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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
121

Bio-Inspired Gas-Entrapping Microtextured Surfaces (GEMS): Fundamentals and Applications

Arunachalam, Sankara 08 1900 (has links)
Omniphobic surfaces, which repel polar and non-polar liquids alike, have proven of value in a myriad of applications ranging from piping networks, textiles, food and electronics packaging, and underwater drag reduction. A limitation of currently employed omniphobic surfaces is their reliance on perfluorinated coatings/chemicals, increasing cost and environmental impact and preventing applications in harsh environments. Thus, there is a keen interest in rendering conventional materials, such as hydrocarbon-based plastics, omniphobic by micro/ nanotexturing rather than via chemical makeup, with notable success having been achieved for silica surfaces with doubly reentrant pillars (DRPs). We discovered a critical limitation of DRPs – they catastrophically lose superomniphobicity in the presence of localized physical damages/defects or on immersion in wetting liquids. In response, we pioneered bio-inspired gas-entrapping microtextured surfaces (GEMS) architecture composed of doubly reentrant cavities (DRCs). DRCs are capable of robustly entrapping air when brought into contact with liquid droplets or on immersion, which prevents catastrophic wetting transitions even in the presence of localized structural damage/defects. This dissertation presents our multifaceted research on DRCs via custom-built pressure cells, confocal laser scanning microscopy, environmental scanning electron microscopy, contact angle goniometry, high-speed imaging, and upright optical microscopy. Specific accomplishments detailed in this thesis include: (i) the microfabrication protocols for silica GEMS developed at KAUST; (ii) the characterization of GEMS’ omniphobicity via apparent contact angles and immersion; (iii) the demonstration of ~ 1000,000,000% delays in wetting transitions in DRCs compared to those in simple cavities (SCs) under hexadecane; (iv) a proposal for immersion of surfaces as a criterion for assessing their omniphobicity in addition to apparent contact angles; (v) effects of surface chemistry, hydrostatic pressure, and cavity dimensions on Cassie-to-Wenzel transitions in DRCs and SCs; (vi) the demonstration of “breathing” (liquid-vapor) interfaces in GEMS under fluctuating hydrostatic pressures; and (vii) the demonstration of directional wetting transitions in DRCs (or cavities in general) arranged in one- and two-dimensional lattices. The last chapter in the thesis presents future research directions such as breathing surfaces capable of preempting vapor condensation and gas replenishment.
122

Investigating The Relationship Between Surface Topology And Functional Characteristics For Injection Moulded Thermoplastic Components

Israr Raja, Tehmeena January 2021 (has links)
Bacteria are known to adhere to surfaces, which allows for the formation of biofilms, possibly causing a surge in hospital-offset infections, perilous diseases, and in some cases, death. Although certain bacteria are present in the natural flora of the human skin, some present extreme clinical significance due to the ability to transmit and adhere, and can be resistant to antibiotics. They also evolve over time to survive in harsh environmental conditions. Current research reveals that design of plastic surfaces containing submicron structures, is becoming a popular approach to tackle issues concerning infection transmission, with inspiration being derived from biomimetics and self-cleaning surfaces, such as the surface of a gecko skin, and the hydrophobic wax layer of forest leaves. Main barriers to adoption include that these surfaces alone are difficult to manufacture on 3D products, expensive to fabricate on a large scale and do not last long when subjected to environmental wear. Replication of nano-scale ridges was carried out using micro-injection, and the various samples were characterised using a range of tools to determine physical and biomechanical parameters. The sample surfaces were then cultured with the pathogenic bacterium Staphylococcus aureus under several environmental conditions, and the results were statistically analysed to reveal that anti-fouling LIPSS (laser induced periodic surface structures) ridges perform better to reduce bacteria cell-substrate adhesion, when compared to flat surfaces, or surfaces containing dual structures (anti-fouling ridges combined with anti-wear walls). It was therefore demonstrated that nanotextured polymeric surfaces with hydrophobic characteristics have exceptional non-fouling properties, preventing S. aureus, a very significant bacterial strain, from initial adhesion, a critical primary mechanism in its ability to proliferate. Collectively, the findings of this study strongly support the literature, suggesting that the bacteria struggle to adhere onto polymeric topography with increased water contact angles and simple nanostructures. However, the addition of certain anti-wear micro-features increased bacterial adhesion, reducing the efficacy of the non-fouling nanostructures from preventing biofilm formation.
123

Análise da distribuição das tensões em restaurações cerâmicas sobre dente natural e implante por meio do método dos elementos finitos /

Freitas Júnior, Amilcar Chagas. January 2008 (has links)
Resumo: As restaurações cerâmicas têm proporcionado resultados satisfatórios estética e biomecanicamente. Porém, a comparação dos dados sobre a distribuição das tensões nos casos de diferentes restaurações suportadas por dente ou por implante é inconclusiva. O objetivo desse estudo foi avaliar, através da análise de elementos finitos bidimensional, a distribuição interna das tensões nos materiais e estruturas de suporte em função de duas possibilidades restauradoras em cerâmica (faceta laminada e coroa total) e dois tipos de suportes (dente natural e implante). Foram confeccionados 8 (oito) modelos (M) no programa AutoCad 2006, variando o tipo de suporte e restauração: MA (controle) - representação do incisivo central maxilar, hígido, seccionado sagitalmente; MB1, MB2 e MB3 - semelhantes ao MA, restaurados com faceta laminada pelo sistema IPS Empress, IPS Empress Esthetic e Laminado Procera, respectivamente; MC1 e MC2 - semelhantes ao MA, com coroa total pelo sistema IPS Empress 2 (MC1) e Procera AllCeram (MC2); MD1 e MD2 - porção coronária semelhante ao MC1 e MC2, respectivamente, com a presença de um implante osseointegrado (Sistema Bränemark - 4,3 X 15,0 mm) e pilar em zircônia. Para análise numérica (Ansys 10.0), os modelos foram carregados (C) sob duas condições (50N): C1 - 45º de inclinação com o longo eixo dental, no terço médio da face palatina; C2 - perpendicular à borda incisal. Adicionalmente, uma terceira condição foi adotada para o MA: C3 - 50N na borda incisal paralelo ao longo eixo dental. Foram obtidas a tensão equivalente de von Mises (σvM) e a máxima tensão principal em tensão (σmax.t) e compressão (σmax.c). Observou-se que C3 proporcionou a menor variação de svM no dente e estruturas de suporte quando comparada à C1 e C2. / Abstract: The ceramics restorations have provided excellent aesthetic and biomechanical clinical results. However, the data about the stress distribution in tooth and implant-supported restorations are inconclusive. Using two-dimensional finite element analysis, the purpose of this study was to evaluate the stress distribution in the materials and support structures based on two ceramics restorative possibilities (laminate veneer and ceramic crown) and two support structures (tooth and implant). 8 models (M) were built in the program AutoCAD 2006, varying the restorations and their support structures: MA (control) - an intact maxillary central incisor in sagittal cut; MB1, MB2 and MB3 - similar to MA, with laminate veneers of IPS Empress, IPS Empress Esthetic and Procera veneer, respectively; MC1 and MC2 - similar to MA, with a full crown of IPS Empress 2 (MC1) and Procera AllCeram (MC2); MD1 and MD2 - coronary portion similar to MC, with an osseointegrated implant (Bränemark System - 4.3 X 15.0 mm) and zircon abutment. To the numerical analysis (Ansys 10.0), the following loadings (L) were performed (50N): L1 - on the medium third of the lingual face, in 45º with the dental long axis; L2 - perpendicular to the incisal edge; L3 - 50N in the incisal edge parallel to the tooth long axis (only for the natural tooth). The von Mises equivalent stress (σvM) and maximum principal stress in tension (σmax.t) and compression (σmax.c) were obtained. It was observed that L3 provided the smallest variation of σvM in the tooth and support structures in comparison with L1 and L2. The beam3 elements used for the periodontal ligament modeling showed an appropriate behavior for parallel loading. In the MB and MC, the ceramics increased the σvM in the adhesive interface, mainly for Procera. In the models with implant, the IPS Empress2 showed higher σvM than that for Procera AllCeram. / Orientador: Eduardo Passos Rocha / Coorientador: Paulo Henrique dos Santos / Banca: Altair Antoninha Del Bel Cury / Banca: Wirley Gonçalves Assunção / Mestre
124

Factors influencing the adoption of nature inspired innovation for sustainability in multinational corporations

Mead, Taryn Lee January 2017 (has links)
In recent decades, many multinational corporations have used nature inspired innovation (NII) strategies as a mechanism of sustainability-oriented innovation (SOI). In this context, these activities are typically initiated by sustainability or innovation managers who are seeking to utilise novel tools and approaches but generally do not have specific innovation goals. For some, NII is viewed as a new product development tool and for others, it is a broad perspective that defines a larger sustainability narrative for the organisation. This analysis of six cases describes the diversity of innovation types of NII in multinational corporations aiming to apply these models to sustainability-oriented innovation at multiple levels. Data was collected via semi-structured interviews (n=45) with NII team members from both inside and outside of the organisation. Additional data included internal project documents and web-based content associated with the NII projects. Cases were then compared and contrasted to identify patterns and anomalies of factors that influence the adoption of NII. While perceptions of NII were relatively consistent across cases, several factors were identified related to sustainability perspectives, the role of management, organisational structures, and innovation culture that influenced adoption. This thesis makes an original contribution to knowledge within the NII, sustainability-oriented innovation, and innovation adoption literatures by differentiating NII as an approach to SOI in MNCs, establishing an innovation typology in this context, and identifying three SOI narratives that influence the adoption of NII. Specific factors related to sustainability narratives, innovation culture and infrastructure, and management styles that support and inhibit SOI and NII in MNCs are used to distinguish three unique SOI narratives – Ambiguous, Accountable, and Aspirational. Conclusions suggest a NII readiness assessment may facilitate the adoption of NII by identifying the most effective approaches depending on the narrative of SOI within the company.
125

Theoretical studies of systems of biochemical interest containing Fe and Cu transition metals

Güell Serra, Mireia 30 July 2009 (has links)
La presència de la química teòrica i computacional està augmentant en quasi tots els camps de la recerca en química. Els càlculs teòrics poden ajudar a entendre millor l'estructura, les propietats i la reactivitat de compostos metàl·lics d'àrees tan diferents com la química inorgànica, organometàl·lica i bioinorgànica. No obstant això, és imprescindible utilitzar la metodologia adequada per obtenir resultats teòrics fiables. Els estudis d'aquesta tesi es poden dividir en dos grups diferents. El primer grup inclou l'estudi teòric del mecanisme de reacció de diversos sistemes que contenen coure i tenen diferents estructures Cun-O2. Aquests estudies s'han dut a terme amb l'objectiu de profunditzar en la natura dels processos oxidants químics i biològics promoguts per sistemes que contenen coure. En la segona part de la tesi, s'estudia la fiabilitat de diferents tècniques utilitzades per estudiar l'estructura electrònica i la reactivitat de sistemes que contenen coure, ferro i altres metalls de transició. / The presence of computational and theoretical chemistry is increasing in chemical research in nearly all fields. Theoretical calculations can help to better explain structure, properties, and reactivity in metallic compounds, in such diverse areas as inorganic, organometallic and bioinorganic chemistry. However, it is essential to use the suitable methodology in order to obtain reliable theoretical results. The studies of this Thesis can be divided into two different groups. The first group includes the theoretical study of the reaction mechanism of several copper-containing systems with different Cun-O2 structures. These studies are carried out with the aim of providing some insight into the nature of the chemical and biological copper-promoted oxidative processes with 1:1 and 2:1 Cu(I)/O2-derived species. In the second part of this Thesis the reliability of different theoretical approaches used to study the electronic structure and reactivity of systems containing copper, iron or other transition metals is evaluated.
126

An Exploration into Biomimicry and its Application in Digital & Parametric [Architectural] Design

Panchuk, Neal January 2006 (has links)
Biomimicry is an applied science that derives inspiration for solutions to human problems through the study of natural designs, systems and processes. This thesis represents an investigation into biomimicry and includes the development of a design method based on biomimetic principles that is applied to the design of curved building surfaces whose derived integral structure lends itself to ease of manufacture and construction. <br /><br /> Three design concepts are produced that utilize a selection of natural principles of design outlined in the initial biomimetic investigation. The first design visualizes the human genome as a template on which the process of architectural design and construction can be paralleled. This approach utilizes an organizational structure for design instructions, the adherence to an economy of means, and a holistic linking of all aspects of a design characteristic of the genetic parallel. The advancement of the first design concept is illustrated through the use of a particular form of parametric design software known as GenerativeComponents. The second design concept applies the biomimetic design approach outlined in concept one to the development of ruled surfaces with an integral structure in the form of developable flat sheets. The final concept documents the creation of arbitrary curved surfaces consisting of an integral reinforcing structure in the form of folded sheet chevrons.
127

An Exploration into Biomimicry and its Application in Digital & Parametric [Architectural] Design

Panchuk, Neal January 2006 (has links)
Biomimicry is an applied science that derives inspiration for solutions to human problems through the study of natural designs, systems and processes. This thesis represents an investigation into biomimicry and includes the development of a design method based on biomimetic principles that is applied to the design of curved building surfaces whose derived integral structure lends itself to ease of manufacture and construction. <br /><br /> Three design concepts are produced that utilize a selection of natural principles of design outlined in the initial biomimetic investigation. The first design visualizes the human genome as a template on which the process of architectural design and construction can be paralleled. This approach utilizes an organizational structure for design instructions, the adherence to an economy of means, and a holistic linking of all aspects of a design characteristic of the genetic parallel. The advancement of the first design concept is illustrated through the use of a particular form of parametric design software known as GenerativeComponents. The second design concept applies the biomimetic design approach outlined in concept one to the development of ruled surfaces with an integral structure in the form of developable flat sheets. The final concept documents the creation of arbitrary curved surfaces consisting of an integral reinforcing structure in the form of folded sheet chevrons.
128

The Interactions of Zinc Thiolate Complexes and Exogenous Metal Species: Investigations of Thiolate Bridging and Metal Exchange

Almaraz, Elky 2009 May 1900 (has links)
Small molecule Zn(II) complexes containing N- and S- donor environments may serve as appropriate models for mimicking Zn protein sites, and thus, their reactions with heavy metal ions such as Pt(II) and W(0) may provide insight into possible adduct formation and zinc displacement. To study such possible interactions between zinc finger proteins and platinum-bound DNA, the ZnN2S2 dimeric complex, N,N?-bis(2- mercaptoethyl)-1,4-diazacycloheptane zinc (II), [Zn-1?]2, has been examined for Znbound thiolate reactivity in the presence of Pt(II) nitrogen ? rich compounds. The reactions yielded Zn/Pt di- and tri- nuclear thiolate-bridged adducts and metalexchanged products, which were initially observed via ESI-mass spectrometry (ESI-MS) analysis of reaction solutions, and ultimately verified by comparison to the ESI-MS analysis, 195Pt NMR spectroscopy, and X-ray crystallography of directly synthesized complexes. The isolation of Zn-(?-SR)-Pt-bridged [(Zn(bme-dach)Cl)(Pt(dien))]Cl adduct from these studies is, to our knowledge, the first Zn-Pt bimetallic thiolatebridged model demonstrating the interaction between Zn-bound thiolates and Pt(II). Additional derivatives involving Pd(II) and Au(III) have been explored to parallel the experiments executed with Pt(II). The [Zn-1?]2 was then modified by cleavage with Na+[ICH2CO2]- to produce (N- (3-Thiabutyl)-N?-(3-thiapentaneoate)-1,4-diazacycloheptane) zinc(II), Zn-1?-Ac or ZnN2SS?O, and 1,4-diazacycloheptane-1,4-diylbis(3-thiapentanoato) zinc(II), Zn-1?-Ac2 or ZnN2S?2O2, monomeric complexes (where S = thiolate, S? = thioether). The [Zn-1?]2 di- and Zn-1?-Ac mono-thiolato complexes demonstrated reactivity towards labile-ligand tungsten carbonyl species, (THF)W(CO)5 and (pip)2W(CO)4, to yield, respectively, the [(Zn-1?-Cl)W(CO)4]- complex and the [(Zn-1?-Ac)W(CO)5]x coordination polymer. With the aid of CO ligands for IR spectral monitoring, the products were isolated and characterized spectroscopically, as well as by X-ray diffraction and elemental analysis. To examine the potential for zinc complexes (or zinc-templated ligands) to possibly serve as a toxic metal remediation agents, Zn-1?-Ac and Zn-1?-Ac2 were reacted with Ni(BF4)2. The formation of Zn/Ni exchanged products confirmed the capability of ?free? Ni(II) to displace Zn(II) within the N-, S-, and O- chelate environment. The Zn/Ni exchanged complexes were analyzed by ESI-MS, UV-visible spectroscopy, IR spectroscopy of the acetate regions, and X-ray crystallography. They serve as foundation molecules for more noxious metal exchange / zinc displacement products.
129

Biomimetic Studies On Anti-Thyroid Drugs And Thyroid Hormone Synthesis

Roy, Gouriprasanna 05 1900 (has links)
Thyroxine (T4), the main secretory hormone of the thyroid gland, is produced on thyroglobulin by thyroid peroxidase (TPO)/hydrogen peroxide/iodide system. The synthesis of T4 by TPO involves two independent steps: iodination of tyrosine and phenolic coupling of the resulting iodotyrosine residues. The prohormone T4 is then converted to its biologically active form T3 by a selenocysteine-containing iodothyronine deiodinase (ID-I), which is present in highest amounts in liver, kidney, thyroid and pituitary. The 5'-deiodination catalyzed by ID-I is a ping-pong, bisubstrate reaction in which the selenol (or selenolate) group of the enzyme (E-SeH or E-Se-) first reacts with thyroxine (T4) to form a selenenyl iodide (E-SeI) intermediate. Subsequent reaction of the selenenyl iodide with an as yet unidentified intracellular cofactor completes the catalytic cycle and regenerates the selenol. Although the deiodination reactions are essential for the function of thyroid gland, the activation of thyroid stimulating hormone (TSH) receptor by auto-antibodies leads to an overproduction of thyroid hormones. In addition, these antibodies stimulate ID-I and probably other deiodinases to produce relatively more amount of T3. Figure 1. Synthesis of thyroid hormones by heme-containing Thyroid Peroxidase(TPO)(Refer PDF File) As these antibodies are not under pituitary feedback control system, there is no negative influence on the thyroid activity and, therefore, the uncontrolled production of thyroid hormones leads to a condition called “hyperthyroidism”. Under these conditions, the overproduction of T4 and T3 can be controlled by specific inhibitors, which either block the thyroid hormone biosynthesis or reduce the conversion of T4 to T3. A unique class of such inhibitors is the thiourea drugs, methimazole (1, MMI), 6-n-propyl-2-thiouracil (3, PTU), and 6-methyl-2-thiouracil (5, MTU). Although these compounds are the most commonly employed drugs in the treatment of hyperthyroidism, the detailed mechanism of their action is still not clear. According to the initially proposed mechanism, these drugs may divert oxidized iodides away from thyroglobulin by forming stable electron donor-acceptor complexes with diiodine, which can effectively reduce the thyroid hormone biosynthesis. It has also been proposed that these drugs may block the thyroid hormone synthesis by coordinating to the metal center of thyroid peroxidase (TPO). After the discovery that the ID-I is responsible for the activation of thyroxine, it has been reported that PTU, but not MMI, reacts with the selenenyl iodide intermediate (E-SeI) of ID-I to form a selenenyl sulfide as a dead end product, thereby blocking the conversion of T4 to T3 during the monodeiodination reaction. The mechanism of anti-thyroid activity is further complicated by the fact that the gold-containing drugs such as gold thioglucose (GTG) inhibit the deiodinase activity by reacting with the selenol group of the native enzyme. Recently, the selenium analogues 2 (MSeI), 4 (PSeU) and 6 (MSeU) attracted considerable attention because these compounds are expected to be more nucleophilic than their sulfur analogues and the formation of an –Se–Se– bond may occur more readily than the formation of an –Se–S– bond with the ID-I enzyme. However, the data derived from the inhibition of TPO by selenium compounds show that these compounds may inhibit the TPO activity by a different mechanism. Therefore, further studies are required to understand the mechanism by which the selenium compounds exert their inhibitory action. Our initial attempts to isolate 2 were unsuccessful and the final stable compound in the synthesis was characterized to be the diselenide (8). In view of the current interest in anti-thyroid drugs and their mechanism, we extended our approach to the synthesis and biological activities of a number of sulfur and selenium derivatives bearing the methimazole pharmacophore. The thesis consists of five chapters. The first chapter gives a general introduction to thyroid hormone synthesis and anti-thyroid drugs. In this chapter, the biosynthesis of thyroid hormones, structure and function of heme peroxidases, activation of thyroid hormones by iodothyronine deiodinases are discussed. This chapter also gives a brief introduction to some common problems associated with the thyroid gland, with a particular emphasis on hyperthyroidism. The structure and activity of some commonly used anti-thyroid drugs and the role of selenium in thyroid are discussed. The literature references related to this work are provided at the end of the chapter. The second chapter deals with the synthesis and characterization of the selenium analogue (MSeI) of anti-thyroid drug methimazole and a series of organoselenium compounds bearing N-methylimidazole pharmacophore are described. The clinically employed anti-thyroid drug, methimazole (MMI), exists predominantly in its thione form, which is responsible for its anti-thyroidal activity. The selenium analogue MSeI, on the other hand, is not stable in air and spontaneously oxidizes to the corresponding diselenide (MSeIox). Experimental and theoretical studies on MSeI suggest that this compound exists in a zwitterionic form in which the selenium atom carries a large negative charge. The structure of MSeI was studied in solution by NMR spectroscopy and the 77Se NMR chemical shift shows a large upfield shift (-5 ppm) in the signal as compared to the true selones for which the signals normally appear in the downfield range (500-2500 ppm). This confirms that MSeI exists predominantly in its zwitterionic form in solution. Our theoretical studies show that the formation of the diselenide (MSeIox) from selenol tautomer is energetically more favored than the formation of the disulfide (MMIox) from the thiol tautomer of MMI. This study also shows that the replacement of the N−H group in MSeI by an N-methyl or N-benzyl substituent does not affect the nature of C−Se bond. In the third chapter, the inhibition of lactoperoxidase-catalyzed oxidation of ABTS by anti-thyroid drugs and related derivatives is described. The commonly used anti-thyroid agent methemazole (MMI) inhibits the lactoperoxidase (LPO) with an IC50 value of 7.0 µM which is much lower than that of the other two anti-thyroid drugs, PTU and MTU. The selenium analogue of methimazole (MSeI) also inhibits LPO with an IC50 value of 16.4 µM, which is about 4-5 times lower than that of PTU and MTU. In contrast to thiones and selones, the S- and Se-protected compounds do not show any noticeable inhibition under identical experimental conditions. While the inhibition of LPO by MMI cannot be reversed by increasing the hydrogen peroxide concentration, the inhibition by MSeI can be completely reversed by increasing the peroxide concentration. Some of the selenium compounds in the present study show interesting anti-oxidant activity in addition to their inhibition propertities. In the presence of glutathione (GSH), MSeI constitutes a redox cycle involving a catalytic reduction of H2O2 and thereby mimics the glutathione peroxidase (GPx) activity in vitro. These studies reveal that the degradation of the intracellular H2O2 by the selenium analogues of anti-thyroid drugs may be beneficial to the thyroid gland as these compounds may act as antioxidants and protect thyroid cells from oxidative damage. Because the drugs with an action essentially on H2O2 can reversibly inhibit thyroid peroxidase, such drugs with a more controlled action could be of great importance in the treatment of hyperthyroidism. Figure 2. (A) Concentration-inhibition curves for the inhibition of LPO-catalyzed oxidation of ABTS by MMI and MSeI at pH 7.0 and 30 °C. (B) Plot of initial rates (vo) for the LPO-catalyzed oxidation of ABTS vs concentration of H2O2. (a) Control activity, (b) 40 µM of MSeI, (c) 40 µM of MSeIox, (d) 80 µM of PTU, (e) 80 µM of MTU, (f) 40 µM of MMI. The incubation mixture contained 6.5 nM LPO, 1.4 mM ABTS, 0.067 M phosphatebuffer(pH7).(Refer PDF File) The fourth chapter describes the inhibition of lactoperoxidase (LPO)-catalyzed iodination of L-tyrosine by anti-thyroid drug methimazole (MMI) and its selenium analogue (MSeI). These inhibition studies show that MSeI inhibits LPO with an IC50 value of 12.4 µM, which is higher than that of MMI (5.2 µM). The effect of hydrogen peroxide on the inhibition of LPO by MMI and MSeI is also discussed. These studies also reveal that the inhibition of LPO-catalyzed iodination by MSeI can be completely reversed by increasing the peroxide concentration. On the other hand, the inhibition by MMI cannot be reversed by increasing the concentration of the peroxide. To under stand the nature of compounds formed in the reactions between anti-thyroid drugs and iodine, the reactions of MSeI with molecular iodine is described. MSeI reacts with I2 to produce novel ionic diselenides, and the nature of the species formed in this reaction appears to be solvent dependent. The formation of ionic species (mono and dications) in the reaction is confirmed by UV-Vis, FT-IR and FT-Raman spectroscopic investigations and single crystal x-ray studies. The major conclusion drawn from this study is that MSeI reacts with iodine, even in its oxidized form, to form ionic diselenides containing iodide or polyiodide anions, which might be possible intermediates in the inhibition of thyroid hormones. Dication X-ray crystal structure of the monocation X-ray crystal structure of the dication In the fifth chapter, the synthesis and characterization of several thiones and selones having N,N-disubstituted imidazole moiety are described. Experimental and theoretical studies were performed on a number of selones, which suggest that these compounds exist as zwitterions in which the selenium atom carries a large negative charge. The structures of selones were studied in solution by NMR spectroscopy and the 77Se NMR chemical shifts for the selones show large upfield shifts in the signals, confirming the zwitterionic structure of the selones in solution. The thermal isomerization of some S- and Se-substituted methyl and benzyl imidazole derivatives to produce the thermodynamically more stable N-substituted derivatives is described. A structure–activity correlation was attempted on the inhibition of LPO-catalyzed oxidation and iodination reactions by several thiouracil compounds, which indicates that the presence of an n-propyl group in PTU is important for an efficient inhibition. In contrast to the S- and Se-substituted derivatives, the selones produced by thermal isomerization exhibited efficient inhibition, indicating the importance of reactive selone (zwitterionic) moiety in the inhibition. The inhibition data on another well-known anti-thyroid agent carbimazole (CBZ) support the assumption that CBZ acts as a prodrug, requiring a conversion to methimazole (MMI) for its inhibitory action on thyroid peroxidase. (Refer pdf file/original thesis)
130

Neue Untersuchungen zu Wachstum und Struktur von Fluorapatit-Gelatine-Nanokompositen

Tlatlik, Harald 17 April 2009 (has links) (PDF)
Die vorliegende Dissertation beschäftigt sich mit Wachstum und Aufbau von Fluorapatit-Gelatine-Nanokompositaggregaten. Diese Aggregate werden im sogenannten Doppeldiffusionsversuch biomimetisch erzeugt und ihre äußere Form bzw. Formentwicklung lässt sich anhand eines fraktalen Modells bis ins Detail nachvollziehen. Sie zeigen einen komplexen inneren Aufbau, in dem die Makromoleküle der organischen Komponente einerseits im Zentrum jeder Nanoeinheit und andererseits zu Strängen, den sogenannten Fibrillen, zusammengelagert am Aufbau der Kompositaggregate beteiligt sind. Im Fall des Kompositkeims ist die innere Architektur in hoher Detailstufe verstanden, auch wenn -- insbesondere bezüglich der späteren Wachstumsphasen -- eine Reihe ungeklärter Fragestellungen verbleibt. Ein zentrales Ergebnis der vorliegenden Arbeit bildet die Entdeckung eines weiteren Wachstumstypen, der im Vergleich zu den bekannten, fraktalen Kompositaggregaten grundsätzliche Unterschiede bezüglich des inneren und äußeren Aufbaus zeigt. Der Grund für die andersartige Formentwicklung liegt in der Versteifung der organischen Komponente durch eine vorangegangene Einlagerung von Calciumionen, wie sowohl experimentell als auch mit atomistischen Computersimulationen gezeigt werden konnte. Aufgrund der hohen Komplexität des Systems ist es bislang allerdings nicht möglich, lokale Ionen-Konzentrationen und pH-Werte vor bzw. während Nukleation und Wachstum der Kompositaggregate im Doppeldiffusionsversuch zu bestimmen. Deshalb wurde ein Ersatzversuch -- der sehr ähnlich strukturierte Aggregate erzeugt, sich aber mit rechnerischen Methoden analysieren lässt -- entworfen und untersucht. Anhand dieser Ergebnisse konnte erstmals die &amp;quot;Geschichte&amp;quot; von Fluorapatit-Gelatine-Nanokompositaggregaten detailliert nachvollzogen werden. Da über die Rolle der Gelatine beim Wachstum der Kompositaggregate nur wenig bekannt ist, wurde eine Reihe von Versuchen durchgeführt, in denen Gelatinen mit verschiedenen Molekülmassenverteilungen eingesetzt wurden. Es stellte sich heraus, dass für selbstorganisiertes und insbesondere fraktales Wachstum der Kompositaggregate lange, möglichst wenig gestörte Makromoleküle von zentraler Wichtigkeit sind. Um die Funktion der organischen Komponente für das Kompositwachstum näher zu untersuchen, wurden Oberflächen von Kompositkeimen mit rasterkraftmikroskopischen Methoden studiert. Durch Säuberung der Oberflächen konnten Austrittsstellen der organischen Komponente durch die Oberfläche der Kompositkeime identifiziert werden. Damit konnte gezeigt werden, dass die organische Komponente aus dem Inneren des Festkörpers teilweise durch die Oberfläche dringt und somit während des Wachstums weit in das Gel hineinreichen sollte. Für die mesoskopische Strukturbildung der Kompositaggregate spielen intrinsische elektrische Felder eine essenzielle Rolle. Deshalb wurde bislang eine Wirkung externer elektrischer Felder auf das Wachstum der Kompositaggregate vermutet. Im Rahmen der vorliegenden Arbeit wurde herausgearbeitet, dass es zwar zu keiner direkten Beeinflussung kommen kann, jedoch in den elektrodennahen Bereichen des Gels eine Ordnung der organischen Moleküle durch externe elektrische Felder zu erwarten ist. Dies könnte eine Wirkung auf wachsende Kompositaggregate zeigen. Da diese Effekte auch aufgrund der elektrischen Felder um die dipolaren Kompositaggregate zu erwarten sind, könnte eine ähnliche Strukturierung der Gelatine in der Nähe der wachsenden Kompositaggregate stattfinden. Insgesamt wurden in dieser Arbeit eine Reihe grundlegender Beiträge zur Erforschung der biomimetisch erzeugten Fluorapatit-Gelatine-Nanokompositaggregate geleistet. Es konnten neue Erkenntnisse zur inneren und äußeren Architektur der Kompositaggregate, zu Mechanismen der Morphogenese und deren wichtigsten Einflussgrößen sowie zum Verständnis der chemisch-physikalischen Vorgänge auf atomarer Größenskala gewonnen werden. Als besonders fruchtbar erwies sich die Verbindung von Experimenten mit theoretischen Untersuchungen, so dass dieser Weg auch in Zukunft grundlegende Erkenntnisse bei der Erforschung der Biomineralisation verspricht und weiterhin verfolgt werden sollte.

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