Mechanistic studies on three different ruthenium-based catalysts have been performed. The catalysts have in common that they have been employed in hydrogen transfer reactions involving alcohols and ketones, amines and imines or both. Bäckvall’s catalyst, η5-(Ph5C5)Ru(CO)2Cl, finds its application as racemization catalyst in dynamic kinetic resolution, where racemic alcohols are converted to enantiopure acetates in high yields. The mechanism of the racemization has been investigated and both alkoxide and alkoxyacyl intermediates have been characterized by NMR spectroscopy and in situ FT-IR measurements. The presence of acyl intermediates supports a mechanism via CO assistance. Substantial support for coordination of the substrate during the racemization cycle is provided, including exchange studies with both external and internal potential ketone traps. We also detected an unexpected alkoxycarbonyl complex from 5-hydroxy-1-hexene, which has the double bond coordinated to ruthenium. Shvo’s catalyst, [Ru2(CO)4(μ-H)(C4Ph4COHOCC4Ph4)] is a powerful catalyst for transfer hydrogenation as well as for dynamic kinetic resolution. The mechanism of this catalyst is still under debate, even though a great number of studies have been published during the past decade. In the present work, the mechanism of the reaction with imines has been investigated. Exchange studies with both an external and an internal amine as potential traps have been performed and the results can be explained by a stepwise inner-sphere mechanism. However, if there is e.g. a solvent cage effect, the results can also be explained by an outer-sphere mechanism. We have found that there is no cage effect in the reduction of a ketone containing a potential internal amine trap. If the mechanism is outer-sphere, an explanation as to why the solvent cage effect is much stronger in the case of imines than ketones is needed. Noyori’s catalyst, [p-(Me2CH)C6H4Me]RuH(NH2CHPhCHPhNSO2C6H4-p-CH3), has successfully been used to produce chiral alcohols and amines via transfer hydrogenation. The present study shows that the mechanism for the reduction of imines is different from that of ketones and aldehydes. Acidic activation of the imine was found necessary and an ionic mechanism was proposed.

Fluorotelomer alcohols (FTOHs, F(CF2)nCH2CH2OH) are emerging contaminants in the environment. Biodegradation of 6:2 and 8:2 FTOHs has been intensively studied using soils and activated sludge. However, little is known about the bacteria responsible for biotransformation of FTOHs. This study deciphered factors affecting biodefluorination of FTOHs and their metabolites, and developed three effective FTOH-degrading consortia. Two alkane-degrading Pseudomonas strains (P. oleovorans and P. butanovora) can defluorinate 4:2, 6:2 and 8:2 FTOHs, with a higher degree of defluorination for 4:2 FTOH. According to the identified metabolites, P. oleovorans transformed FTOHs via two pathways I and II. Pathway I led to formation of x:2 ketone (x = n-1), x:2 sFTOH and perfluorinated carboxylic acids (PFCAs). Pathway II resulted in the formation of x:3 polyfluorinated acid and relatively minor shorter-chain PFCAs. Conversely, P. butanovora transformed FTOHs by pathway I only. Mycobacterium vaccae JOB5 (a C1-C22alkane-degrading bacterium) and P. fluorescens DSM 8341 (a fluoroacetate-degrading bacterium) can transform 6:2 FTOH via both pathways I and II with the formation of odd-numbered short-chain PFCAs. In the presence of dicyclopropylketone or formate, P. oleovorans transformed 6:2 FTOH six times faster and produced odd-numbered PFCAs. P. butanovora, utilized both pathways I and II in the presence of lactate, and it also produced odd-numbered PFCAs. Unlike P. oleovorans, P. fluorescens DSM 8341 could slightly convert 5:3 polyfluorinated acid (a key metabolite during 6:2 FTOH degradation, [F(CF2)5CH2CH2COOH]) to 4:3 acid and PFPeA via one-carbon removal pathways. Three FTOH-degrading consortia transformed FTOHs, with enhanced removal of FTOHs in the presence of n-octane. A higher copy number of alkB gene was found to correspond to better removal of FTOHs, suggesting that alkane-degrading bacteria might be the key degraders in the enrichments. The three enrichment cultures showed a similar microbial community structure. This is the first study reporting that pure strains of alkane- and fluoroacetate-degrading bacteria can bio-transform FTOHs via different or preferred transformation pathways to remove multiple –CF2– groups from FTOHs to form shorter-chain PFCAs, and to other perfluorinated acids. The results of this study also suggest that enhanced FTOH biodegradation is possible through co-substrate addition and/or using enrichment cultures.

This thesis presents a new developed method for first intermolecular aldehyde/ketone cross benzoin coupling. Protected &amp / #945 / -keto tertiary alcohols are synthesized starting from easily available acyl phosphonates and ketones via Brook rearrangement in the presence of catalytic amount of cyanide ion. The scopes and the limitations of the methods for the synthesis of tertiary alcohols with &amp / #945 / -keto group are discovered.

Chiral cyclic alpha azido ketones are very important compounds in organic chemistry. Because, the reduced forms of them are amino alcohols and these amino alcohols are interesting compounds for their biological activities. They have some pharmaceutical activities such as: potassium channel open up properties, treatment of central nervous system, antihypertensive properties, the agent of dopamin receptor activator, hypolipemic agent and dopamine agonist. These types of compounds have highly acidic alpha-protons, and many kinds of reactions can be performed with them. In this study, mainly, selective protonation of racemic compounds was performed with a new practical method and there are not so many examples related to deracemization in the literature. Alpha-azido derivatives of tetralone, indanone, chromanone, and thiochromanone structures are chosen as starting materials because of their importance for biological activities arising from their cyclic structures. Firstly, these &alpha / -azido compounds were synthesized according to literature. The acidic alpha-protons do not require strong bases. Their enantioselective deracemization and deracemization processes were screened by using Cinchona derivatives as organocatalysts. This screening process was monitored by chiral HPLC columns. The parameters such as catalyst loading, solvent, temperature, reaction time and additives were optimized to obtain high enantioselectivities up to 98%. In addition to deracemization reactions, Michael addition reactions were also performed by starting from &alpha / -azido chromanones. In these reactions different type of urea catalyst was used to activate the electrophilic part of trans-&beta / -nitrostyrene compound. Again by controlling the temperature, time and catalyst loading, two diastereomers were formed and the screening process was monitored by chiral HPLC columns again. The Michael products were obtained in up to 94% ee and 75% yield.

No description available.

The purpose of this study is to develop catalysts for conversion of synthesis gas (H₂ and CO) to higher alcohols, primarily ethanol and propanol. Crude oil is consumed at a rate of more than 20 million barrels a day in the United States, mainly for producing fuels and chemical feedstocks. However, the total amount of crude oil is limited, and alternative ways of producing alcohols as precursors for chemical feedstocks are desirable. In this study, using a known K/MoS₂/metal oxide catalyst as the starting point, two different approaches were explored to improve catalytic properties: 1) Co promotion on K/MoS₂/mixed metal oxide (MMO) catalysts, and 2) Preparation of K/MoS₂/metal oxide catalysts with molybdenum carbide as a precursor, instead of molybdenum oxide. With respect to Co promotion on K/MoS₂/MMO catalysts, the effect of varying the Co content in the K/Mo-Co/MMO catalysts prepared by a co-impregnation method did not produce significant changes in catalytic acitivities or selectivities. It was due to the premature precipitation of cobalt molybdate during synthesis. Cobalt molybdate precipitation can generally be prevented by using water as a solvent, but this approach is not appropriate for this study because of the use of hydrotalcite-derived mixed metal oxide as the support. Co loadings on K/Mo/MMO-Co catalysts did not change selectivities significantly, either. However, they changed catalytic activities, represented by gas hourly space velocity (GHSV) required to obtain 8% conversion while maintaining high selectivities for higher alcohols. As a result, C ₂₊ alcohol productivities reached 0.01g(alcohol)/g(catalyst)/hr with Co loadings higher than 8%. With respect to using Mo2C as the precursor of Mo species instead of MoO3, comparisons between catalysts with different precursors for Mo species and different pretreatments were investigated. In this study, both K/Mo catalysts supported on MgO and α-Al₂O₃ showed similar tendencies of catalytic activities and selectivities. The highest C₂₊ alcohol selectivities and productivities were obtained on presulfided MoO₃ catalysts on both supports. In comparison of K/Mo ₂C catalysts with different pretreatments, higher C₂₊ alcohol selectivities and lower MeOH selectivities were obtained on presulfided catalysts compared to non-pretreated catalysts.

Objective: Decrease of olfactory function in Parkinson's disease (PD) is a well-investigated fact. Studies indicate that pharmacological treatment of PD fails to restore olfactory function in PD patients. The aim of this investigation was whether patients with PD would benefit from “training” with odors in terms of an improvement of their general olfactory function. It has been hypothesized that olfactory training should produce both an improved sensitivity towards the odors used in the training process and an overall increase of olfactory function. Methods: We recruited 70 subjects with PD and olfactory loss into this single-center, prospective, controlled non-blinded study. Thirty-five patients were assigned to the olfactory training group and 35 subjects to the control group (no training). Olfactory training was performed over a period of 12 weeks while patients exposed themselves twice daily to four odors (phenyl ethyl alcohol: rose, eucalyptol: eucalyptus, citronellal: lemon, and eugenol: cloves). Olfactory testing was performed before and after training using the “Sniffin' Sticks” (thresholds for phenyl ethyl alcohol, tests for odor discrimination, and odor identification) in addition to threshold tests for the odors used in the training process. Results: Compared to baseline, trained PD patients experienced a significant increase in their olfactory function, which was observed for the Sniffin' Sticks test score and for thresholds for the odors used in the training process. Olfactory function was unchanged in PD patients who did not perform olfactory training. Conclusion: The present results indicate that olfactory training may increase olfactory sensitivity in PD patients.

Thesis (M.S.); Submitted to Central Missouri State University, Warrensburg, MO (US); 17 Dec 2004. / Published through the Information Bridge: DOE Scientific and Technical Information. Kerr, Kent. NNSA Kansas City Site Office (US) NNSA Kansas City Site Office. 12/17/2004. Report is also available in paper and microfiche from NTIS.

Orientador: Ely Nahas / Banca: Regina Teresa Rosim Monteiro / Banca: Jonas Contiero / Banca: Antônio Carlos Monteiro / Banca: Lúcia Maria Carareto Alves / Resumo: Devido a baixa disponibilidade de P no solo e a alta capacidade do fungo Aspergillus niger F111 em solubilizar fosfatos inorgânicos, este trabalho teve por objetivo geral avaliar a possibilidade de inocular no solo esporos ou pellets imobilizados com vista a prolongar sua habilidade de solubilização e averiguar o mecanismo de solubilização de fosfatos inorgânicos de Ca, Al e Fe por este fungo. Os pellets inoculados em meio de cultura agitado proporcionaram maior solubilização dos fosfatos, principalmente o fosfato de Fe por ser de baixa solubilidade. No solo, os pellets livres e imobilizados promoveram as maiores solubilizações de fosfato de Fe e maior produção de CO2. Avaliando-se o efeito da fonte de N, as seguintes proporções foram obtidas na solubilização dos fosfatos de Ca, glicina > Al, nitrato de amônio > Fe, ácido l-glutâmico. Os açúcares que mais solubilizaram os fosfatos foram manitol, maltose e d-galactose. Dentre os metais somente o FeCl3.6H2O promoveu maior solubilização do fosfato de Fe e os metais FeSO4.7H2O e FeCl3.6H2O promoveram maiores solubilizações do fosfato de Ca. As concentrações de álcoois que mais favoreceram a solubilização do fosfato de Fe foram 3 e 4% de etanol e metanol, para o fosfato de Ca foi 3% de etanol. A combinação dos metais com o metanol, indicou que o metanol foi o principal responsável pela solubilização. Fatores como queda do pH, a maior produção de ácidos e o menor crescimento do fungo influíram neste trabalho, principalmente em relação a solubilização do fosfato de Fe. No solo, os pellets solubilizaram quantidades semelhantes de fosfato de Fe que os esporos imobilizados de A. niger, podendo ser utilizados com vantagem devido a sua facilidade de obtenção. / Abstract: Considering the low P availability in the soil and the high capability of Aspergillus niger F111 in solubilizing inorganic phosphates, this work aimed to evaluate the possibility of inoculating spores or immobilized pellets in the soil to prolong the solubilization capability and study the solubilization mechanism of inorganic calcium phosphate, aluminum phosphate and iron phosphate by this fungus. Pellets inoculated in culture medium under agitation allowed higher phosphate solubilization, especially iron phosphate, which is low soluble. In the soil, free and immobilized pellets allowed the highest solubilization of iron phosphate and CO2 production. Evaluating the effect of N sources, the following proportions were obtained in the solubilization of calcium phosphates, glycine > Al, ammonium nitrate > Fe, l-glutamic acid. The sugars that most solubilized phosphates were mannitol, maltose and d-galactose. Among the metals, only FeCl3.6H2O promoted higher iron phosphate solubilization, and FeSO4.7H2O and FeCl3.6H2O promoted higher solubilization of calcium phosphate. The alcohol concentrations that most favored iron phosphate solubilization were 3 and 4% of ethanol and methanol, while the highest solubilization of calcium phosphate was reached with 3% ethanol. The combination of metals with methanol indicated this alcohol was mainly responsible for solubilization. Factors as pH decrease, higher acid production and lower A. niger growth influenced the results, especially in the solubilization of iron phosphate. In the soil, pellets and immobilized spores solubilized similar amounts of iron phosphate. Pellets are thus preferable because they are more easily obtained. / Doutor

L’hygiène des mains (HDM) est déterminante dans la prévention du risque infectieux associé aux soins. Les pratiques actuelles privilégient l’utilisation de produits hydro-alcooliques (PHA), généralement formulés avec de l’éthanol, de l’isopropanol et/ou du n-propanol, en présence de co-formulants pour une meilleure acceptabilité cutanée. L’efficacité antimicrobienne sur un temps court, nécessaire en raison des situations fréquentes de pratique d’HDM, est atteinte par des teneurs élevées en alcools pouvant excéder 80 % p/p. Cela soulève la question de la toxicité cutanée et respiratoire associée à l’utilisation des PHA. L’évaluation de la toxicité cutanée basée sur les données publiées et des essais in vitro d’irritation cutanée (OCDE 439) et de phototoxicité (OCDE 432) conclut à l’absence d’irritation cutanée aiguë et de phototoxicité en relation avec l’exposition cutanée à ces alcools, y compris en présence de co-formulants, tels que fournis dans les PHA. Il est ressorti de nos essais le possible manque de spécificité, déjà décrit dans la littérature, des modèles d’épidermes humains reconstitués (RhE) vis-à-vis de certaines substances, qu’il convient de garder à l’esprit dans le cadre de l’évaluation de l’irritation cutanée in vitro. Des investigations complémentaires et une évaluation par l’approche Weight of Evidence peuvent être utiles avant de conclure aux propriétés irritantes d’un item d’essai. En termes de génotoxicité, une différence entre les alcools ressort de la revue bibliographique, avec des propriétés génotoxiques décrites uniquement pour l’éthanol. Dans une certaine mesure, nos essais ont confirmé une différence de profil. L’isopropanol et le n-propanol testés dans une batterie de tests in vitro permettant d’appréhender les différents mécanismes génotoxiques (test d’Ames et test du micronoyau (MN) sur cellules humaines p53 compétentes : cellules lymphoblastoïdes TK6 et cellules pulmonaires NCI H292) ont donné des résultats négatifs, y compris lorsqu’ils étaient formulés avec des co-formulants, ou administrés sous forme de vapeurs sur les cellules NCI H292 cultivées en interface air-liquide (IAL). Pour l’éthanol, la réalisation de la même batterie de tests a conduit à des résultats équivoques uniquement dans le test du MN sur cellules TK6 avec l’éthanol seul. Un test du MN supplémentaire sur cellules TK6 en co-culture avec un RhE mimant la barrière cutanée a donné des résultats négatifs. Par ailleurs, aucune exposition systémique significative aux alcools induite par les pratiques d’HDM ne ressort des études publiées chez l’homme, avec des taux indiscernables des valeurs endogènes existantes pour l’éthanol et l’isopropanol. L’ensemble de ces données est en faveur de l’absence de risque génotoxique systémique consécutif à l’utilisation des PHA, et de l’absence de génotoxicité pulmonaire locale liée à l’exposition aux vapeurs d’alcools. En conclusion, en situation d’utilisation des PHA pour l’HDM, aucun risque pour la santé humaine en termes d’irritation cutanée aiguë, de phototoxicité et de génotoxicité ne ressort de ce travail de recherche. / Hand hygiene (HH) is a key factor in preventing healthcare-associated infections. Current practices favor the use of alcohol-based hand rubs (AbHR), generally formulated with ethanol, propan-2-ol and/or propan-1-ol, in the presence of co-formulants for a better skin acceptability. The antimicrobial efficiency within a short time, essential because of the frequent situations of HH practice, is achieved by high levels of alcohols which can exceed 80% w/w. This raises the question of dermal and respiratory toxicity associated with the use of AbHR. The assessment of dermal toxicity based on published data and in vitro skin irritation (OECD 439) and phototoxicity tests (OECD 432) conclude to non acute dermal irritation and phototoxicity risk linked to dermal exposure to these alcohols, even in the presence of co-formulants, as provided in the AbHR. We encountered in our trials the possible lack of specificity, already described in the literature, of the reconstructed human epidermis (RhE) models for some substances, which should be kept in mind in the context of the evaluation of skin irritation in vitro. Additional investigations and an assessment using the Weight of Evidence approach may be useful before concluding the irritant properties of a test item. In terms of genotoxicity, a difference between the alcohols emerges from the bibliographic review, with genotoxic properties described only for ethanol. To a certain extent, our tests confirmed a difference in profile. Propan-2-ol and propan-1-ol tested in a battery of in vitro tests to explore the various genotoxic mechanisms (Ames test and micronucleus test (MN) on p53 competent human cells: lymphoblastoid cells TK6 and pulmonary cells NCI H292) gave negative results, even in the presence of co-formulants, or administered as vapors on air-liquid interface (ALI) NCI H292 cells. For ethanol, the same battery of tests gave equivocal results only in the MN test on TK6 cells with ethanol alone. An additional MN test on TK6 cells co-cultured with a RhE mimicking the existing skin barrier gave negative results. In addition, no significant systemic exposure to alcohols induced by HH practices is apparent from published studies in humans, with indiscernible levels of existing endogenous values for ethanol and isopropanol. All of these data support the absence of an increased systemic genotoxic risk resulting from the use of AbHR and the absence of local pulmonary genotoxicity due to exposure to alcohol vapors. In conclusion, during AbHR use for HH, no risk to human health in terms of acute skin irritation, phototoxicity and genotoxicity is apparent from this research.