[Truncated abstract] Chapter 1 provides an introduction to the 'sarcophagine' class of ligands and the field of metallopolymers. The synthesis, stereochemistry, physical properties and functionalisation of 'sarcophagines' and their metal complexes are discussed. A brief overview of the burgeoning field of metallopolymers is given with specific mention of the synthetic routes to pendant metallopolymers, and how these could be employed to prepared cage amine containing metallopolymers. Chapter 2 deals with the synthesis, characterisation and reactivity of cinnamylamino and styrylamido derivatives of the cage amines [Co((NH2)2sar)]3+, [Co((CH3)(NH2)sar)]3+ and [Cu((NH2)2sar)]2+. The cinnamylamino derivatives were prepared using reductive alkylation of the aforementioned amines with cinnamaldehyde. Procedures were developed to isolate the complexes without causing unwanted additions to the double bond. The cinnamylamino derivatives displayed unexpected reactivity towards a range of reducing agents, resulting in unexpected reduction of the double bond and cleavage of the cinnamyl group, but ultimately in the preparation of phenylpropylamino derivatives of [Co((NH2)2sar)]3+ and [Co((CH3)(NH2)sar)]3+. Attempts to rationalise the reactivity of the double bond have been explored based upon the physical properties and reactivity of the double bond. The styrylamido derivatives were prepared by treatment of the cage amines with 4-vinylbenzoyl chloride, and the complexes isolated in a similar manner to those of the cinnamylamino derivatives to ensure the amide linkage remained intact. Most of the complexes have been structurally characterised. ... Both the 2-thienyl and 3-thienyl derivatives of [Co((NH2)2sar)]3+ and [Co((CH3)(NH2)sar)]3+ have been prepared using reductive alkylation with the respective carboxaldehydes of thiophene. One of the optically pure isomers has been prepared. The complexes have been fully characterised including structural characterisation. Polymerisation of the thiophene-cage amine complexes was investigated under a range of chemical and electrochemical conditions, though polymerisation was never observed. Cleavage of the thienyl groups was observed when ceric ammonium nitrate in nitric acid was used as the oxidant. The attachment of oligothiophenes and mixed pyrrole-thiophene oligomers to cage amines were investigated using reductive alkylation and various pyrrole ring-forming reactions about the apical amino groups, though none of the desired complexes were isolated, reasons for the lack of reactivity were discussed. An efficient synthesis of N-(4-benzoic acid)- 2,5-di(2-thienyl)pyrrole was developed and was shown to the electropolymerisable, albeit the polymer films were non-conducting. Attempts to couple N-(4-benzoic acid)- 2,5-di(2-thienyl)pyrrole with a cage amine via its acid chloride were complicated by decomposition reactions, the nature of one of these products is discussed. Chapter 5 presents investigations into the preparation of simple complexes containing multiple cage amines using alkylation and acylation procedures with aromatic substrates. The complexes were found to exhibit some interesting electrochemical and chemical properties, demonstrating that even simple multiple cage amine species can display complicated and interesting behaviour.

Ziel dieser Arbeit ist die retrospektive Auswertung der operativ mit ventraler Dekompression und intersomatischer Fusion (ACDF) durch stand alone Cage versorgten Patienten und die Diskussion, ob eine postoperative Sinterung Einfluss auf das Outcome hat. Material und Methoden: Es wurden 33 Segmente operativ durch ACDF mit standalone-Cage bei 17 Patienten (11 Frauen und 6 Männer) Durchschnittsalter 56 Jahre (33 bis 82 Jahre) versorgt und nach durchschnittlich jeweils 8 und 26 Monaten klinisch, radiologisch und durch Scoreerhebung nachuntersucht. Ergebnisse: 70,6 % der Patienten (12/17) und 50,5% der Segmente (18/33) zeigten eine Sinterung. 36,3% der Sinterungen (12/33) bereits zur 1. NU nach 8 Monaten. Zur 2. NU nach 26 Monaten fand sich bei 100% eine Fusion ohne Pseudarthrose. Zusammenfassung: Die Sinterung des Cages hat keinen negativen Einfluss auf das Outcome. Wesentlich für das Outcome sind das Ausmaß und die Dauer der vorbestehenden Symptome. Es sollte besonders bei festgestellter Myelopathie frühzeitig eine operative Intervention erfolgen.

In this study a number of cage alkenes were synthesised and tested for activity towards ringopening metathesis polymerisation (ROMP) with the commercially available catalysts 55 (Grubbs-I) and 56 (Grubbs-II). The first group of monomers are derivatives of tetracyclo[6.3.0.04,1105,9]undec-2-en-6-one (1). The synthesis of these cage alkenes are summarised in Scheme 7.1. The cage alkene 126b was synthesised by a Diels-Alder reaction between 1 and hexachlorocyclopentadiene (9, Scheme 7.2). The geometry of 126b was determined from XRD data. Knowledge of the geometry of 126b also established the geometry of 127 since conformational changes during the conversion from 126b to 127 are unlikely. Synthesis of the cage alkene 125 by the cycloaddition of 9 to 118 failed. The cage alkene exo-11- hydroxy-4,5,6,7,16,16-hexachlorohexacyclo[7.6.1.03,8.02,13.010,14]hexa-dec-5-ene (124, Scheme 7.3) could therefore not be prepared. Synthesis of 125 by reduction of 126b with various reduction systems was not successful. Theoretical aspects of these reactions were investigated with molecular modelling. A possible explanation for the unreactive nature of 126b towards reduction is presented, but the lack of reactivity of 118 towards 9 eluded clear explanations. The synthesis of cage alkenes from 4-isopropylidenepentacyclo[5.4.0.02,6.03,10.05,9]-undecane-8,11- dione (23) did not meet with much success (Scheme 7.4). Numerous synthetic methods were investigated to affect the transformation from 134a/134b to 135 (Scheme 7.5). These attempts evolved into theoretical investigations to uncover the reasons for the observed reactivity. Possible explanations were established by considering the differences and similarities between the geometries and electronic structures of reactive and unreactive cage alcohols. ROMP of cage monomers based on 1 were mostly unsuccessful. Only the cage monomer 127 showed some reactivity. Endocyclic cage monomers with a tetracycloundecane (TCU) framework showed no reactivity. The results from NMR experiments verified the experimental results. Hexacyclo[8.4.0.02,9.03,13.04,7.04,12]tetradec-5-en-11,14-dione (3) exhibited notable ROMP reactivity. Examination of the orbitals of the cage alkenes used in this study suggested that the reactivity of 1 and 3 could possibly be enhanced by removal of the carbonyl groups. Decarbonylation of 1 and 3 yielded the cage hydrocarbons 159 and 175, respectively. ROMP tests revealed that 175 is an excellent monomer, but 159 was unreactive. The results obtained for the ROMP reactions in this study was rationalised by considering aspects such as ring strain, energy profiles, steric constraints, and frontier orbital theory. The concept of ring strain is less useful when describing the reactivity of cage alkenes towards ROMP and therefore the concepts of fractional ring strain and fractional ring strain energy (RSEf) were developed. A possible link between RSEf and the ROMP reactivity of cage alkenes was also established. The following criteria were put forth to predict the reactivity or explain the lack of reactivity of cage alkenes towards ROMP reactions with Grubbs-I and Grubbs-II. The criteria for ROMP of cage monomers: 1. Sufficient fractional ring strain energy (RSEf). 2. A reasonable energy profile when compared to a reference compound such as cyclopentene. 3. Ability to form a metallacyclobutane intermediate with reasonable distances between different parts of the cage fragment. 4. Sufficient ability of the polymer fragment to take on a conformation that exposes the catalytic site. 5. Sufficient size, shape, orientation and energy of HOMO and/or NHOMO at the alkene functionality of the cage monomer and of the LUMO at the catalytic site. / Thesis (Ph.D. (Chemistry))--North-West University, Potchefstroom Campus, 2012

Dissertation: Hamburg University, 2008 / Includes bibliographical references.

Dissertation: Hamburg University, 2008 / Includes bibliographical references.

Made available in DSpace on 2016-12-23T14:41:51Z (GMT). No. of bitstreams: 1 Layla Rosario Barbosa - Parte 1.pdf: 8944574 bytes, checksum: b07d86b3bd865ddac9f267f552fe554f (MD5) Previous issue date: 2013-02-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Neste trabalho foram estudados quatro compostos rígidos policíclicos (cage-like) obtidos a partir de um aduto de Diels-Alder proveniente da reação entre a para-benzoquinona e o ciclopentadieno. Analisou-se os espectros de RMN desses compostos através de técnicas unidimensionais (RMN de 1H, RMN de 13C, DEPT-135) e bidimensionais (COSY, HMBC, HSQC e NOESY). Os dados experimentais obtidos a partir da atribuição dos valores de deslocamento químico de RMN de 1H e RMN de 13C e de acoplamento spin-spin (J) foram confrontados com dados teóricos obtidos por meio de cálculos computacionais, os quais foram analisados os valores de desvio médio (MD), desvio padrão (SD) e coeficiente de correlação linear (R) para os adutos endo e exo de cada composto. Estudos sistemáticos foram realizados a fim de avaliar a eficiência do efeito do solvente na etapa de otimização (comparando-se duas Rotinas de cálculo diferentes) e de avaliar qual método GIAO ou CSGT apresentava melhor correlação com os dados experimentais. Além disso foi avaliado, se o modelo B3LYP/cc-pVTZ apresentava bons resultados no cálculo de tensores de blindagem (σ) e constantes de acoplamento spin-spin (J). Em todos os estudos os valores de desvio médio, desvio padrão e coeficiente de correlação linear foram melhores para o aduto endo frente ao aduto exo. Grandes diferenças foram observadas nos valores de RMN de 1H do composto 15. Nesse caso, o valor de desvio médio do aduto exo foi cerca de 9 vezes maior que o valor de desvio médio do auto endo. Da mesma forma, o valor de desvio padrão foi cerca de 6 vezes maior para o aduto exo quando comparado ao aduto endo. A partir da correlação entre os dados teóricos e experimentais foi possível fazer uma atribuição inequívoca dos sinais de RMN dos cinco compostos de estudo. Também conclui-se que o modelo utilizado (B3LYP/cc-pVTZ) foi eficiente no cálculo de tensores de blindagem e constante de acoplamento e que os compostos analisados correspondem ao aduto endo. Ao se analisar a eficiência do solvente na etapa de otimização (comparação entre as Rotinas 1 e 2), concluiu-se que a Rotina 2 (que desconsidera o efeito do solvente) se mostrou eficaz em descrever os deslocamentos químicos de RMN de 13C e de RMN de 1H e as constantes de acoplamento JH,H, associada a um menor custo computacional. Comparando-se os dois métodos de cálculo de propriedades de RMN GIAO e CSGT, pode-se concluir que o método CSGT foi eficaz em descrever os deslocamentos químicos de RMN de 13C e de RMN de 1H, associado a um melhor custo benefício / This study analyzed four cage-like rigid polycyclic compounds obtained from a Diels-Alder adduct deriving from the reaction between para-benzoquinone and cyclopentadiene. The NMR spectra of these compounds were analyzed employing unidimensional techniques (1H NMR, 13C NMR, DEPT-135) and bidimensional (COSY, HMBC, HSQC and NOESY). The experimental data obtained from the attribution of chemical displacement values of 1H NMR and 13C NMR and spin-spin coupling (J) were compared with theoretical data obtained through computational calculations, which analyzed the standard mean deviation (MD), standard deviation (SD) and linear correlation coefficient (R) for the endo and exo adducts of each compound. Systematic studies were carried out in order to validate de efficiency of the solvent effect during the optimization stage (comparing two different calculation routines) and to evaluate which method GIAO or CSGT showed better correlation with the experimental data. Also, the study evaluated if model B3LYP/cc-pVTZ showed good results during the shielding tensor (σ) calculation and spin-spin coupling (J) constant calculation. In all the experiments, the mean deviation, standard deviation, and linear correlation coefficient values were better for the endo adduct compared to the exo adduct. Large differences were observed for the 1H NMR values of compound 15. In this case, the mean deviation value of exo adduct was about 9 times bigger than the mean deviation of the endo adduct. Likewise, the standard deviation value was 6 times bigger for the exo adduct compared to endo. Based on the correlation between theoretical and experimental data, it was possible to unmistakably attribute the NMR signals of the study compounds. We can also conclude that the model used (B3LYP/cc-pVTZ) was efficient to calculate the shielding tensors and coupling constant, and that the compounds analyzed correspond to the endo adduct. When analyzing the solvent efficiency during the optimization stage (comparing Routines 1 and 2), we concluded that Routine 2 (which disregards solvent effect) showed to be effective to describe the chemical displacements of 13C NMR and 1H NMR and the coupling constants JH,H, which are associated to lower computational costs. If both methods for NMR property calculation are compared, we can conclude that CSGT was effective to describe the chemical displacements of 13C NMR and 1H NMR, which are associated to higher cost-effectiveness

The synthesis of a novel, cage spiro-oxetane was carried out. Pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9]undecane-8- one (PCUD-8-one) undergoes one-carbon homologation to a mixture of endo- and exo- PCUD-carboxaldehydes which then are converted into 8,8-bis(hydroxymethyl)PCUD. The monotosylate obtained via reaction of 8,8- bis(hydroxymethyl)PCUD with tosyl chloride(1 equivalent) reacts with sodium hydride to afford the corresponding spiro-oxetane via intramolecular Williamson reaction. Six new substituted heptacyclo[6.6.0.0^2,6.0^3,13.0^4,11. 0^5,9.0^10,14]tetradecanes (HCTD) were synthesized. These compounds will be used as substrates in a photoelectron spectroscopic study. The ring-expansion reaction of PCUD-8-one with ethyl diazoacetate in the presence of BF_3:OEt_2 was performed. The major product was converted into an alcohol, and the structure of the 3,5-dinitrobenzoate of this alcohol was elucidated by single crystal x-ray structural analysis.

Ziel dieser Arbeit ist die retrospektive Auswertung der operativ mit ventraler Dekompression und intersomatischer Fusion (ACDF) durch stand alone Cage versorgten Patienten und die Diskussion, ob eine postoperative Sinterung Einfluss auf das Outcome hat. Material und Methoden: Es wurden 33 Segmente operativ durch ACDF mit standalone-Cage bei 17 Patienten (11 Frauen und 6 Männer) Durchschnittsalter 56 Jahre (33 bis 82 Jahre) versorgt und nach durchschnittlich jeweils 8 und 26 Monaten klinisch, radiologisch und durch Scoreerhebung nachuntersucht. Ergebnisse: 70,6 % der Patienten (12/17) und 50,5% der Segmente (18/33) zeigten eine Sinterung. 36,3% der Sinterungen (12/33) bereits zur 1. NU nach 8 Monaten. Zur 2. NU nach 26 Monaten fand sich bei 100% eine Fusion ohne Pseudarthrose. Zusammenfassung: Die Sinterung des Cages hat keinen negativen Einfluss auf das Outcome. Wesentlich für das Outcome sind das Ausmaß und die Dauer der vorbestehenden Symptome. Es sollte besonders bei festgestellter Myelopathie frühzeitig eine operative Intervention erfolgen.:1. Einleitung 1 2. Zielsetzung 4 3. Grundlagen 5 3.1. Pathophysiologie 5 3.2. Symptome 8 3.2.1. Allgemeine Symptome 8 3.2.2. Radikulopathie 9 3.2.3. Myelopathie 10 3.3. Diagnostik 13 3.3.1. Anamnese und klinische Untersuchung 14 3.3.2. Bildgebende Diagnostik 15 3.3.3. Spezielle Zusatzdiagnostik 16 3.3.4 Differenzialdiagnosen 17 3.4. Therapie 18 3.4.1. Konservative Therapie 18 3.4.2. Operative Therapie 19 4. Material und Methoden 28 4.1. Patientenkollektiv 28 4.2. Vor - und Nachuntersuchung 30 4.2.1. Oswestry Neck Disability Index 31 4.2.2. Pain DETECT - Fragebogen 33 4.2.3. Die gesundheitsbezogene Lebensqualität – MOS SF – 36 33 4.2.4. Visuelle Analogskala (VAS) 34 4.3. Cagesystem und Implantatmaterial 35 4.4. Operationsverfahren 37 4.5. Radiologische Messungen 42 4.6. Statistische Auswertung 43 5. Ergebnisse 44 5.1. Ergebnisse des Gesamtkollektives 45 5.1.1. Auswertung Schmerzen 45 5.1.2. Auswertung Alltagsbeeinträchtigung 46 5.1.3. Auswertung der gesundheitsbezogenen Lebensqualität 47 5.2. Ergebnisse nach Geschlecht 48 5.3. Ergebnisse nach Alter 52 5.4. Ergebnisse des Sinterungsverhaltens 56 5.4.1. Schmerzen abhängig vom Sinterungsverhalten 59 5.4.2. Alltagsbeeinträchtigung abhängig vom Sinterungsverhalten 61 5.4.3. Lebensqualität nach MOS- SF 36 abhängig vom Sinterungsverhalten 61 5.5. Komplikationen 62 6. Diskussion 64 7. Zusammenfassung 79 8. Literaturverzeichnis 83 9. Tabellenverzeichnis 107 10. Abbildungsverzeichnis 108 11. Erklärung über die eigenständige Abfassung der Arbeit 111 12. Lebenslauf und wissenschaftlicher Werdegang 112 13. Danksagung 114 14. Anlagen 115 Anlage 1 - Oswestry Neck Disability Index Fragebogen 115 Anlage 2 - Pain Detect Fragebogen 117 Anlage 3 - MOS SF 36 Fragebogen 119

<p dir="ltr">Methods of protein engineering and mutation to achieve selective and designed enzymatic function are often challenged by issues with foldamer stability. Molecular nanocages present an exciting new opportunity for biomimetic-defined cavities capable of biomolecule recognition and catalysis. While many different types of molecular cages exist, covalent organic molecular cages offer great flexibility and control over the design of the cage. Furthermore, the covalent linkages provide a robust framework resistant to degradation and stable in many chemical environments. Lastly, covalent organic cages may be designed for the precise placement of functional groups, including group placement inside the cage cavity for molecular recognition and binding. I report our recent advances in developing new synthetic methods for robust organic molecular cages with well-defined cavities and tunable functions for artificial enzyme catalysis and recognition. The basic design philosophy for such protein-mimetic structures will be introduced for the scalable synthesis of these macromolecules. Herein, we report two approaches to a [8+12] triazine-linked organic cage and a similar [8+12] triazine and boroxine-linked cage. While our first approach attempts a kinetically controlled tethered cage formation, our second method relies on the principles of dynamic covalent chemistry in the thermodynamically controlled self-assembly of the final cage structure.</p>

Inovação em produção animal tem sido cada vez mais exigido pelos consumidores. No ambito de produção de postura, a maior demanda é por ovos provenientes de sistemas alternativos às gaiolas tradicionais, majoritariamente pelas tendencias observadas na Europa, e dessa forma, pesquisas ressaltando a realidade brasileira estão sendo realizadas. O objetivo deste estudo foi avaliar parametros produtivos e de bem-estar em dois contextos de sistemas produtivos, sob variadas densidades de alojamento. Para isso 250 aves Lohmann Brown&reg; foram distribuídas em delineamento inteiramente casualizado (DIC) com os tratamentos organizados em esquema fatorial 2 x 4, sendo 2 sistemas de alojamento (convencional e cage-free) e 4 densidades (375,00; 450,00; 562,50 e 750,00 cm2/ave), com 6 repetições. O período experimental foi de 21 a 36 semanas de idade das poedeiras, totalizando 4 ciclos de 28 dias cada. Foram avaliados desempenho produtivo (produção de ovos, consumo de ração, conversão alimentar por kg de ovos), qualidade de ovos (peso, coloração de gema, índice gema, % de gema, % albumen, % casca, espessura e resistência a quebra, e unidade Haugh) e indicadores de bem-estar (frequência respiratória e cardíaca, temperatura clocal, escore de lesão corporal, concentração d eIgY na gema) Observou-se interação entre sistema de produção e densidade de alojamento para: % postura, consumo de ração, conversão alimentar por kg de ovos, peso do ovo, % de gema, % albúmen, espessura de casca. O aumento de densidade promoveu efeito significativo para % postura, consumo de ração, temperatura cloacal, lesão em quilha e em pés. O tipo de sistema de produção afetou consumo de ração, conversão alimentar por kg de ovos, peso do ovo, coloração de gema, índice gema, resistência à quebra, frequência cardíaca temperatura cloacal, lesões de quilha e pés e concentração de IgY na gema. Os resultados deste estudo demonstram que tanto o sistema de produção quanto a densidade de alojamento estão ligados a efeitos produtivos, de qualidade de ovos, e de bem-estar animal. / Innovation in animal production has been increasingly demanded by consumers. In the field of egg production, the greatest demand is for eggs coming from alternative systems to traditional cages, mostly from the trends observed in Europe, and thus, research highlighting the Brazilian reality is being carried out. The objective of this study was to evaluate productive and welfare parameters in two contexts of productive systems, under different stocking densities. For this purpose, 250 Lohmann Brown&reg; birds were distributed in a completely randomized design with treatments arranged in a 2 x 4 factorial scheme, with 2 housing systems (conventional and cage-free) and 4 densities (375.00; 450.00, 562.50 and 750.00 cm2 / bird), with 6 replicates. The experimental period was 21 to 36 weeks of age, totalling 4 cycles of 28 days each. (Egg weight, feed intake, feed conversion per kg of egg), egg quality (weight, yolk color, yolk index, % yolk,% albumen,% shell, shell thickness and resistance to breakage, and Haugh unit) and indicators of welfare (respiratory rate and heart rate, body temperature, body lesion score, IgY concentration in the yolk). The interaction between production system and housing density was observed for: % laying, feed intake , feed conversion per kg of eggs, egg weight, % yolk, % albumen, shell thickness. The increase in density had a significant effect on % laying, feed intake, cloacal temperature, keel and foot injury. The type of production system affected feed intake, feed conversion per kg of egg, egg weight, yolk color, yolk index, breaking strength, cloacal temperature, keel and foot lesions, and IgY concentration in the yolk. The results of this study demonstrate that both the production system and housing density are linked to productive effects, egg quality, and animal welfare.