No description available.

Metallorganische Gerüstverbindungen (MOFs) sind hochporöse Materialien, welche aus Metallionen oder –clustern und sogenannten organischen Linkern bestehen. Aufgrund ihres modularen Aufbaus lassen sich gewünschte Eigenschaften der Materialien relativ leicht konstruieren und somit für Anwendungen hoch spezialisierte Materialien generieren. Neben klassischen Anwendungen poröser Materialen wie Gasspeicherung, Gastrennung und Katalyse kommen sie auch für speziellere Anwendungsgebiete in Sensoren oder als Wirkstoffträger für Medikamente in Frage. Insbesondere das flexible Verhalten einiger MOFs unter physikalischen oder chemischen Stimuli schafft dabei interessante Möglichkeiten. Flexible MOFs verändern zum Beispiel unter Einwirkung von Druck oder Gasen ihre Kristallstruktur, sodass bei Adsorptionsprozessen variables Verhalten auftreten kann. Einer der MOFs, welcher derartiges Verhalten aufweist ist DUT-13 (Dresden University of Technology Material Nummer 13). Dieser MOF hat eine offenporige (op) Phase, welche bei der Adsorption von Gasen wie Stickstoff, Methan und CO2 zu einer geschlossenen (cp) Phase kontrahiert. Eine weitere Drucksteigerung beim Adsorptionsprozess öffnet das Porensystem wieder. Diese Art der Flexibilität wird als breathing bezeichnet. Ein anderer MOF der diese Art von Flexibilität aufweist, ist DUT-49. Im Gegensatz zu DUT 13 zeigt dieser MOF allerdings zusätzlich das kontraintuitive Phänomen der negativen Gasadsorption (NGA). Bei dieser wird während des Adsorptionsprozesses in einem bestimmten Druckbereich bei der Phasentransformation von der op zur cp Phase Gas desorbiert, da in der op Phase zu diesem Zeitpunkt bereits mehr Gas adsorbiert ist, als in die cp Phase hineinpasst. Wichtig für das Auftreten dieses Phänomens ist also die Metastabilität der teilweise beladenen op Phase. Diese kann durch Faktoren wie Kristallitgröße, Temperatur, Adsorptiv, Metall im MOF und Porengröße beeinflusst werden. Da das Phänomen bisher nur in DUT-49 und isoretikulären Strukturen (Strukturen gleicher Netzwerktopologie) aufgetreten ist, soll das Phänomen im Rahmen dieser Arbeit auf andere Netzwerktopologien übertragen werden. Da der Flexibilitätsmechanismus in DUT-49 auf dem Verbiegen des Linkers beruht und dessen Eigenschaften somit großen Einfluss auf die Phasentransformation haben, wurde mit der näheren Untersuchung eines MOFs mit sehr ähnlichem Linker, DUT-13, begonnen. In dieser Arbeit wird die bisher unbekannte cp Phase von DUT-13 und der zugrundeliegende Flexibilitätsmechanismus des Netzwerkes aufgeklärt. Außerdem wird der Einfluss der Temperatur auf das Adsorptionsverhalten von DUT-13 geprüft. Zusätzlich wird durch die Synthese einer isoretikulären Serie von DUT-13-analogen MOFs der Einfluss der Porengröße auf die Flexibilität des Netzwerkes untersucht. So wird unter Anderem der hochflexible neue MOF DUT-190 hergestellt, welcher über den gesamten Temperaturbereich von Siedepunkt bis zum kritischen Punkt bei der Methanadsorption flexibles Verhalten zeigt. Außerdem wird an diesem neuen MOF der Einfluss des Metalls auf die Flexibilität untersucht, indem ein postsynthetischer Metallaustausch durchgeführt wird. Da die synthetisierten Linker der isoretikulären Reihe zu hohe Flexibilität in den MOFs induziert haben, wurden außerdem Linker hergestellt, welche die beiden äußeren Phenylringe am Linker durch eine Ethyleneinheit verbrücken. Auf Basis der so entstandenen Linker wurden weitere neue MOFs synthetisiert, welche das seltene Motiv von Siebenringen in MOFs einführen. Einer der so erhaltenen MOFs, DUT-193, weist dabei eine bisher unbekannte neue Netzwerktopologie auf. DUT 193 zeigt zudem hohe Porosität und rigides Verhalten. Um das Verständnis für die Anforderungen an den Linker zur Erzeugung von NGA zu erweitern, wurden abschließend einige Tests zum postsynthetischen Linkeraustausch an DUT-13 und DUT-49 durchgeführt, um den rigideren DUT-49-Linker in DUT-13 einzubauen und umgekehrt.:Danksagung I Inhaltsverzeichnis III Abkürzungsverzeichnis VI Theoretischer Teil 1 1 Motivation 1 2 Stand der Forschung 3 2.1 Was sind Metallorganische Gerüstverbindungen? 3 2.2 Isoretikuläre Chemie und Netzwerktopologien 4 2.3 MOF-Synthese und Aktivierung 8 2.3.1 Konventionelle Synthesen 8 2.3.2 Postsynthetischer Linkeraustausch 9 2.3.3 Postsynthetischer Metallaustausch 10 2.3.4 Aktivierung von MOFs 11 2.4 Röntgendiffraktometrie 12 2.5 Adsorption 16 2.6 Strukturelle Flexibilität in MOFs 22 Experimenteller Teil 28 3 Generelle Angaben 28 3.1 Chemikalien 28 3.2 Methoden 30 3.2.1 Methoden zur Charakterisierung der organischen Verbindungen 30 3.2.2 Methoden zur Handhabung und Charakterisierung synthetisierter MOFs 31 4 Synthesen.. 37 4.1 Linkersynthesen 37 4.1.1 Synthese des Linkers H4ndtb (Naphthalen-2,6-diamin-tetrabenzoesäure) 37 4.1.2 Synthese des Linkers H4benztb (Benzidintetrabenzoesäure) 38 4.1.3 Route 1 zur Synthese des Linkers H4benztpb (Benzidin-tetra-(p-phenylbenzoesäure)) 39 4.1.4 Route 2 zur Synthese des Linkers H4benztpb 40 4.1.5 Synthese des Linkers H4tpdatb (p-Terphenyldiamin-tetrabenzoesäure) 42 4.1.6 Synthese des Linkers H4BBCDC (9,9'-([1,1'-Biphenyl]-4,4'-diyl)bis(9H-carbazole-3,6-dicarbonsäure)) 44 4.1.7 Synthese der Linker H4TBBDDADC (5,5'-(3,3',5,5'-Tetramethyl-[1,1'-biphenyl]-4,4'-diyl)bis(10,11-dihydro-5H-dibenzo[b,f]azepin-2,8-dicarbonsäure)) und H4BBDDADC (5,5'-([1,1'-Biphenyl]-4,4'-diyl)bis(10,11-dihydro-5H-dibenzo[b,f]azepin-2,8-dicarbonsäure)) 45 4.1.8 Synthesen weiterer Linker und Linkervorstufen 51 4.2 MOF-Synthesen 53 4.2.1 Basierend auf H4ndtb 53 4.2.2 Basierend auf H4benztb 54 4.2.3 Basierend auf H4tpdatb 54 4.2.4 Basierend auf H4benztpb 55 4.2.5 Basierend auf H4BBCDC 56 4.2.6 Basierend auf den Azepinlinkern H2DDADC, H4TBBDDADC und H4BBDDADC 56 5 Ergebnisse und Diskussion 58 5.1 DUT-13 (Zn4O(benztb)3/2) 58 5.1.1 Charakterisierung von DUT-13cp und dem Mechanismus der Phasentransformation 58 5.1.2 Methanadsorption bei unterschiedlichen Temperaturen 60 5.2 H4tpdatb basierte MOFs DUT-180 und DUT-190 61 5.2.1 DUT-180 (Zn2(tpdatb)(H2O)2) 62 5.2.2 DUT-190 (Zn4O(tpdatb)3/2) 64 5.2.3 Metallaustausch an DUT-190(Zn) 70 5.3 H4ndtb und H4benztpb basierte MOFs (DUT-181 und DUT-191 bzw. DUT-182 und DUT-192) 76 5.3.1 DUT-181 und DUT-191 basierend auf Zink und H4ndtb 77 5.3.2 DUT-182 und DUT-192 basierend auf Zink und H4benztpb 78 5.4 Azepinlinker basierte MOFs DUT-183, DUT-184, DUT-193 und DUT-194 81 5.4.1 DUT-193 (Zn4O(TBBDDADC)3/2) 84 5.4.2 DUT-184 (Zn2(BBDDADC)(NMP)2) 87 5.4.3 DUT-194 89 5.4.4 DUT-183 (Zn4O(DDADC)3) 90 5.5 DUT-13 und DUT-49 mit gemischten Linkern 91 6 Zusammenfassung und Ausblick 97 Literaturverzeichnis 101 Anhang 106 Kristallstrukturdaten 106 Abbildungen der Analytik zum Experimentalteil 108 NMR-Spektren: 111 ATR-IR-Spektren: 131 Ergänzende Abbildungen zur Auswertung 135

No description available.

Directed assembly of molecular solids continues to attract widespread interest with its fundamental application in a wide range of commercial settings where control of the crystalline state of materials corresponds with product performance. These arenas include pharmaceuticals, personal care formulations, foods, paints and pigments and explosives. In recent times, the assembly of multicomponent organic systems has achieved considerable impetus with the widespread interest in co-crystal systems. However, cogent assembly (or engineering) of multicomponent materials is still in its infancy. Considerable advances in crystal design have been made through consideration of intermolecular ‘synthons’ – identifiable motifs utilising hydrogen bonds – but the translation of other molecular information (conformation, chirality, etc.) into solid state properties (e.g. long-range (translational) symmetry, crystal chirality) remains poorly understood. In this study, we have attempted to evaluate the influence of a chiral centre adjacent to molecular synthons to identify potential translation of information into the solid form. We have compared the co-crystallisation of nicotinamide with both the racemic mixture of malic acid against that with an enantiomerically pure form of the acid (L-malic acid). As well as DL-phenyllactic acid and L-phenyllactic acid. iii It is apparent that recognition between enantiomeric molecular forms play a significant role in the assembly of these systems. This mechanism can be considered independently from the H-bonding networks supporting the hetero-molecular interactions (e.g. acid-amide recognition). Discrimination and control of such interactions may play a role in transmitting chiral molecular information into solid state multi-component assemblies. In order to develop an understanding of co-crystal formation in chiral and achiral forms with intermolecular interactions, the CSD and crystal structures were obtained to do the analysis of how co-crystals pack. This study has also investigated the use of boronic acids. The aim of this study was to investigate the modification of the hydrogen bonding environment within the hydrogen bonded multi-component systems of boroxines. The study also attempted to determine how the starting materials drive the systems between the boronic acid co-crystal and the boroxine adduct.

Directed assembly of molecular solids continues to attract widespread interest with its fundamental application in a wide range of commercial settings where control of the crystalline state of materials corresponds with product performance. These arenas include pharmaceuticals, personal care formulations, foods, paints and pigments and explosives. In recent times, the assembly of multicomponent organic systems has achieved considerable impetus with the widespread interest in co-crystal systems. However, cogent assembly (or engineering) of multicomponent materials is still in its infancy. Considerable advances in crystal design have been made through consideration of intermolecular ‘synthons’ – identifiable motifs utilising hydrogen bonds – but the translation of other molecular information (conformation, chirality, etc.) into solid state properties (e.g. long-range (translational) symmetry, crystal chirality) remains poorly understood. In this study, we have attempted to evaluate the influence of a chiral centre adjacent to molecular synthons to identify potential translation of information into the solid form. We have compared the co-crystallisation of nicotinamide with both the racemic mixture of malic acid against that with an enantiomerically pure form of the acid (L-malic acid). As well as DL-phenyllactic acid and L-phenyllactic acid. iii It is apparent that recognition between enantiomeric molecular forms play a significant role in the assembly of these systems. This mechanism can be considered independently from the H-bonding networks supporting the hetero-molecular interactions (e.g. acid-amide recognition). Discrimination and control of such interactions may play a role in transmitting chiral molecular information into solid state multi-component assemblies. In order to develop an understanding of co-crystal formation in chiral and achiral forms with intermolecular interactions, the CSD and crystal structures were obtained to do the analysis of how co-crystals pack. This study has also investigated the use of boronic acids. The aim of this study was to investigate the modification of the hydrogen bonding environment within the hydrogen bonded multi-component systems of boroxines. The study also attempted to determine how the starting materials drive the systems between the boronic acid co-crystal and the boroxine adduct.

Catalytic combustion is a promising combustion technology for gas turbines, which results in ultra low emission levels of nitrogen oxides (NOx), carbon monoxide (CO) and unburned hydrocarbons (UHC). Due to the low temperature achieved in catalytic combustion almost no thermal NOx is formed. This thesis is concentrated on the first stage in a catalytic combustion chamber, i.e. the ignition catalyst. The catalyst used for this application is often a supported palladium based catalyst due to its excellent activity for methane combustion. However, this type of catalyst has a serious drawback; the methane conversion decreases severely with time during operation. The unstable activity will result in increasing difficulties to ignite the fuel. The parameters that govern the poor stability and other features of the palladium catalysts are discussed in the thesis. The objective of the work is to improve the catalytic performance of supported palladium catalysts, with focus on stabilising the methane conversion. A large number of different bimetallic palladium catalysts have been evaluated, where the influence of co-metals, molar ratio and support material is addressed. Results from the activity tests of methane combustion showed that it is possible to stabilise the activity by adding certain co-metals into the palladium catalyst. An extensive characterisation study has been carried out on the various bimetallic catalysts in order to gain a better understanding of how their morphology and physicochemical properties determine the various patterns of combustion behaviour. The environment inside a gas turbine combustor is very harsh for a catalyst. Since the stability of the catalyst is of great importance for ignition catalysts, it is essential to evaluate the risk of deactivation. In this work special emphasis has been given to thermal deactivation, water inhibition and sulphur poisoning. It was found that a bimetallic Pd Pt catalyst is significantly more tolerant to the various deactivation processes investigated than the monometallic palladium catalyst. Finally, the influence of pressure on the catalytic performance has been investigated. The catalysts were assessed at more realistic conditions for gas turbines, in a high-pressure test facility with 100 kW fuel power. / QC 20100916

Submitted by Alison Vanceto (alison-vanceto@hotmail.com) on 2017-02-16T16:22:40Z No. of bitstreams: 1 DissBCDO.pdf: 4309058 bytes, checksum: 4f5cf3d0dbedd0e22b67ee37cbc653e9 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-03-13T18:12:23Z (GMT) No. of bitstreams: 1 DissBCDO.pdf: 4309058 bytes, checksum: 4f5cf3d0dbedd0e22b67ee37cbc653e9 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-03-13T18:12:35Z (GMT) No. of bitstreams: 1 DissBCDO.pdf: 4309058 bytes, checksum: 4f5cf3d0dbedd0e22b67ee37cbc653e9 (MD5) / Made available in DSpace on 2017-03-13T18:20:51Z (GMT). No. of bitstreams: 1 DissBCDO.pdf: 4309058 bytes, checksum: 4f5cf3d0dbedd0e22b67ee37cbc653e9 (MD5) Previous issue date: 2015-09-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Pharmaceutical cocrystals are multicomponent crystalline solids comprised of an active pharmaceutical ingredient (API) and one or more co-formers interacting through hydrogen bonding or other weak interactions like the π-stack and van der Waals interactions. Fluconazole (FLZ) is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. It is also used to prevent and treat meningitis. Cocrystallization is an alternative approach for enhancement of drug. It can be performed using neat grinding, solvent assisted grinding, solvent evaporation, cooling evaporation and slurry cocrystallization. In this work, a new cocrystal Fluconazol-Fumaric acid monohydrate was synthesized via 1:1 stoichiometric amount of FLZ and FUM at different conditions. The characterization of the synthesized cocrystals was achieved using Raman spectroscopy, differential scanning calorimetry, powder X-ray diffraction and single crystal X-ray diffraction. The results obtained for the characterization of the samples showed some obvious differences among the spectra, diffractograms and thermograms. The single crystal X-ray diffraction analysis of the new structure shows a cocrystal where the fluconazole molecules are attached to the fumaric acid and water molecules respectively through hydrogen bonds, gave unique cell dimensions for an assumed structure C17H18F2N6O6 with a space group of P21/n, a = 17.053(3) Å, b = 5.5995(10), c=21.154(3), α = 90°, β=105.418(4)°, γ= 90°, V = 1947.3(6) Å3. This work is the first to report a monohydrate cocrystal structure of fluconazole and fumaric acid. / Cocristais farmacêuticos são sólidos cristalinos multi-componentes compostos de um ingrediente ativo farmacêutico (API) e um ou mais co-formadores interagindo através de ligações de hidrogênio ou outras interações fracas como as π-stack e Van der Waals. Fluconazol (FLZ), é um fármaco anti-fúngico triazol utilizado no tratamento e prevenção de infecções fúngicas superficiais e sistémicas. É também utilizado para prevenir e tratar a meningite. Cocristalização é uma abordagem alternativa para melhorar as propriedades de fármacos. Pode ser realizada através de moagem a seco, moagem assistida por solvente, evaporação de solvente e cristalização em suspensão. Neste trabalho, um novo co-cristal Fluconazol-Ácido Fumarico monohidrato foi sintetizado utilizando uma estequimetria 1:1 em diferentes condições. A caracterização dos co-cristais sintetizados foi realizada utilizando espectroscopia Raman, calorimetria exploratória diferencial, difração de raios-X em pó é por monocristal. Os resultados obtidos para a caracterização das amostras mostrou algumas diferenças obvias entre os espectros, difratogramas e termogramas. A difração de raios-X de monocristal mostrou uma nova estrutura onde as moléculas de fluconazol estão ligadas ao ácido fumárico e a uma molécula de água através de ligações de hidrogênio, originando uma estrutura única C17H18F2N6O6 de grupo espacial P21/n e dimensões da célula unitária a = 17.053(3) Å, b = 5.5995(10), c=21.154(3), α = 90°, β=105.418(4)°, γ= 90°, V = 1947.3(6) Å3. Este trabalho é o primeiro a relatar uma estrutura de co-cristal mono-hidrato de fluconazol e acido fumárico.

No description available.

The production of stable solid crystalline material is an important issue in the pharmaceutical industry and the challenge to control the desired active pharmaceutical ingredient (API) with the specific chemical and physical properties has led to more development in the drug industry. Increasing the solubility and the dissolution of the drug will increase its bioavailability; therefore the solubility can be improved with the change in the preparation method. The formation of co-crystals has emerged as a new alternate to the salts, hydrates and solvate methods since the molecules that cannot be formed by the usual methods might crystallise in the form of co-crystals. Co-crystals are multicomponent crystals which can be known as supramolecules and are constructed by the non covalent bonds between the desired former and co-former. Therefore the synthon approach was utilised to design co-crystals with the specific properties, this involves the understanding of the intermolecular interactions between these synthons. These interaction forces can be directed to control the crystal packing in the design of the new crystalline solid with the desired chemical and physical properties. The most familiar synthon was the amide group with its complementary carboxylic group, in this work isonicotinamide and benzoic acid were chosen to design co-crystal and much literature exist that introduce the determination of co-crystal growth from these two compounds. The growth of co-crystals was carried out in water, ethanol and ethanol / water mixed solvent (30 - 90 % ethanol) by utilising the Cryo-Compact circulator. Co-crystals (1:1) and (2:1) were grown in ethanol and water respectively and a mixture of both phases were grown in the mixed solvent. All the phases were examined by powder X-ray diffraction (PXRD), Raman, Infrared and 1H-NMR spectroscopy. The solubility of isonicotinamide, benzoic acid, co-crystals (1:1) and (2:1) in water, ethanol and ethanol/water mixed solvent (30 - 90 % ethanol) were determined at 25 °C, 35 °C and 40 °C by utilising the React-Array Microvate. It was important to understand some of the thermodynamic factors which control the formation of these polymorphs such as the change in the enthalpy and the change in the entropy. Also it was important to study the pH behaviour during dissolution of the former, co-former and co-crystals in water, ethanol and ethanol/water mixed solvent (30 - 90 % ethanol) in-order to examine the affect of the solvent composition on the solubility and to identify if some ions were formed during the dissociation and how this could affects the formation of co-crystals. A discussion has been introduced in this research of how similar solubility of the compounds maps the formation of the typical ternary phase diagram of the mixture of 1:1 while compounds with different solubility maps the formation of skewed phase diagram as shown in section 1.6.2.3. In this project an isotherm ternary phase diagram at 20 °C and 40 °C was constructed to map the behaviour of benzoic acid and isonicotinamide and to show all possible phases formed and the regions where all phases are represented in the ternary phase diagram were determined by the slurry method. The ternary phase diagram was used to design a drawn out and cooling crystallisation at 100 cm3 solution of 50 % ethanol / water mixed solvent and a study of the impact of seeds of co-crystals 1:1 on the cooling crystallisation method.

<p>  </p> <p>A multidisciplinary study that evaluated Quality Control (QC) laboratory (lab) accreditation, and a salt screen for bedaquiline. Medicines testing facilities always seek to ensure the accuracy of data from their QC labs by attaining accreditation. This research proposed that an understanding of the cross-linkages in the requirements for implementing the 2 most widely used lab standards will facilitate testing efficiencies, and reduce the risks of accreditation failures. For the salt project, the study proposed that new salts of bedaquiline will be formed from acid-base reactions following the pKa rule. Characterizing the salts will provide specifications for the new molecular entities, and form a selection-criteria for a lead candidate.</p> <p>The research reviewed 2 lab standards: the ISO/IEC17025:2017 and the WHO Good Practices for Pharmaceutical QC labs, and identified the areas of overlap in their requirements. It then developed and tested affordable models that mitigate the 3 identified areas of high risks to lab accreditation. Additionally, it mixed<em> equimolar amounts of bedaquiline base with select counterions that have ≥ 2 pKa units in organic solvents, to yield salts</em>. ICHQ6 guidance was used to characterize the new salts.</p> <p>The highest risks to laboratory accreditation were linked to 3 quality system metrics, namely: ‘Proficiency Testing’, ‘Validation’, and ‘Measurement Traceability’. Using the identified areas of overlap in the 2 laboratory standards, this research provided tutorial videos, a competency matrix, and some instrument validation data, to optimize the requirements for lab accreditation. For the salt screen, five new candidates were synthesized as alternatives to the existing fumarate salt of bedaquiline. The results of their physicochemical properties were used for selecting a lead moiety.</p> <p>The research provided evidence that the multipronged models developed will improve efficiencies in QC labs, and increase their chances of attaining international accreditations. It also discovered the best modes for synthesizing the new salts of bedaquiline, and provided critical data to help Pharma make an informed choice for a lead candidate.</p>