Made available in DSpace on 2016-06-02T19:19:54Z (GMT). No. of bitstreams: 1 DANTAS_Patricia_2011.pdf: 2256820 bytes, checksum: e36b1fbb6b7a53c4ba196910208d1dd3 (MD5) Previous issue date: 2011-12-16 / Financiadora de Estudos e Projetos / Hydrogels derived from cellulose acetate propionate (CAP) and cellulose acetate (CA) were synthesized with the cross-linking agents PMDA (Pyromellitic Dianhydride) and BTDA (Dianhydride 3, 3 ', 4, 4' Benzophenone Tetracarboxylated) with 3:1 stoichiometry in relation to the mass of the crosslinker agent x mass of available hydroxyls in the polymer chain. The gels were obtained in the form of films and particles, the raw materials were characterized with Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Spectroscopy in Region of Fourier Transform Infrared (FTIR) and in relation to the degree of substitution (GS). The gels synthesized were characterized using FTIR techniques in order to show the esterification, TGA and DSC to perform comparative analysis and study of thermal properties between the CAP and CA reagents and gels, and Scanning Electron Microscopy (SEM) were used for observation of the gels synthesized and the geometry of the particles obtained, the porosity of observation and observation of surface changes, was performed to determine the crosslinking density of the second theory of Flory Rehner, study the density of the gels, and degree of swelling of the study best solvent for swelling of the gels. Gels derived from CAP were tested in the adsorption studies and controlled release of the herbicide paraquat. For the phenomenon of controlled release, we studied the phenomena of transport and release curves. The release profiles were studied by using the mathematical model published by Korsmeyer-Peppas and the mainly results has showed that model was appropriated for process data analysis of controlled release in long periods. / Hidrogéis derivados de Propionato Acetato de Celulose (CAP) e Acetato de Celulose (CA) foram sintetizados com os agentes reticuladores PMDA (Dianidrido Piromelítico) e BTDA (Dianidrido 3, 3´, 4, 4´ Benzofenona Tetracarboxílico), com estequiometrias 3:1 em relação à massa do agente reticulador x massa de hidroxilas disponíveis na cadeia polimérica, com obtenção de géis em formato de filmes e particulados; as matérias-primas foram caracterizadas com Análise Termogravimétrica (TGA), Calorimetria Diferencial de Varredura (DSC), Espectroscopia na Região do Infravermelho com Transformada de Fourier (FTIR) e em relação ao Grau de Substituição (GS). Os géis sintetizados foram caracterizados utilizando as técnicas de FTIR, para evidenciação da esterificação; TGA e DSC para realização de análise comparativa e estudo das propriedades térmicas entre os reagentes CAP e CA e os géis obtidos; e Microscopia Eletrônica de Varredura (MEV), utilizada para observação dos géis sintetizados em relação à geometria das partículas obtidas, observação da porosidade e observação de alterações superficiais; foi realizada a determinação da densidade de ligações cruzadas segundo a Teoria de Flory Rehner; estudo da densidade dos géis, que variaram de 0,4 a 1,51 g/cm3; grau de inchamento que obteve variações entre os diferentes géis de 6,53 à 11,8; e o estudo do melhor solvente para intumescimento dos géis. Nos géis derivados de CAP, foram realizados ensaios de adsorção e liberação controlada do herbicida Paraquat. Para o fenômeno de liberação controlada, foram estudados os fenômenos de transporte e as curvas de liberação; os perfis de liberação foram estudados pelo modelo matemático de Korsmeyer-Peppas; e apresentaram como o gel com maior porcentagem de adsorção e melhor potencial para liberação controlada por longos períodos o gel CAP 3B1.

Orientador: Marcelo de Almeida Silva / Coorientador : Giuseppina Pace Pereira Lima / Banca: Carlos Alexandre Costa Crusciol / Banca: João Domingos Rodrigues / Banca: Laurício Endres / Banca: Gustavo Maia Souza / Resumo: A cana-de-açúcar é uma cultura de grande importância econômica no mundo. No Brasil, sua expansão tem sido impulsionada para novas áreas agrícolas não tradicionais que apresentam deficiência hídrica. Estudos que visam à seleção de cultivares que apresentem tolerância aos estresses ambientais se constituem numa alternativa viável para aumentar a produtividade nessas regiões. Neste sentido, o objetivo deste trabalho foi estudar de maneira comparativa as respostas fisiológicas e bioquímicas em cana-de-açúcar cultivada sob deficiência hídrica bem como analisar os efeitos fisiológicos do herbicida Paraquat, visando constituir uma alternativa para caracterizar cultivares tolerantes em programas de melhoramento genético da cana-de-açúcar. Para isso, experimentos foram conduzidos em vasos em casa de vegetação e no laboratório da Unidade de Pesquisa e Desenvolvimento da APTA em Jaú (SP). Foram utilizadas quatro cultivares de cana-de-açúcar RB92579, SP81-3250, SP83-2847 e IAC91-5155 em cada experimento. Para o estudo de deficiência hídrica, a primeira avaliação foi realizada nas plantas sem estresse após 85 dias do plantio, em seguida foram implementados dois tratamentos, sem deficiência (-D) e com deficiência (+D) por suspensão da rega por 15 dias e posterior reidratação por 12 dias. Para os estudos com herbicida Paraquat (PQ) um segundo experimento foi instalado dividido em duas partes. Na primeira, foi pulverizado Paraquat, na dose de 150 μM, 24 horas antes das avaliações em plantas conduzidas simultaneamente ao experimento de deficiência hídrica. Na segunda parte, segmentos foliares das cultivares foram cortados em discos e imersos em solução de Paraquat em placas de Petri e analisados quanto à degradação de clorofila. Todos os experimentos foram conduzidos em delineamento inteiramente casualizado, em... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Sugarcane is one of the most economically important crops used in the production of sugar and of bioethanol. In Brazil, this plant has been introduced to non-traditional agricultural areas, with adverse agro-climatic conditions where water deficit is highlighted. Studies aimed at selecting drought-tolerant cultivars are a viable alternative to increase the productivity of these regions. The main goal of this research includes to study comparatively the physiological and biochemical responses in sugarcane under drought stress and recovering as well as analyzing the physiological effects induced by the herbicide paraquat, aiming to establish a scoring system for selecting sugarcane drought tolerant cultivars in breeding programs. The experiments were carried out in a greenhouse located in the Unit of Research and Development of APTA, Jaú, SP., where the cultivars RB92579, SP81-3250, SP83-2847 and IAC91-5155 were grown in pots and used for each set of experiments. For the study of water stress, the first assessment was done in plants without stress after 85 days of planting, and after that two treatments were implemented, i.e. without water deficit (-D) and with water deficit (+D) by withholding in the water supply for 15 days and rewatering for 12 days after the stress period. For the study of paraquat (PQ), another set of experiments were carried out simultaneously to the water stress experiments. Two different experimental methods were used for spraying the PQ solution (150 μM). In the first one, the PQ solution was sprayed onto leaves of the sugarcane plants and the assessments took place 24 hours after spraying. In the second experiment, leaf disks were floated in PQ solutions for 24 hours for analyzing chlorophyll degradation. All experimental designs were completely randomized in 4x2 factorial scheme (four sugarcane... (Complete abstract click electronic access below) / Doutor

Supramolecular host-guest chemistry is a topic of great current interest. However, the further development of host-guest chemistry is still limited by the number of available host-guest recognition motifs. This makes it necessary and valuable to find new host-guest recognition motifs and apply known host-guest recognition motifs in the preparation of novel supramolecular systems. By comparing the crystal structures of the host and its taco complex, we proved that folding is a necessary step during the formation of taco complexes. Based on the known bis(m-phenylene)-32-crown-10/paraquat recognition motif, the first solid-state supramolecular poly(taco complex) was prepared. We demonstrate not only that bis(m-phenylene)-32-crown-10-based cryptands are powerful hosts for paraquat derivatives compared with the simple crown ether, but also that cooperative complexation can be obtained with the cryptand structure. It was shown that the significant improvement in complexation was the result of the combination of the preorganization of the cryptand hosts and the introduction of additional and optimized binding sites. Furthermore, it was demonstrated that improved complexation of bis(secondary ammonium) and bisparaquat salts could also be achieved by the formation of the pseudocryptand structure. We also prepared two dimers of inclusion cryptand/paraquat complexes driven by dipole-dipole and face-to-face p-stacking interactions. An interesting complex based on dibenzo-24-crown-10 and diquat was prepared. In its crystal structure the diquat guest lies in the concave cavity provided by two dibenzo-24-crown-8 hosts. Monopyridinium-based [2]- and [3]-pseudorotaxanes were prepared based on the newly discovered bis(m-phenylene)-32-crown-10/monopyridinium salt and cryptand/monopyridinium salt recognition motifs. Inspired by the formation of solid-state taco complexes between bis(m-phenylene)-32-crown-10 and paraquat derivatives, we designed and synthesized the first cylindrical bis(crown ether) host for paraquat derivatives and studied its complexation with paraquat. We prepared three slow-exchange C3-symmetric inclusion complexes based on a newly discovered cryptand/trispyridinium recognition motif, in which 1,3,5-trispyridiniumbenzene salts act as guests. Finally the application of several new and known recognition motifs in the preparation of a supramolecular poly[3]pseudrotaxane, and the first pseudorotaxane-type supramolecular star-shaped polymer, and the first supramolecular hyperbranched polymer was discussed. / Ph. D.

The research presented in this thesis focused on pseudorotaxanes and supramolecular polymers based on a new recognition motif, the dibenzo-24-crown-8/paraquat recognition motif. Main kinds of pseudorotaxanes and rotaxanes and various protocols used for the study of them were discussed first. By preparation and characterization of a series of pesudorotaxanes based on DB24C8 and paraquat derivatives, it was found that these complexes were stabilized by N+...O interactions, C-H...O hydrogen bonding, and face-to-face p-stacking interactions. Because methyl protons of paraquat are involved in hydrogen bonding to the host, the substitution of any methyl hydrogen on paraquat causes apparent association constant of the pseudorotaxane to decrease. The concentration dependence of apparent association constants, Ka,exp, of fast exchange host-guest systems was studied for the first time by using complexes based on viologens and crown ethers as examples. While the bis(hexafluorophosphate) salts of paraquat derivatives are predominantly ion paired in acetone (and other low dielectric constant solvents presumably) the complex based on dibenzo-24-crown-8 and paraquat is not ion paired in solution, resulting in concentration dependence of Ka,exp. However, four complexes of two different bis(m-phenylene)-32-crown-10 (BMP32C10) derivatives and bis(p-phenylene)-34-crown-10 (BPP3C10) with viologens are ion paired in solution, as shown by the fact that Ka,exp is not concentration dependent for these systems involving hosts with freer access to bound guests. X-ray crystal structures support these soluton-based assessments in that there is clearly ion pairing of the cationic guest and its PF6- counterions in the solid states of the latter four examples, but not in the former. The complexes based on the new dibenzo-24-crown-8/paraquat recognition motif are thus different from the complexes based on two old recognition motifs: the BPP34C10/BMP32C10-paraquat and DB24C8-ammonium motives. In order to compare these recognition motives further, the selectivity between two hosts, DB24C8 and BPP34C10, and two guests, dimethyl paraquat and dibenzyl ammnonium salt, was discussed. By individual and competitive complexation studies, it was demonstrated that DB24C8 is a better host than BPP34C10 for paraquat, and that paraquat is a better guest than dibenzyl ammonium salt for DB24C8. Finally the DB24C8-paraquat recognition motif was successfully applied in the preparation the first star-shaped supramolecular polymer based on a tetraparaquat guest and a DB24C8 functionalized polystyrene oligomer. A model system based on this guest and DB24C8 was also studied for comparison. It was found that the complexation in these two systems is cooperative, as are most biological complexations of multitopic species. Due to the ready availability of DB24C8 and paraquat derivatives, the new recognition motif should prove to be very valuable for self-assembly of other more sophisticated supramolecular systems. / Master of Science

帕金森氏症是現今常見的神經退化性疾病，其特徵主要表現在運動功能上的缺失包含靜止時振顫、步態不穩及肢體僵硬等特徵。而基因研究指出當PTEN-induced putative kinase 1 (PINK1)及Parkin基因發生突變可能會導致粒腺體功能失常，進而導致帕金森氏症之神經退化性疾病，另外PINK1基因突變的果蠅亦會產生嗅覺辦識功能障礙。在環境因素方面，一種廣效使用的除草劑百草枯(paraquat)被認為與誘發帕金森氏症有關。根據中醫生理學概念，消化系統功能紊亂，不但影響腸道功能亦會影響其他系統的運作,包含中樞神經系統。因此本實驗採用中草藥紫蘇初萃取物作為實驗藥物，紫蘇(Perilla frutescens)在中醫臨床的主要功能用於治療因飲食不節而導致的腸胃氣滯，進而減緩其他表症的不適感，另外紫蘇另一項功能在於能解食魚蟹之毒。因此我們評估紫蘇可能對於野生型及突變型果蠅因百草枯引發之毒性具有保護作用。實驗結果顯示，紫蘇可以有效的降低因曝露在百草枯(24-72小時)下的致死率，不論在野生型Oregon-R品系及PINK1B9或Parkin25的突變型(年齡：3-7天, 10-14天)。然而紫蘇對於果蠅的運動爬行功能只有在施予百草枯後的野生型Oregon-R 品系(年齡：3-7天)有些微改善，但是在嗅覺辨識功能被百草枯破壞的PINK1B9 突變果蠅，則能經由紫蘇而減少嗅覺辨識的損害。綜合以上實驗結果得知紫蘇對於百草枯所造成的毒性具有保護效果，期望未來可作為治療帕金森氏症的潛在藥物。 / Parkinson’s disease (PD) is the most common neurodegenerative disease characterized by motor deficits including resting tremor, akinesia, and rigidity. The olfactory disturbance appears to be an earlier symptom prior to the onset of motor dysfunction in PD. Genetic research has shown that mutations of the PTEN-induced putative kinase 1 (PINK1) and Parkin genes could lead to mitochondrial dysfunction and neuronal degeneration in PD. Moreover, the environmental neurotoxin paraquat (PQ), a widely used pesticide, is known to induce PD-like symptoms. According to Traditional Chinese medicine physiology theory, that the central nervous system and gut interact bidirectionally in functional gastrointestinal disorders. Perilla frutescens, a traditional herbal medicine, is mainly prescribed for the treatment of gastrointestinal discomfort after eating and symptom of qi stagnation. In addition, perilla has an important role in detoxification of seafood intake. Therefore, this study evaluated the protective effects of perilla on paraquat-induced toxicity in Drosophila PINK1 and parkin mutants and wild type flies. Result showed that perilla can effectively alleviate lethality of drosophila, including PINK1 and parkin mutant flies, exposed to paraquat for 24-72 hours. However, their motor dysfunctions induced by paraquat were little ameliorated by perilla. Importantly, the olfactory dysfunction, particularly olfactory discrimination, elicited by paraquat in PINK1 mutant fly was improved by perilla. Taken together, our findings provide the protective potential of perilla for treatment of PD syndromes.

中文摘要 厚朴，採用厚朴植物之樹皮，是ㄧ種已知可應用於治療精神疾病的傳統天然藥物，例如：憂鬱症等。厚朴主要的有效多酚環成分已被證實具有抗氧化、抗發炎及抗興奮性毒殺等神經保護作用，因此，推測厚朴可作為一種潛在治療像是帕金森氏症這累神經退化性疾病之藥物。本研究之目的為探討厚朴是否可以預防與治療因百草枯及MPTP所誘導的毒害及學習、記憶和運動功能缺失等行為異常現象。本研究監測Oregon-R品系之果蠅(年齡：1-2, 20天或30天)之壽命在長期暴露於百草枯(5-20 mM)並先給予厚朴(100, 300或600 mg/L)治療之變化。其結果顯示，厚朴無法延長暴露在百草枯環境下之果蠅壽命。另外，我們給予雄性ICR小鼠(30-35 g)，連續五天，每日一劑MPTP(25 mg/kg, i.p.)，誘導神經毒性及行為異常現象。在共同投藥組別，在給予MPTP注射前一小時，先以灌餵方式給予小鼠厚朴(100或300 mg/kg)預防，連續五天後，只單獨給予厚朴治療連續十四天。後投藥組別，在給予最後一劑MPTP後，連續十四天給予厚朴(100或300 mg/kg).治療。在控制組別中，給予生理食鹽水(0.9%, i.p.)及灌餵玉米油。結果顯示，MPTP與厚朴並不影響小鼠之運動協調功能，然而，可利用新位置辨識能力測試及新物體辨識認知行為測試，檢測因MPTP所引起之認知功能障礙現象，由我們結果中顯示，不論是與MPTP共同給予厚朴治療抑或是後處理厚朴皆可恢復因MPTP所造成的認知功能障礙現象，此外，厚朴也可恢復因MPTP所造成多巴胺神經元及多巴胺轉運子受損之情形，另外，我們也初步發現，厚朴可在海馬迴中使Nrf2表現量提升。因此，初步結果表明，厚朴將可成為未來治療帕金森氏症之天然藥物。 / Cortex Magnoliae, the bark of Magnolia officinalis, has been prescribed in the traditional herbal medicine to treat a variety of mental disorders including depression. The main constituents of cortex Magnoliae contain the biphenyl compounds such as honokiol and magnolol. Both biphenyl compounds were shown to have the neuronal protective effect which is related to the anti-oxidation, anti-inflammation, and anti-excitatory toxicity. Thus, it was proposed that cortex Magnoliae may act as the potential therapeutic agent for the treatment of neurodegenerative disorders such as Parkinson’s disease (PD). The aim of the present study was to examine whether cortex Magnoliae exhibits the neuroprotective and therapeutic action against the neuronal toxicity and behavioral deficits in learning, memory, and motor function induced by neurotoxin paraquat and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in PD-like models. The lifespan of flies from Oregon-R strain of Drosophila melanogaster (age: 1-2, 20 or 30 days) chronically exposed to paraquat (5-20 mM) with pre-treatment of Cortex Magnoliae (100, 300 or 600 mg/L) were measured. Results showed that pre-treatment of Cortex Magnoliae could not extend the lifespan of the flies reduced by paraquat. On the other hand, male ICR mice (30-35g) were administered with MPTP (25 mg/kg, i.p.) once daily for 5 consecutive days to induce neurotoxicity and behavioral impairment. In co-treatment group, male mice were orally administrated with cortex Magnoliae (100 or 300 mg/kg) 1 hour before MPTP injection for 5 days and then followed by oral administration of cortex Magnoliae alone for consecutive 14 days. Mice in post-treatment group were orally administered with cortex Magnoliae (100 or 300 mg/kg) for consecutive 14 days after the final injection of MPTP. Mice in control group were injected with saline (0.9%, i.p.) and orally administrated with vehicle (corn oil). Our results showed that MPTP and cortex Magnoliae did not affect mouse coordination and balance in beam walking test. However, cortex Magnoliae improved the cognitive impairments determined by novel-location recognition task (NLRT) and novel-object recognition task (NORT) in MPTP-induced PD mouse. Additionally, cortex Magnoliae restored MPTP-induced loss of dopaminergic neurons and recovered MPTP-induced loss of dopamine transporters in striatum. Cortex Magnoliae also activated Nrf2 in hippocampus. Therefore, the preliminary results suggest that cortex Magnoliae may be a novel candidate for the treatment of Parkinson's disease in the future. The pharmacological mechanism of cortex Magnoliae in PD treatment needs further study.

Visando contribuir para o conhecimento da dinâmica do estresse celular por agentes químicos e físicos e suas possíveis implicações sobre a mobilização de elementos transponíveis presentes em Drosophila, foram realizadas diferentes abordagens experimentais utilizando a espécie cosmopolita Drosophila melanogaster, e as espécies neotropicais do subgrupo willistoni, D. willistoni (três linhagens) D. equinoxialis, D. paulistorum, D. insularis e D. tropicalis. Foi verificado o efeito tóxico de disseleneto de difenila ((PhSe)2) durante diferentes estágios do ciclo de vida da Drosophila melanogaster e das espécies do subgrupo willistoni. Em D. melanogaster, as moscas adultas foram mais resistentes a intoxicação por (PhSe)2 do que larvas e pupas. De uma maneira geral as espécies do subgrupo willistoni são mais sensíveis à intoxicação por selênio do que a D. melanogaster, possivelmente explicado e de acordo com a recentemente demonstrada ausência de homologia de genes para selenoproteínas no genoma de D. willistoni com todas as onze outras espécies sequenciadas. O potencial do selênio para promover estresse celular em D. melanogaster foi evidenciado através da transcrição do gene hsp83 por Northern blot. Nas espécies do subgrupo willistoni a expressão deste gene e do hsp70 foi abordada através de Real Time PCR em resposta ao selênio e ao paraquat, que igualmente foi mais tóxico nos estágios iniciais de desenvolvimento. Os resultados da expressão dos genes de estresse, entretanto, não foram conclusivos, bem como a procura da transposase do elemento P em resposta aos tratamentos. Apesar disso foram estabelecidas às condições experimentais para a realização de experimentos futuros. / Aiming to contribute to the knowledge of the dynamics of cell stress caused by chemical and physical agents and the likely implications thereof in the mobilization of transposable elements present in Drosophila, different experimental approaches were adopted using the cosmopolitan species Drosophila melanogaster and the Neotropical species of the willistoni subgroup, D. willistoni (three strains), D. equinoxialis, D. willistoni, D. paulistorum, D. insularis and D. tropicalis. The toxic effect of diphenyl diselenide [(PhSe)2] was observed in the different life cycles of Drosophila melanogaster and of the species of the willistoni subgroup. D. melanogaster adult flies were more resistant to intoxication by (PhSe)2 as compared to larvae and pupae. Generally speaking the species belonging to the willistoni subgroup are more sensitive to intoxication by selenium as compared to D. melanogaster, which is possibly explained and in accordance to the recently demonstrated absence of gene homology of selenoproteins in the D. willistoni genome with all that of the other eleven species sequenced. The evidence of the potential exhibited by selenium to promote cell stress in D. melanogaster is shown by the hsp83 gene transcription analyzed by Northern blot. In the species of the willistoni subgroup, the expression of the hsp83 and of the hsp70 genes was analyzed by Real Time PCR in response to selenium and paraquat, which was equally more toxic in the early development stages. Nevertheless, the results of the stress gene expression were inconclusive, as well as the search for P element transposase in response to treatments. In spite of that, the experimental conditions required for future research have been established.

Visando contribuir para o conhecimento da dinâmica do estresse celular por agentes químicos e físicos e suas possíveis implicações sobre a mobilização de elementos transponíveis presentes em Drosophila, foram realizadas diferentes abordagens experimentais utilizando a espécie cosmopolita Drosophila melanogaster, e as espécies neotropicais do subgrupo willistoni, D. willistoni (três linhagens) D. equinoxialis, D. paulistorum, D. insularis e D. tropicalis. Foi verificado o efeito tóxico de disseleneto de difenila ((PhSe)2) durante diferentes estágios do ciclo de vida da Drosophila melanogaster e das espécies do subgrupo willistoni. Em D. melanogaster, as moscas adultas foram mais resistentes a intoxicação por (PhSe)2 do que larvas e pupas. De uma maneira geral as espécies do subgrupo willistoni são mais sensíveis à intoxicação por selênio do que a D. melanogaster, possivelmente explicado e de acordo com a recentemente demonstrada ausência de homologia de genes para selenoproteínas no genoma de D. willistoni com todas as onze outras espécies sequenciadas. O potencial do selênio para promover estresse celular em D. melanogaster foi evidenciado através da transcrição do gene hsp83 por Northern blot. Nas espécies do subgrupo willistoni a expressão deste gene e do hsp70 foi abordada através de Real Time PCR em resposta ao selênio e ao paraquat, que igualmente foi mais tóxico nos estágios iniciais de desenvolvimento. Os resultados da expressão dos genes de estresse, entretanto, não foram conclusivos, bem como a procura da transposase do elemento P em resposta aos tratamentos. Apesar disso foram estabelecidas às condições experimentais para a realização de experimentos futuros. / Aiming to contribute to the knowledge of the dynamics of cell stress caused by chemical and physical agents and the likely implications thereof in the mobilization of transposable elements present in Drosophila, different experimental approaches were adopted using the cosmopolitan species Drosophila melanogaster and the Neotropical species of the willistoni subgroup, D. willistoni (three strains), D. equinoxialis, D. willistoni, D. paulistorum, D. insularis and D. tropicalis. The toxic effect of diphenyl diselenide [(PhSe)2] was observed in the different life cycles of Drosophila melanogaster and of the species of the willistoni subgroup. D. melanogaster adult flies were more resistant to intoxication by (PhSe)2 as compared to larvae and pupae. Generally speaking the species belonging to the willistoni subgroup are more sensitive to intoxication by selenium as compared to D. melanogaster, which is possibly explained and in accordance to the recently demonstrated absence of gene homology of selenoproteins in the D. willistoni genome with all that of the other eleven species sequenced. The evidence of the potential exhibited by selenium to promote cell stress in D. melanogaster is shown by the hsp83 gene transcription analyzed by Northern blot. In the species of the willistoni subgroup, the expression of the hsp83 and of the hsp70 genes was analyzed by Real Time PCR in response to selenium and paraquat, which was equally more toxic in the early development stages. Nevertheless, the results of the stress gene expression were inconclusive, as well as the search for P element transposase in response to treatments. In spite of that, the experimental conditions required for future research have been established.

Visando contribuir para o conhecimento da dinâmica do estresse celular por agentes químicos e físicos e suas possíveis implicações sobre a mobilização de elementos transponíveis presentes em Drosophila, foram realizadas diferentes abordagens experimentais utilizando a espécie cosmopolita Drosophila melanogaster, e as espécies neotropicais do subgrupo willistoni, D. willistoni (três linhagens) D. equinoxialis, D. paulistorum, D. insularis e D. tropicalis. Foi verificado o efeito tóxico de disseleneto de difenila ((PhSe)2) durante diferentes estágios do ciclo de vida da Drosophila melanogaster e das espécies do subgrupo willistoni. Em D. melanogaster, as moscas adultas foram mais resistentes a intoxicação por (PhSe)2 do que larvas e pupas. De uma maneira geral as espécies do subgrupo willistoni são mais sensíveis à intoxicação por selênio do que a D. melanogaster, possivelmente explicado e de acordo com a recentemente demonstrada ausência de homologia de genes para selenoproteínas no genoma de D. willistoni com todas as onze outras espécies sequenciadas. O potencial do selênio para promover estresse celular em D. melanogaster foi evidenciado através da transcrição do gene hsp83 por Northern blot. Nas espécies do subgrupo willistoni a expressão deste gene e do hsp70 foi abordada através de Real Time PCR em resposta ao selênio e ao paraquat, que igualmente foi mais tóxico nos estágios iniciais de desenvolvimento. Os resultados da expressão dos genes de estresse, entretanto, não foram conclusivos, bem como a procura da transposase do elemento P em resposta aos tratamentos. Apesar disso foram estabelecidas às condições experimentais para a realização de experimentos futuros. / Aiming to contribute to the knowledge of the dynamics of cell stress caused by chemical and physical agents and the likely implications thereof in the mobilization of transposable elements present in Drosophila, different experimental approaches were adopted using the cosmopolitan species Drosophila melanogaster and the Neotropical species of the willistoni subgroup, D. willistoni (three strains), D. equinoxialis, D. willistoni, D. paulistorum, D. insularis and D. tropicalis. The toxic effect of diphenyl diselenide [(PhSe)2] was observed in the different life cycles of Drosophila melanogaster and of the species of the willistoni subgroup. D. melanogaster adult flies were more resistant to intoxication by (PhSe)2 as compared to larvae and pupae. Generally speaking the species belonging to the willistoni subgroup are more sensitive to intoxication by selenium as compared to D. melanogaster, which is possibly explained and in accordance to the recently demonstrated absence of gene homology of selenoproteins in the D. willistoni genome with all that of the other eleven species sequenced. The evidence of the potential exhibited by selenium to promote cell stress in D. melanogaster is shown by the hsp83 gene transcription analyzed by Northern blot. In the species of the willistoni subgroup, the expression of the hsp83 and of the hsp70 genes was analyzed by Real Time PCR in response to selenium and paraquat, which was equally more toxic in the early development stages. Nevertheless, the results of the stress gene expression were inconclusive, as well as the search for P element transposase in response to treatments. In spite of that, the experimental conditions required for future research have been established.

Design and preparation of novel host/guest systems, such as pseudorotaxanes, semirotaxanes, rotaxanes and catenanes, with high association constants, enhanced yields and the abilities to respond to external stimuli are of great importance and significance due to their topological novelty and potential application. The convergence of supramolecular chemistry with polymer science provides an important way to extend the scope of polymer and material sciences by incorporating designed host/guest systems into polymers, and the resulting non-covalently linked supramolecular polymers are expected to have unusual properties due to their unique architectures compared with traditional polymers. After discovery of bis(meta-phenylene)-32-crown-10 (BMP32C10) derivative/paraquat complexes, for about a quarter century only “taco”-shaped complexes were observed by X-ray crystallography. Here, by the self-assembly of a BMP32C10 bearing two electron-donating groups (carbazoles) with electron-accepting paraquat derivatives, the first [2]pseudorotaxane and the first pseudocryptand-type poly[2]pseudorotaxane based on BMP32C10 were isolated as crystalline solids as shown by X-ray analyses. The first dual component pseudocryptand-type [2]pseudorotaxanes were designed and prepared via the self-assembly of synthetically easily accessible BMP32C10 pyridyl, quinolyl and naphthyridyl derivatives with paraquat. The formation of the pseudocryptand structures in the complexes remarkably improved the association constants by forming the third pseudo-bridge via H-bonding with the guest and π-stacking of the heterocyclic units. A pseudocryptand-type [2]pseudorotaxane was formed via the self-assembly of a dipyridyl BMP32C10 derivative and a paraquat derivative. Due to the basicity of the pyridyl group, which forms the third pseudo-bridge of the pseudocryptand, this pseudorotaxane represents the first system with acid-base adjustable association constants, i. e., finite both under acidic and neutral conditions. The first pseudocryptand-type supramolecular [3]pseudorotaxane was designed and prepared via the self-assembly of a bispicolinate BMP32C10 derivative and a bisparaquat. The complexation behavior was cooperative. In addition, the complex comprised of the BMP32C10 derivative and a cyclic bisparaquat demonstrated strong binding; interestingly, a poly[2]pseudocatenane structure was formed in the solid state for the first time. Two novel BMP32C10 cryptands, bearing covalent and metal complex linkages, were designed and prepared. By employing the self-assembly of these biscryptands, which can be viewed as AA monomers, and a bisparaquat, which can be viewed as a BB monomer, the first AA/BB-type linear supramolecular polymers with relatively high molecular weights were successfully prepared. Via the self-assembly of two BMP32C10-based cryptands, bearing covalent and metal complex (ferrocene) linkages, with dimethyl paraquat, novel [3]pseudorotaxanes were formed statistically and anticooperatively, respectively. From a hydroxyl-functionalized secondary ammonium salt a [2]semirotaxane and a [2]rotaxane were prepared successfully with dibenzo-24-crown-8 (DB24C8). X-ray analysis of a single crystal of the [2]semirotaxane confirmed its semirotaxane nature. In addition, the formation of the [2]semirotaxane can be reversibly controlled by adding KPF6 and 18C6 sequentially. This system affords a way to prepare novel supramolecular polymers. Dibenzo-30-crown-10 (DB30C10) derivatives and pyridine-based DB30C10 cryptands were prepared by employing the templating method established by our group. A [2]pseudorotaxane was prepared based on DB30C10 diol and paraquat diol. The [3]pseudorotaxane formed via the self-assembly between DB30C10 cryptand and bisparaquat diol occurred in a cooperative manner. In addition, a bromo-functionalized DB30C10 cryptand was successfully designed and prepared. An alkyne-functionalized DB30C10 cryptand was designed and is under preparation; its precursors have been prepared successfully. In the future, based on these functionalized cryptands and paraquat salts, AA and AB type monomers will be prepared. Via the self-assembly between these monomers, non-covalent supramolecular polymers with high molecular weight will be afforded. A novel DB30C10 cryptand bearing an organometallic bridge, ferrocene, was prepared via 1-(3'-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) coupling of the crown ether diol with ferrocene dicarboxylic acid. The cryptand is dimerized in the solid state via π, π-stacking and hydrogen bonds. The ferrocene-based cryptand formed novel [2]pseudorotaxanes with paraquat and diquat PF₆ salts with association constants (Kₐ) of 1.7 ± 0.1 x 10³ and 4.2 ± 0.3 x 10⁴ M⁻¹ in acetone-d₆, respectively. In order to prepare linear polycatenanes, the preparation of which represent a real synthetic challenge, a series phenanthroline derivatives were designed and prepared. A “U” shaped monomer was successfully prepared in relative high yield with good solubility. In the future, real linear polycatenanes will be prepared. In addition, a novel diphenanthroline-based BMP32C10 derivative was prepared in high yield and the complexation behavior between it and dimethyl paraquat was studied. / Ph. D.