A set of 15 carboxylic acids of various structural types was used to test a new procedure of esterification of these substances in the urine without previous extraction. The acids were first measured by a reference method without the matrix, and then by a procedure, where lyophilized urine was treated with derivatizing reagent alcohol·HCl, which was then evaporated, the residue dissolved in water, esters extracted into an organic solvent and subsequently determined by GC/FID and GC/MS. The work is mainly focused on 2-hydroxyethyl- and carboxymethyl-mercapturic acids, but the procedure was also tested on di-, tri- and hydroxy-carboxylic acids, known as physiological urinary components or markers of metabolic disorders. Key words: carboxylic acids mecapturic acids freeze-dried urine esterification gas chromatography

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第20814号 / 工博第4418号 / 新制||工||1686(附属図書館) / 京都大学大学院工学研究科都市環境工学専攻 / (主査)教授 伊藤 禎彦, 教授 田中 宏明, 准教授 西村 文武 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

In this doctoral thesis, we have studied the oxidation of carboxylic acids to obtain the corresponding acyloxy radicals, using visible light and non-toxic and inexpensive organic dyes, as photocatalysts. On the one hand, we study the photooxidation of aromatic carboxylic acids to obtain acyloxy radicals, whose decarboxylation is relatively slow (Chapter I and Chapter II). On the other hand, we describe the photooxidation of aliphatic carboxylic acids, to take advantage of the rapid decarboxylation of the corresponding acyloxy radicals, to generate nucleophilic radicals that were trapped by different reagents (Chapter III to Chapter V). It should be noted that all the protocols are free of expensive and toxic noble metals, the reactions were promoted with visible light at room temperature and the scalability of some reactions was demonstrated in batch conditions or using flow chemistry. In addition, mechanistic studies were carried out to propose plausible photocatalytic routes to all the reactions studied.

The interaction of carboxylic acids with copper is a phenomenon found both outdoors and, more commonly, indoors. The influence on copper of some carboxylic acids (formic, acetic, propionic, and butyric) have so far been studied at concentrations levels at least three or four orders of magnitude higher than actual indoor conditions (< 20 ppb, volume parts per billion), and with only limited emphasis on any mechanistic approach. In this licentiate study a unique analytical setup has been successfully applied for in situ characterization and quantification of corrosion products formed during initial atmospheric corrosion of copper in the presence of acetic, formic or propionic acid. The setup is based on monitoring mass changes by the quartz crystal microbalance (QCM) and simultaneously identifying the chemical species by infrared reflection-absorption spectroscopy (IRAS). Post-analysis of corrosion products was performed by coulometric reduction (mass of copper (I) oxide formed), grazing incidence x-ray diffraction (phase identification) and atomic force microscopy (surface topography). The absolute amounts of mass of individual constituents in the corrosion products, mainly copper (I) oxide or cuprite, copper (II) carboxylate and water or hydroxyl groups, have been deduced in situ during exposure in 120 ppb of carboxylic acid concentration, 95% relative humidity and 20ºC. An overall result is the consistency of analytical information obtained. For copper (I) oxide the quantified data estimated from IRAS, QCM or coulomeric reduction agrees with a relative accuracy of 12 % or better. The interaction of copper with the carboxylic acids seems to follow two spatially separated main pathways. A proton-induced dissolution of cuprous ions followed by the formation of copper (I) oxide, and a carboxylate-induced dissolution followed by the formation of copper (II) carboxylate. The first pathway is initially very fast but levels off with a more uniform growth over the surface. This pathway dominates in acetic acid. The second pathway exhibits a more constant growth rate and localized growth, and dominates in formic acid. Propionic acid exhibits low rates for both pathways. The difference between the carboxylic acids with respect to both total corrosion rate and carboxylate-induced dissolution can be attributed to differences in acid dissociation constant and deposition velocity.

The growth of Fe₃O₄ and FeOOH crystals was investigated. Growth modifiers were used to alter the formation of iron oxides from ferrous hydroxide precipitates. Multifunctional carboxylic acids were found to have a strong influence on morphology of FeOOH. Dicarboxylic acids, containing two and seven carbons, changed the characteristics of α-FeOOH. These changes included alteration of the isoelectic point of the particulates and changes in particle size and shape. EDTA was found to alter the phase of FeOOH formation, favoring the synthesis of γ-FeOOH over α-FeOOH at temperatures below 50°C. The effects of multifunctional carboxylic acids were dependent upon the time of addition, and the presence of other growth modifiers. The changes in FeOOH formation were postulated to occur due to interaction between the acid molecules and Green Rust II, a common intermediate in iron oxide growth. The growth of Fe₃O₄ was found to be sensitive to solution pH, and the form of the iron starting materials. Examination of reaction intermediates by x-ray diffraction showed that other Crystalline phases formed prior to the production of Fe₃O₄. Different intermediate phases occurred depending on the amount of hydroxide in the reaction, and differences in Fe³⁺ starting materials. The production of different intermediate phases affected the morphology of Fe₃O₄. Early precipitation of Fe₃O₄ led to small particles, while formation of crystalline Fe(OH)₂ led to large crystals. Formation of a mixture of Green Rust II and Fe(OH)₂ early in the oxidation process led to formation of multiple nuclei, and produced smaller average particles with a wide particle size distribution. Fe₃O₄ particles prepared from α-FeOOH seed crystals were spherical, while Fe₃O₄ particles prepared from FeSO₄ alone were octahedral crystals. / Ph. D.

Despite its extremely low solubility in water, fullerite C₆₀ can form colloidally stable aqueous suspensions containing nanoscale C₆₀ particles (nC₆₀) when it is subject to contact with water. nC₆₀ is the primary fullerene form following its release to the environment. The aim of the present study was to provide fundamental insights into the properties and environmental impacts of nC₆₀. nC₆₀ suspensions containing negatively charged and heterogeneous nanoparticles were produced via extended mixing in the presence and absence of citrate and other carboxylates. These low-molecular weight acids were employed as simple surrogates of natural organic matter. The properties of nC₆₀ were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and UV-Vis spectroscopy. nC₆₀ produced in the presence of carboxylate differs from that produced in water alone (aq/nC₆₀) with respect to surface charge, average particle size, interfacial properties, and UV-Vis spectroscopic characteristics. Importantly, regularly shaped (spheres, triangles, squares, and nano-rods) nC₆₀ nanoparticles were observed in carboxylate solutions, but not in water alone. This observation indicates that a carboxylate-mediated 'bottom-up' process occurs in the presence of carboxylates. Changes in the UV-Vis spectra over time indicate that reactions between C₆₀ and water or other constituents in water never stop, potentially leading to significant morphologic changes during storage or as a result of simple dilution. These results suggest that studies examining the transport, fate, and environmental impacts of nC₆₀ should take the constituents of natural waters into consideration and that careful examination on the properties of the tested nC₆₀ should be conducted prior to and during each study. / Ph. D.

No

Ces dernières années, les recherches industielles et académiques ont connu des bouleversements sansprécédents liés à la notion de Développement Durable. Le choix des matières premières, des réactions,des procédés, et la caractérisation du produit final obligent les industriels à repenser leur mode deproduction. Ce changement peut notamment s’effectuer par « la conception de produits et de procédéschimiques permettant de réduire ou d’éliminer l’utilisation et la synthèse de leurs substancesdangereuses. » Les travaux de recherche décrits dans cette thèse s’inscrivent dans ce contexte etconcernent la mise au point de nouveaux systèmes réducteurs utilisant des hydrosiloxanes commesubstituts des hydrures d’aluminium et de bore.Dans cet objectif, plusieurs systèmes réducteurs basés sur l’utilisation du 1,1,3,3-tétraméthyldisiloxane(TMDS) associé à un complexe métallique ont pu être développés au laboratoire. Selon la nature dumétal employé, les réductions sélectives de diverses fonctions organiques ont été effectuées. Ainsi, lefer (III) acétylacétonate associé au TMDS a permis la réduction de nitro aromatiques en anilinescorrespondantes ; le palladium sur charbon la synthèse d’alcoxysiloxanes à partir de cycles oxygénés,d’alcools ou de carbonyles ; les esters ont également été réduits en alcools par action d’un complexede molybdène ou de vanadium ; la réduction d’acides ainsi que la cyclisation de diacides ont pu êtreeffectuées à l’aide de tribromure d’indium et ce dernier complexe a également montré une bonneefficacité pour la réduction d’oxydes de phosphine. / In recent years, industrial and academic researches have experienced unprecedented changes related tothe concept of sustainable development. The choice of raw material, reactions, processes, andcharacterization of final products are constraining the industrials to rethink their production methods.This change can be accomplished by “the conception of chemical products and processes that reduceor eliminate the use and synthesis of hazardous materials.” The research work described in this thesisis focused on the development of new reducing systems using hydrosiloxanes as substitutes foraluminum and boron hydrides.In this context, several reducing systems based on the use of 1,1,3,3-tetramethyldisiloxane (TMDS)associated with a metal complex have been developed in the laboratory. Depending on the metal,selective reductions of various organic functions were performed. Thus, iron (III) acetylacetonate andTMDS allowed the reduction of aromatic nitro compounds; palladium on charcoal was used for thesynthesis of alcoxysiloxanes from oxygenated rings, alcohols or carbonyl compounds; esters were alsoreduced into alcohols by the action of a molybdenum or a vanadium complex; reduction of carboxylicacids as well as the cylization of dicarboxylic acids have been carried out using indium tribromide andthe latter complex also proved efficiency for the reduction of phosphine oxides derivatives

O presente estudo teve como objetivo caracterizar o processo de cicatrização e investigar os efeitos da suplementação (gavagem) com OL e Li em estudos in vivo. Após anestesia, uma área de 10 mm2 de pele foi removida cirurgicamente da região dorsal dos animais. A suplementação com Li reduziu o tamanho das feridas no sétimo dia após a indução. Esse resultado foi acompanhado de aumento na produção de peróxido de hidrogênio (H2O2). O OL reduziu o conteúdo de H2O2 após 24 horas. Li acelerou a resposta migratória, aparecendo células inflamatórias uma hora após o ferimento. OL induziu ativação do fator de transcrição NF-<font face=\"Symbol\">kB e o Li ativou AP-1 após uma hora. Em 24 horas, ambos AGs inibiram o NF-<font face=\"Symbol\">kB e não alteraram o AP-1. Li elevou as concentrações de CINC-2<font face=\"Symbol\">a<font face=\"Symbol\">b e OL aumentou TNF-<font face=\"Symbol\">a, no homogenato, uma hora após a indução da ferida. Em 24 horas, ambos AGs reduziram a expressão e as concentrações de IL-1<font face=\"Symbol\">b, IL-6 e MIP-3<font face=\"Symbol\">a. A suplementação com OL e Li acelerou a fase inflamatória do processo de cicatrização. / This study aimed to characterize the healing process and to investigate the effects of supplementation (gavage) with OL and Li on the healing process through in vivo experiments. After anesthesia, an area of 10 mm2 of skin was surgically removed from the dorsum. Li reduced the size of the wounds on the seventh day after induction. This result was accompanied by increased production of hydrogen peroxide (H2O2). OL reduced the H2O2 content after 24 hours. Li accelerated the migratory response, since inflammatory cells were found one hour after the wound. OL activated the transcription factor NF-<font face=\"Symbol\">kB and Li increased the activation of AP-1 one hour after wound induction. Both fatty acids reduced the activation of NF-<font face=\"Symbol\">kB and did not alter AP-1 after 24 hours. Li raised the concentrations of CINC-2<font face=\"Symbol\">a<font face=\"Symbol\">b and OL increased TNF-<font face=\"Symbol\">a, in the homogenate, one hour after wound induction. In 24 hours, the FA reduced expression and concentrations of IL-1<font face=\"Symbol\">b, IL-6 and MIP-3<font face=\"Symbol\">a. Putting together, our results demonstrate that OL and Li accelerate the inflammatory phase of the wound healing.

Este trabalho está dividido em: obtenção e caracterização de amido termoplástico (TPS); estudo do envelhecimento do TPS e blendas de PP/TPS. O estudo do TPS, foi realizado utilizando amido de milho, 30% em massa de glicerol e outros componentes que variam entre as amostras. Primeiramente foi realizado um planejamento estatístico para obter a composição ótima de TPS. Foram escolhidos cinco parâmetros de entrada: 2 de composição (umidade e teor de ácido cítrico) e 3 de processamento (temperatura, velocidade dos rotores e tempo), visando obter um TPS com propriedades térmicas e mecânicas superiores. De acordo com os resultados de infravermelho, termogravimetria, microscopia ótica (MO) e microscopia eletrônica de varredura (MEV) foram escolhidas 2 composições. Estas foram calandradas e confeccionadas para obtenção dos corpos de prova de tração. Os resultados dos ensaios mecânicos mostraram que amostras com teor de ácido cítrico de aproximadamente 2% em massa apresentam os maiores valores de módulo de elasticidade e resistência à tração. Com estes resultados foram realizadas novas composições com outros ácidos carboxílicos: adípico, málico e tartárico e amostras sem ácidos. As curvas de torque indicaram que as amostras sem ácido carboxílico e com ácido adípico perdem água durante o processamento. Analisando os resultados verifica-se que o TPS com os ácidos málico e tartárico apresentam melhores propriedades mecânicas e térmicas. Também foi analisado o envelhecimento, e notou-se que com o tempo as amostras tendem a perder plastificante, modificando suas propriedades mecânicas e sua cristalinidade. Entretanto, durante o intervalo de um ano, as amostras de TPS com ácido málico e tartárico não sofreram perda significativa de plastificante. Por último, foram obtidas blendas de PP reciclado com TPS nas composições 50/50, 60/40 e 70/30 em massa, respectivamente, com e sem adição de ácidos: cítrico, málico e tartárico e anidrido maleico. As amostras foram caracterizadas por FTIR, DRX, reometria capilar, MEV e por teste de resistência à tração. Micrografias obtidas por MEV indicaram que todas as composições estudadas possuem morfologia predominantemente co-contínua. A presença dos ácidos, geralmente, reduz os valores das propriedades mecânicas da blenda de PP com TPS e a adição de PP-g-MA é mais efetiva nas blendas sem adição de ácido. Ao analisar o envelhecimento das blendas com adição de ácidos tartárico e málico, notou-se que as propriedades mecânicas não foram alteradas em função do tempo de estocagem. / This work is divided in four parts: obtention and characterization of thermoplastic starch (TPS), study of TPS ageing, and characterization of PP/TPS blends. This study used TPS with cornstarch, glycerol (30 wt.%) and other components. First of all, a statistic study about thermoplastic starch preparation methods was performed in order to obtain the best TPS composition. Five parameters were evaluated: the starch water content, citric acid concentration, and three process parameters: temperature, time and rotor speed. According to infrared, thermogravimetry, optical microscopy, and scanning electron microscopy results, we have chosen two compositions to be mechanically tested. The mechanical tests required the samples to be calendered and cut with knife. The results of the mechanical tests showed that samples containing 2 wt.% of citric acid had the highest Young modulus and tensile strength values. Based on these results, new compositions were prepared with other carboxylic acids, such as adipic, malic and tartaric acids, as well as pure samples. The torque curves showed that the samples without carboxylic and adipic acid loose water during the processing. Analyzing the results, it is possible to see that TPS with malic and tartaric acids have better mechanical and thermal properties. Ageing was also analyzed and it was noted that the samples tend to loose plasticizer, altering their mechanical properties and crystallinity with time. However, during the one-year period, TPS samples with malic and tartaric acid suffered no significant plasticizer loss. Finally, recycled PP blends were obtained with the following compositions of PP/TPS: 50/50, 60/40, and 70/30. To these blends, some acids were added, such as citric, malic and tartaric, and maleic anhydride. Their properties were compared to the ones for pure blend. The samples were characterized by FTIR, XRD, capillary rheometry, SEM, and for tensile strength. SEM micrographs showed that all studied blends have predominantely co-continuous morphology. Usually, the presence of the acid reduces the mechanical property values of the PP/TPS blends. The addition of PP-g-MA is more effective in blends without acids. By analyzing the ageing of the blends with malic and tartaric acid it was noted that the mechanical properties were not changed as a function of the storage time.