O fluxo de injeção e o solvente orgânico, utilizado no preparo de nanoesferas poliméricas, são parâmetros experimentais que controlam o diâmetro e a distribuição de diâmetro das nanopartículas, formadas pelo processo conhecido como nucleação. Considerando as nanocápsulas de núcleo lipídico, formadas pelo processo de auto-organização, estes parâmetros experimentais ainda não foram explorados. Assim, esse trabalho propõe avaliar o fluxo de injeção e o solvente orgânico na preparação destas suspensões aquosas, caracterizando físicoquimicamente estes sistemas. Para variação de fluxo de injeção, utilizou-se uma bomba peristáltica, sendo possível a avaliação dos seguintes fluxos: 5, 8, 12, 15, 21 e 38 mL min¯¹. O diâmetro das nanocápsulas diminuiu de 256±9 nm a 127 ±8 nm pela técnica de difração de laser e 220±9 nm a 124±13 nm, segundo a técnica de espectroscopia de correlação de fótons. Os solventes orgânicos avaliados foram a acetona, acetonitrila e 1,4-Dioxano. Observou-se que a acetonitrila se mostrou adequada para a condição previamente otimizada com acetona, ao passo que o 1,4-Dioxano apresentou um pico micrométrico em sua distribuição. Assim, foi possível modelar este estudo através de um fatorial de design 2², onde têm-se dois fatores, fluxo de injeção e solvente orgânico, em dois níveis, nos fluxos de 5 e 38 mL min¯¹ e considerando os solventes acetona e acetonitrila. Como resultado, viu-se que o fluxo de injeção é o parâmetro de maior influência na preparação destas suspensões aquosas, se comparado ao solvente orgânico selecionado. Para elucidar o papel do solvente orgânico na preparação destes sistemas, calculouse os parâmetros de solubilidade e os coeficientes de difusão solvente orgânico\água e água\solvente orgânico para os três pares avaliados neste trabalho. Viu-se que os parâmetros de solubilidade e os coeficientes de difusão solvente orgânico\água explicam a não variação do diâmetro de partícula em função do solvente orgânico. Ainda, realizou-se um estudo de viscosidade, em função do log [PCL], para fases orgânicas preparadas com acetonitrila e 1,4- dioxano. Obteve-se o valor de 2,30 mg mL¯¹ para a concentração de agregação crítica quando utilizado o 1,4-Dioxano e 10,47 mg mL¯¹ para a fase orgânica preparada com acetonitrila. Então, pode-se dizer que este valor elevado encontrado para a acetonitrila é uma vantagem de sua utilização, uma vez que as características nanoscópicas são mantidas e um maior número de partículas pode ser formado. / Flow rate and organic solvent, used to prepare polimeric nanospheres, are experimental parameters that control the size and the size distribution curves of these nanoparticles, formed by particle nucleation. Considering the lipid core nanocapsules, formed by self-assembled process, these experimental parameters are not evaluated yet. Considering those, this work proposes to evaluate the flow rate and the organic solvent in the preparation of these aqueous suspensions, characterizing them physicochemically. To change the flow rate, it was used a peristaltic pump, it being possible to evaluate the following flows: 5, 12, 15, 21 and 38 mL min‾¹. The nanocapsules diameters decreased from 256±9 nm to 127 ±8 nm, by laser difratometry and 220±9 nm to 124±13 nm, by the photon correlation spectroscopy technique. The organic solvents evaluated were acetone, acetonitrle and 1,4-dioxane. It was observed that the acetonitrile was adequate for the condition previously optimized with acetone, whereas in the 1,4-dioxane distribution apears a micrometric peak. So, it was possible to modelate this study by a 2² factorial design, two factors, flow rate and organic solvent, in two levels, 5 and 38 mL min‾¹, considering acetone and acetonitrile. As a result, it was seen that the flow rate is the most influential parameter in the preparation of aqueous suspensions, compared to organic solvent selected. To elucidate the role of organic solvent in these systems, it was calculated the solubility parameter and the diffusion coefficients organic solvent/water and water/organic solvent to the three pairs evaluated in this work. It was seen that the solubility parameter and diffusion coefficient organic solvent/water explain the same diameter of the nanocapsules, even the change on the organic solvent. Even so, it was done a viscosity study, as a function of log [PCL], to organic phases prepared with acetonitrile and 1,4-dioxane. It was obtained a value of 2,30 mg mL‾¹ to the critical aggregation concentration to the 1,4-dioxane solvent, and the value of 10,47 mg mL‾¹ to the acetonitrile solvent. So, it can be said that this high value found for acetonitrile is an advantage in its use, since the nanoscopic characteristics are maintained and a larger number of nanoparticles can be formed.

Values of the rate constant for the alkaline hydrolysis of methyl acetate in various aqueous-organic solvent mixtures (dimethyl sulfoxide 0<x40.2, dioxane 0 <, x., < 0.2, methyl ethyl ketone 0<x<0.06 and diglyme, i. e. ether-bis (2-methyloxethyl) 0x<0.10) have been determined for the temperatures 15 0 C, 25 0C and 35 0C conductometrically. To interpret these results the approach adapted is to experimentally determine the activity coefficient of the ester (YE ) and the activity of the water (aH20', mechanistically, at least one molecule of water is involved in the rate-determining step) and then to use the Bronsted-Bjerrum equation to determine the residual activity coefficient ratio of the participating ions, y (Yf - for Oil the transition state). Values of YE and aH 20 have been determined by a transpiration method, using gas-chromatographic analysis of the vapours of solutions of methyl acetate in aqueous-organic solvent mixtures of dir. ethyl sulfoxide, dioxane, methyl ethyl ketone and diglyme in the same composition ranges as above, tetrahydrofuran 04x org z<, 0.15, methanol, ethanol and tert-butanol in t1h6e range 04x0.20'at 25oC. These results indicate that on changing org the solvent composition YE varies by a larger factor than is predicted for the ratio YOH-/yýO_ by the Debye-Iluckel approach, and hence is the dominant factor in determining the effects of solvent composition on the rates of the hydrolysis. This is in contradiction to the assumptions of the electrostatic theories of Laidler and Eyring, and of Amis and Jaffe. The gas-chromatographic results also indicate that whilst the concentration of the water varies in each mixture studied, the activity coefficient varies in the opposite way to produce almost constant values of aý, 0* Using the transpiratioii/gas-chromatogralýlic method, the thermodynamic properties of the ternary systems, methyl acetate-water-organic Solvcat, using the organic solvents mentioned above (excepting, diglyme) have been investigated, and the results indicate that the variation of *ýE with solvent composition, for the dilute solutions of ester used, can be estimated from the thermodynamic properties of the binary water-organic solvent mixtures, using the Gibbs-Dahem equation. Single ion activity coefficients in the literature for small negative ions, to represent the OH_ ion, and for large ions, to rep-resent the transition state ion, have been used to explain the experimentally fomd variation of the residual activity coefficient -ratio with solvent composition. Hence, it is concluded that the importance of the parameters involved in the hydrolysis of esters - an ion-molecule reaction - in aqueousorganic solvent mixtures are in the order of Ymolecule > aH 20> YOH_/YM+ -> (dielectric constant), and that the nonelectrostatic effects -- thermodynamic effects - are more important in these studies than the electrostatic effects. From a preliminary investigation of the data in the literature the thermodynamic approach also yields a valid interpretation of the effect of solvent composition on the rates of the acid hydrolysis of esters.

O fluxo de injeção e o solvente orgânico, utilizado no preparo de nanoesferas poliméricas, são parâmetros experimentais que controlam o diâmetro e a distribuição de diâmetro das nanopartículas, formadas pelo processo conhecido como nucleação. Considerando as nanocápsulas de núcleo lipídico, formadas pelo processo de auto-organização, estes parâmetros experimentais ainda não foram explorados. Assim, esse trabalho propõe avaliar o fluxo de injeção e o solvente orgânico na preparação destas suspensões aquosas, caracterizando físicoquimicamente estes sistemas. Para variação de fluxo de injeção, utilizou-se uma bomba peristáltica, sendo possível a avaliação dos seguintes fluxos: 5, 8, 12, 15, 21 e 38 mL min¯¹. O diâmetro das nanocápsulas diminuiu de 256±9 nm a 127 ±8 nm pela técnica de difração de laser e 220±9 nm a 124±13 nm, segundo a técnica de espectroscopia de correlação de fótons. Os solventes orgânicos avaliados foram a acetona, acetonitrila e 1,4-Dioxano. Observou-se que a acetonitrila se mostrou adequada para a condição previamente otimizada com acetona, ao passo que o 1,4-Dioxano apresentou um pico micrométrico em sua distribuição. Assim, foi possível modelar este estudo através de um fatorial de design 2², onde têm-se dois fatores, fluxo de injeção e solvente orgânico, em dois níveis, nos fluxos de 5 e 38 mL min¯¹ e considerando os solventes acetona e acetonitrila. Como resultado, viu-se que o fluxo de injeção é o parâmetro de maior influência na preparação destas suspensões aquosas, se comparado ao solvente orgânico selecionado. Para elucidar o papel do solvente orgânico na preparação destes sistemas, calculouse os parâmetros de solubilidade e os coeficientes de difusão solvente orgânico\água e água\solvente orgânico para os três pares avaliados neste trabalho. Viu-se que os parâmetros de solubilidade e os coeficientes de difusão solvente orgânico\água explicam a não variação do diâmetro de partícula em função do solvente orgânico. Ainda, realizou-se um estudo de viscosidade, em função do log [PCL], para fases orgânicas preparadas com acetonitrila e 1,4- dioxano. Obteve-se o valor de 2,30 mg mL¯¹ para a concentração de agregação crítica quando utilizado o 1,4-Dioxano e 10,47 mg mL¯¹ para a fase orgânica preparada com acetonitrila. Então, pode-se dizer que este valor elevado encontrado para a acetonitrila é uma vantagem de sua utilização, uma vez que as características nanoscópicas são mantidas e um maior número de partículas pode ser formado. / Flow rate and organic solvent, used to prepare polimeric nanospheres, are experimental parameters that control the size and the size distribution curves of these nanoparticles, formed by particle nucleation. Considering the lipid core nanocapsules, formed by self-assembled process, these experimental parameters are not evaluated yet. Considering those, this work proposes to evaluate the flow rate and the organic solvent in the preparation of these aqueous suspensions, characterizing them physicochemically. To change the flow rate, it was used a peristaltic pump, it being possible to evaluate the following flows: 5, 12, 15, 21 and 38 mL min‾¹. The nanocapsules diameters decreased from 256±9 nm to 127 ±8 nm, by laser difratometry and 220±9 nm to 124±13 nm, by the photon correlation spectroscopy technique. The organic solvents evaluated were acetone, acetonitrle and 1,4-dioxane. It was observed that the acetonitrile was adequate for the condition previously optimized with acetone, whereas in the 1,4-dioxane distribution apears a micrometric peak. So, it was possible to modelate this study by a 2² factorial design, two factors, flow rate and organic solvent, in two levels, 5 and 38 mL min‾¹, considering acetone and acetonitrile. As a result, it was seen that the flow rate is the most influential parameter in the preparation of aqueous suspensions, compared to organic solvent selected. To elucidate the role of organic solvent in these systems, it was calculated the solubility parameter and the diffusion coefficients organic solvent/water and water/organic solvent to the three pairs evaluated in this work. It was seen that the solubility parameter and diffusion coefficient organic solvent/water explain the same diameter of the nanocapsules, even the change on the organic solvent. Even so, it was done a viscosity study, as a function of log [PCL], to organic phases prepared with acetonitrile and 1,4-dioxane. It was obtained a value of 2,30 mg mL‾¹ to the critical aggregation concentration to the 1,4-dioxane solvent, and the value of 10,47 mg mL‾¹ to the acetonitrile solvent. So, it can be said that this high value found for acetonitrile is an advantage in its use, since the nanoscopic characteristics are maintained and a larger number of nanoparticles can be formed.

O fluxo de injeção e o solvente orgânico, utilizado no preparo de nanoesferas poliméricas, são parâmetros experimentais que controlam o diâmetro e a distribuição de diâmetro das nanopartículas, formadas pelo processo conhecido como nucleação. Considerando as nanocápsulas de núcleo lipídico, formadas pelo processo de auto-organização, estes parâmetros experimentais ainda não foram explorados. Assim, esse trabalho propõe avaliar o fluxo de injeção e o solvente orgânico na preparação destas suspensões aquosas, caracterizando físicoquimicamente estes sistemas. Para variação de fluxo de injeção, utilizou-se uma bomba peristáltica, sendo possível a avaliação dos seguintes fluxos: 5, 8, 12, 15, 21 e 38 mL min¯¹. O diâmetro das nanocápsulas diminuiu de 256±9 nm a 127 ±8 nm pela técnica de difração de laser e 220±9 nm a 124±13 nm, segundo a técnica de espectroscopia de correlação de fótons. Os solventes orgânicos avaliados foram a acetona, acetonitrila e 1,4-Dioxano. Observou-se que a acetonitrila se mostrou adequada para a condição previamente otimizada com acetona, ao passo que o 1,4-Dioxano apresentou um pico micrométrico em sua distribuição. Assim, foi possível modelar este estudo através de um fatorial de design 2², onde têm-se dois fatores, fluxo de injeção e solvente orgânico, em dois níveis, nos fluxos de 5 e 38 mL min¯¹ e considerando os solventes acetona e acetonitrila. Como resultado, viu-se que o fluxo de injeção é o parâmetro de maior influência na preparação destas suspensões aquosas, se comparado ao solvente orgânico selecionado. Para elucidar o papel do solvente orgânico na preparação destes sistemas, calculouse os parâmetros de solubilidade e os coeficientes de difusão solvente orgânico\água e água\solvente orgânico para os três pares avaliados neste trabalho. Viu-se que os parâmetros de solubilidade e os coeficientes de difusão solvente orgânico\água explicam a não variação do diâmetro de partícula em função do solvente orgânico. Ainda, realizou-se um estudo de viscosidade, em função do log [PCL], para fases orgânicas preparadas com acetonitrila e 1,4- dioxano. Obteve-se o valor de 2,30 mg mL¯¹ para a concentração de agregação crítica quando utilizado o 1,4-Dioxano e 10,47 mg mL¯¹ para a fase orgânica preparada com acetonitrila. Então, pode-se dizer que este valor elevado encontrado para a acetonitrila é uma vantagem de sua utilização, uma vez que as características nanoscópicas são mantidas e um maior número de partículas pode ser formado. / Flow rate and organic solvent, used to prepare polimeric nanospheres, are experimental parameters that control the size and the size distribution curves of these nanoparticles, formed by particle nucleation. Considering the lipid core nanocapsules, formed by self-assembled process, these experimental parameters are not evaluated yet. Considering those, this work proposes to evaluate the flow rate and the organic solvent in the preparation of these aqueous suspensions, characterizing them physicochemically. To change the flow rate, it was used a peristaltic pump, it being possible to evaluate the following flows: 5, 12, 15, 21 and 38 mL min‾¹. The nanocapsules diameters decreased from 256±9 nm to 127 ±8 nm, by laser difratometry and 220±9 nm to 124±13 nm, by the photon correlation spectroscopy technique. The organic solvents evaluated were acetone, acetonitrle and 1,4-dioxane. It was observed that the acetonitrile was adequate for the condition previously optimized with acetone, whereas in the 1,4-dioxane distribution apears a micrometric peak. So, it was possible to modelate this study by a 2² factorial design, two factors, flow rate and organic solvent, in two levels, 5 and 38 mL min‾¹, considering acetone and acetonitrile. As a result, it was seen that the flow rate is the most influential parameter in the preparation of aqueous suspensions, compared to organic solvent selected. To elucidate the role of organic solvent in these systems, it was calculated the solubility parameter and the diffusion coefficients organic solvent/water and water/organic solvent to the three pairs evaluated in this work. It was seen that the solubility parameter and diffusion coefficient organic solvent/water explain the same diameter of the nanocapsules, even the change on the organic solvent. Even so, it was done a viscosity study, as a function of log [PCL], to organic phases prepared with acetonitrile and 1,4-dioxane. It was obtained a value of 2,30 mg mL‾¹ to the critical aggregation concentration to the 1,4-dioxane solvent, and the value of 10,47 mg mL‾¹ to the acetonitrile solvent. So, it can be said that this high value found for acetonitrile is an advantage in its use, since the nanoscopic characteristics are maintained and a larger number of nanoparticles can be formed.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The use of organic solvents in the work environment represents a significant risk to workers health. The painters composed, among others, a group of individuals who are in direct contact with solvents through the respiratory and dermal route. The biological monitoring, through biological exposure index (BEI) determination, can ensure the emergence of chronic occupational diseases, even in a long-term exposure. Thus, it was aimed to optimize and validate a methodology using high performance liquid chromatography with ultraviolet detector (HPLC-UV), for the simultaneous quantification of the following BEI: hippuric acid (HA), 3-methylhippuric acid (3mHA), mandelic acid (MA) and phenylglyoxylic acid (PGA) in urine to the solvents toluene, xylene, styrene (MA and PGA) and ethylbenzene (MA) respectively. In addition, there are reports that organic solvents, among other agents, cause imbalance in pro - and antioxidant defenses of the body, causing damage to the health of workers due to the oxidative stress. So, we quantified some blood biomarkers of oxidative stress, and its possible relationship to the levels of BEI in painters (n = 50) of an industry in Caxias do Sul, Brazil, and compared with non-exposed subjects. Thus, the biomarkers analyzed were: endogenous antioxidants such as reduced glutathione (GSH), the enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx); exogenous antioxidants such as vitamins C and E; in addition we determined two biomarkers of oxidation, in lipid peroxidation, we evaluate the levels of malondialdehyde (MDA) and in oxidation of proteins, we analysed protein carbonyl (PCO). The analytical parameters evaluated were linearity, accuracy, recovery and limits of detection (LOD) and quantification (LOQ). For all the analysed BEI, the linear regression coefficient > 0.99; CV% < 6 %; bias% < ± 10; recovery > 95%; LOD between 0.001 to 0.009 g.L-1 and LOQ between 0.04 to 0.02 g.L-1. In the application of the method, in exposed group (n=50), everyone had urinary concentration of HA; 2.5% of those were above the reference values (RV) and only 8% of these, had values above the biological exposure limit (BEL). Methylhippuric acid was found in 96%, PGA in 30%, and MA in 26% of the samples analyzed, those values, were all below the BEL. Among non-exposed ones, only urinary HA has been found, the values were 0.058 to 0.23 g / g creatinine. In relation to the oxidative stress biomarkers, the levels of plasma MDA and serum PCO were significantly increased compared to controls (p <0.01). The levels of erythrocyte GSH (p<0.05); blood SOD, CAT and GPx (p<0.001) were also significantly increased, showing an increase in antioxidant system in response to the deleterious effects of exposure to paints. The levels of exogenous antioxidants, such as vitamin C and vitamin E were significantly reduced in these subjects (p<0.05) compared to control. Moreover, it was observed a correlation between the biomarkers of oxidative stress and some BEI. The urinary mandelic acid, biological exposure index for styrene and ethylbenzene, showed a positive correlation with the enzymes SOD and CAT, and the MDA (p<0.01) and a negative correlation with vitamin E (p<0. 05). The hippuric acid found in urine samples showed a positive correlation with the blood levels of GPx (p<0.001). Furthermore, a positive correlation was found between MDA and PCO (p<0.001), and negative correlation between PCO with GPx, with vitamin C and with E (p <0.05). The results of the validation methodology showed linearity, precision and accuracy, allowing conclude that the method is reliable to quantify the biological exposure indices, HA, mHA, MA and PGA, simultaneously. Furthermore, the levels of these BEI showed to be within the biological exposure limits. The biomarkers of oxidative stress related to lipid peroxidation and the oxidation of proteins were significantly increased even with an increase in endogenous antioxidants analyzed, GSH, SOD, CAT and GPx. Moreover, there was a depletion of exogenous antioxidants, such as vitamins C and E. So with this work we can suggest that the biological exposure limit for the metabolites of toluene, xylene, styrene and ethylbenzene analyzed, failed to ensure the balance in antioxidant/oxidant status to exposed workers. / O uso de solventes orgânicos no meio ocupacional representa significativo risco à saúde do trabalhador. Os pintores compõem, dentre outros, um grupo de indivíduos ocupacionalmente expostos aos solventes, através da via respiratória e dérmica. A monitorização de indicadores biológicos de exposição (IBE) pode assegurar, em longo prazo, o não aparecimento de doenças crônicas ocupacionais. Desta forma, objetivou-se otimizar e validar uma metodologia utilizando cromatografia líquida de alta eficiência com detector ultravioleta (CLAE-UV), para a quantificação simultânea dos seguintes IBE: ácidos hipúrico (HA), 3-metilhipúrico (3mHA), mandélico (MA) e fenilglioxílico (PGA) em urina, dos solventes tolueno, xileno, estireno (MA e PGA) e etilbenzeno (MA) respectivamente. Além disso, existem relatos de que solventes orgânicos, dentre muitos outros agentes, ocasionam desequilíbrio nas defesas pró- e antioxidantes do organismo, ocasionando danos à saúde dos trabalhadores devido ao estresse oxidativo. Portanto, quantificou-se alguns biomarcadores sangüíneos do estresse oxidativo, verificando-se sua possível relação com os níveis dos indicadores biológicos em pintores (n=50) de uma indústria da cidade de Caxias do Sul, RS, comparando-os com os indivíduos não expostos ocupacionalmente. Assim, os biomarcadores analisados foram: antioxidantes endógenos como a glutationa reduzida (GSH), as enzimas superóxido dismutase (SOD), catalase (CAT) e glutationa peroxidase (GPx); antioxidantes exógenos como as vitaminas C e E; e os biomarcadores de oxidação, no caso da peroxidação lipídica, o malondialdeído (MDA), e da oxidação de proteínas, as proteínas carboniladas (PCO). Os parâmetros analíticos de validação foram linearidade, precisão, exatidão, recuperação e limites de detecção (LD) e quantificação (LQ). Para todos os IBE analisados, os coeficientes de regressão linear > 0.99; CV% < 6%; bias% < ±10; recuperação > 95%, LD entre 0,001 a 0,009 g.L-1 e LQ de 0,04 a 0,02 g.L-1. Na aplicação do método validado, das amostras de indivíduos expostos (n=50), todos apresentaram concentração urinária de HA; 2,5% destes, acima dos valores de referência (VR) e apenas 8% destes, apresentaram valores acima do índice biológico máximo permitido (IBMP). Foram encontrados mHA em 96%, PGA em 30%, e MA em 26% das amostras analisadas, sendo estes valores, todos abaixo do IBMP. Dentre os indivíduos não expostos (n=30), somente HA foi encontrado, os valores foram de 0,058 0,23 g/g de creatinina urinária. Quanto aos biomarcadores do estresse oxidativo, os níveis de MDA plasmático e de PCO sérica foram significativamente aumentados comparados aos controles (p<0,01). Os níveis de GSH eritrocitária (p<0,05); SOD, CAT e GPx (p<0,001) sangüíneas também foram significativamente aumentados, demonstrando um aumento no sistema antioxidante em resposta aos efeitos deletérios da exposição às tintas. Os níveis de antioxidantes exógenos, vitamina C e vitamina E estavam significativamente diminuídos nestes indivíduos (p<0,05) quando comparados aos controles. Além disso, foi observada correlação entre os biomarcadores do estresse oxidativo e os IBE. O ácido mandélico urinário, indicador de exposição ao estireno e ao etilbenzeno, apresentou correlação positiva com as enzimas SOD e CAT, e com o MDA (p<0,01), e uma correlação negativa com a vitamina E (p<0,05). O ácido hipúrico urinário apresentou correlação positiva com os níveis sangüíneos de GPx (p<0,001). Além disso, foi encontrada correlação positiva entre MDA e PCO (p<0,001); e correlação negativa das PCO com GPx, com vitamina C e E (p<0,05). Os resultados da validação metodológica demonstraram linearidade, precisão e exatidão, permitindo concluir que o método é confiável para quantificar os indicadores biológicos de exposição, HA, mHA, MA e PGA, simultaneamente. Além disso, os níveis dos IBE mostraram-se quase que na sua totalidade, dentro dos índices biológicos máximos permitidos. Os biomarcadores do estresse oxidativo relacionados com a peroxidação lipídica e com a oxidação de proteínas apresentaram-se significativamente aumentados mesmo com um aumento dos antioxidantes endógenos analisados, GSH, SOD, CAT e GPx. Por outro lado, observou-se uma depleção dos antioxidantes vitamínicos exógenos, como as vitaminas C e E. Assim, com este trabalho é possível sugerir que os IBMP, para os IBE dos solventes orgânicos tolueno, xileno, estireno e etilbenzeno analisados, não asseguram o equilíbrio antioxidante/oxidante nos trabalhadores expostos.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第18326号 / 農博第2051号 / 新制||農||1022(附属図書館) / 学位論文||H26||N4833(農学部図書室) / 31184 / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 植田 充美, 教授 喜多 恵子, 教授 栗原 達夫 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

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Values of the rate constant for the alkaline hydrolysis of methyl acetate in various aqueous-organic solvent mixtures (dimethyl sulfoxide 0<x40.2, dioxane 0 <, x., < 0.2, methyl ethyl ketone 0<x<0.06 and diglyme, i. e. ether-bis (2-methyloxethyl) 0x<0.10) have been determined for the temperatures 15 0 C, 25 0C and 35 0C conductometrically. To interpret these results the approach adapted is to experimentally determine the activity coefficient of the ester (YE ) and the activity of the water (aH20', mechanistically, at least one molecule of water is involved in the rate-determining step) and then to use the Bronsted-Bjerrum equation to determine the residual activity coefficient ratio of the participating ions, y (Yf - for Oil the transition state). Values of YE and aH 20 have been determined by a transpiration method, using gas-chromatographic analysis of the vapours of solutions of methyl acetate in aqueous-organic solvent mixtures of dir. ethyl sulfoxide, dioxane, methyl ethyl ketone and diglyme in the same composition ranges as above, tetrahydrofuran 04x org z<, 0.15, methanol, ethanol and tert-butanol in t1h6e range 04x0.20'at 25oC. These results indicate that on changing org the solvent composition YE varies by a larger factor than is predicted for the ratio YOH-/yýO_ by the Debye-Iluckel approach, and hence is the dominant factor in determining the effects of solvent composition on the rates of the hydrolysis. This is in contradiction to the assumptions of the electrostatic theories of Laidler and Eyring, and of Amis and Jaffe. The gas-chromatographic results also indicate that whilst the concentration of the water varies in each mixture studied, the activity coefficient varies in the opposite way to produce almost constant values of aý, 0* Using the transpiratioii/gas-chromatogralýlic method, the thermodynamic properties of the ternary systems, methyl acetate-water-organic Solvcat, using the organic solvents mentioned above (excepting, diglyme) have been investigated, and the results indicate that the variation of *ýE with solvent composition, for the dilute solutions of ester used, can be estimated from the thermodynamic properties of the binary water-organic solvent mixtures, using the Gibbs-Dahem equation. Single ion activity coefficients in the literature for small negative ions, to represent the OH_ ion, and for large ions, to rep-resent the transition state ion, have been used to explain the experimentally fomd variation of the residual activity coefficient -ratio with solvent composition. Hence, it is concluded that the importance of the parameters involved in the hydrolysis of esters - an ion-molecule reaction - in aqueousorganic solvent mixtures are in the order of Ymolecule > aH 20> YOH_/YM+ -> (dielectric constant), and that the nonelectrostatic effects -- thermodynamic effects - are more important in these studies than the electrostatic effects. From a preliminary investigation of the data in the literature the thermodynamic approach also yields a valid interpretation of the effect of solvent composition on the rates of the acid hydrolysis of esters. / Ministry of Science and Higher Education of Iran

Yes / Objectives  In this work we investigated the residual organic solvent content and physicochemical properties of spray-dried chlorothiazide sodium (CTZNa) and potassium (CTZK) salts. Methods  The powders were characterised by thermal, X-ray diffraction, infrared and dynamic vapour sorption (DVS) analyses. Solvent levels were investigated by Karl–Fischer titration and gas chromatography. Key findings  Spray-drying from water, methanol (MeOH) and mixes of MeOH and butyl acetate (BA) resulted in amorphous microparticles. The glass transition temperatures of CTZNa and CTZK were ∼192 and ∼159°C, respectively. These materials retained their amorphous nature when stored at 25°C in dry conditions for at least 6 months with no chemical decomposition observed. DVS determined the critical relative humidity of recrystallisation of CTZNa and CTZK to be 57% RH and 58% RH, respectively. The inlet temperature dependant oxidation of MeOH to formaldehyde was observed; the formaldehyde was seen to deposit within the amorphous matrix of spray-dried product. Spray-drying in the open blowing mode coupled with secondary drying resulted in a three-fold reduction in residual BA (below pharmacopoeial permitted daily exposure limit) compared to spray-drying in the closed mode. Conclusions  Experiments showed that recirculation of recovered drying gas increases the risk of deposition of residual solvents in the spray-dried product. / The Irish Research Council for Science and Engineering Technology (IRCSET), the Solid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under grant number (07/SRC/B1158) and the Irish Drug Delivery Research Network, a Strategic Research Cluster grant (07/SRC/B1154) under the National Development Plan co-funded by EU Structural Funds and Science Foundation Ireland.

La synthèse de matériaux polymères stables en milieu organique a été réalisée sur la base d’une série de copolymères à blocs de type polyuréthane. La synthèse de membranes denses autosupportées a permis la caractérisation des différents polyuréthanes et la sélection des formulations les plus adaptées pour l’obtention de membranes composites à peau dense. Les propriétés des membranes ont été ajustées par modulation des réactifs de départ. Une bonne résistance aux solvants organiques a été notée et les flux de perméation les plus importants ont été obtenus avec les matériaux les plus souples. Une membrane rigide a été testée pour la récupération du catalyseur Grubbs-HoveydaII du toluène. Malgré un faible taux de gonflement, le taux de rejet était limité à 48%, permettant de rompre avec l’idée liant la rigidité du réseau à une bonne sélectivité. Une démarche compréhensive du mécanisme de transport en nanofiltration organique (NFO) a été menée sur des membranes en polydiméthylsiloxane (PDMS). L’effet de la pression sur le gonflement a été examiné à travers deux appareils mimant les conditions de pression en NFO. Il a été démontré que la pression n’affectait pas l’équilibre amont de sorption mais induisait une diminution du gonflement de l’interface aval de la membrane. Le gradient de gonflement a été proposé comme force motrice du transport des solvants. La perméation des solvants purs et des solutés a été ensuite étudiée. Le modèle de solution-diffusion a pu être proposé comme mécanisme de transport des solvants purs. La sélectivité des membranes s’est avérée être indépendante de l’affinité solvant-membrane mais dépendante de l’affinité soluté - solvant et soluté - membrane / The synthesis of polymeric solvent stable materials was carried out on the basis of block copolymers polyurethane. A series of self-supported dense membranes allowed characterizing the different polymers and the selection of the most suitable ones to prepare composite membranes with a dense top layer. The properties of the membranes were adjusted by tailoring the starting reagents. Good resistance of the membranes in organic solvents was observed and the most important permeation flows were obtained with the softer materials. A rigid membrane was tested for the recovery of the Grubbs-HoveydaII catalyst from toluene. Despite a low swelling rate, the selectivity of the membrane was limited to 48%. This result is in contradiction with the common idea stating that high selectivity is due to rigid polymer network. A comprehensive approach of the transport mechanism in organic solvent nanofiltration (OSN) was conducted using polydiméthylsiloxane membranes (PDMS). The effect of pressure on the swelling was examined using two devices mimicking the pressure conditions in OSN. It has been shown that the pressure does not affect the upstream equilibrium sorption but induced a decrease of the swelling of the downstream interface of the membrane. The swelling gradient between the two sides of the membrane was proposed as driving force of solvents transport. The nanofiltration of solvents and solutes were then studied. The results showed that the solution–diffusion model was fully valid for pure solvents transport. The selectivity of the membrane was found to be independent of the membrane-solvent interaction but affected by the solute-membrane affinity and solute-solvent interaction