Chemical separation undoubtedly accounts for a large proportion of process industries' activities. In the past few decades, 10-15% of the world's energy consumed was resulted from separation process. Tremendous efforts have been made in separating the components of large quantities of chemical mixtures into pure or purer forms in most industrial chemists. In addition, industrial development and population growth would lead to a further increase in the global demand for energy in the future. This makes the effective and efficient energy separation process one of the most challenging tasks in engineering. Adsorptive separation using porous materials is widely used in industry today. In order for an adsorptive separation process to be efficient, the essential requirement is a selective adsorbent that possesses high surface area and preferentially adsorbs one component (or class of similar components). Metal-organic frameworks (MOFs) are promising materials for separation purposes as their diversity, due to their building block synthesis from metal clusters and organic linker, gives rise to a wide range of porous structures. Engineering of a separation process is a multi-disciplinary problem that requires a holistic approach. In particular, material selection for industrial applications in the field of MOFs is one of the most significant engineering challenges. The complexity of a screening exercise for adsorptive separations arises from the multitude of existing porous adsorbents including MOFs. There are more than 80,000 structures that have been synthesised so far, as well as the multivariate nature of that performance criteria that need to be considered when selecting or designing an optimal adsorbent for a separation process. However, it is infeasible to assess all the potential materials experimentally to identify the promising structure for a particular application. Recently, molecular simulation and mathematical modelling have seen an ever- growing contribution to the research field of MOFs. The development of these computational tools offers a unique platform for the characterisation, prediction and understanding of MOFs, complementary to experimental techniques. In the first part of this research, Monte Carlo molecular simulation and a number of advanced mathematical methods were used to investigate newly synthesised or not well-known MOFs. These computational techniques allowed not only to characterise materials with their textural properties, but also to predict and understand adsorption performances at the atomic level. Based on the insight gained from the molecular simulation, two computational high-throughput screening approaches were designed and assessed. A multi-scale approach has been proposed and used which combined high-throughput molecular simulation, data mining and advanced visualisation, process system modelling and experimental synthesis and testing. The focus here was on two main applications. On one hand, the challenging CO/N2 separation, which is critical for the petrochemical sector, where two molecules have very similar physical properties. On the other hand, the separation of chiral molecules. For CO/N2 separation, a database of 184 Cu- Cu paddle-wheels MOFs, which contains unsaturated metal centres as strong interaction sites, was extracted from CSD (Cambridge Structural Database) MOF subset for material screening. In the case of chiral separation, an efficient high-throughput approach based on calculation of Henry's constant was developed in this research. Owning to the nature of chirality, this separation of relevance to the pharmaceutical sector is crucially important. A database of 1407 homochiral MOFs was extracted, again, from CSD MOF subset for material screening of enantioselective adsorption. The results obtained in these computational high-throughput approaches allows the screening of interesting, existing structures, and would have a huge impact on making MOFs to be industrially interesting adsorbents as well as guiding the synthesis of these materials. From the many different possibilities, the ultimate interest of this work is in developing an integrated systematic study of the structure-adsorption performance relationship working with a limited library of candidate MOF structures in order to identify promising trends and materials for the specific applications mentioned above. In summary, the overall aim of this research was exploiting different computational techniques, developing novel high-throughput approaches in order to tackle important engineering challenges.

In response to the ever-increasing global energy demand and the need to move away from non-renewable and CO2-emitting fossil fuels as the primary energy production method, renewable energy sources have become more and more viable as energy production methods. However, given the unreliable and instantaneous nature of these energy sources, reliable, renewable energy storage methods are required. Hydrogen is an excellent candidate as a chemical energy store, as it is highly abundant, relatively easily produced as diatomic hydrogen (including from water electrolysis), and only produces water upon its complete combustion. Hydrogen also has the highest gravimetric energy density of any known chemical fuel, meaning that not very much of it is required relative to other chemical fuels. However, hydrogen gas is incredibly sparse, and therefore hydrogen has a very low volumetric energy density, making storage of the material a key challenge in the development of the so-called “hydrogen economy”. Most commonly, hydrogen is stored by compressing it to 70 MPa. However, this technique has a number of flaws, including the high expense of strong tanks (and in the case of light duty vehicles, lightweight materials are also required), and the inherent safety risks that high pressure, highly flammable gas poses. One of the alternatives to compression is to store hydrogen by adsorption, which uses high surface area materials to densify hydrogen via the formation of weak physical bonds. This research line is well developed, and a number of different materials has been created that show good potential as hydrogen storage materials, such as activated carbons and metal organic frameworks. However, the vast majority of materials developed for this purpose are tailored only with the hydrogen uptake in mind, which can cause issues as the focus of development shifts from small scale tests to full tank scale. One adsorptive that shows a number of highly useful engineering properties on the large scale, such as good thermal resistance and solution processability, is the polymer of intrinsic microporosity PIM-1. This material can be processed into a number of morphologies without losing porosity, and shows good thermal and mechanical resistance. However, its adsorption capacity is rather limited, with the BET surface area generally reported in the 700 – 800 m2 g-1 range, and hydrogen uptake of 1.45 wt% at 77 K and 1 MPa. This thesis presents two separate studies on attempting to improve the hydrogen uptake of PIM-1 without adversely affecting the material properties that make it attractive. The first of these was the creation of mixed-matrix-membrane style composite films solution cast from PIM-1 and the metal organic framework MIL-101. PIM-1 proved slightly difficult to synthesise consistently with high molecular weight, but MIL-101 is an easy hydrothermal synthesis. Film casting was successfully performed, producing flat, homogeneous films that maintained the MOF crystallinity. These materials were tested for their thermal properties – thermal decompositions proceeded according to the rule of mixtures of the two starting materials, whilst an increasing concentration of MOF was shown to decrease the specific heat capacity. Both PIM-1 and MIL-101 were shown to adsorb nitrogen as previously reported. The composites showed increasing uptake with MIL-101 content, but at a lower rate than the rule of mixtures. This was a common theme for the N2 (77 K), CO2 (293 K) and low pressure H2 isotherms performed. High pressure isotherms up to 17 MPa were performed on PIM-1 for the first time, showing a maximum excess uptake of 1.8 wt% on the powder and 1.6 wt% on the film, both at 77 K. The composites showed improved uptake with increasing MIL-101, but the maximum uptakes did not meet the rule of mixtures. The uptakes at the highest pressure did, however. Multiple temperature isotherm sets were performed on the PIM-1 film and powder, as well as the 30 wt% composite. These data sets were hampered largely by machine faults, but contained sufficient valuable data to be able to proceed with parameter fitting. The sensitivity of the isotherms produced in this study to the value of skeletal density is also examined closely. The second theme of improved H2 uptake in PIM-1 was to carbonise the material. TGA studies on PIM-1 showed good thermal stability in anoxic conditions, and TGA twinned with mass spectroscopy was able to confirm a previously proposed mechanism of thermal decomposition. Carbonised and activated PIM-1 film samples, and a carbonised powder, were produced using physical activation methods. The adsorption performance of the carbons was disappointing, as the uptakes of N2 and H2 (< 0.1 MPa) were reduced post-carbonisation, with little recovery in the activated film. CO2 uptakes were improved, however. High pressure H2 isotherms on both the carbonised and activated films showed unusual ‘stepping’ behaviour in the adsorption curve, but maximum uptakes for both (1.0 – 1.3 wt%) were less than that seen for PIM-1 alone. Parameter fitting was performed on all of the high pressure H2 isotherms performed in this study, using a method previously proposed by the Mays group. The parameter fits all showed effective hydrogen densification in the adsorbate layer, although the repeatability of parameter values, and the smoothness of the parameters as a function of temperature were undermined by the low quality of some of the isotherms. Using the parameters acquired, it was possible to calculate the isosteric enthalpy of adsorption for PIM-1 powder (-9.5 kJ mol-1), film (- 8.0 kJ mol-1) and the 30 wt% composite (-9.3 kJ mol-1). The stored and deliverable hydrogen contained within tanks featuring the tested materials were estimated, although only the MIL-101 powder on its own competes with other hydrogen storage adsorbents currently reported.

Attention worldwide has been placed towards reducing the global carbon footprint. To this end the scientific community has been involved in improving many of the available methods of carbon capture and storage (CCS). CCS involves scrubbing flue gases of greenhouse gases and safely storing them deep underground. MOFs, a family of functionally tunable three dimensional nanoporous frameworks, have been shown to adsorb gases with great selectivity and capacity. Investigating these frameworks using computational simulations, although faster than in-lab synthetic methods, involves a tedious and meticulous input preparation process which is subject to human error. This thesis presents Dave's Occupancy Automation Package (DOAP),a software which provides a means to automatically determine the gas uptake of many three dimensional frameworks. By providing atomic coordinates for a unit simulation cell, the software acts to performs the necessary calculations to construct and execute a Grand Canonical Monte Carlo simulation, determining the gas uptake in a metal organic framework. Additionally an analysis of different convergence assessment tests for describing the end point of the GCMC simulation is presented.

Attention worldwide has been placed towards reducing the global carbon footprint. To this end the scientific community has been involved in improving many of the available methods of carbon capture and storage (CCS). CCS involves scrubbing flue gases of greenhouse gases and safely storing them deep underground. MOFs, a family of functionally tunable three dimensional nanoporous frameworks, have been shown to adsorb gases with great selectivity and capacity. Investigating these frameworks using computational simulations, although faster than in-lab synthetic methods, involves a tedious and meticulous input preparation process which is subject to human error. This thesis presents Dave's Occupancy Automation Package (DOAP),a software which provides a means to automatically determine the gas uptake of many three dimensional frameworks. By providing atomic coordinates for a unit simulation cell, the software acts to performs the necessary calculations to construct and execute a Grand Canonical Monte Carlo simulation, determining the gas uptake in a metal organic framework. Additionally an analysis of different convergence assessment tests for describing the end point of the GCMC simulation is presented.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Water-resistant MOF-235 was used to adsorb N,N-dimethylamine (DMA) from aqueous solutions. It was synthesized from terephthalic acid and FeCl3.6H2O under air-free conditions and characterized by its crystalline structure, functional groups and temperature resistance. The kinetic data results were best adjusted to the pseudo-second order model (R2>0.963). The best-fit isotherm, Langmuir model, suggested the adsorption of DMA is localized on homogenously distributed active sites on the surface. This fit was confirmed by the value of β = 1 on the Redlich-Peterson model. Our study suggests that the manipulation of novel materials such as MOF-235 promises new avenues for water treatment solutions. Schematic structure of MOF-235 and its application as adsorbent. / Revisión por pares

Made available in DSpace on 2014-06-12T15:58:48Z (GMT). No. of bitstreams: 2 arquivo4701_1.pdf: 1621449 bytes, checksum: 6b5c6ef55f58ad1d27736c6c74fd4ca4 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2003 / Nos últimos anos, com o crescimento dos sistemas de informação, metadados tornaram-se peças chave no gerenciamento de todo o ciclo de vida desses sistemas. Muitos esforços recentes, tanto das áreas acadêmicas quanto da indústria, estão sendo concentrados em pesquisas relacionadas a metadados. Esses estudos tentam definir metodologias e padrões para construção e interoperabilidade de sistemas de informação baseados em metadados. Atualmente, metadados são utilizados em diversas áreas, como Data Warehouse, bibliotecas eletrônicas, engenharia de software e integração de aplicações heterogêneas. Com o advento da internet, novas aplicações surgem, juntamente com novos padrões para representação. Esses padrões incluem XML (Extensible Markup Language), DTD (Document Type Definition), XML Schema, RDF (Resource Description Framework), RDF Schema, XSLT (Extensible Stylesheet Language Transformation), entre outros. Cada padrão foi desenvolvido para determinados tipos de aplicação. Por exemplo, DTD e XML Schema são padrões para descrição de estruturas de dados, RDF é utilizado para descrição de recursos como páginas Web enquanto que XSLT é utilizado na transformação de documentos XML. A especificação de metadados, aliada à sua gerência eficiente, são os grandes desafios de um ambiente de construção de um Data warehouse. Este trabalho tem como objetivo a construção de uma solução de metadados para o ambiente REDIRIS (Research Environment on Data Integration, Reuse and Quality in Information Systems). O REDIRIS propõe auxiliar os usuários nas tarefas de análise, modelagem, construção e reuso de solução de Data warehouse. O módulo de metadados será responsável por gerenciar toda a informação necessária para a funcionalidade e gerenciamento do ambiente. Para isto, foram projetados e implementados vários metamodelos baseados nos padrões, citados anteriormente. Foi utilizado o MOF (Meta Object Facility) para a construção dos metamodelos e JMI (Java Metadata Interface) para a implementação dos mesmos. As vantagens deste tipo de abordagem são um conjunto de interfaces comuns para gerenciamento dos metadados representados em qualquer padrão (XML, DTD, RDF) e um formato único para intercâmbio desses metadados, o XMI (XML Metadata Interchange)

Submitted by Rafael Santana (rafael.silvasantana@ufpe.br) on 2018-02-20T18:35:23Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertacao TIAGO FRANCA BARRETO versao final revisada com ficha.pdf: 1881406 bytes, checksum: 12e01eebda9019e211cef41ad935a421 (MD5) / Made available in DSpace on 2018-02-20T18:35:23Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertacao TIAGO FRANCA BARRETO versao final revisada com ficha.pdf: 1881406 bytes, checksum: 12e01eebda9019e211cef41ad935a421 (MD5) Previous issue date: 2017-01-25 / CAPES / O parasita Trypanosoma cruzi é o agente etiológico da doença de Chagas, que figura como um dos graves problemas de saúde pública de países em desenvolvimento. Único fármaco disponível para a terapêutica da doença de Chagas, o benznidazol (BNZ) é um derivado 2- nitroimidazol com largo espectro de atividade farmacológica antiparasitária. Entretanto, o BNZ apresenta entraves biofarmacotécnicos: grandes doses administradas, tratamentos prolongados, a alta incidência de reações adversas; tudo devido a sua baixa solubilidade aquosa, uma vez que pertence à classificação biofarmacêutica de classe II. O papel da tecnologia farmacêutica é, então, prover alternativas capazes de incrementar a solubilidade do BNZ e modular sua liberação a fim de obter um tratamento alternativo de maior qualidade e com maior aceitação pelo paciente. Neste contexto, o presente trabalho objetivou desenvolver Drug Delivery Systems (DDS) à base de BNZ e do excipiente inovador Zeolitic Imidazolate Framework (ZIF-8), a fim de utilizá-lo nos estudos de pré-formulação de forma farmacêutica de liberação prolongada para o tratamento alternativo da doença de Chagas. Os sistemas foram obtidos em diferentes proporções molares após otimização de um método ex situ de incorporação do fármaco. A maior eficiência de incorporação foi o critério escolhido para a seleção do melhor DDS. Em seguida, foram realizadas diferentes caracterizações físico-químicas visando avaliar a formação do sistema e a cinética de liberação in vitro do fármaco através de ensaios de dissolução e diálise sob condições sink e non-sink. Para fins comparativos, foram utilizadas misturas físicas na proporção molar de 1:1. Os dados de liberação foram analisados através da área sob a curva (AUC) e ajuste dos resultados quanto aos métodos modelo-dependente e -independente. O sistema BNZ:ZIF-8 1:1 (mol:mol) obtido em acetona foi o selecionado por apresentar maior eficiência de incorporação (em média 38%) após 4 dias de agitação intermitente. As diferentes técnicas de caracterização utilizadas corroboraram a formação do sistema. Os estudos de liberação in vitro do BNZ através de dissolução e de diálise mostraram que houve modulação da liberação do fármaco de acordo com o pH utilizado em condições sink e non-sink. A modulação da liberação foi corroborada tanto pelo ajuste dos resultados a diferentes modelos cinéticos e alteração do mecanismo de liberação do fármaco, quanto pela diferença entre os perfis de liberação comprovada pelo fator de semelhança. Assim, em pH 4,5 o sistema apresentou uma liberação mais rápida, com efeito burst, enquanto que em pH 7,6 houve uma liberação prolongada, mais lenta e sem efeito burst. Em vista dos argumentos apresentados, fica evidente que foi obtido um DDS pH-dependente promissor a ser utilizado como inovador carreador do BNZ em formas farmacêuticas destinadas ao tratamento alternativo da doença de Chagas. / Trypanosoma cruzi is the etiologic agent of Chagas’ disease and consist in one of the major public health problems in developing countries. Only drug available for the treatment of Chagas’ disease, benznidazole (BNZ) is a 2-nitroimidazole derivative with broad-spectrum antiparasitic activity. However, BNZ has biopharmaceutical barriers: large doses, prolonged treatments, the high incidence of adverse reactions; all due to its low aqueous solubility, since it belongs to the biopharmaceutical classification II. Therefore, pharmaceutical technology provides alternatives capable of increasing the solubility of the BNZ and modulate its release in order to obtain an alternative treatment with higher quality and greater patient acceptance. In this context, this study aimed to develop a Drug Delivery Systems (DDS) based on BNZ and the innovative excipient Zeolitic Imidazolate Framework (ZIF-8) aiming to use it in the pre- formulation studies of extended release dosage forms to alternative treatment of Chagas’ disease. The systems were obtained at different molar ratios after optimization of an ex situ method of drug incorporation. The largest uptake efficiency was the criterion used for selecting the best DDS. Then, different characterizations were performed to evaluate the system obtainment, including the kinetics of drug in vitro release through dissolution tests and dialysis under sink and non-sink conditions. For comparison, physical mixtures (PM) were used in the molar ratio 1:1. The release data were analyzed by the area under the curve (AUC) and setting the kinetic results through methods model dependent and independent. The BNZ:ZIF-8 1:1 (mol:mol) system was selected because of its higher incorporation efficiency (38%) after 4 days of intermittent agitation. The different characterization techniques corroborated the obtainment of the system. In vitro release studies of BNZ through dissolution and dialysis showed that there was modulation of the drug release according to the pH used in sink and non-sink conditions. Modulation of the release was corroborated by the adjustment of the results to different kinetic models and alteration of the mechanism of drug release, as well as by the difference between the release profiles evidenced by the similarity factor. Thus, at pH 4.5 the system showed a faster release with burst effect, while at pH 7.6 there was a prolonged, slower release with a reduce in the burst effect. Finally, it is evident that a promising DDS pH-sensitive was obtained to be used as the novel carrier of BNZ in dosage forms intended for the alternative treatment of Chagas' disease.

Attention worldwide has been placed towards reducing the global carbon footprint. To this end the scientific community has been involved in improving many of the available methods of carbon capture and storage (CCS). CCS involves scrubbing flue gases of greenhouse gases and safely storing them deep underground. MOFs, a family of functionally tunable three dimensional nanoporous frameworks, have been shown to adsorb gases with great selectivity and capacity. Investigating these frameworks using computational simulations, although faster than in-lab synthetic methods, involves a tedious and meticulous input preparation process which is subject to human error. This thesis presents Dave's Occupancy Automation Package (DOAP),a software which provides a means to automatically determine the gas uptake of many three dimensional frameworks. By providing atomic coordinates for a unit simulation cell, the software acts to performs the necessary calculations to construct and execute a Grand Canonical Monte Carlo simulation, determining the gas uptake in a metal organic framework. Additionally an analysis of different convergence assessment tests for describing the end point of the GCMC simulation is presented.

Metal-organic frameworks are porous materials resulting from the coordination of a metal ion (the Lewis acid) and organic polydentated ligands. In the case of the MOFs, the SBU (Secondary Building Unit) is defined by taking the active groups of the ligands involved in coordination and the metal ion as a block. The remaining part of the organic ligand is therefore called simply a linker, so that MOFs can also be defined, in a supra-molecular view, as a material composed of SBUs and linkers combined together to form regular, periodic and porous structures. The possible textures and the possible combinations are virtually infinite, depending especially on the properties ofthe linkers, much more than of the metal ions involved, in order to design the pore size, the pore dimensionality and the catalytic properties. It gives this class of nano-materials a very interesting perspective in the most various applications, by allowing to ”tune” each relevant chemical or physical parameter concerning porous materials and their applications in nanotechnology.

Combining enzymes with synthetic materials is the new frontier of biocatalysis, materials science, and protein engineering. Enzymes are biological macromolecule catalysts with incredible efficiency and specificity that are desirable for use in a variety of different fields. However, commercial applications have been limited by the stability and reusability of un-altered enzymes. An avenue for overcoming the challenges to harnessing enzyme power is to combine enzymes with materials to create an enzymatically-active material that has enhanced stability and activity. Unfortunately, the catalytic activity of the hybrid material is often lower than that of the enzyme alone. The activity of an enzyme is directly dependent on its structure and dynamics. Therefore, a deeper understanding of enzyme structure and dynamics upon incorporation into materials will provide the data necessary to rationally design enzymatically-active materials with the desired features. This dissertation explores the behavior of a model enzyme, T4 Lysozyme, with two different artificial material systems, metal-organic frameworks and polyethylene glycol. The underlying structural rationale for the behavior is probed using a variety of techniques, notably, Electron Spin Paramagnetic Resonance. Herein, the implications of structural alterations on activity and opportunities for exploitation are discussed. T4 Lysozyme is a perfect model for this study because it has a well characterized structure-activity relationship, thus providing a vast literature understanding which can be pulled from to verify and assist with interpretation of data. The structural basis of enzyme activity alteration in artificial materials can be used to rationally design systems with desired characteristics. After successfully demonstrating the tunability of proteins in artificial materials using T4L as a model, human Cu/Zn superoxide dismutase 1 was chosen for continuing studies due to its importance in diseased states. However, the superoxide dismutase mutant chosen is aggregation prone, which makes it difficult to express recombinantly in large amounts. Therefore, an efficient protocol for producing the superoxide dismutase protein was developed to set the stage for future studies.