The objective of this research was to aid in the development of a new method for removing and destroying soil contaminants. In particular, 1,2,4,5-tetrachlorobenzene (TeCB) was selected for this research. Hydrodehalogenation (HDH) was paired with hydrogenation for remedially destroying TeCB without generating a secondary waste stream in a single batch reactor. Palladium- and rhodium-catalyzed HDH and hydrogenation were applied in a batch reactor at room temperature and moderate hydrogen pressure. Cyclohexane was formed as an end product with benzene as an intermediate reactant. An analytical method was developed to measure TeCB, benzene, and cyclohexane in a solution of water and ethanol, 50:50 by volume before mixing, by gas chromatography with electron capture detection (ECD) and flame-ionization detection (FID). Experimental data were consistent with a model in which dehalogenation and hydrogenation were considered sequential processes with first order reaction kinetics.

Polymeric membranes have been essential to increasing the efficiency of membrane separation processes. The viability of membrane systems for industrial gas applications lies in the tolerance of such membranes to contamination. While membrane contamination from volatile species can be addressed using purge streams and heat treatment, contamination from non-volatile hydrocarbons can cause a significant decline in membrane permselectivity. This study was focused on the characterization and remediation of cellulose acetate (CA) hollow fibre membranes contaminated by heavy hydrocarbons. CA membranes have a moderate resistance against performance decline from hydrocarbons found in natural gas. Hollow fibre CA membranes were coated with motor oil lubricant to simulate heavy hydrocarbon contamination from large-scale gas compressors and industrial feed streams, and remediation of the CA fibres was conducted using solvent extraction methods. The permeabilities of the membranes to carbon dioxide, helium, hydrogen, methane, nitrogen and oxygen were measured at pressures 300 – 1500kPa and at temperatures 25° – 50°C. It was shown that even a thin layer of oil on the membrane surface can result in substantial losses in membrane performance, with faster permeating gases (e.g. He and H₂) suffering the worst losses. Solvent exchange, in which the membrane was washed using a series of solutions of varying organic content, was unable to remediate the membrane effectively, while the removal of the heavy hydrocarbons by a direct cyclohexane rinse was found to work well to restore the membrane performance.

In dieser Arbeit wird die partielle Autoxidation von Cyclohexan zu Cyclohexanol und Cyclohexanon mit Luftsauerstoff in einem Kapillarrohrreaktor untersucht. Gegenüber dem konventionellen Verfahren wurde die Temperatur auf 180-250°C und der Druck auf 20-80 bar angehoben. Auf diese Weise konnte eine Steigerung der Raum-Zeit-Ausbeute um etwa den Faktor 200 (von 25 kg/m³*h auf ca. 6000 kg/m³*h) erreicht werden. Die Umsätze sind dabei denen der industriellen Anlage vergleichbar. Die Selektivität der partiellen Oxidation zu den Wertprodukten cyclohexanol, Cyclohexanon und Cyclohexylhydroperoxid liegt im Kapillarrohrreaktor mit 80-90 % etwas unter den in der industriellen Anlage erreichbaren Selektivität von ca. 90-95 %. Die Reaktion im Kapillarrohrreaktor wurde auch aus sicherheitstechnischer Perspektive untersucht. Cyclohexan ist in die Explosionsgruppe IIA eingeordnet. Um das System in konservativer Weise zu betrachten, wurde als Stoffsystem Ethen (Referenzgas der Explosionsgruppe IIB) im Gemisch mit Sauerstoff bzw. Lachgas ausgewählt. Es wurde ein Versuchsaufbau konstruiert, mit dem ex möglich war stabile Detonationen zu erzeugen, diese in die Mikrostruktur einzuleiten und deren Ausbreitung und ggf. Austritt aus der Mikrostruktur zu beobachten. Im Versuchsprogramm wurde der Anfangsdruck im Bereich von 0,1 bis 10 bar und der Rohrdruchmesser der eingesetzten Kapillarrohr im Bereich von 0,13 - 1 mm variiert. Es zeigt sich, dass sich stabile Detonationen von stöchiometrischen Ethen/Sauerstoff-Gemischen bei einem Anfangsdruck von 1 bar abs gerade noch durch eine Kapillare mit einem Innendurchmesser von 0,13 mm ausbreiten können. Es wurde aus den Messdaten und theoretischen Betrachtungen eine Kennzahl für die Bewertung von Mikrostrukturierten Bauteilen entwickelt und diskutiert: der maximale sichere Rohrdurchmesser. / In this thesis a process is described for the uncatalyzed selective oxidation of cyclohexane with air at high-p, T-conditions in a micro capillary reactor. At 533 K a spacetime-yield of about 6000 kg/(m3 ? h) is reached, which corresponds to a size of 2 m x 2 m x 2 m(8 m3) of the microstructured reactor assuming a capacity of 100000 t/a compared to 500 m3 total reactor volume realized with a cascade of bubble columns of each about 100 m3. Unfortunately, selectivity drops at this temperature below 80 % which is significantly lower than the selectivity in the conventional process. With the help of the Hatta number, mass transfer limitations can be excluded for the micro capillary reactor, whereas the bubble column reactor is weakly limited by the gas/liquid mass transfer of the molecular oxygen. Thus, process intensification by enhancing mass transfer using a microstructured reactor for cyclohexane oxidation with air is quite low. Furthermore a method and its corresponding results are presented for the determination of maximum safe capillary diameters, which may be used to describe the extended range of safe operation conditions for gas phase oxidation reactions in microstructured reactor devices. Sections of stainless steel micro capillaries of different inner diameters are mounted between a primary and a secondary chamber. An explosion is ignited in the primary chamber, where also a deflagration to detonation transition occurs. The propagation of the detonation through the stainless steel micro capillaries is monitored by pressure transducers located between the sections of the micro capillaries. This setup is used in order to determine explosion velocities inside the capillaries, maximum safe initial pressures and corresponding maximum safe capillary diameters. Initial investigations are performed with an ideal stoichiometric mixture necessary for complete combustion of ethene with oxygen respectively ethene and nitrous oxide at room temperature. The measured maximum safe capillary diameters obey an indirect proportionality to the initial pressures. The maximum safe capillary diameter can be estimated on the basis of the lambda/3-rule.

Submitted by Alison Vanceto (alison-vanceto@hotmail.com) on 2017-02-09T10:54:21Z No. of bitstreams: 1 DissHRAD.pdf: 15161052 bytes, checksum: e10c4924acc9cc8afc5ecbec12ee85aa (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-03-20T17:16:45Z (GMT) No. of bitstreams: 1 DissHRAD.pdf: 15161052 bytes, checksum: e10c4924acc9cc8afc5ecbec12ee85aa (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-03-20T17:16:55Z (GMT) No. of bitstreams: 1 DissHRAD.pdf: 15161052 bytes, checksum: e10c4924acc9cc8afc5ecbec12ee85aa (MD5) / Made available in DSpace on 2017-03-20T17:24:11Z (GMT). No. of bitstreams: 1 DissHRAD.pdf: 15161052 bytes, checksum: e10c4924acc9cc8afc5ecbec12ee85aa (MD5) Previous issue date: 2015-03-13 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Nowadays, the Brazilian petroleum is extracted from very deep fields and possesses a high naphthenic hydrocarbons composition, which imposes new challenges to refineries and specially to the catalytic cracking process. In that process, the catalyst must act maximizing the production of the highly demanded gasoline, diesel and light olefins from heavy fractions. Taking into consideration the above discussed context, this work aimed to evaluate the effect of basic or acid treatments applied on ZSM-5 zeolites (Si/Al=12 or 23) in the activity to cyclohexane or methylcyclohexane transformation. XRD and 27Al-NMR showed that the dealuminated zeolites presented an increase in their crystallinity due to the extra-framework aluminum lixiviation. On the other hand, in the desilicated zeolites occurred a decrease in their crystallinity as a consequence of the extra-framework aluminum generation. MEV images do not evidence any morphological change that could have been produced by the acid or basic treatments, however, the desilicated ZSM-5 zeolites treated under harder conditions presented significant textural modifications. As expected, the chemical ICP analyses showed a decrease in the Si/Al ratio in the desilicated zeolites and an increase of that ratio for those dealuminated ones, being the last variation more significative in the external surface of the zeolite crystals, as was evidenced by XPS analyses. Data from NH3-TPD showed that the acid treatment resulted in a higher ratio of strong acid sites, which suffered more deactivation during reaction. N2 fisisorption analyses of the ZSM-5 zeolites, showed that the desilication done at higher temperature was more efficient to mesopore generation. In the cyclohexane and methylcyclohexane transformation, the dealuminated zeolites were less active due to their lower aluminum content, nevertheless were more stable and presented a small increase to light olefins selectivity. The desilicated ZSM-5 zeolites presented higher activity and higher yield to light olefins that were supported by their lower Si/Al ratio and mainly by the presence of mesoporosity that enhanced the reagents and products internal diffusivity. / A produção nacional de petróleo, extraído de jazidas cada vez mais profundas, possui um elevado teor de hidrocarbonetos naftênicos, o que impõe novos desafios às refinarias brasileiras e, em particular, ao processo de craqueamento catalítico. Nesse processo, o catalisador deve maximizar a transformação das frações pesadas em produtos de alta demanda como gasolina, diesel e olefinas leves. Nesse contexto, esta dissertação objetivou avaliar o efeito de tratamentos de lixiviação ácida ou básica em zeólitas ZSM-5 (Si/Al=12 ou 23), na atividade para a transformação de cicloexano ou metilcicloexano. Dados de DRX e 27Al-RMN mostraram que as zeólitas desaluminizadas apresentaram um aumento da sua cristalinidade devido à remoção de átomos de alumínio extra-rede, por outro lado, nas zeólitas dessilicalizadas ocorreu uma redução da cristalinidade devido à geração de alumínio extra rede. As micrografias de MEV não evidenciaram modificação morfológica devido aos tratamentos, entretanto nas amostras dessilicalizadas sob condições mais severas, houve significativa mudança das propriedades texturais. Como esperado, as análises químicas por ICP mostraram uma redução na razão Si/Al para as amostras dessilicalizadas e um aumento dessa razão para as zeólitas desaluminizadas, sendo essa variação mais significativa na superfície externa dos cristais, como mostraram resultados de XPS. As análises de DTP-NH3 mostraram que o tratamento ácido resultou numa maior proporção de sítios ácidos fortes, os quais sofreram maior desativação durante a reação. Dados de fisissorção de N2 das zeólitas mostraram que a dessilicalização em temperatura mais elevada foi mais eficiente na geração de mesoporos. Na transformação do cicloexano e do metilcicloexano, as zeólitas desaluminizadas apresentaram menor conversão como resultado da diminuição do teor de alumínio, entretanto tiveram maior estabilidade e apresentaram um ligeiro aumento na seletividade a olefinas leves. As amostras dessilicalizadas apresentaram maiores conversões e rendimentos a olefinas leves, que se justificaram em função da diminuição da razão Si/Al, mas principalmente, como resultado da presença de mesoporosidade, que melhorou a difusão interna de reagentes e produtos.

Photo-initiated reactions involve the use of ultraviolet (UV) or visible light radiation to effect chemical transformations. Some of the advantages of photo-initiated reactions over thermal or high pressure reactions include mild reaction conditions like ambient temperature and pressure, good control over the reaction by the simple switching on/off the light source, and faster reaction kinetics. Usually, semiconductor photocatalysts or oxidizing agents are used to enhance the rate of photo reactions. “Photocatalysis” involves the generation of valence band holes and conduction band electrons by the band gap excitation of a semiconductor photocatalyst. These charge carriers produce reactive hydroxyl and superoxide radicals, which mediate oxidation and reduction reactions. However, the oxidizing agents are decomposed by the incident radiation to generate reactive radicals, which accelerate the photo reaction. Today, photocatalysis and photo-oxidative reactions are widely being practiced for environmental pollution abatement, synthesis of fine chemicals, synthesis of polymers, generation of hydrogen as a clean energy carrier, and in anti-fogging and self-cleaning surface treatments. The present investigation focuses on elucidating the mechanism and kinetics of environmentally and synthetically relevant photo-initiated reactions for a better understanding of the fundamental aspects of the photo processes. The different photo-initiated reactions studied in this dissertation can be grouped under the broad categories of (i) photocatalytic degradation of organic compounds like dyes and phenols, and reduction of metal ions, (ii) photocatalytic degradation of polymers, (iii) selective photocatalytic oxidation of cyclohexane, (iv) sonophotocatalytic degradation of dyes, (v) photopolymerization, and (vi) sonophotooxidative degradation of polymers. Nano-sized TiO2, synthesized by solution combustion technique (henceforth denoted as CS TiO2), was used as the photocatalyst for most of the above reactions, except for the last two polymer reactions, where organic initiators were used. Invariably, the photocatalytic activity of CS TiO2 was compared with the commercially available Degussa P-25 TiO2 (DP25). Based on the experimental results, detailed mechanisms were proposed for the different reactions, kinetic models were derived, and the rate coefficients signifying the importance of the underlying reaction steps were evaluated. Pd2+ substituted and Pd0 impregnated TiO2 were synthesized by solution combustion and reduction techniques, respectively, and characterized by powder XRD, XPS, TEM, BET surface area, UV/visible, TGA, FT-IR and photoluminescence measurements. While the above catalysts are known to be more active compared to CS TiO2 for the gas phase NO reduction and NO decomposition reactions, it was found in this study, that these catalysts exhibit lower activity for the degradation of organic compounds like dyes, phenol and 4-chlorophenol, in the aqueous phase. The decrease in activity was correlated with a reduction in surface area and photoluminescence intensity of these catalysts, compared to CS TiO2. Ag+ substituted (Ag sub) and Ag0 impregnated (Ag imp) nano-TiO2 were synthesized by solution combustion and reduction techniques, respectively, and characterized by the above standard measurements. These catalysts were used for the photodegradation of dyes, and the selective photooxidation of cyclohexane to cyclohexanone. For the photocatalytic degradation of dyes, unsubstituted CS TiO2 exhibited the highest activity, followed by 1% Ag imp and 1% Ag sub. However, for the photooxidation of cyclohexane, the total conversion of cyclohexane and the selectivity of cyclohexanone followed the order: 1% Ag sub > DP-25 > CS TiO2 > 1% Ag imp. The kinetics of photodegradation of the dyes and the photooxidation of cyclohexane was modeled using Langmuir-Hinshelwood rate equation, and a free radical mechanism, respectively. This study proves that the photoactivity of a catalyst is not solely determined by a single physical property, but rather by a number of variables including the surface area, band gap, surface hydroxyl content, oxide ion vacancy and surface charge of the catalyst. The photocatalytic degradation of five anionic, eight cationic and three solvent dyes, containing different functional groups, was evaluated. The degradation of the dyes was quantified using the initial rate of decolorization and overall percent mineralization. The decolorization of the anionic dyes with CS TiO2 followed the order: Indigo Carmine > Eosin Y > Amido Black 10B > Alizarin Cyanine Green > Orange G. The decolorization of the cationic dyes with DP-25 followed the order: Malachite Green > Pyronin Y > Rhodamine 6G > Azure B > Nile Blue Sulfate > Auramine O ≈ Acriflavine ≈ Safranin O. CS TiO2 exhibited higher rates of decolorization and mineralization for all the anionic dyes, while DP-25 was better in terms of decolorization for most of the cationic dyes. The solvent dyes exhibited adsorption dependent decolorization. The observed results were rationalized based on the molecular structure and degradation pathway of the dyes. The simultaneous photocatalytic degradation of phenolic compounds like phenol and 4-nitrophenol, and the reduction of metal ions like copper (Cu2+) and chromium (Cr6+) were studied. It was found that the presence of phenol accelerated the reduction of Cu2+ to Cu+, and the presence of phenol and 4-nitrophenol accelerated the adsorption of Cr6+ onto CS TiO2. A detailed dual-cycle, multi-step reaction mechanism was proposed for the simultaneous degradation and reduction, and a model was developed using the network reduction technique. The kinetic rate constants in the model were evaluated for the systems studied. The simultaneous UV and ultrasound (US) degradation of anionic dyes was carried out in presence of CS TiO2. The rates of degradation and mineralization of the dyes were higher for the sonophotocatalytic process compared to the individual photo-and sonocatalytic processes. The effect of dissolved gases and US intensity on the sonophotocatalytic degradation of the dyes was evaluated. A dual-pathway network mechanism of sonophotocatalytic degradation was proposed for the first time, and the rate equations were modeled using the network reduction technique. The kinetic rate coefficients of the individual steps were evaluated for all the systems by fitting the model with the experimental data. Eosin Y and Fluorescein dye sensitized visible light degradation of phenol, 4chlorophenol, 2,4-dichlorophenol and 2,4,6-trichlorophenol was studied. A detailed mechanism of sensitized degradation was proposed, and a mechanistic model for the rate of degradation of the phenolic compound was derived by using the pyramidal network reduction technique to evaluate the rate coefficients. An important conclusion of this study indicates that at low initial dye concentrations, the rate of degradation of the phenolic compound is first order in the concentration of the dye, while at high initial dye concentrations, the rate is first order in the concentration of the phenolic compound. The different phenolic and dye intermediates that were formed during degradation were identified by mass spectrometry, and a most probable pathway of degradation was proposed. The solution photopolymerization of methyl-, ethyl-, butyl-and hexylmethacrylates in presence of benzoyl peroxide as the initiator was studied. The effect of initiator and monomer concentrations on the time evolution of polymer concentration, number average molecular weight (Mn) and polydispersity (PDI) was examined. The reversible chain addition and β-scission, and primary radical termination steps were included in the mechanism along with the classical initiation, propagation and termination steps. The rate equations were derived using continuous distribution kinetics and solved numerically to fit the experimental data. The model predicted the instantaneous increase of Mn and PDI of the polymers to steady state values. The rate coefficients exhibited a linear increase with the size of the alkyl chain of the alkyl methacrylates. Poly(acrylamide-co-acrylic acid) copolymers of different compositions were synthesized and characterized. The copolymers were statistical with a relatively high percentage of acrylamide units, as determined by 13C-NMR. The aqueous phase photolytic and photocatalytic degradation of the copolymers and the homopolymers was conducted. The degradation was modeled using continuous distribution kinetics. The degradation followed a two step mechanism, wherein the rapid first step comprised of the scission of weak acrylic acid units along the chain, which was followed by the breakage of the relatively strong acrylamide units. The rate constants for the weak and strong links followed a linear trend with the percentage of acrylic acid and acrylamide in the copolymer, respectively. The photocatalytic degradation of the copolymers of methyl methacrylate with butyl methacrylate (MMA-BMA), ethyl acrylate (MMA-EA) and methacrylic acid (MMA-MAA) was carried out in toluene. The copolymers and the corresponding homopolymers degraded randomly along the chain. The degradation rate coefficient was determined using continuous distribution kinetics. The time evolution of the hydroxyl and hydroperoxide stretching vibration in the FT-IR spectra of the copolymers indicated that the degradation rate follows the order: MMA-MAA > MMA-EA > MMA-BMA. The photodegradation rate coefficients were compared with the activation energy of pyrolytic degradation. The observed contrast in the order of thermal stability compared to the photostability of these copolymers was attributed to the two different mechanisms governing the scission of the polymers and the evolution of the products. The mechano-chemical degradation of poly(methyl methacrylate), poly(ethyl methacrylate) and poly(n-butyl methacrylate) using US and UV radiation, in presence of benzoin as the photoinitiator, was carried out. A degradation mechanism that included the decomposition of the initiator, generation of polymer radicals by hydrogen abstraction of the initiator radicals, and reversible chain transfer between the stable polymer and the polymer radicals, was proposed. The mechanism assumed mid-point chain scission due to US and random chain scission due to UV radiation. The steady state evolution of PDI was successfully predicted by the continuous distribution kinetics model. The rate coefficients of polymer scission due to US and UV radiation exhibited a linear increase and decrease with the size of the alkyl group of the poly(alkyl methacrylate)s, respectively.

In dieser Arbeit wird die partielle Autoxidation von Cyclohexan zu Cyclohexanol und Cyclohexanon mit Luftsauerstoff in einem Kapillarrohrreaktor untersucht. Gegenüber dem konventionellen Verfahren wurde die Temperatur auf 180-250°C und der Druck auf 20-80 bar angehoben. Auf diese Weise konnte eine Steigerung der Raum-Zeit-Ausbeute um etwa den Faktor 200 (von 25 kg/m³*h auf ca. 6000 kg/m³*h) erreicht werden. Die Umsätze sind dabei denen der industriellen Anlage vergleichbar. Die Selektivität der partiellen Oxidation zu den Wertprodukten cyclohexanol, Cyclohexanon und Cyclohexylhydroperoxid liegt im Kapillarrohrreaktor mit 80-90 % etwas unter den in der industriellen Anlage erreichbaren Selektivität von ca. 90-95 %. Die Reaktion im Kapillarrohrreaktor wurde auch aus sicherheitstechnischer Perspektive untersucht. Cyclohexan ist in die Explosionsgruppe IIA eingeordnet. Um das System in konservativer Weise zu betrachten, wurde als Stoffsystem Ethen (Referenzgas der Explosionsgruppe IIB) im Gemisch mit Sauerstoff bzw. Lachgas ausgewählt. Es wurde ein Versuchsaufbau konstruiert, mit dem ex möglich war stabile Detonationen zu erzeugen, diese in die Mikrostruktur einzuleiten und deren Ausbreitung und ggf. Austritt aus der Mikrostruktur zu beobachten. Im Versuchsprogramm wurde der Anfangsdruck im Bereich von 0,1 bis 10 bar und der Rohrdruchmesser der eingesetzten Kapillarrohr im Bereich von 0,13 - 1 mm variiert. Es zeigt sich, dass sich stabile Detonationen von stöchiometrischen Ethen/Sauerstoff-Gemischen bei einem Anfangsdruck von 1 bar abs gerade noch durch eine Kapillare mit einem Innendurchmesser von 0,13 mm ausbreiten können. Es wurde aus den Messdaten und theoretischen Betrachtungen eine Kennzahl für die Bewertung von Mikrostrukturierten Bauteilen entwickelt und diskutiert: der maximale sichere Rohrdurchmesser. / In this thesis a process is described for the uncatalyzed selective oxidation of cyclohexane with air at high-p, T-conditions in a micro capillary reactor. At 533 K a spacetime-yield of about 6000 kg/(m3 ? h) is reached, which corresponds to a size of 2 m x 2 m x 2 m(8 m3) of the microstructured reactor assuming a capacity of 100000 t/a compared to 500 m3 total reactor volume realized with a cascade of bubble columns of each about 100 m3. Unfortunately, selectivity drops at this temperature below 80 % which is significantly lower than the selectivity in the conventional process. With the help of the Hatta number, mass transfer limitations can be excluded for the micro capillary reactor, whereas the bubble column reactor is weakly limited by the gas/liquid mass transfer of the molecular oxygen. Thus, process intensification by enhancing mass transfer using a microstructured reactor for cyclohexane oxidation with air is quite low. Furthermore a method and its corresponding results are presented for the determination of maximum safe capillary diameters, which may be used to describe the extended range of safe operation conditions for gas phase oxidation reactions in microstructured reactor devices. Sections of stainless steel micro capillaries of different inner diameters are mounted between a primary and a secondary chamber. An explosion is ignited in the primary chamber, where also a deflagration to detonation transition occurs. The propagation of the detonation through the stainless steel micro capillaries is monitored by pressure transducers located between the sections of the micro capillaries. This setup is used in order to determine explosion velocities inside the capillaries, maximum safe initial pressures and corresponding maximum safe capillary diameters. Initial investigations are performed with an ideal stoichiometric mixture necessary for complete combustion of ethene with oxygen respectively ethene and nitrous oxide at room temperature. The measured maximum safe capillary diameters obey an indirect proportionality to the initial pressures. The maximum safe capillary diameter can be estimated on the basis of the lambda/3-rule.

La contribution de l’inhalation et de la voie percutanée à l’exposition totale à des composés organiques volatils (COV) présents dans l’eau potable est une problématique qui suscite un intérêt grandissant en santé publique et au niveau réglementaire. Jusqu’à tout récemment, seule l’ingestion était considérée dans l’évaluation du risque des contaminants de l’eau. L’objectif de ce projet était de caractériser l’impact de l’exposition multivoie sur la pharmacocinétique et la dose interne de trois COV : le toluène (TOL), le n-hexane (HEX) et le cyclohexane (CYCLO). À cette fin, un modèle expérimental animal a été utilisé et un modèle toxicocinétique à base physiologique (TCBP) a été adapté pour le TOL. Des rats Sprague-Dawley ont été exposés par voies uniques (inhalation, orale et percutanée) ou simultanées (multivoie) aux solvants. Pour le TOL, les trois voies ont été expérimentées, alors que la voie percutanée n’a pas été retenue pour le HEX et le CYCLO. Des prélèvements sanguins ont permis de caractériser les cinétiques sanguines. Les niveaux sanguins, obtenus lors des expositions multivoies, étaient généralement plus élevés que la somme des niveaux associés aux expositions par voies uniques, fait illustré par le rapport des surfaces sous la courbe expérimentale versus les prédictions (TOL : 1,30 et 2,19 ; HEX : 1,55 ; CYCLO : 0,98 et 0,99). Le modèle TCBP prédit bien la cinétique du TOL lors d’expositions par voies uniques et par multivoies. Les données expérimentales obtenues suggèrent que la dose interne résultant d’une exposition multivoie ne peut pas toujours être prédite par la somme des doses internes obtenues lors d’expositions par voies uniques. Ce phénomène serait explicable par la saturation du métabolisme. La modélisation TCBP est un outil efficace pour l’estimation du risque relatif à l’exposition multivoie aux COV présents dans l’eau potable. / The contribution of dermal and inhalation routes of exposure to volatile organic chemicals (VOCs) in drinking water is increasingly drawing attention. Until recently, ingestion was the only route considered in risk assessment of drinking water contaminants. The general objective of this study was to characterize multi-route exposures on the pharmacokinetics and internal dose of three VOCs: toluene (TOL), n-hexane (HEX) and cyclohexane (CYCLO). Towards this goal, an experimental animal model was developed and a physiologically-based toxicokinetic (PBTK) model was adapted in order to take account route-specific absorption parameters of TOL. Sprague-Dawley rats were given a single dose of VOCs by oral ingestion, inhalation or dermal route. Additional groups of rat were exposed by the three routes simultaneously. In the case of HEX and CYCLO, dermal route was not considered. Blood samples were collected in order to compare kinetics following simple and multiroute exposures. Blood levels obtained following multiroute exposures were generally higher than predictions (i.e., the sum of the blood levels obtained for single route exposures) (as revealed by area under curve ratio: TOL :1,30 et 2,19; HEX : 1,55; CYCLO : 0,98 et 0,99). The PBTK model described adequately the kinetics of TOL in rats following single and multiroute exposures. The results suggest that internal dose arising from multiple routes is not necessarely comparable to the sum of the blood levels obtained for single route exposures. This phenomenon would be attributable to degree of saturation during aggregate exposures. Furthermore, the present study demonstrated that PBTK model can be used to predict/interpret blood levels associated with multiroute exposures to VOCs in drinking water, using toluene as a model substance.

A atividade catalítica de clusters trigonais de acetato de rutênio e porfirinas supramoleculares contendo quatro unidades de clusters periféricos ou complexos de bis(bipiridina)rutênio, na oxidação de substratos orgânicos por iodosil-benzeno ou terc-butil-hidroperóxido, é abordada nesta tese. Foram feitos estudos cinéticos para elucidar o mecanismo de catálise, com especial destaque para duas espécies supramoleculares isoméricas representadas por Mn(3-TRPyP) ou Mn(4-TRPyP), nos quais os complexos de bis(bipiridina)(cloro)rutênio se coordenam à tetrapiridilporfirina através das posições meta ou para da ponte piridínica, respectivamente. Além da maior seletividade proporcionada pelos catalisadores supramoleculares, a substituição do íon cloreto pela água nos complexos periféricos de rutênio, intensificou a atividade catalítica, gerando novos sítios ativos, do tipo Ru(IV)=O. Também foram estudados clusters trinucleares de rutênio, altamente reativos, no estado Ru(III)Ru(IV)Ru(IV)=O. Estes foram gerados eletroquimicamente em solução aquosa, apresentando pronunciada atividade catalítica na oxidação do alcool benzílico. Finalmente, uma espécie dimérica de cluster, ainda inédita, com ponte oxo, foi caracterizada e investigada do ponto de vista catalítico. / The catalytic activity of trinuclear ruthenium clusters and supramolecular tetrapyridylporphyrins containing four peripheral cluster units or bis(bipyridine)ruthenium complexes, in the oxidation of organic substrates by iodosylbenzene or tert-butil-hydroperoxide, is dealt with in this thesis. Kinetic studies were performed in order to elucidate the mechanisms of catalysis involving two isomeric species denoted Mn(3-TRPyP) or Mn(4-TRPyP), in which the bis(bipyridine)(chloro)ruthenium complexes are bound to the tetrapyridylporphyrin center, at the meta or para positions of the pyridine bridge, respectively. In addition to the improved selectivity by such supramolecular catalysts, the substitution of the chloride ion by water in the peripheral ruthenium complexes, greatly enhanced their catalytic activity by generating new Ru(IV)=O reactive sites. Highly reactive trinuclear ruthenium clusters of the type Ru(III)Ru(IV)Ru(IV)=O were also generated electrochemically in aqueous solution, exhibiting pronounced catalytic activity in the oxidation of benzyl alcohol. Finally, a novel dimeric oxo-bridged cluster species was characterized, and its role in catalysis investigated.

A atividade catalítica de clusters trigonais de acetato de rutênio e porfirinas supramoleculares contendo quatro unidades de clusters periféricos ou complexos de bis(bipiridina)rutênio, na oxidação de substratos orgânicos por iodosil-benzeno ou terc-butil-hidroperóxido, é abordada nesta tese. Foram feitos estudos cinéticos para elucidar o mecanismo de catálise, com especial destaque para duas espécies supramoleculares isoméricas representadas por Mn(3-TRPyP) ou Mn(4-TRPyP), nos quais os complexos de bis(bipiridina)(cloro)rutênio se coordenam à tetrapiridilporfirina através das posições meta ou para da ponte piridínica, respectivamente. Além da maior seletividade proporcionada pelos catalisadores supramoleculares, a substituição do íon cloreto pela água nos complexos periféricos de rutênio, intensificou a atividade catalítica, gerando novos sítios ativos, do tipo Ru(IV)=O. Também foram estudados clusters trinucleares de rutênio, altamente reativos, no estado Ru(III)Ru(IV)Ru(IV)=O. Estes foram gerados eletroquimicamente em solução aquosa, apresentando pronunciada atividade catalítica na oxidação do alcool benzílico. Finalmente, uma espécie dimérica de cluster, ainda inédita, com ponte oxo, foi caracterizada e investigada do ponto de vista catalítico. / The catalytic activity of trinuclear ruthenium clusters and supramolecular tetrapyridylporphyrins containing four peripheral cluster units or bis(bipyridine)ruthenium complexes, in the oxidation of organic substrates by iodosylbenzene or tert-butil-hydroperoxide, is dealt with in this thesis. Kinetic studies were performed in order to elucidate the mechanisms of catalysis involving two isomeric species denoted Mn(3-TRPyP) or Mn(4-TRPyP), in which the bis(bipyridine)(chloro)ruthenium complexes are bound to the tetrapyridylporphyrin center, at the meta or para positions of the pyridine bridge, respectively. In addition to the improved selectivity by such supramolecular catalysts, the substitution of the chloride ion by water in the peripheral ruthenium complexes, greatly enhanced their catalytic activity by generating new Ru(IV)=O reactive sites. Highly reactive trinuclear ruthenium clusters of the type Ru(III)Ru(IV)Ru(IV)=O were also generated electrochemically in aqueous solution, exhibiting pronounced catalytic activity in the oxidation of benzyl alcohol. Finally, a novel dimeric oxo-bridged cluster species was characterized, and its role in catalysis investigated.

Human African trypanosomiasis (sleeping sickness) is a devastating disease which is endemic in parts of sub-Saharan Africa. It is caused by the protozoan parasite T. brucei, which are transmitted by the bite of infected tsetse flies. Although the disease is fatal if left untreated, there is a lack of safe, effective and affordable drugs available; therefore new drugs are urgently needed. The aim of the work presented in this thesis is to develop novel trypanocidal compounds. It is divided into two parts to reflect the two distinct strategies employed to achieve this aim. The first part focuses on the inhibition of glycophosphoinositol (GPI) anchor synthesis by inhibiting the Zn2+-dependent enzyme, GlcNAc-PI de-N-acetylase. Trypanosomes have a variable surface glycoprotein (VSG) coat, which allows them to evade the human immune system. The GPI anchor attaches the VSG to the cell membrane; therefore inhibiting GPI synthesis should expose the parasite to the immune system. Initially, large substrate analogues were synthesized. These showed weak inhibition of the enzyme. Zinc-binding fragments were screened, and small molecule inhibitors based on salicylhydroxamic acid were then synthesized. These compounds showed modest inhibition, but the excellent ligand efficiency of salicylhydroxamic acid indicates this may be a promising starting point for further inhibitors. The second part details the P2 strategy. The P2 transporter is a nucleoside transporter unique to T. brucei, which concentrates adenosine. The transporter also binds and selectively concentrates compounds that contain benzamidine and diaminotriazine P2 motifs, which can enhance the potency and selectivity of these compounds. The sleeping sickness drugs melarsoprol and pentamidine contain P2 motifs. Compounds comprising a P2 targeting motif, a linker and a trypanocidal moiety were synthesized. Initially, a diaminotriazine P2 motif was attached to a trypanocidal tetrahydroquinoline (THQ) protein farnesyl transferase (PFT) inhibitor, with limited success. The P2 strategy was also applied to a non-selective, trypanocidal, quinol moiety. The quinol moiety was attached to diaminotriazine and benzamidine P2 motifs, and an increase in selectivity for T. brucei over MRC5 cells was observed.