DQ_PhD http://hdl.handle.net/10362/1049 2013-05-22T05:57:00Z 2013-05-22T05:57:00Z Duarte, Filipe José Santos http://hdl.handle.net/10362/9420 2013-04-30T11:02:18Z 2009-01-01T00:00:00Z

Title: Organocatálise assimétrica: estudo mecanístico de reacções intramoleculares de aldol Authors: Duarte, Filipe José Santos Abstract: Reacções assimétricas, catalisadas por organocatalisadores quirais, têm sido alvo de intensos estudos durante os últimos anos, em virtude da crescente necessidade de obtenção de compostos enantiomericamente puros, com potencial actividade farmacológica. A busca incessante de melhores rendimentos químicos e de maior controlo régio- e estéreo-selectivo das reacções orgânicas assimétricas, tem motivado, igualmente, uma enorme procura de novos organocatalisadores. Estes são, na sua maioria, aminoácidos ou seus derivados, estando a sua performance associada à formação de intermediários do tipo imina ou enamina. Associadas à vertente experimental, têm surgido diversas propostas de mecanismos reaccionais, com o objectivo de racionalizar os inúmeros resultados empíricos obtidos, de modo a prever a estereoquímica dos processos, bem como propor novos catalisadores com performance melhorada. No âmbito desta tese realizaram-se diversos estudos experimentais e teóricos, com vista ao estudo mecanístico de reacções intramoleculares assimétricas de aldol e de Baylis-Hillman, assistidas por organocatalisadores quirais. Dentro das reacções intramoleculares de aldol, foram analisadas as reacções de 1,6- e 1,7-dialdeídos, enquanto que na reacção de Baylis-Hillman foi testado apenas o hepta-2-enedial. O trabalho desenvolvido no âmbito das reacções de aldol, pode ser dividido em três fases distintas: • Antes do estudo da reacção na sua vertente assimétrica, e com o objectivo de testar a detecção e caracterização dos diversos intermediários possíveis na coordenada reaccional, efectuou-se uma análise detalhada da reacção intramolecular de aldol do mesodimetil- 2,3-bis(2 oxoetil)-succinato, catalisada por aminas aquirais (pirrolidina e isopropilamina), através da técnica espectroscópica de ressonância magnética nuclear(RMN). Foi possível detectar e caracterizar alguns dos intermediários reaccionais, o que permitiu, de seguida, efectuar estudos dirigidos de modelação molecular, com base nos resultados experimentais obtidos. Os estudos teóricos efectuados, em conjunto com os dados obtidos por RMN, permitiram a formulação de um perfil energético para a reacção do meso-dimetil-2,3-bis(2-oxoetil)-succinato catalisada por pirrolidina com a identificação clara do passo limitante da reacção. • Na segunda fase, efectuou-se um estudo teórico com vista à racionalização do efeito da estrutura de diferentes catalisadores quirais (L-prolina (2S,4R)-(+)-trans-4-hidroxiprolina e ácido (S)-indolina-2-carboxílico) na enantiosselectividade da reacção intramolecular de aldol do 2,2’-((3S,4R)-1-benzil-2,5-dioxopirrolidine 3,4-diil)-diacetaldeído. • Na terceira fase, e com base nos resultados obtidos nas duas fases anteriores, desenvolveu-se um estudo de modelação molecular sobre as reacções de uma família alargada de 1,7-dialdeídos, usando como catalisador a L-prolina, visando compreender o efeito da estrutura do dialdeído na selectividade da reacção. Foram calculadas todas as possíveis estruturas de transição associadas aos passos determinantes da velocidade da reacção que, segundo os nossos resultados, poderão ser o passo de formação do ião imónio inicial (passo de condensação do catalisador com o dialdeído) ou o passo de ciclização, de modo semelhante aos resultados obtidos para os estudos com 1,6-dialdeídos. Foram consideradas duas vias reaccionais (condições anidras e inclusão de água no meio reaccional), o que permitiu sugerir que a água não deverá estar presente no processo de ciclização. Esta fase do trabalho permitiu a racionalização de parte significativa dos dados experimentais conhecidos. Description: Dissertação apresentada para obtenção do Grau de Doutor em Química, especialidade de Química Orgânica, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

2009-01-01T00:00:00Z Ferreira, Ana Raquel Santos http://hdl.handle.net/10362/9369 2013-04-23T10:06:10Z 2012-01-01T00:00:00Z

Title: A systems biology framework for pathway level culture media engineering: pplication to Pichia pastoris cultures Authors: Ferreira, Ana Raquel Santos Abstract: Culture media (CM) formulations contain hundreds of ingredients in aqueous solutions that may be involved in complex interactions in the same or competing pathways within the cell. This thesis proposes a new methodology for determining the optimal composition of CM that migrates from an empirical to a mechanistic or hybrid mechanistic CM development approach. A framework consisting in the execution of an array of cell cultures, endpoint exometabolomic assays and bioinformatics algorithm were brought together into a platform for CM engineering called Cell Functional Enviromics. This technology consists of a largescale reverse engineering approach that reconstructs cellular function on the basis of measured dynamic exometabolome data. To support this concept, a computational algorithm, called “envirome-guided Projection to Latent Pathways”, was developed. This method yields envirome-wide Functional Enviromics Maps (FEM), with rows representing medium factors, columns representing elementary (orthogonal) cellular functions and color intensity values, the strength of up-/down- regulation of cellular functions by medium factors. This method was applied to optimize Pichia Trace Metal salts for the yeast Pichia pastoris to improve the expression of heterologous proteins. An array of shake flasks experiments of the P. pastoris X33 strain were performed and used to build a FEM. Then, optimized CM formulations were calculated targeting predefined single-chain Fragment variable antibody (scFv) production improvements. Experimental validation shows a scFv productivity increase of approximately twofold, in relation to the control BSM recipe proposed by Invitrogen. These results were further validated in 2 L bioreactor experiments. Thereafter, scale-up to 50 L bioreactors was developed a mathematical model for further optimization of BSM salts in experiments of P. pastoris GS115. Direct adaptive (DO)-stat feeding controller that maximizes glycerol feeding through the regulation of DO concentration at 5% of saturation was developed and applied to the 50 L bioreactor, with the fully optimized CM composition. Description: Dissertação para obtenção do Grau de Doutor em Engenharia Química e Bioquímica

2012-01-01T00:00:00Z Gomes, Pedro Miguel Vidinha http://hdl.handle.net/10362/9364 2013-04-19T11:08:25Z 2007-01-01T00:00:00Z

Title: Strategies for the enhancement of the catalytic performance of cutinase in nonaqueous media Authors: Gomes, Pedro Miguel Vidinha Description: Dissertação para obtenção do Grau de Doutor em Engenharia Química e Bioquímica

2007-01-01T00:00:00Z Costa, Cláudia Brito da http://hdl.handle.net/10362/9317 2013-04-15T10:28:33Z 2013-01-01T00:00:00Z

Title: Printed electronics for ubiquitous computing applications Authors: Costa, Cláudia Brito da Abstract: This Ph.D. project is focused on the synthesis of functional inorganic materials, their formulation into inks and their deposition using inkjet printing on non-conventional substrates, such as paper, with the ultimate goal of advancing the state-of-the-art in the area of printed electrochromic displays. Other materials, inks,techniques and substrates were also explored. The first step in building a printed electrochromic display is to synthesize the functional materials necessary for the different layers of the device; this part of the work focused on inorganic electrochromic materials (tungsten oxide and vanadium oxide) and on transparent conductive oxides (TCO). ATO(antimony tin oxide) was synthesized using the Pechini method and the results obtained were promising. Tungsten oxide and vanadium oxide nanoparticles were also synthesized via a sol-gel route. FTIR,Raman and X-ray diffraction spectroscopic measurements showed that tungsten oxide nanoparticles synthesized via sol-gel are mainly in an amorphous state, with hexagonal crystalline domains, and allowed the analysis of the hydration extent of those nanoparticles. Vanadium oxide gel synthesized in this work is similar to those previously described in the literature, consisting of V2O5.6H2O, with microstructures similar to orthorhombic V2O5, while Raman spectroscopy also showed the presence of amorphous domains. The nanoparticle sizes were measured combining Dynamic Light Scattering, sedimentation and microscopic techniques (AFM and TEM). Tungsten oxide particles presented an average nanoparticle size between 160 and 200 nm, and vanadium oxide of 60 nm. The nanoparticles were used to produce ink formulations for application in inkjet printing. In addition to tungsten oxide and vanadium oxide, other electrochromic materials were printed. This part of the work examined the possibility of inkjet printing several organic (poly(thiophene)s) and inorganic electrochromic materials (metal oxides and metal hexacyanometallates) and also evaluated the performance of the resulting electrochromic devices. Poly(3,4-ethylenedioxythiophene)poly(styrenesulfonate), poly(3-hexylthiophene), tungsten oxide, vanadium oxide and Prussian blue were inkjet printed on flexible substrates, such as plastic and paper. Solid-state electrochromic devices were assembled at room temperature on plastic and on paper substrates, without sintering the printed films, showing, in some cases, excellent contrast between the on and off state. The tungsten oxide and vanadium oxide devices were then tested through spectroelectrochemistry by Visible/NIR absorption spectroscopy. Tungsten oxide showed a dual spectroscopic response depending on the applied voltage and vanadium oxide presented several redox steps, which give rise to a variety of color transitions, also as a function of the applied voltage. Color space analysis was used to characterize the electrochromic transitions; monitorization of the color contrast and cycling tests, as well as techniques such as cyclic voltammetry, were also used to characterize device performance. Description: Dissertação para obtenção do Grau de Doutor em Química

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