Yes / Due to the environmental legislations related to sulfur content and proceeding with the challenges to find an appropriate catalyst of such contamination producing clean fuel, a main thrust for improving of more efficient technologies on new oxidative catalyst is viewed a vital issue in fuel quality development. So, in this study, the sulfur compound (ethyl mercaptan) presents in light naphtha feedstock is removed by oxidative desulfurization (ODS) in a batch reactor using a new homemade nano-catalyst and air as oxidant under different reaction conditions (reaction temperatures, reaction time and the initial sulfur concentrations) that has not been studied in such field. The catalyst is zinc oxide supported on zeolite nanoparticles which is locally prepared by Incipient Wetness Impregnation (IWI) method. Mathematical model of the relevant reactions is also developed in this study to match the experimental results via obtaining the optimal kinetic parameters utilizing optimization techniques within gPROMS program. Such optimization is conducted using two approaches (linear and nonlinear regression) and the results showed that the nonlinear approach is more accurate than linear approach. The optimal kinetic parameters are then used to achieve a clean fuel via getting the optimal operation conditions based on the maximum conversion. Where, higher than 99% of the process conversion has obtained at temperature of 327.4 K, reaction time at163.6 min and initial concentration of 335.3 ppm.

Indiscriminate use of pesticides appears to alter immune response in non-target organisms such as humans and other animals. Thus, immune modulation is considered as one of the potential risks and consequences following exposure to these chemicals. Because of the widespread usage, exposure to mixtures of pesticides during the lifetime of individuals is unavoidable and can result in potentiation of the toxic effects. Because immune cells are more susceptible to toxic insults at a lower dose than most other cell types, the effects of pesticides and their mixtures on murine splenocytes were evaluated. C57BL/6 male mouse splenocytes, in vitro, were exposed to permethrin and endosulfan, individually and in-combination (25-200 µM). The immunotoxic potential of these pesticides was monitored using a flow cytometric technique in combination with 7-Amino Actinomycin D (7-AAD) staining. Endosulfan exposures (25-150 µM) resulted in time- and dose-dependent increase in apoptotic and necrotic cell death in murine splenocytes, in vitro. Permethrin exposure (50-200 µM) resulted in neither a time-dependent/dose-dependent loss of splenocyte viability nor induction of apoptosis in splenocytes. With mixtures of permethrin and endosulfan, depressed viability and enhanced early apoptosis and late apoptosis/necrosis were observed. Exposure to mixtures of 50 µM endosulfan with 50 or 100 µM permethrin increased late apoptosis/necrosis compared to exposure to either chemical alone. DNA fragmentation, a hall mark of apoptosis was observed by DNA ladder technique, confirming the occurrence of apoptosis. Morphological observation using cytospun slides was also carried out to further confirm the presence of apoptosis and necrosis. These findings suggest that the immunotoxicity of endosulfan both individually and in mixtures with permethrin is associated with the occurrence of apoptotic and necrotic processes. Further, the ability of these pesticides to alter the oxidative status of the cells, via reactive oxygen species (ROS) generation and modulation of intracellular antioxidant enzymes levels, was investigated. We monitored the generation of ROS such as hydrogen peroxide (H₂O₂) with 2´, 7´- dichlorofluorescin diacetate (DCFH-DA) assay and superoxide anion (O₂⁻) with hydroethidine (HE) assay in combination with flow cytometry. Spectrophotometric techniques were used to measure antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPX). Results of the analyses revealed that individual pesticides increased the production of H₂O₂ in a time and dose-dependent manner. Both time and dose-dependent increases in O₂⁻ production were caused by permethrin; whereas endosulfan exposure resulted in only a dose-dependent increase. However, exposure to mixtures of these pesticides had little or no effect on the generation of H₂O₂ and O₂⁻ radicals as compared to individual pesticides. The levels of SOD and GPX in pesticide-treated splenocytes were found to be not different from solvent control. An increase in GR and CAT levels in cells was noticed with permethrin (100 µM) exposure. These findings suggest that permethrin and endosulfan have the ability to affect the cellular oxidative status and can cause toxicity in immune cells, in vitro. / Master of Science

Malignant mesothelioma (MM) is a rare tumor associated with occupational exposure to asbestos with no effective treatment regime. Evaluation of mitochondrial function in human MM cell lines revealed a common tumor phenotype: in comparison to immortalized or primary human mesothelial cells, MM tumor cells displayed a more oxidized mitochondrial environment, increased expression of mitochondrial antioxidant enzymes, and altered mitochondrial metabolism. Earlier work by our laboratory indicated that increases in mitochondrial reactive oxygen species (mROS) in MM cell lines supports expression of FOXM1, an oncogenic transcription factor that contributes to increased cell proliferation and chemoresistance. These studies sought to investigate targeting of mitochondrial structure and function as a therapeutic avenue in MM. MM cells have reduced mitochondrial reserve capacity, a redox vulnerability exploitable by pro-oxidant therapeutics. Targeting of the mitochondrial peroxidase peroxiredoxin 3 (PRX3) with the anti-cancer compound thiostrepton (TS) induces irreversible modifications to PRX3 protein, increased mROS, and selective MM cell death. Mass spectrometry showed TS targets conserved cysteine residues in PRX3. In vitro and in MM cells, TS failed to modify human PRX3 harboring mutations to Cys108, Cys127 or Cys229. Pre-incubation of MM cells with dimedone blocked cysteine adduction of PRX3 by TS, suggesting adduction requires an active PRX3 catalytic cycle. Studies with immortalized and primary human mesothelial cells showed adduction of PRX3 by TS occurred at a much lower rate in normal cells than MM cells, and this difference correlated with markedly decreased cytotoxicity. Moreover, MM cells transduced with shRNA to PRX3 grew more slowly and were less sensitive to TS than their wild type counterparts, indicating PRX3 is a major target of TS in MM cells. Studies with a xenoplant mouse model of MM showed TS alone or in combination with the TRX2 inhibitor gentian violet significantly reduced tumor volume. Tumor cell mitochondria have an increased mitochondrial membrane potential, therefore numerous drugs have been developed that selectively accumulatte into energized mitochondria to enhance drug efficacy and specificity. Here two mitochondrial-targeted nitroxides, Mito-carboxy-proxyl (MCP) and Mito-TEMPOL (MT), were investigated for their anti-cancer effects. Treatment of MM cells with MCP or MT led to rapid disruption of the mitochondrial reticulum, increased oxidant levels, and reduced FOXM1 and PRX3 protein expression. Immunostaining revealed a pool of cytoplasmic FOXM1 associated with PRX3 in mitochondria, suggesting PRX3 participates in regulating FOXM1 expression. Combination of MCP or MT with TS led to synergistic effects on MM cell viability. Upregulation of mitochondrial antioxidant enzymes is an adaptive response that ameliorates mitochondrial oxidative stress and supports tumor cell survival. Studies here indicate that enhanced dependency on the PRX3 catalytic cycle in tumor cells promotes inactivation of PRX3 by TS, providing a therapeutic window dependent on a mitochondrial phenotype common to many human tumor types. Therefore TS, alone or in combination with other agents, may prove useful in the management of intractable tumors such as MM.

La dystrophie facioscapulohumérale (FSHD) est une dystrophie musculaire autosomique dominante, dégénérative et progressive. Les traitements élaborés jusqu'à présent n'ont pas réussi à améliorer le quotidien des patients FSHD. Plusieurs études se sont focalisées sur les mécanismes moléculaires de cette pathologie, néanmoins plusieurs d'entre elles sont contradictoires. La vision actuelle de la FSHD est celle d'une pathologie due à un mécanisme épigénétique complexe et les mécanismes moléculaires responsables de cette pathologie sont encore mal connus. Plusieurs analyses comparatives des profils d'expression des ARNm et des protéines de muscles de patients atteints de FSHD et de contrôles ont permis de montrer que plusieurs gènes impliqués dans le stress oxydant sont dérégulés de façon spécifique dans les muscles FSHD. Nos travaux ont permis de montrer dans la FSHD, aussi bien au niveau systémique, musculaire et cellulaire (cultures primaires musculaires) une augmentation des dommages oxydatifs qui se traduisent par une augmentation des peroxydes lipidiques et protéines oxydées, associés à une altération des défenses antioxydantes. Ce stress oxydant dans les biopsies musculaires et cultures primaires musculaires est associé à un dysfonctionnement mitochondrial. Des analyses plus fines sur l'action des espèces réactives de l'oxygène et leurs sources pourraient contribuer à une meilleure compréhension des bases physiopathologiques de la FSHD et permettre la sélection de thérapeutiques adaptées aux anomalies des patients FSHD. / Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal inherited muscular dystrophy. Actually no treatment led to improve the quality of life. Many studies have been focused on the molecular mechanisms of this disease, several of them were contradictory. The present view of the FSHD seems to be due to a complex epigenetic mechanism. Actually, no gene has been identified. Several comparative studies permit the identification of many genes involved in oxidative stress, deregulated in FSHD myoblasts and biopsies in comparison to healthy ones. Analysis of oxidative stress markers show that patients with FSHD present increased oxidative damage in blood as well as in biopsy muscle and muscular primary cell culture associated with altered antioxidant enzyme defenses. Oxidative stress is also associated with mitochondrial dysfunction. Complementary studies focusing in pathway of reactive oxygen species would contribute to a better understanding of pathophysiological bases of FSHD in order to establish a very helpful therapeutics for FSHD patients.

L'insulinorésistance (IR), touchant 80% des sujets obèses, forme, aux côtés du déficit insulinosécrétoire, l'un des deux mécanismes physiopathologiques clés du diabète de type 2. Sa prévention nécessite de bien en comprendre les mécanismes inducteurs. Les facteurs nutritionnels tels que la surconsommation d'aliments hypercaloriques pauvres en micronutriments antioxydants jouent un rôle majeur. Ils conduisent à une production de radicaux libres excédant les défenses antioxydantes et donc à un stress oxydant qui a été proposé comme étant un trait d'union entre la surconsommation alimentaire et l'IR. Dans ce contexte, mon travail de thèse a visé à évaluer si des polyphénols (PP) de raisin rouge, composés phytochimiques antioxydants, étaient capables de moduler favorablement la cascade d'évènements conduisant de la suralimentation au stress oxydant et à l'IR. Ainsi des sujets sains à risque de développer une IR ont été supplémentés durant 9 semaines avec un extrait de raisin riche en PP. Pour sensibiliser les effets potentiels des PP, une surcharge en fructose a été donnée au cours des 6 derniers jours du protocole. Chez nos volontaires nous avons étudié : le statut redox, l'inflammation, la production d'adipokines, l'activité mitochondriale et l'insulinosensibilité par clamp euglycémique à deux paliers. Les résultats obtenus démontrent que les PP de raisins préviennent l'IR hépatique et musculaire en inhibant le stress oxydant et la dysfonction mitochondriale induite par une surcharge en fructose. En conclusion, ces travaux suggèrent l'intérêt thérapeutique d'une supplémentation en antioxydants naturels à doses nutritionnelles de PP de raisins, pour la prévention de l'IR. / Insulin resistance (IR), found in 80% of obesity cases, constitutes with insulin secretory deficiency one of the two key physiopathological mechanisms of type 2 diabetes. In order to better prevent it, in depth knowledge of its inducing mechanisms is required. Nutritional factors such as overconsumption of hypercaloric foods poor in antioxidant micronutrients play a pivotal role. The latter activate an overproduction of free radicals exceeding antioxidant defenses leading to oxidant stress, which is considered to be a unifying mechanism for nutrient overconsumption and IR. In this context, my thesis work aimed to determine if red grape polyphenols (PP), antioxidant phytochemicals, were capable to favorably modulate the cascade of events leading from overconsumption to oxidant stress to IR. Thus healthy subjects at risk of developing IR were supplemented for 9 weeks with an enriched PP grape extract. In order to study PP potential effects in a environment under metabolic stress, during the last 6 days of the protocol volunteers received a fructose overload. Throughout investigations the following parameters were studied: inflammation, adipokine production, mitochondrial activity and insulin sensitivity evaluated by a 2 step glucose clamp.The results obtained demonstrate how red grape PP prevent hepatic and muscular IR by inhibiting oxidant stress and mitochondrial dysfunction induced by fructose overload.In conclusion, this study illustrates the therapeutic efficiency of natural antioxidant supplementation in the form of nutritional doses of grape PP in the prevention of IR.

Ischaemia-reperfusion (IR) injury makes a major contribution to graft damage during kidney transplantation and increases the risks of primary non-function, delayed graft function and rejection. Oxidative damage to mitochondria is a key early event in IR injury. The aim of this project was to examine the safety and efficacy of the mitochondria-targeted antioxidant MitoQ in reducing pig and human kidney IR injury using an ex vivo normothermic perfusion (EVNP) system. Over a range of 500 nM to 250 µM using a 150 pig kidneys and 80 declined deceased human kidneys, MitoQ was successfully taken up by pig and human kidneys in a concentration-dependent manner, resulting in stable tissue concentrations over 24 hours of cold storage followed by 6 hours of EVNP. The uptake of MitoQ was increased approximately 2-fold when MitoQ was administered to warm (rather than cold) kidneys and when kidneys were preserved using hypothermic machine perfusion (rather than cold static storage). 50 µM MitoQ, administered to pig kidneys at the end of warm ischaemia, significantly increased renal blood and urine output flow at the end of 6 h EVNP compared to the control group. Creatinine clearance was numerically higher in the 50 µM MitoQ group compared to the control group but the difference did not reach statistical significance. To test the safety and efficacy of MitoQ in human kidney IRI, pairs of declined deceased human kidneys were used, with one kidney in each pair used as control. The total urine output, creatinine clearance and percentage fall of serum creatinine were numerically higher in the 50 µM MitoQ group compared to the control group, although the differences did not reach statistical significance during 3 h of EVNP. There was a significant difference in the renal blood flow between the 50 µM MitoQ group and the control group at the end of the first hour of EVNP. The renal blood flow remained relatively stable during the first hour of EVNP in the 50 µM MitoQ group compared to a significant decrease in renal blood flow in the control group. There was no effect on fractional excretion of sodium or oxidative injury markers (protein carbonyl formation, lipid peroxidation) in pig or human kidneys, which is consistent with previous studies that demonstrated the requirement of >24 hour after reperfusion for manifestation of changes in these parameters. In this thesis, I was able to successfully demonstrate the safety and potential efficacy of MitoQ in ameliorating renal IRI using pig kidneys. While more declined deceased human kidneys need to be analysed to fully explore the potential efficacy of MitoQ in ameliorating renal IRI, this study provides important data that will help inform future studies and ultimately a clinical trial for assessing the efficacy of the mitochondria-targeted antioxidant MitoQ in human kidney transplantation. My findings suggest that MitoQ has the potential to increase the use of marginal kidneys and to improve graft and patient outcomes.

Dióxido de titânio com alta área superficial específica na fase anatase é considerado um material promissor para aplicações ambientais. Neste trabalho, TiO2 com boa aplicabilidade em processos fotocatalíticos e na produção de hidrogênio foi obtido pelo método com baixo consumo de energia baseado na rota dos peróxidos oxidantes combinado com tratamento solvotermal assistido por microondas. Para preparar o material, propóxido de titânio, peróxido de hidrogênio e álcool isopropílico foram utilizados. A influência do tempo, do pH e da temperatura durante a etapa solvotermal nas propriedades como morfologia, cristalinidade, composição de fase, área superficial específica e comportamento fotocatalítico foram investigados. As amostras foram caracterizadas por difração de raios X (DRX), microscopia eletrônica de varredura (MEV), microscopia eletrônica de transmissão (MET), análise termogravimétrica (ATG), teoria Brunauer-Emmett-Teller (BET), reflectância difusa e espectroscopia por emissão fluorescente. A fotoatividade foi determinada usando o método de decomposição do corante alaranjado de metila em luz UV-A e a produção de hidrogênio foi realizada em água usando etanol como agente de sacrifício. Com o aumento da temperatura durante a etapa solvotermal, as propriedades fotocatalíticas foram melhoradas. As nanoestruturas de TiO2 sintetizadas a 200°C e 30 min a partir deste método mostraram atividade fotocatalítica comparável ao do TiO2 P25 comercial Aeroxide©. Isso pode ser atribuído ao fato de que a energia associada a esta temperatura tenha sido suficiente para converter a maioria dos precursores em produtos cristalinos e pouca fase amorfa está presente. Foi possível produzir, com sucesso, nanoestruturas de TiO2, via método dos peróxidos oxidantes e tratamento solvotermal assistido por microondas em diferentes pHs. O material tratado em pH 1 exibiu melhor comportamento fotocatalítico na degradação da solução contendo alaranjado de metila. Aparentemente, o pH do meio não afetou significativamente a microestrutura das amostras. Foi observado uma diminuição na intensidade fotoluminescente da amostra preparada em pH ácido. Isso ocorre provavelmente porque as modificações ácidas em TiO2 favorecem eficientemente a separação das cargas, que está também relacionada com o comportamento dessa amostra durante o processo de degradação. Em relação à produção de hidrogênio, foi possível observar que a razão aumentou com o aumento do pH da solução. Isso pode ser atribuído ao aumento da concentração de OH- fisisorvidos, os quais podem participar dos processos de trapeamento das lacunas e nas reações de transferência de cargas. Por último, esses resultados foram notáveis porque foi utilizado um método de preparação com baixo consumo de energia onde apenas precursores orgânicos e baixas temperaturas foram empregados. Além disso, calcinação ou dopagem não foram necessários para alcançar tal desempenho, uma vez que, os catalisadores assim preparados exibiram boa atividade fotocatalítica na remoção de poluentes da água como o alaranjado de metila e na produção de hidrogênio. / Titanium dioxide with high specific surface area in the crystalline anatase phase is a promising material for environmental applications. In this work, TiO2 with good applicability for photocatalytic processes and hydrogen production has been obtained using the low energy consumption synthesis based on oxidant peroxide method combined with microwave-assisted low temperature solvothermal treatment. To prepare the material, titanium propoxide, hydrogen peroxide, and isopropyl alcohol were used. The influence of time, pH and temperature during the solvothermal step on properties like, morphology, crystallinity, phase composition, specific surface area, and photocatalytic behavior were investigated. The samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), scanning electron transmission (TEM), thermal gravimetric analysis (TGA), Brunauer- Emmett-Teller theory (BET), UV–Vis diffuse reflectance and fluorescence emission spectroscopy. Photoactivity was determined using the methyl orange decomposition method in UV-A light and hydrogen production was performed in water using ethanol as sacrificial agent. Increasing temperature during solvothermal step, photocatalytic properties could be improved. The nanostructured TiO2 particles synthesized at 200ºC and 30 min with this method showed photocatalytic activity comparable to commercial Aeroxide® TiO2 P25. This can be attributed to the fact that the energy associated with this temperature has been sufficient to convert most of precursors into crystalline products and small amount of amorphous phase is present. We successfully produced nanostructured TiO2 via the oxidant peroxide method and microwave-assisted solvothermal treatment at different pHs. The material that we treated at pH 1 exhibited better photocatalytic performance on the degradation of methyl orange solutions. It appears that the pH of the medium does not significantly affect the microstructure of the samples. It was observed a decrease in the photoluminescence intensity of the sample prepared at acidic pH. This finding likely occurred because the acidic modification of TiO2 favors efficiently separating the charge carriers, which is also related to the behavior of this sample during the degradation process. Related to hydrogen production, it was possible to observe that the rate increases with increasing solution pH. This has been attributed to the increased concentrations of physisorbed OH− groups at basic solutions, which participate in hole trapping processes and charge transfer reactions. Lastly, these results are remarkable because of the low energy consumption preparation method: only organic-metalic compounds and low temperatures were employed. Furthermore, calcination or doping was not necessary to achieve such performance, since the asprepared catalysts exhibited good photocatalytic activity on removal of pollutants from water as the methyl orange and on hydrogen production.

Commiphora species (from which myrrh is obtained) has been a source of several novel and bio-active natural compounds. Traditionally, Commiphora (Burseraceae) is used in southern Africa for the treatment of ulcers, fevers, and as a remedy for snake and scorpion bites. In western Africa, the macerated stem is used in the treatment of rheumatic conditions. The resin of some Commiphora species is applied topically to aid in wound healing. Documented uses include antibacterial and antifungal properties, as well as cytotoxic, cytostatic and anti-oxidant activity. The botanical diversity of this genus in South Africa warrants a study of this plant group, to provide scientific evidence for the traditional use of Commiphora species in African healing rites. Ten Commiphora species were investigated. Fresh plant material of the selected species were identified and collected from natural populations in the Limpopo Province. Active compounds, viz. kaempferol and dihydrokaempferol, in C. glandulosa (stem) were isolated using bioassay-guided fractionation and identified using nuclear magnetic resonance spectroscopy. The stem and leaf extracts of each species were analysed for in vitro anti-oxidant, antimicrobial, anti-inflammatory, anticancer activity, as well as cytotoxicity. The anti-oxidant activity of the extracts was investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and the 2,2’-azino-bis(3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) assays. Extracts generally exhibited poor anti-oxidant activity in the DPPH assay, with the exception of C. schimperi (stem), C. neglecta (stem), C. tenuipetiolata (stem and leaf), and C. edulis (stem), which possessed IC50 values ranging between 7.31 μg/ml and 10.81 μg/ml. Isolated compounds were subjected to the DPPH assay to determine the anti-oxidant potential of each compound, separately and in combination to establish possible synergistic, antagonistic or additive effects. The flavonol, kaempferol (IC50 = 3.32 μg/ml) showed exceptional radical scavenging activity, in contrast to the low activity displayed by dihydrokaempferol (IC50 = 301.57 μg/ml), their combination being antagonistic. Greater anti-oxidant activity was observed for most species in the ABTS assay when compared to the results obtained in the DPPH assay. The best activity was observed for the stem extracts of C. neglecta (IC50 = 7.28 μg/ml) and C. mollis (IC50 = 8.82 μg/ml). In vitro antimicrobial efficacy was determined against Gram-positive and Gram-negative bacteria as well as yeasts using the MIC microtiter plate assay. A greater selectivity was exhibited by the extracts against the Gram-positive bacteria and yeast than against the Gram-negative bacteria. Using death kinetics studies (time-kill studies), the rate at which the antimicrobial agent kills pathogens over a 24-hour period was determined. The antibacterial activity of Commiphora marlothii (stem) was observed to begin at ca. 30 min of the exposure of S. aureus to the different concentrations of plant extract. All concentrations exhibited antibacterial activity, with a complete bactericidal effect achieved by all test concentrations by the 24th hour. Commiphora pyracanthoides (stem) displayed anti-inflammatory activity through good inhibition of the 5-LOX enzyme (IC50 = 27.86 μg/ml). The ability of extracts and kaempferol to inhibit the in vitro growth of three human cancer cell lines, namely the colon adenocarcinoma (HT-29), breast adenocarcinoma (MCF-7), and the neuronal glioblastoma (SF-268), was evaluated using the sulforhodamine (SRB) antiproliferative assay. The most active Commiphora species against the HT-29 cells were C. glandulosa (leaf and stem) and C. marlothii (leaf). The MCF-7 cell line was the most sensitive to indigenous Commiphora species, with C. edulis (leaf and stem), C. glandulosa (leaf and stem), C. marlothii (leaf), C. pyracanthoides (leaf and stem), C. schimperi (stem), and C. viminea (stem) all possessing an inhibition greater than 80% at 100 μg/ml. Commiphora glandulosa (leaf and stem) and C. pyracanthoides (leaf and stem) were the two most active species against the SF-268 cells, with IC50 values ranging between 68.50 μg/ml and 71.45 μg/ml. The inhibition of the cancer cell proliferation by kaempferol in all three-cancer cell lines was determined, with IC50 values of 9.78 μg/ml in HT-29 cells, 20.21 μg/ml in MCF-7 cells and 43.83 μg/ml in SF-268 cells. The microculture tetrazolium cellular viability (MTT) assay was used to determine the cellular toxicity of the extracts against transformed human kidney epithelium (Graham) cells. Commiphora glandulosa (stem) proved to be most toxic (IC50 = 30.5 μg/ml). The IC50 values for all other extracts were in excess of 95 μg/ml suggesting low in vitro toxicity for the majority of the species. A phytochemical investigation of the non-volatile constituents of the leaf and stems was conducted using high performance liquid chromatography (HPLC). The HPLC profiles and UV spectra of the stem extracts, and the representative flavonoid patterns in the leaf extracts of the species indicate that a similarity exists in their chemical fingerprint.

O manganês (Mn) é um elemento químico abundante na natureza, principalmente em minérios e presente também em alimentos e na água. É o cofator de enzimas importantes, como a superóxido dismutase mitocondrial. Entretanto, mineradores e outras pessoas expostas a produtos manufaturados de Mn podem apresentar uma concentração excessiva desse metal no cérebro, adquirindo uma desordem neurológica similar ao mal de Parkinson conhecida por manganismo. Basicamente a neurotoxicidade do Mn pode estar associada com os vários estados de oxidação que ele pode alcançar, gerando espécies reativas de oxigênio durante a interconversão dessas espécies. Dessa forma, neste trabalho sintetizamos e avaliamos as propriedades pró-oxidantes e neurotóxicas de complexos de Mn(III) com desferrioxamina, [Mn(dfb)]; acetohidroxamato, [Mn(aha)3]; citrato, [Mn(cit)]; cloro-salen, EUK 8; e aceto-salen, EUK 108. Tais compostos são propostos como miméticos da SOD e/ou catalase, entretanto podem apresentar atividade pró-oxidante. Estes complexos foram caracterizados espectrofotometricamente (UV/Vis e IV) e por voltametria cíclica. Foram determinadas as absortividades molares dos complexos [Mn(aha)3], EUK 8 e EUK 108. Os EUK\'s apresentaram dois processos redutivos, sendo apenas um reversível, enquanto o [Mn(cit)] apresentou apenas um processo redutivo reversível e os hidroxamatos [Mn(dfb)] e [Mn(aha)3] não apresentaram processos redox na faixa de potenciais utilizada. Em teste de lipofilicidade todos os complexos apresentaram maior afinidade pela fase aquosa, sendo muito pouco particionados para a fase orgânica. Através do ensaio de supressão de fluorescência de calceína foi possível estabelecer que os EUK\'s são relativamente mais estáveis do que os outros complexos, sendo o [Mn(aha)3] o menos estável dos compostos estudados. Nas análises de atividade pró-oxidante, o [Mn(dfb)] oxidou fortemente a sonda mesmo na ausência de outros cofatores, mas este processo é dependente da concentração de O2 no meio. Os EUK\'s atuaram como pró-oxidantes em função da concentração de peróxido no meio. A atividade pró-oxidante foi suprimida por ascorbato, glutationa e Trolox®, que agiram como antioxidantes, sugerindo implicações para a terapia do manganismo. O teste de toxicidade aguda em paulistinhas (Danio rerio) adultos resultou na mortalidade de alguns animais quando expostos a [Mn(dfb)] e [Mn(aha)3]. Comparando o telencéfalo de peixes expostos ao [Mn(dfb)] com um controle em microscópio, não se visualizou nenhuma alteração morfológica na região do núcleo dorsal, indicando que o complexo não causou nenhum dano visível nessa região. / Manganese (Mn) is an abundant element which is present also in food and water. It is the cofactor of important enzymes such as mitochondrial superoxide dismutase. However, miners and other occupationally exposed individuals may present an excessive load of Mn in brain and develop manganism, a neurological disorder akin to Parkinson Disease. Basically, Mn neurotoxicity may stem from its wide redox cycle, generating reactive oxygen species in the process of converting from one oxidation state to another. Thus, in this work we synthesized and evaluated the pro-oxidant and neurotoxic characteristics of Mn(III) complexes with desferrioxamine, [Mn(dfb)]; acetohydroxamate, [Mn(aha)3]; citrate, [Mn(cit)]; chlorosalen, EUK 8; and aceto-salen, EUK 108. Such compounds are proposed as mimetics of superoxide dismutase and/or catalase, however they may also be prooxidant. These complexes were characterized spectrophotometrically (UV/Vis and IR) and by cyclic voltammetry. Molar absorptivities were determined for [Mn(aha)3], EUK 8 and EUK 108. EUK\'s displayed two reductive processes, only one of which was reversible, while [Mn(cit)] displayed only one (reversible) reductive process and hydroxamates [Mn(dfb)] and [Mn(aha)3] did not display redox processes in the working range of potentials. Lipophilicity tests showed that all complexes have very low partition to the organic phase. Calcein fluorescence quenching studies showed that both EUK complexes are relatively more stable than the others, while [Mn(aha)3] is the least stable. In the pro-oxidant activity studies, [Mn(dfb)] strongly oxidized the fluorescent probe even in the absence of ancillary substances such as peroxide. However, this effect was dependant on O2 saturation in the solution. Both EUK acted as pro-oxidants with a linear dependence on peroxide concentration. Pro-oxidant activity was eliminated by the treatment with antioxidants such as ascorbate, glutathione and Trolox®, which is of interest for the therapy of manganism. In the acute toxicity tests induced some mortality in adult Danio rerio exposed to [Mn(dfb)] or [Mn(aha)3]. Comparison of the telencephalus of [Mn(dfb)]-exposed individuals with controls failed to indicate morphological alterations in the dorsal nucleus area, indicating that the complex did not affect visibly this brain region.

In situ chemical oxidation (ISCO) is a leading-edge technology for soil and groundwater remediation, and involves injecting a chemical oxidant (e. g. , permanganate, hydrogen peroxide, or persulfate) into the subsurface to deplete contaminant mass through oxidation. Since the delivery of the chosen oxidant to the target treatment zone must occur in situ, the interaction between the injected oxidant and the aquifer material is a key controlling factor for a successful ISCO application. While many published ISCO studies have focused on the interaction between an oxidant and target contaminants, many questions still remain on the interaction between a potential oxidant and the aquifer material. Through a series of bench-scale experiments with aquifer materials collected from 10 sites throughout North America, the research presented in this thesis provides insight into the interaction between these aquifer materials and two widely used ISCO oxidants; permanganate and hydrogen peroxide. <br /><br /> The investigation into the interaction between aquifer materials and permanganate consisted of three series of bench-scale experiments: (1) long-term batch experiments which were used to investigate permanganate consumption in response to fundamental geochemical properties of the aquifer materials, (2) short-term batch experiments which were designed to yield kinetic data that describe the behavior of permanganate in the presence of various aquifer materials, and (3) column experiments which were used to investigate permanganate transport in a system that mimics the subsurface environment. The long-term experiments which involved more than 180 batch reactors monitored for ~300 days showed that the unproductive permanganate consumption by aquifer materials or natural oxidant demand (NOD) is strongly affected by the initial permanganate concentration, permanganate to solid mass ratio, and the reductive components associated with each aquifer material. This consumption cannot be represented by an instantaneous reaction process but is kinetically controlled by at least a fast and slow reactive component. Accordingly, an empirical expression for permanganate NOD in terms of aquifer material properties, and a hypothetical kinetic model consisting of two reaction components were developed. In addition, a fast and economical permanganate NOD estimation procedure based on a permanganate COD test was developed and tested. The investigation into short-term permanganate consumption (time scale of hours) was based on the theoretical derivation of the stoichiometric reaction of permanganate with bulk aquifer material reductive components, and consisted of excess permanganate mass experiments and excess aquifer material mass experiments. The results demonstrated that permanganate consumption by aquifer materials can be characterized by a very fast reaction on the order of minutes to hours, confirming the existence of the fast reaction component of the hypothetical kinetic model used to describe the long-term permanganate NOD observations. A typical experimental column trial consisted of flushing an aquifer-material packed column with the permanganate source solution until sufficient permanganate breakthrough was observed. The permanganate column results indicated the presence of a fast and slow consumption rate consistent with the long-term batch test data, and an intermediate consumption rate affecting the shape of the rising limb of the breakthrough curve. Finally, a comparison of the experimental results between batch and column systems indicated that permanganate NOD was significantly overestimated by the batch experiments; however, permanganate consumption displayed some similarity between the batch and column systems and hence an empirical expression was developed to predict permanganate consumption in physically representative column systems from batch reactor data. <br /><br /> The interaction between hydrogen peroxide and aquifer materials was also investigated with both batch and column experiments. A series of batch experiments consisting of a mixture of 2% hydrogen peroxide and 15 g of aquifer materials was used to capture the overall hydrogen peroxide behavior in the presence of various aquifer materials. The results indicated that the decomposition of hydrogen peroxide in the presence of various aquifer materials followed a first-order rate law, and was strongly affected by the content of amorphous transition metals (i. e. , Fe and Mn). Although hydrogen peroxide decomposition is related to the total organic carbon (TOC) content of natural aquifer materials, the results from a two-week long exposure to hydrogen peroxide suggests that not all forms of natural organic matter contributed to this decomposition. A multiple linear regression analysis was used to generate predictive relationships to estimate hydrogen peroxide decomposition rate coefficients based on various aquifer material properties. The enhanced stability of hydrogen peroxide was investigated under six scenarios with the addition of chelating reagents. The impact of a new green chelating reagent, S,S'-ethylenediaminedisuccinate (EDDS), on the stability of hydrogen peroxide in the presence of aquifer materials was experimentally examined and compared to that of the traditional and widely used chelating reagent, Ethylenediaminetetraacetic (EDTA). The results demonstrated that EDDS was able to significantly increase the stability of hydrogen peroxide, especially for aquifer materials with low TOC contents and/or high dissolvable Fe and Mn contents. Finally, to complement and expand the findings from the batch experiments, column experiments were conducted with aquifer materials from five representative sites. Each column was flushed with two types of source solutions (with or without EDDS addition) at two flow rates. The column experiments showed that the use of EDDS resulted in an earlier breakthrough and a higher stable concentration of hydrogen peroxide relative to the case without the addition of EDDS. The hydrogen peroxide decomposition rate coefficients generated from the column data were significantly higher than those generated from the batch test data and no correlation between hydrogen peroxide decomposition coefficients obtained from column and batch experiments was observed. Based on the column experimental results, a one-dimensional transport model was also calibrated to capture the hydrogen peroxide breakthrough process. <br /><br /> Data from bench-scale tests are routinely used to support both ISCO design and site screening, and therefore the findings from this study can be used as guidance on the utility of these tests to generate reliable and useful information. In general, the behavior of both permanganate and hydrogen peroxide in the presence of aquifer materials in batch and the column systems clearly indicates that the use of batch test data for ISCO system design is questionable since column experiments are believed to mimic in situ conditions better since column systems provide more realistic aquifer material contact. Thus the scaling relationships developed in this study provide meaningful tools to transfer information obtained from batch systems, which are widely employed in most bench-scale studies, to column systems.