Made available in DSpace on 2015-05-14T13:21:31Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2255792 bytes, checksum: 5043ebf08321332b3a5629d90122a0e8 (MD5) Previous issue date: 2013-08-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Oxidative stress is a biological condition in which there is an imbalance between the release of reactive species and their reuptake by biological systems, leading to the production of peroxides and free radicals that damage different cellular components, including proteins, lipids and DNA. Porphyrins and their metal complexes can be used as mimics of the enzyme superoxide dismutase (SOD) in the modulation of oxidative stress. The in vivo efficacy of porphyrins is related, among other factors, to their bioavailability, which is strongly influenced by lipophilicity and can also be related to different structural and electronic properties of these molecules. In this context, the present work has the aim of analyzing the influence of certain molecular properties on the lipophilicity of a series of N-pyridylporphyrins, by means of theoretical calculations, intending to provide useful information for the design of new porphyrin derivatives. Initially, the logarithm of the octanol/water partition coefficient (log P) of these molecules was estimated by using different free software, as well as based on the difference of octanol/water free energy of solvation, employing the Density Functional Theory (DFT), with different hybrid functionals (B3LYP, M06 and M062X). From DFT calculations, electronic and structural properties were also obtained, such as atomic partial charges, molecular orbitals, dipole moment, polarizability, surface area and molecular volume. The obtained data were compared to the available experimental measure of lipophilicity to this series of porphyrins, the chromatographic retention factor (Rf). The results show that traditional and well established methods for log P calculation, such as fragmental methods, do not provide reliable results for the studied porphyrins, unlike the calculations based on free energy of solvation, which have provided similar trends to the experimental log P of manganese porphyrins analogous to the studied ones. Furthermore, the obtained results suggests that charge distribution on the porphyrin structure may be related to the observed differences in lipophilicity and, consequently, with the passage of these molecules across the cellular membrane. It also became evident that the molecular volume is strongly related to lipophilicity, since a larger relaxation of the structures in the n-octanol phase is observed due to the lipophilic character of the long alkyl chains attached to the pyridyl group. Low correlations between Rf values and the other molecular properties calculated were obtained, indicating that the lipophilicity of porphyrins can only be modulated by the size of alkyl changes and the introduction of groups that favorably alter the charge distribution. / O estresse oxidativo é uma condição biológica na qual há um desequilíbrio entre a liberação de espécies reativas e a sua captação pelos sistemas biológicos, podendo provocar a produção de peróxidos e radicais livres que danificam diferentes componentes celulares, incluindo proteínas, lipídios e o DNA. As porfirinas e seus complexos metálicos podem ser usados como mímicos da enzima superóxido dismutase (SOD) na modulação do estresse oxidativo. A eficácia in vivo das porfirinas está relacionada, entre outros fatores, com sua biodisponibilidade, que é fortemente influenciada pela lipofilicidade e pode também ser relacionada a diferentes propriedades estruturais e eletrônicas dessas moléculas. Neste contexto, o presente trabalho teve o intuito de analisar a influência de determinadas propriedades moleculares na lipofilicidade de uma série de N-piridilporfirinas, por meio de cálculos teóricos, visando fornecer informações úteis para o planejamento de novos derivados de porfirinas. Inicialmente, o logaritmo do coeficiente de partição octanol/água (log P) dessas moléculas foi estimado utilizando diferentes programas computacionais livres, bem como com base na diferença de energia livre de solvatação octanol/água, empregando a Teoria do Funcional da Densidade (DFT), com diferentes funcionais híbridos (B3LYP, M06 e M062X). A partir dos cálculos DFT foram obtidas, ainda, propriedades eletrônicas e estruturais, tais como cargas parciais atômicas, orbitais moleculares, momento de dipolo, polarizabilidade, área superficial e volume molecular. Os dados obtidos foram comparados à medida experimental de lipofilicidade disponível para esta série de porfirinas, o fator de retenção cromatográfica (Rf). Os resultados mostram que métodos tradicionais e bem estabelecidos de cálculo do log P, como os métodos fragmentais, não fornecem resultados confiáveis para as porfirinas estudadas, ao contrário dos cálculos baseados na energia livre de solvatação, que forneceram tendências semelhantes aos valores experimentais de log P de porfirinas de manganês análogas às estudadas. Além disso, os resultados obtidos sugerem que a distribuição de cargas na estrutura das porfirinas pode estar relacionada com as diferenças observadas na lipofilicidade e, consequentemente, com a passagem destas moléculas através da membrana celular. Também ficou evidente que o volume molecular está fortemente relacionado à lipofilicidade, uma vez que se observa um maior relaxamento da estrutura na fase n-octanol devido ao caráter lipofílico das longas cadeias alquílicas ligadas ao grupo piridil. Baixas correlações entre os valores de Rf e as demais propriedades moleculares calculadas foram obtidas, indicando que a lipofilicidade das porfirinas pode ser modulada apenas pelo tamanho das cadeias alquílicas e pela introdução de grupos que alterem favoravelmente a distribuição de cargas.

During the Geological Survey of Canada’s Cumberland Peninsula Integrated Geoscience project a ~150km long NE-SW trending volcanic belt, now termed the North Touak-Cape Dyer volcanic belt, was mapped. The volcanic rocks that comprise the belt are dominantly green weathering komatiitic rocks with some black weathering tholeiitic occurrences. Given the similar stratigraphic position, textures, mineralogy, and geochemical characteristics of the volcanic rocks throughout the belt they have been termed the Totnes Road formation, after the locality from which they were first described. The komatiitic rocks possess numerous unusual characteristics for ultramafic volcanic rocks including: fragmental textures, lack of spinifex texture, young eruption age (Paleoproterozoic), eruption through ancient continental crust, and enrichment in the HFSEs including the REEs. This places them in the uncommon and poorly understood sub-type of komatiites termed Karasjok-type komatiites. Given the ultramafic nature of the rocks and their within-plate geochemical signatures, a mantle plume is the most likely source of these rocks, with the komatiites being sourced from the hot plume axis and the tholeiites from the cooler plume head. Incorporation and melting of mantle enriched by the addition of subduction zone recycled, garnet-bearing eclogitic material, beneath thick lithosphere could cause the rocks geochemical enrichment. Stratigraphically overlying the Totnes Road formation is a variety of chemical sedimentary rocks including chert, sulphide and silicate facies iron formation, and sulphide-rich boulders. Given their consistent stratigraphic position and parallel REE patterns, these rocks have been interpreted as a co-genetic suite and are grouped under the Clephane Bay formation, after a locality that exposes a spectacular section of the chemical rocks. The variety of lithologies is believed to be due to mixing of hydrothermal and detrital inputs during deposition within an anoxic basin. Regional correlations in the area are tentative due to the lack of available geochronological and geochemical data. Mafic-ultramafic volcanic occurrences to both the north and the south of the Cumberland Peninsula show remarkably similar geochemical characteristics to the Totnes Road formation. Thus it is possible that one plume was the source for numerous volcanic occurrences within in the region but more detailed study is required to prove or disprove this possibility.