Graduate / 0485

Thesis (Ph. D.)--University of Oregon, 2007. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 195-207). Also available for download via the World Wide Web; free to University of Oregon users.

Thesis (Ph. D.)--University of Kansas, 1927. / A reprint of an article, by C.M. Suter and F.B. Dains, published in the Journal of the American chemical Society, v. 50, no. 10, Oct., 1928.

Made available in DSpace on 2014-06-11T19:29:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2002-06-07Bitstream added on 2014-06-13T19:38:00Z : No. of bitstreams: 1 azevedo_rc_me_araiq.pdf: 304556 bytes, checksum: ded49f14a2e14cead8af1a701b99e4ec (MD5) / Os hidrocarbonetos policíclicos aromáticos nitrados (NHPAs) constituem a classe de compostos aromáticos que têm pelo menos um grupo nitro (-NO2) ligado à cadeia aromática de um hidrocarboneto policíclico aromático (HPA). Nos anos 70 a descoberta das propriedades mutagênicas destes compostos, presentes em material particulado atmosférico e na exaustão de motores a diesel, aumentaram o interesse científico sobre a ocorrência dos mesmos no ambiente. Estes compostos, como os HPAs, estão associados a fontes de combustão como automóveis, sistemas de aquecimento (baseados na queima de biomassa ou de combustíveis fósseis); queima de biomassa (cigarro, florestas, culturas agrícolas, etc), por causa disso pode-se prever que tenham uma distribuição abrangente no ambiente. Os NHPAs são produtos da reação dos HPAs com óxidos de nitrogênio na atmosfera, apresentando-se em concentrações muito baixas neste compartimento ambiental. A análise de NHPAs é muito difícil, principalmente pelos artefactos de amostragem e pela interferência analítica causada por HPAs e outros compostos. Assim sendo, a investigação de métodos alternativos que sejam sensíveis e seletivos são de extrema importância na determinação de NHPAs em amostras atmosféricas. Neste trabalho estudou-se um método para determinação de 1-nitropireno em material particulado proveniente da queima de cana-de-açúcar. O método inclui a redução do grupo nitro a amino, com posterior determinação por HPLC/fluorescência. O método proposto tem limite de detecção de 0,930ng mL-1 e limite de determinação de 1,250ng mL-1, apresentando recuperação entre 77,00 e 86,34%, para 5,00 e 50,00ng mL-1 respectivamente. / Nitrated Polycyclic Aromatic Hydrocarbons (NPAHs) are the class of aromatic compounds with at least one nitro group (-NO2) enhanced to aromatic chain of a Polycyclic Aromatic Hydrocarbon (PAH). In 70’s the discovery of mutagenic properties of these compounds present in atmospheric particulate matter and in gas exhaust of diesel motors are increased the scientific interess on occurrence of NPAHs into environment. These compounds, as PAHs, are associated with combustion sources as automobiles; harming systems (biomass and combustible based); burning of biomass (cigarette, florest, agricultural cultures, etc), because this they have a ubicous dissemination on environment. NPAHs are product of reaction of PAHs with nitrogen oxides on atmosphere, and they are present there at very low concentrations. The analysis of NPAHs in atmospheric samples is very difficult, because of artefacts of sampling process and PAH and other compounds interference on analytical determination. Because this, investigation of alternative methods sensitive and selective is necessary for NPAHs determination in atmospheric samples. In this work is studied a method for determination of 1-nitropyrene from particulate matter of sugar cane burning. The method include reduction of nitro group to amino, and analysis by HPLC/ Fluorescence. The proposed method has detection limit of 0, 930ng mL-1 and quantification limit of .1,250ng mL-1 showing recovery ranged between 77,00 and 86,34% for concentrations of 5,00 and 50,00ng mL-1, respectively.

The purpose of this investigation is to study the polarographic characteristics of p-nitroacetophenone.

Nitrated polycyclic aromatic hydrocarbons (nitro-PAH) are environmental contaminants that have been identified in extracts of particulates obtained from automobile exhaust, diesel exhaust, and power plant emissions. One of the most abundant nitro-PAH, 1-nitropyrene, has been found to be a powerful bacterial mutagen and a carcinogen in animal tests. In a bacterial strain (Salmonella tvphimurium TA98) 1- nitropyrene undergoes reduction and concomitant covalent binding to DNA, presumably via the N-hydroxy-l-aminopyrene. This labile compound was prepared by the ascorbic acid reduction of 1-nitrosopyrene and was characterized by high performance liquid chromatography (HPLC), combined liquid chromatography-mass spectrometry (LC-MS), ultraviolet-visible (UV-VIS), fluorescence and nuclear magnetic resonance (NMR) spectroscopy (1H and 15N) . In addition the pH stability and some reactions of this compound were studied. The 1,6- and 1,8-hydroxylaminonitropyrenes derived from the very potent mutagens 1,6- and 1,8 dinitropyrene were also synthesized and characterized by high performance liquid chromatography, ultraviolet-visible and nuclear magnetic resonance spectroscopy (1H and 15N) . / Thesis / Master of Science (MSc)

No description available.

A busca de alternativas terapêuticas para o tratamento da doença de Chagas é de grande importância, visto que atualmente existem apenas dois fármacos disponíveis, o benznidazol e o nifurtimox. Ambos apresentam efeitos adversos consideráveis, sendo utilizado, no Brasil, apenas o benznidazol. Compostos nitro-heterocíclicos com atividade frente ao Trypanosoma cruzi, agente causal da doença de Chagas, tem apresentado resultados promissores. Assim, este trabalho abrange o planejamento, síntese, identificação, avaliação da atividade anti-T. cruzi de 5-nitro furfurilidênicos (IC50 T. cruzi) e a citotoxicidade destes compostos frente a macrófagos de linhagem J774 (IC50 J774). A nifuroxazida, composto-protótipo, inspirou as modificações moleculares originando duas séries de compostos furfurilidênicos, uma com estrutura azometínica, série I, e outra com estrutura oxadiazolínica, série II. A escolha de substituintes foi baseada no diagrama de Craig, sendo selecionados dez substituintes para cada série. Foi avaliada a atividade dos vinte compostos planejados frente ao T. cruzi, dos quais os mais ativos foram: 4-butil-[N\'- (5-nitrofuran-2-il)metileno]benzidrazida (4g - IC50 T. cruzi = 1,05 µM, DP = 0,07) e 3-Acetil-5-(4-butilfenil)-2-(5-nitrofuran-2-il)-2,3-di-idro-1,3,4-oxadiazol (5g - IC50 T. cruzi = 8,27 µM, DP = 0,42). Comparados com os fármacos de referência, benznidazol (IC50 T. cruzi = 22,69 µM, DP = 1,96) e nifurtimox (IC50 T. cruzi = 3,78 µM, DP = 0,10), o composto 4g demonstrou atividade anti-T. cruzi superior a ambos. Todos os compostos apresentaram atividade maior do que a nifuroxazida (IC50 T. cruzi = 120,46 µM, DP = 4,06). Para os ensaios de citotoxicidade, obteve-se para o composto mais ativo frente ao T. cruzi, 4g, IC50 J774 = 28,05 µM, DP = 1,05, e para o composto 5g, obteve-se IC50 J774 = > 400 µM, o que representa que a concentração máxima avaliada deste composto não afetou as células. Ambos apresentaram boa seletividade ao efetuar a relação entre o IC50 J774 e o IC50 T. cruzi. Adicionalmente, foram realizados cálculos de propriedades físico-químicas das estruturas tridimensionais dos compostos, seguido pela análise exploratória de dados por análise de agrupamentos hierárquicos (hierarchical clusters analysis - HCA) e análise de componentes principais (principal component analysis, PCA), possibilitando a identificação das propriedades que mais influenciam na atividade anti-T. cruzi nas séries dos compostos estudados. Os resultados indicaram uma forte influência das propriedades ClogP e momento dipolo, evidenciando a necessidade de um equilíbrio lipofílico/hidrofílico no planejamento de novas moléculas com ação anti-T. cruzi. / The search for alternative therapies for the treatment of Chagas disease presents great importance, since there are only two currently available drugs, nifurtimox and benznidazole. Both have considerable adverse effects and, in Brazil, is used only benznidazole. Nitro-heterocyclic compounds with activity against Trypanosoma cruzi, the causative agent of Chagas disease, has shown promising results. Thus, this work includes the design, synthesis, identification, evaluation of anti-T. cruzi activity of 5-nitro-2- furfuriliden (IC50 T. cruzi) and cytotoxicity of these compounds against J774 macrophages cell line (IC50 J774). The nifuroxazide, as a lead compound, inspired the molecular modification leading to two series of furfuriliden compounds, a azometinic structure, series I, and other with oxadiazolinic structure, series II. The choice of substituents was based on the Craig\'s diagram, and ten substituents were selected for each series. We evaluated the activity of twenty compounds designed against T. cruzi, and the most active compounds were: 4-butyl-[N\'-(5-nitrofuran-2-yl) methylene] benzidrazide (4g - IC50 T. cruzi = 1.05 µM, SD = 0.07) and 3-acetyl-5-(4-butylphenyl)-2 -(5-nitrofuran-2-yl)- 2,3-dihydro, 1,3,4-oxadiazole (5g - IC50 T. cruzi = 8.27 µM, SD = 0.42). Compared to the reference drugs, benznidazole (IC50 T. cruzi = 22.69 µM, SD = 1.96) and nifurtimox (IC50 T. cruzi = 3.78 µM, SD = 0.10), the compound 4g demonstrated anti-T. cruzi activity superior to both drugs. All compounds showed better activity than nifuroxazide (IC50 T. cruzi = 120.46 µM, SD = 4.06). For cytotoxicity assays, was found for the most active compound against T. cruzi, 4g, IC50 J774 = 28.05 µM, SD = 1.05, and for compound 5g was obtained IC50 J774 = >400 µM, that represents the maximum concentration of the compound evaluated which did not affect the cells. Both showed good selectivity in the calculation of the ratio between the IC50 T. cruzi and IC50 J774. Additionally, we performed calculations of the physicochemical properties of three-dimensional structures of the compounds, followed by exploratory data analysis including hierarchical cluster analysis (HCA) and principal component analysis (PCA), which contributed to the identification of properties that influence the activity anti-T. cruzi in the series of compounds studied. The findings indicated a significant influence of ClogP and dipole moment properties, pointing out the need of a lipophilic/hydrophilic balance in the designing of novel anti-T. cruzi molecules.

A busca de alternativas terapêuticas para o tratamento da doença de Chagas é de grande importância, visto que atualmente existem apenas dois fármacos disponíveis, o benznidazol e o nifurtimox. Ambos apresentam efeitos adversos consideráveis, sendo utilizado, no Brasil, apenas o benznidazol. Compostos nitro-heterocíclicos com atividade frente ao Trypanosoma cruzi, agente causal da doença de Chagas, tem apresentado resultados promissores. Assim, este trabalho abrange o planejamento, síntese, identificação, avaliação da atividade anti-T. cruzi de 5-nitro furfurilidênicos (IC50 T. cruzi) e a citotoxicidade destes compostos frente a macrófagos de linhagem J774 (IC50 J774). A nifuroxazida, composto-protótipo, inspirou as modificações moleculares originando duas séries de compostos furfurilidênicos, uma com estrutura azometínica, série I, e outra com estrutura oxadiazolínica, série II. A escolha de substituintes foi baseada no diagrama de Craig, sendo selecionados dez substituintes para cada série. Foi avaliada a atividade dos vinte compostos planejados frente ao T. cruzi, dos quais os mais ativos foram: 4-butil-[N\'- (5-nitrofuran-2-il)metileno]benzidrazida (4g - IC50 T. cruzi = 1,05 µM, DP = 0,07) e 3-Acetil-5-(4-butilfenil)-2-(5-nitrofuran-2-il)-2,3-di-idro-1,3,4-oxadiazol (5g - IC50 T. cruzi = 8,27 µM, DP = 0,42). Comparados com os fármacos de referência, benznidazol (IC50 T. cruzi = 22,69 µM, DP = 1,96) e nifurtimox (IC50 T. cruzi = 3,78 µM, DP = 0,10), o composto 4g demonstrou atividade anti-T. cruzi superior a ambos. Todos os compostos apresentaram atividade maior do que a nifuroxazida (IC50 T. cruzi = 120,46 µM, DP = 4,06). Para os ensaios de citotoxicidade, obteve-se para o composto mais ativo frente ao T. cruzi, 4g, IC50 J774 = 28,05 µM, DP = 1,05, e para o composto 5g, obteve-se IC50 J774 = > 400 µM, o que representa que a concentração máxima avaliada deste composto não afetou as células. Ambos apresentaram boa seletividade ao efetuar a relação entre o IC50 J774 e o IC50 T. cruzi. Adicionalmente, foram realizados cálculos de propriedades físico-químicas das estruturas tridimensionais dos compostos, seguido pela análise exploratória de dados por análise de agrupamentos hierárquicos (hierarchical clusters analysis - HCA) e análise de componentes principais (principal component analysis, PCA), possibilitando a identificação das propriedades que mais influenciam na atividade anti-T. cruzi nas séries dos compostos estudados. Os resultados indicaram uma forte influência das propriedades ClogP e momento dipolo, evidenciando a necessidade de um equilíbrio lipofílico/hidrofílico no planejamento de novas moléculas com ação anti-T. cruzi. / The search for alternative therapies for the treatment of Chagas disease presents great importance, since there are only two currently available drugs, nifurtimox and benznidazole. Both have considerable adverse effects and, in Brazil, is used only benznidazole. Nitro-heterocyclic compounds with activity against Trypanosoma cruzi, the causative agent of Chagas disease, has shown promising results. Thus, this work includes the design, synthesis, identification, evaluation of anti-T. cruzi activity of 5-nitro-2- furfuriliden (IC50 T. cruzi) and cytotoxicity of these compounds against J774 macrophages cell line (IC50 J774). The nifuroxazide, as a lead compound, inspired the molecular modification leading to two series of furfuriliden compounds, a azometinic structure, series I, and other with oxadiazolinic structure, series II. The choice of substituents was based on the Craig\'s diagram, and ten substituents were selected for each series. We evaluated the activity of twenty compounds designed against T. cruzi, and the most active compounds were: 4-butyl-[N\'-(5-nitrofuran-2-yl) methylene] benzidrazide (4g - IC50 T. cruzi = 1.05 µM, SD = 0.07) and 3-acetyl-5-(4-butylphenyl)-2 -(5-nitrofuran-2-yl)- 2,3-dihydro, 1,3,4-oxadiazole (5g - IC50 T. cruzi = 8.27 µM, SD = 0.42). Compared to the reference drugs, benznidazole (IC50 T. cruzi = 22.69 µM, SD = 1.96) and nifurtimox (IC50 T. cruzi = 3.78 µM, SD = 0.10), the compound 4g demonstrated anti-T. cruzi activity superior to both drugs. All compounds showed better activity than nifuroxazide (IC50 T. cruzi = 120.46 µM, SD = 4.06). For cytotoxicity assays, was found for the most active compound against T. cruzi, 4g, IC50 J774 = 28.05 µM, SD = 1.05, and for compound 5g was obtained IC50 J774 = >400 µM, that represents the maximum concentration of the compound evaluated which did not affect the cells. Both showed good selectivity in the calculation of the ratio between the IC50 T. cruzi and IC50 J774. Additionally, we performed calculations of the physicochemical properties of three-dimensional structures of the compounds, followed by exploratory data analysis including hierarchical cluster analysis (HCA) and principal component analysis (PCA), which contributed to the identification of properties that influence the activity anti-T. cruzi in the series of compounds studied. The findings indicated a significant influence of ClogP and dipole moment properties, pointing out the need of a lipophilic/hydrophilic balance in the designing of novel anti-T. cruzi molecules.

This thesis discusses the preparation of a-(o-nitro-p-methylphenylmercapto)-acetophenone by the reaction between acetophenone and o-nitro-p-methylbenzenesulfenyl chloride in boiling chloroform. The use of stannous chloride in glacial acetic acid for the reduction of nitro groups to amino groups was found generally satisfactory in spite of the difficulty often met with in isolating the amino product.