On the interaction of bovine serum albumin with ionic surfactants: Temperature induced EPR changes of a maleimide nitroxide reflect local protein dynamics and probe solvent accessibility

The interaction of bovine serum albumin (BSA) with the ionic surfactants sodium dodecylsulfate (SDS, anionic), cetyltrimethylammonium chloride (CTAC, cationic) and N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS, zwitterionic) was studied by electron paramagnetic resonance (EPR) spectroscopy of spin label covalently bound to the single free thiol group of the protein. EPR spectra simulation allows to monitor the protein dynamics at the labeling site and to estimate the changes in standard Gibbs free energy, enthalpy and entropy for transferring the nitroxide side chain from the more motionally restricted to the less restricted component. Whereas SDS and CTAC showed similar increases in the dynamics of the protein backbone for all measured concentrations. HPS presented a smaller effect at concentrations above 1.5 mM. At 10 mM of surfactants and 0.15 mM BSA, the standard Gibbs free energy change was consistent with protein backbone conformations more expanded and exposed to the solvent as compared to the native protein, but with a less pronounced effect for HPS. In the presence of the surfactants, the enthalpy change, related to the energy required to dissociate the nitroxide side chain from the protein, was greater, suggesting a lower water activity. The nitroxide side chain also detected a higher viscosity environment in the vicinity of the paramagnetic probe induced by the addition of the surfactants. The results suggest that the surfactant-BSA interaction, at higher surfactant concentration, is affected by the affinities of the surfactant to its own micelles and micelle-like aggregates. Complementary DLS data suggests that the temperature induced changes monitored by the nitroxide probe reflects local changes in the vicinity of the single thiol group of Cys-34 BSA residue. (C) 2011 Elsevier B.V. All rights reserved.

Parâmetros citogenéticos de espécies comerciais de carangidae (perciformes), com vistas a sua empregabilidade na conservação biológica e piscicultura marinha

Worldwide, families Carangidae and Rachycentridae represent one of the groups most important commercial fish, used for food, and great potential for marine aquaculture. However, the genetic bases that can underpin the future cultivation of these species, cytogenetic between these aspects are very weak. The chromosomal patterns have provided basic data for the exploration of biotechnological processes aimed at handling chromosomal genetic improvement, such as induction of polyploidy, androgenesis and ginogenesis, as well as obtaining monosex stocks and interspecific hybridizations. This paper presents a comprehensive cytogenetic survey in 10 species, seven of the family Carangidae and the monotypic family Rachycentridae. Classical cytogenetic analysis and in situ mapping of multigene sequences were employed, and additionally for the genus Selene and morphotypes of Caranx lugubris, comparisons were made using geometric morphometrics. In general, conservative species exhibit a marked chromosome number (2n=48). Although present in large part, different karyotypic form, retain many characteristics typical of chromosomal Order Perciformes, the high number of elements monobrachyal, Ag-NORs/18S rDNA sites and heterochromatin simply reduced, preferably centromeric. The main mechanisms involved in karyotypic diversification are the pericentric inversions, with secondary action of centric fusions. In addition to physical mapping and chromosome detail for the species are presented and discussed patterns of intra-and interspecific diversity, cytotaxonomic markers. This data set provides a better understanding of these patterns caryoevolutyonary groups and conditions for the development of protocols based on Biotechnology for chromosomal manipulation Atlantic these species

Influência da adição de cálcio nas propriedades de pastas geopoliméricas destinadas a cimentação de poços de petróleo

Nowadays, the search for new technologies that are able to follow the upcoming challenges in oil industry is a constant. Always trying properties improvements of the used materials, looking for the best performance and greater life time. Besides the search for technologies that show an improvement of performance, the search for materials environmentally correct along the whole production process. In Oil well cementing, this search for new technologies passes through the development of slurry systems that support these requests and that are also environmentally friendly. In this context, the use of geopolymer slurries is a great alternative route to cementing oil wells. Besides having good properties, comparable to Portland cement slurries, this alternative material releases much less CO2 gas in the production of their root materials when compared the production of Portland cement, which releases tons of CO2. In order to improve the properties of geopolymer slurries has been added Calcium Oxide, as observed in other studies that slurries where the Calcium is present the values of compressive strength is greater. The addition has been realized based in the CaO/SiO2 molar ratio of 0.05, 0.10 and 0.15. Have been performed compressive strength tests, thickening time, rheology and fliud loss control test of the slurries, following NBR 9831, as well as the physical chemical characterization of XRD, SEM and TG. Has been observed in most of the tests the slurries follow a tendency until the ratio of 0.10, which inverses in the ratio 0.15. This behavior can be explained by two phenomena that occur simultaneously, the first one is the break of the polymer chains and a consequent increase in molucules mobility, which prevails until the ratio of 0.1, and the second is possible approach of the chains due to the capacity of the calcium ions stabilize the charges of two different aluminum. There is only one linearity in the mechanical behavior that can be attributed to the appereance of the C-S-H phase. Based on this, it is concluded that the phenomenon of breaking the polymer chains predominates until the ratio of 0.1, causing an increase of the filtrate volume, lower rheological parameters and increasing thickening time. From the ratio of 0.15 the approach of the chains predominates, and the behavior is reversed

Étude de propriétés physico-chimiques des membranes lipidiques chargées d’acide palmitique/stérol et de stéarylamine/cholestérol

Les stérosomes, des vésicules artificielles composées d’amphiphiles monoalkylés et d’un grand pourcentage de stérols, sont prometteurs dans plusieurs domaines comme les industries pharmaceutiques et alimentaires. Il existe des stérosomes chargés négativement, positivement et neutres. Dans ce mémoire, nous avons approfondi nos connaissances sur les propriétés physico-chimiques des stérosomes chargés : acide palmitique (PA)/stérol et stéarylamine (SA)/cholestérol (Chol). Premièrement, afin de mesurer la diffusion latérale de PA dans les membranes PA/stérol (30/70 mol/mol) par RMN à gradients pulsés, nous avons tenté de former des bicouches liquide-ordonnées (lo) orientées magnétiquement avec ce mélange. En s'inspirant de l’idée que l’ajout de 1,2-dihexanoyl-sn-glycéro-3-phosphocholine (DHPC), un lipide à courtes chaînes, dans le système 1,2-dimyristoyl-sn-glycéro-3-phosphocholine (DMPC) mène à la formation de bicouches orientées, nous avons étudié la formulation PA perdeutéré/acide hexanoïque (HA)/Chol avec une proportion molaire de 25/18/57 à plusieurs températures; aucune formation de bicouches orientées n’a été observée. Ce résultat pourrait être expliqué par la solubilisation partielle de HA en milieu aqueux. Alors, une quantité insuffisante serait insérée dans la bicouche pour induire son orientation. La formulation PA perdeutéré/DHPC/Chol n’a pas conduit, elle non plus, à des bicouches orientées magnétiquement à des températures et concentrations lipidiques variées. En étudiant le mélange DMPC/DHPC/Chol (67/17/14), nous avons remarqué que la présence de Chol inhibait l'orientation magnétique des bicouches. Tandis que le mélange DMPC/DHPC/stigmastérol (SS) avec les proportions molaires 67/19/14 et 72/21/7 conduisait à des bicouches orientées avec leur normale (n) perpendiculaire au champ magnétique à 40 °C et 50 °C. Ces résultats suggèrent que le mélange PA/SS avec une proportion de lipide à courtes chaînes, HA et DHPC, pourrait mener à des bicouches orientées magnétiquement. Le mélange PA/Chol avec un lipide à courtes chaînes pourrait aussi être étudié en présence des lanthanides. Deuxièmement, nous avons examiné la possibilité de moduler la libération de matériel encapsulé dans des liposomes essentiellement composés de PA et d’un stérol. Il est connu que le mélange PA/Chol (30/70) à pH ≥ 7,5 forme des liposomes très peu perméables. Il est avantageux de pouvoir moduler la perméabilité pour avoir un contrôle sur le temps de libération de leur contenu, qui est un paramètre de grande importance pour les formulations liposomales de médicaments. D’abord, il a été montré que l’acide oléique (OA)/Chol (30/70) est capable de former des vésicules, ce qui n’avait jamais été prouvé auparavant. Par contre, les bicouches OA/Chol (30/70) ne sont pas plus perméables que les bicouches PA/Chol (30/70). L’ajout de 1-palmitoyl-2-oléoyl-sn-glycéro-3-phosphatidylcholine (POPC) dans le mélange PA/Chol n’augmente pas plus la perméabilité. En effet, les cinétiques de relargage de calcéine des vésicules PA/POPC/Chol (15/27.5/57.5), POPC/Chol (40/60) et POPC étaient très semblables à celle de PA/Chol (30/70). Il a été remarqué que les études littéraires se contredisent à propos de la perméabilité à la calcéine des bicouches de phosphatidylcholine (PC). L’explication de ces divergences est inconnue pour le moment. En remplaçant la moitié de la proportion molaire de Chol par le cholate de sodium (SC) dans le mélange PA/Chol (30/70), la membrane n’était pas plus apte à libérer son contenu. Il se pourrait que le SC se retrouvant dans la bicouche n’induit pas une diminution d’empilement. Il est aussi possible que le SC ne s'insère pas dans la membrane à cause de son hydrophilie considérable et il pourrait alors former seul des micelles. En remplaçant complètement le Chol par le sulfate de cholestérol (SChol), un stérol chargé négativement, et en préparant les vésicules à un bas pH, la formulation PA/SChol (30/70) mène à une très grande perméabilité à pH 7.5; le relargage est provoqué par un saut de pH. Nos travaux suggèrent qu'il serait possible de moduler la perméabilité des liposomes en les préparant avec le mélange PA/SChol/Chol en variant les proportions entre 30/63/7 à 30/70/0. Le diagramme pH-composition du mélange PA/SChol/Chol indique que ces proportions conduisent, à pH 7.4, à la coexistence de phases solide et lo en différentes proportions, ce qui pourrait moduler la perméabilité membranaire. Troisièmement, les résultats de perméabilité obtenus avec la calcéine et les difficultés survenues lors de l’extrusion des vésicules encapsulant cette sonde nous ont amené à nous demander si la calcéine interagit avec les bicouches chargées. L’impact de certains anions, dont la calcéine, a été examiné sur les bicouches chargées positivement SA/Chol (50/50). La calorimétrie différentielle à balayage (DSC, de l’anglais differential scanning calorimetry), indique qu’il n’y a aucune transition entre 25 et 90 °C pour les liposomes SA/Chol (50/50) à pH = 7.4. L’ajout de chlorure de sodim (375 mM) n’a pas mené à la formation d’agrégats et aucune transition n’a été observée sur le thermogramme. La formation d’agrégats macroscopiques instantanément après l’ajout d’hydrogénophosphate de sodium (125 mM), de sulfate de sodium (125 mM) et de calcéine (3 mM) a été observée. Une transition a été observée sur les thermogrammes en présence de ces sels. Les agrégats observés pourraient être associés à la transition de phase. L’effet des anions sur la température et l’enthalpie de transition suivent le même ordre que la série d’Hofmeister : sulfate > hydrogénophosphate > chlorure (pas de pic). La calcéine avait l’impact le plus prononcé sur l’agrégation; ceci illustre que la calcéine n’est pas une sonde fluorescente inerte avec le mélange SA/Chol. Elle pourrait être un chaotrope volumineux. De plus, les interactions SA-calcéine plus fortes, menant à l’agrégation des vésicules, que les interactions PC-calcéine pourraient s’expliquer par le fait que la SA est chargée positivement.

Magnetic Nanoparticle-based Targeted Drug Delivery for Treatment of Neuro-AIDS and Drug Addiction

Brain is one of the safe sanctuaries for HIV and, in turn, continuously supplies active viruses to the periphery. Additionally, HIV infection in brain results in several mild-to-severe neuro-immunological complications termed neuroAIDS. One-tenth of HIV-infected population is addicted to recreational drugs such as opiates, alcohol, nicotine, marijuana, etc. which share common target-areas in the brain with HIV. Interestingly, intensity of neuropathogenesis is remarkably enhanced due to exposure of recreational drugs during HIV infection. Current treatments to alleviate either the individual or synergistic effects of abusive drugs and HIV on neuronal modulations are less effective at CNS level, basically due to impermeability of therapeutic molecules across blood-brain barrier (BBB). Despite exciting advancement of nanotechnology in drug delivery, existing nanovehicles such as dendrimers, polymers, micelles, etc. suffer from the lack of adequate BBB penetrability before the drugs are engulfed by the reticuloendothelial system cells as well as the uncertainty that if and when the nanocarrier reaches the brain. Therefore, in order to develop a fast, target-specific, safe, and effective approach for brain delivery of anti-addiction, anti-viral and neuroprotective drugs, we exploited the potential of magnetic nanoparticles (MNPs) which, in recent years, has attracted significant importance in biomedical applications. We hypothesize that under the influence of external (non-invasive) magnetic force, MNPs can deliver these drugs across BBB in most effective manner. Accordingly, in this dissertation, I delineated the pharmacokinetics and dynamics of MNPs bound anti-opioid, anti-HIV and neuroprotective drugs for delivery in brain. I have developed a liposome-based novel magnetized nanovehicle which, under the influence of external magnetic forces, can transmigrate and effectively deliver drugs across BBB without compromising its integrity. It is expected that the developed nanoformulations may be of high therapeutic significance for neuroAIDS and for drug addiction as well.

Étude de propriétés physico-chimiques des membranes lipidiques chargées d’acide palmitique/stérol et de stéarylamine/cholestérol

Les stérosomes, des vésicules artificielles composées d’amphiphiles monoalkylés et d’un grand pourcentage de stérols, sont prometteurs dans plusieurs domaines comme les industries pharmaceutiques et alimentaires. Il existe des stérosomes chargés négativement, positivement et neutres. Dans ce mémoire, nous avons approfondi nos connaissances sur les propriétés physico-chimiques des stérosomes chargés : acide palmitique (PA)/stérol et stéarylamine (SA)/cholestérol (Chol). Premièrement, afin de mesurer la diffusion latérale de PA dans les membranes PA/stérol (30/70 mol/mol) par RMN à gradients pulsés, nous avons tenté de former des bicouches liquide-ordonnées (lo) orientées magnétiquement avec ce mélange. En s'inspirant de l’idée que l’ajout de 1,2-dihexanoyl-sn-glycéro-3-phosphocholine (DHPC), un lipide à courtes chaînes, dans le système 1,2-dimyristoyl-sn-glycéro-3-phosphocholine (DMPC) mène à la formation de bicouches orientées, nous avons étudié la formulation PA perdeutéré/acide hexanoïque (HA)/Chol avec une proportion molaire de 25/18/57 à plusieurs températures; aucune formation de bicouches orientées n’a été observée. Ce résultat pourrait être expliqué par la solubilisation partielle de HA en milieu aqueux. Alors, une quantité insuffisante serait insérée dans la bicouche pour induire son orientation. La formulation PA perdeutéré/DHPC/Chol n’a pas conduit, elle non plus, à des bicouches orientées magnétiquement à des températures et concentrations lipidiques variées. En étudiant le mélange DMPC/DHPC/Chol (67/17/14), nous avons remarqué que la présence de Chol inhibait l'orientation magnétique des bicouches. Tandis que le mélange DMPC/DHPC/stigmastérol (SS) avec les proportions molaires 67/19/14 et 72/21/7 conduisait à des bicouches orientées avec leur normale (n) perpendiculaire au champ magnétique à 40 °C et 50 °C. Ces résultats suggèrent que le mélange PA/SS avec une proportion de lipide à courtes chaînes, HA et DHPC, pourrait mener à des bicouches orientées magnétiquement. Le mélange PA/Chol avec un lipide à courtes chaînes pourrait aussi être étudié en présence des lanthanides. Deuxièmement, nous avons examiné la possibilité de moduler la libération de matériel encapsulé dans des liposomes essentiellement composés de PA et d’un stérol. Il est connu que le mélange PA/Chol (30/70) à pH ≥ 7,5 forme des liposomes très peu perméables. Il est avantageux de pouvoir moduler la perméabilité pour avoir un contrôle sur le temps de libération de leur contenu, qui est un paramètre de grande importance pour les formulations liposomales de médicaments. D’abord, il a été montré que l’acide oléique (OA)/Chol (30/70) est capable de former des vésicules, ce qui n’avait jamais été prouvé auparavant. Par contre, les bicouches OA/Chol (30/70) ne sont pas plus perméables que les bicouches PA/Chol (30/70). L’ajout de 1-palmitoyl-2-oléoyl-sn-glycéro-3-phosphatidylcholine (POPC) dans le mélange PA/Chol n’augmente pas plus la perméabilité. En effet, les cinétiques de relargage de calcéine des vésicules PA/POPC/Chol (15/27.5/57.5), POPC/Chol (40/60) et POPC étaient très semblables à celle de PA/Chol (30/70). Il a été remarqué que les études littéraires se contredisent à propos de la perméabilité à la calcéine des bicouches de phosphatidylcholine (PC). L’explication de ces divergences est inconnue pour le moment. En remplaçant la moitié de la proportion molaire de Chol par le cholate de sodium (SC) dans le mélange PA/Chol (30/70), la membrane n’était pas plus apte à libérer son contenu. Il se pourrait que le SC se retrouvant dans la bicouche n’induit pas une diminution d’empilement. Il est aussi possible que le SC ne s'insère pas dans la membrane à cause de son hydrophilie considérable et il pourrait alors former seul des micelles. En remplaçant complètement le Chol par le sulfate de cholestérol (SChol), un stérol chargé négativement, et en préparant les vésicules à un bas pH, la formulation PA/SChol (30/70) mène à une très grande perméabilité à pH 7.5; le relargage est provoqué par un saut de pH. Nos travaux suggèrent qu'il serait possible de moduler la perméabilité des liposomes en les préparant avec le mélange PA/SChol/Chol en variant les proportions entre 30/63/7 à 30/70/0. Le diagramme pH-composition du mélange PA/SChol/Chol indique que ces proportions conduisent, à pH 7.4, à la coexistence de phases solide et lo en différentes proportions, ce qui pourrait moduler la perméabilité membranaire. Troisièmement, les résultats de perméabilité obtenus avec la calcéine et les difficultés survenues lors de l’extrusion des vésicules encapsulant cette sonde nous ont amené à nous demander si la calcéine interagit avec les bicouches chargées. L’impact de certains anions, dont la calcéine, a été examiné sur les bicouches chargées positivement SA/Chol (50/50). La calorimétrie différentielle à balayage (DSC, de l’anglais differential scanning calorimetry), indique qu’il n’y a aucune transition entre 25 et 90 °C pour les liposomes SA/Chol (50/50) à pH = 7.4. L’ajout de chlorure de sodim (375 mM) n’a pas mené à la formation d’agrégats et aucune transition n’a été observée sur le thermogramme. La formation d’agrégats macroscopiques instantanément après l’ajout d’hydrogénophosphate de sodium (125 mM), de sulfate de sodium (125 mM) et de calcéine (3 mM) a été observée. Une transition a été observée sur les thermogrammes en présence de ces sels. Les agrégats observés pourraient être associés à la transition de phase. L’effet des anions sur la température et l’enthalpie de transition suivent le même ordre que la série d’Hofmeister : sulfate > hydrogénophosphate > chlorure (pas de pic). La calcéine avait l’impact le plus prononcé sur l’agrégation; ceci illustre que la calcéine n’est pas une sonde fluorescente inerte avec le mélange SA/Chol. Elle pourrait être un chaotrope volumineux. De plus, les interactions SA-calcéine plus fortes, menant à l’agrégation des vésicules, que les interactions PC-calcéine pourraient s’expliquer par le fait que la SA est chargée positivement.

Physicochemical complexity in complex chemical systems

Self-replication and compartmentalization are two central properties thought to be essential for minimal life, and understanding how such processes interact in the emergence of complex reaction networks is crucial to exploring the development of complexity in chemistry and biology. Autocatalysis can emerge from multiple different mechanisms such as formation of an initiator, template self-replication and physical autocatalysis (where micelles formed from the reaction product solubilize the reactants, leading to higher local concentrations and therefore higher rates). Amphiphiles are also used in artificial life studies to create protocell models such as micelles, vesicles and oil-in-water droplets, and can increase reaction rates by encapsulation of reactants. So far, no template self-replicator exists which is capable of compartmentalization, or transferring this molecular scale phenomenon to micro or macro-scale assemblies. Here a system is demonstrated where an amphiphilic imine catalyses its own formation by joining a non-polar alkyl tail group with a polar carboxylic acid head group to form a template, which was shown to form reverse micelles by Dynamic Light Scattering (DLS). The kinetics of this system were investigated by 1H NMR spectroscopy, showing clearly that a template self-replication mechanism operates, though there was no evidence that the reverse micelles participated in physical autocatalysis. Active oil droplets, composed from a mixture of insoluble organic compounds in an aqueous sub-phase, can undergo processes such as division, self-propulsion and chemotaxis, and are studied as models for minimal cells, or protocells. Although in most cases the Marangoni effect is responsible for the forces on the droplet, the behaviour of the droplet depends heavily on the exact composition. Though theoretical models are able to calculate the forces on a droplet, to model a mixture of oils on an aqueous surface where compounds from the oil phase are dissolving and diffusing through the aqueous phase is beyond current computational capability. The behaviour of a droplet in an aqueous phase can only be discovered through experiment, though it is determined by the droplet's composition. By using an evolutionary algorithm and a liquid handling robot to conduct droplet experiments and decide which compositions to test next, entirely autonomously, the composition of the droplet becomes a chemical genome capable of evolution. The selection is carried out according to a fitness function, which ranks the formulation based on how well it conforms to the chosen fitness criteria (e.g. movement or division). Over successive generations, significant increases in fitness are achieved, and this increase is higher with more components (i.e. greater complexity). Other chemical processes such as chemiluminescence and gelation were investigated in active oil droplets, demonstrating the possibility of controlling chemical reactions by selective droplet fusion. Potential future applications for this might include combinatorial chemistry, or additional fitness goals for the genetic algorithm. Combining the self-replication and the droplet protocells research, it was demonstrated that the presence of the amphiphilic replicator lowers the interfacial tension between droplets of a reaction mixture in organic solution and the alkaline aqueous phase, causing them to divide. Periodic sampling by a liquid handling robot revealed that the extent of droplet fission increased as the reaction progressed, producing more individual protocells with increased self-replication. This demonstrates coupling of the molecular scale phenomenon of template self-replication to a macroscale physicochemical effect.

Novos complexos micelares de metais de transição para aplicação na terapia dirigida contra o cancro

O cancro é a segunda causa de mortalidade a nível mundial. Um dos problemas nos tratamentos atuais de quimioterapia relaciona-se com os efeitos secundários causados pela falta de seletividade dos fármacos utilizados. Assim, um dos desafios atuais é o desenvolvimento de sistemas terapêuticos que permitam potenciar o efeito dos fármacos e diminuir os seus efeitos nocivos. Neste contexto, neste trabalho, foram sintetizados complexos de Fe, Co e Zn com fórmula geral [M(bipy-R)3]x+, a partir dos quais foi possível obter sistemas micelares formados in situ pela adição de um copolímero de PLA-b-PEG ou por introdução de macroligandos poliméricos anfifílicos. Os resultados mostram que as nanopartículas formadas apresentam tamanho e características adequadas para aplicações na terapia dirigida contra o cancro. Os resultados preliminares de citotoxicidade na linha tumoral humana da mama MDAMB231 indicam que todos os compostos estudados apresentam atividade citotóxica relevante, sendo os compostos micelares os mais promissores; Abstract: New micellar transition metals complexes for targeted therapy of cancer Cancer is the second leading cause of mortality worldwide. One problem in the current chemotherapy treatments is related to the severe side effects caused by the lack of selectivity of the drugs in clinical use. Thus, one of the current challenges is the development of new therapeutic systems that allow maximizing the effect of the drugs and reducing their harmful effects. In this context, several Fe, Co and Zn compounds of the general formula [M (bipy-R)3]x+ were synthesized in order to obtain micellar systems, either by in situ addition of a PLA-b-PEG copolymer or by introducing amphiphilic macroligands. The results show that the formed nanoparticles have size and characteristics suitable for applications in targeted therapy against cancer. Preliminary results of cytotoxicity in human breast cancer line MDAMB231 indicate that all the studied compounds show significant cytotoxic activity, being the micellar compounds the most promising agents.

On the etiology of cardiovascular diseases: a new framework for understanding literature results

The interpretative framework presented here provides a rationale for many well-known features of cardiovascular diseases. Prolonged acidemia with high blood levels of free fatty acids is proposed to shape the basic context for formation of fatty acid micelles and vesicles with an acidic core that fuse with the endothelia, disrupt vital cell processes, and initiate atherosclerotic plaque formation. It offers an explanation for the distributed localization of atherosclerotic lesions, and how mild cases of occurrence of fatty acids vesicles formed within the heart and the arteries close to the heart may cause such lesions. It provides a rationale for how acute events, namely heart attacks and strokes, may arise from stormy development of fatty acid vesicles within the heart. Additionally, a process is proposed for clot development from the existing fatty acid vesicles.

CRESCIMENTO ECONÔMICO E DESENVOLVIMENTO: REFLEXÕES GEOGRÁFICAS A PARTIR DA REALIDADE SÓCIO-ESPACIAL DE JUAZEIRO E PETROLINA, BRASIL

O presente artigo aborda a realidade socioeconômica das duas principais cidades que compreendem o denominado eixo Juazeiro-Petrolina, situadas, respectivamente, nos estados federativos brasileiros da Bahia e de Pernambuco, considerando os processos de organização territorial da produção à luz das principais teorias de desenvolvimento regional e local. Pretende-se, a partir da análise dos conceitos de crescimento e de desenvolvimento, analisar, sob uma ótica geográfica, as implicações sócio-espaciais do acelerado crescimento econômico das duas cidades e os condicionantes políticos que repercutem neste processo. Enquanto metodologia de análise utilizou-se revisão bibliográfica baseada em artigos, periódicos e livros, observação de campo ocorrida no pólo Juazeiro – Petrolina no período de 28 de julho a 01 de agosto do ano de 2010 e análise de dados estatísticos. Os resultados apontam para um crescimento econômico com o advento da fruticultura irrigada acompanhado da expansão do setor de serviços, aumento dos níveis de emprego e de renda, além de modificações significativas na infra-estrutura local proporcionadas, sobretudo, por intervenções governamentais. Por outro lado, o desenvolvimento, em uma perspectiva ambiental e social, não tem acompanhado esta tendência de crescimento econômico, evidenciando as inversões de prioridades por parte dos atores políticos locais. 

Radical chemistry of the catechol/quinone system and its role in the control of lipid peroxidation and melanin biosynthesis

The catechol (1,2-dihydroxybenzene) is a privileged structural motif among natural antioxidants like flavonoids, owing to its reactivity with alkylperoxyl radicals due to the stability of the semiquinone radical. The exploration of the relevance and mechanism of this non-conventional antioxidant chemistry in heterogenous biomimetic systems (aqueous micelles and unilamellar liposomes) is explored for the first time in Chapter 1. Results show antioxidant behaviour that surpasses that of nature’s premiere antioxidant α-tocopherol and relies on the cross-dismutation of alkylperoxyl and hydroperoxyl radicals at the water-lipid interface with regeneration of the catechol function from the oxidized quinone. The design and synthesis of new biomimetic catechol-type antioxidants by conjugation of thiols (e.g. cysteine) with quinones highlighted an unusual 1,6-type regioselectivity, which had been previously reported but never fully rationalized. Owing to its importance both in nature and in the development of new antioxidants, we investigated it in detail in Chapter 2. We could prove the onsetting of a radical-chain mechanism intermediated by thiyl and thiosemiquinone radicals at the basis of the “anomalous nucleophilic addition” of thiols to ortho-quinones, which paves the way to better understanding of the chemistry of such systems. The oxidation of catechols to the corresponding quinones is also a key reaction in the biosynthesis of melanins, mediated by enzyme Tyrosinase.

Kinetic and mechanistic studies on peroxidation and stabilization of lipids with industrial and biological relevance

Lipid peroxidation is a complex mechanism that causes the degradation of lipid material of both industrial and biological significance. During processing, it is known that thermal stress produces oxidation and polymerization of oils. Additionally, biological lipids with both structural and bioactive roles are prone to peroxidation, which can have pathogenic effects including cancer and long-term degenerative disorders. To create innovative strategies to slow down the deterioration of lipids, it is crucial to improve our understanding of oxidation reactions and kinetics. To this purpose, Chapter II of this thesis focuses on the kinetic study of the oxidation reactions that take place during the thermal processing of bio-oils for industrial application. Through a new method it was possible to evaluate the kinetic parameters of oxidation of various lipid materials. This allowed us to distinguish between the different lipid materials based on their intrinsic properties. The effect of 18 antioxidants from the major families of natural and synthetic phenols were studied using the same methodology in order to acquire crucial data for enhancing the antioxidant activity of phenols based on structure-activity at high temperatures. Finally, it has been described how the antioxidant activity of α-tocopherol, revealed to be scarce in our conditions, can be improved in the presence of gamma-terpinene, through a synergistic action. Chapter III describes the synthesis and study of the antioxidant activity of polydopamine nanoparticles, in order to clarify the unclear mechanism of action of this material. Finally, in Chapter IV it was reported how the gamma-terpinene strongly inhibits the peroxidation of unsaturated lipids in heterogeneous model systems (micelles and liposomes) by forming hydroperoxyl radicals which diffuse outside the lipid nucleus, blocking the propagation of the chain radical. Furthermore, gamma-terpinene shows a very potent protective activity against ferroptosis being effective in the nanomolar range in the human neuroblastoma cell model.