizados para investigar propriedades estruturais e eletrônicas de Hidróxidos Duplos Lamelares (HDL) de composição Mg-Al-Tereftalato e Mg-Al-CO3 nas razões molares, x, de 0,25, 0,33 e 0,50. Foi feita uma análise estrutural, baseada na energia total com mapeamento angular do tereftalato (TA) e cálculos de RMN de carbono 13C, que demonstrou a existência de orientações preferenciais na região interlamelar. As diferenças de densidade de carga demonstraram maior transferência de carga das moléculas de água do que do ânion com as lamelas, sendo mais pronunciada em Mg-Al-TA com x = 0,50. O cálculo de ΔG de formação demonstrou que a síntese de Mg-Al-CO3 com x = 0,50 não é espontânea à temperatura ambiente, ao contrário do Mg-Al-TA. Apesar da relação entre as áreas ocupadas pelos ânion e moléculas de água por carga da lamela permitirem a acomodação na estrutura lamelar verificou-se que existe uma competição pelos sítios das lamelas. O resultado da otimização de geometria mostrou a preferência das moléculas de água formarem ligações de hidrogênio com as hidroxilas da lamela, que deslocam o carbonato no Mg-Al-CO3. Este íon passa então a adotar uma posição inclinada em relação à lamela, demonstrado pelos cálculos da energia de formação como sendo desfavorável. Foi simulada a desidratação do Mg-Al-TA e o acordo encontrado para a temperatura de desidratação reportada experimentalmente foi excelente. Foi observada uma modificação mensurável no deslocamento químico do 13C de um dos núcleos de carbono na nova orientação do TA na estrutura desidratada. A influência do cátion divalente nos HDL estudados foi verificada pela substituição do Mg2+ por Zn2+ ou Ni2+. Foram observadas diferenças nos parâmetros geométricos relacionadas à diferenças nos raios iônicos. A análise de carga de acordo com os critérios de Bader indicaram que as cargas dos átomos de oxigênio do TA e das moléculas de água não são alterados de forma significativa pelo tipo da cátion divalentes escolhido. / First principles calculations based on Density Functional Theory (DFT) were used to investigate the structural and electronic properties of Layered Double Hydroxides (LDH) of Mg-Al-terephthalate and Mg-Al-CO3 composition with molar ratios, x, of 0.25, 0.33 and 0.50. The structural analysis was based on total energy angular mapping of terephthalate (TA) and NMR calculations of carbon 13C, which demonstrated the existence of preferred orientations in the interlayer region. The charge density differences demonstrated greater load transfer of water molecules than the anion with the layer being more pronounced in Mg-Al-TA with x = 0.50. The calculated ΔG of formation demonstrated that the synthesis of Mg-Al-CO3 with x = 0.50 is not spontaneous at room temperature, unlike the Mg-Al-TA. Although the ratio between the areas occupied by the anion and water molecules per positive charge area permit the accommodation in the layer structure, it was found that there is a competition for the layer sites. The lower energy geometry optimization showed the preference of the water molecules to form hydrogen bonds with the hydroxyl groups of the layer, displacing the carbonate of Mg-Al-CO3. This ion then will adopt an inclined position regarding to the layer, shown by the Gibbs free energy formation to be unfavorable. The Mg-Al-TA dehydration reaction simulated found an excellent agreement with experimental values. A measurable change in the 13C chemical shift of the carbon nuclei was verified in the new position of the TA in the dehydrated structure. The influence of divalent cation was verified by substitution of Mg2+ by Zn2+ or Ni2+. Differences were observed in geometric parameters related to differences in the ionic radii. Charge analysis based on Bader criteria indicated no significant variation in oxygen atoms of TA and water molecules by the type of divalent cation chosen.

The intercalation of surfactant anions, namely sodium dodecyl sulphate, sodium benzene sulphonate and lauric acid, into commercial layered double hydroxides (LDH-CO3) with approximate composition [Mg0.654AI0.346 (OH)2](CO3)0.173.0.5H2O] was explored. LDH-CO3 is commercially available in bulk form owing to its large scale applications as a PVC stabiliser and acid scavenger in polyolefins. It is therefore of interest to investigate intercalation methods using LDH-CO3 as starting material. The intercalation method used was compared with the pre existing procedures, for instance the co-precipitation, ion exchange and regeneration methods. Due to the tenacity with which the carbonate ion is held in LDH-CO3, direct ion exchange is an intricate matter. Hence, in the regeneration method the carbonate ion is removed by thermal treatment and the LDH-surfactant is obtained by reaction of the LDH and surfactant in an aqueous medium. Nevertheless, the resulting products are impure and poorly crystallised, and only partial intercalation is achieved. The underlying principle of the current method is protonation of the carbonate anion to a monovalent anion that is easily exchanged with surfactant anions. Improved results were obtained when water-soluble organic acids were used, the most suitable being lower aliphatic carboxylic acids, e.g. acetic, butyric and hexanoic acid. In contrast, higher linear aliphatic carboxylic acids are preferentially intercalated to the anionic surfactants. In both cases the carboxylic acids are assumed to assist intercalation by facilitating the elimination of the carbonate ions present in the anionic clay galleries. X-ray diffraction analysis, thermal analysis and infrared spectroscopy confirmed the monolayer intercalation of LDH-dodecyl sulphate and LDH-dodecylbenzene sulphonate. In contrast, LDH-laurate featured a bilayer structure. / Dissertation (MSc)--University of Pretoria, 2009. / Chemistry / unrestricted

Os fármacos antiinflamatórios não-esteróides (FAINEs) são amplamente utilizados no combate a processos inflamatórios e dores, mas apresentam restrição de uso em razão de sérios efeitos colaterais sobre o trato gastrointestinal. A atividade biológica de complexos metálicos tem sido objeto de pesquisa de grande interesse na área de metalofármacos e compostos do tipo Cu(II)-FAINEs apresentam boa atividade antiinflamatória e efeitos colaterais reduzidos em relação aos fármacos orgânicos. Nesse trabalho, com o objetivo de contribuir para ampliar os estudos sobre o desenvolvimento de alternativas aos FAINEs, foram preparados e caracterizados complexos cobre(lI) com ibuprofeno, indometacina, naproxeno, sulindaco, meloxicam. Os compostos foram imobilizados em Hidrotalcita, um hidróxido duplo lamelar (HDL) de magnésio e alumínio (Mg/AI = 3) que é biocompatível e tem uso como antiácido estomacal. As interações dos metalofármacos com o HDL geraram materiais híbridos bioinorgânicos do tipo Cu-FAINElHDL, nos quais os complexos podem estar presentes de duas maneiras: intercalados entre as Ia meias ou adsorvidos nas superfícies externas do hidróxido duplo lamelar, dependendo do solvente utilizado. A intercalação de complexos neutros é favorecida em solvente misto álcooVamida no qual a Hidrotalcita sofre esfoliação promovida por um processo de hidrólise da amida. A estabilidade alguns dos complexos e dos materiais híbridos em condições gástricas simuladas (pH e temperatura) e as atividades antiinflamatória, analgésica e ulcerogênica in vivo dos sistemas contendo indometacina (Indo) foram investigadas. A intercalação do complexo Cu-Indo no HDL favorece sua estabilização, contribuindo para potencializar a sua atividade farmacolágica. Os materiais híbridos bioinorgânicos obtidos neste trabalho apresentam propriedades interessantes com vistas a potencial aplicação como sistemas de liberação controlada de fármacos. / Non-steroidal anti-inflammatory drugs are widely consumed to treat inflammatory diseases and pain but their clinical use are limited due to serious side-effects on the gastrointestinal tract. The bioactivity of metal complexes exhibits great interest in metal-based drug research. Cu(II)-NSAID compounds show good anti-inflammatory property and decreased side-effects compared to their organic parent drugs. This work aimed to contribute for development of alternative NSAIDs. Cu-NSAlD compounds containing the drugs Ibuprofen, Indomethacin, Naproxen, Sulindac and Meloxicam were synthesized and characterized. The compounds were also immobilized on Hydrotalcite, a layered double hydroxide (LDH) of magnesium and aluminum (Mg/Al = 3), that is biocompatible and used as stomach antacid. The interactions of the copper drugs with LDH led to Cu-NSAID/LDH- bioinorganic hybrid materiais. Two kinds of complex-LDH interactions were observed by changing the solvent: intercalation between LDH layers or adsorption on the LDH external surfaces. The intercalation of neutral complexes is favored in an alcohollamide solvent mixture where Hydrotalcite undergoes exfoliation process promoted by the amide hydrolysis. The stability of some complexes and their correspondent hybrid materials under gastric conditions (pH and temperature) and also in vivo anti-inflammatory, analgesic and ulcerogenic activities for Indomethacin (Indo)-containing systems were investigated. The stabilization of the Cu-Indo structure is promoted by intercalation of the complex into the LDH layers, contributing to increase its pharmacological activity. The bioinorganic hybrid materials here investigated also exhibit interesting properties for applications as controlled drug delivery systems.