Ovarian toxicants 4-vinylcychlohexene (VCH) and 7,12-dimethylbenz[a]anthracene (DMBA) requires bioactivation to induce follicle loss. VCH is bioactivated to monoepoxides (1,2-VCM and 7,8-VCM), and subsequently to an ovotoxic diepoxide (VCD) by hepatic CYP 2A and CYP 2B. DMBA is sequentially bioactivated to the ovotoxicant DMBA-3,4-diol-1,2-epoxide by hepatic CYP 1B1, microsomal epoxide hydrolase (mEH), and CYP 1A1/1B1 enzymes. Even though the liver is the primary organ metabolizing VCH and DMBA to reactive intermediates, several studies suggest that the ovary can also metabolize these two compounds. Studies were designed to investigate the role of ovarian metabolism in the resulting ovotoxicity of these two compounds using a novel mouse ovarian culture system. The hypothesis was that the ovary can participate in bioactivation and detoxification of VCH/VCM and DMBA and thereby influence the resulting ovotoxicity.Postnatal day 4 CYP 2E1 wild-type, null and B6C3F1 mouse ovaries were incubated with 1,2-VCM, VCD or DMBA for various lengths of time. 28 day old female CYP 2E1 wild-type and null mice were dosed (15d, i.p) with VCH, 1,2-VCM, VCD, or sesame oil (control). Following incubations and dosing, ovaries were prepared for histological evaluation of follicle numbers, mEH mRNA level, or mEH protein level. Medium from cultures were analyzed by LC/MS for VCD-GSH adducts.DMBA was found to be a potent ovotoxicant compared to VCH/VCM/VCD. In the ovarian culture system, VCM-induced toxicity required the CYP 2E1 enzyme. However, in vivo dosing studies indicated that in the presence of hepatic metabolism the ovary plays a minimal role in VCH/VCM-induced toxicity. Studies utilizing LC/MS showed that once bioactivated to VCD, this ovotoxic metabolite can be detoxified by glutathione conjugation in the ovary. Follicle loss induced by the ovotoxicant DMBA was found to involve mEH enzyme in culture.Collectively, these studies show that the ovary has the capacity to bioactivate and detoxify ovotoxicants. In the presence of hepatic metabolism ovarian effects might play only a minimal role in the resulting toxicity. The role of ovarian metabolism in the whole animal needs to be further investigated, especially for potent toxicants such as DMBA that can induce ovotoxicity at nanomolar concentrations.

No description available.

Orientador: Teresa Dib Zambon Atvars / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-10T13:29:22Z (GMT). No. of bitstreams: 1 Cossiello_RafaelDiFalco_D.pdf: 19466365 bytes, checksum: 4613f44ad7300b66e793fa6de43b2c82 (MD5) Previous issue date: 2007 / Resumo: O copolímero SAA (poli(estireno-co-ácido acrílico-co-1-metacrilato de pirenilmetila)) foi sintetizado por via radicalar em agua e caracterizado por analises termicas (DSC, TGA), espectroscopicas (NMR C e H, UV-VIS, FTIR, fluorescência estacionária e resolvida no tempo) e elétricas (eletroluminescência). As blendas com poli[2-metóxi-5-(2¿-etilóxi)-p-fenilenovinileno] MEH-PPV foram estudadas desde 0,01; 0,05; 0,10; 0,50; 1,0; 10,0; 25; 50; 75 e 90 (% em massa) de MEH-PPV em SAA para ánalise da evolucao da morfologia por microscopia óptica, de fluorescência e eletrônica de varredura em espessuras de 70 mm (fratura criogênica) e 70 nm (espessura do dispositivo). Em baixas concentracões os domínios de MEH-PPV se apresentam em forma de núcleos dispersos e empacotados e conforme se aumenta a concentracao de MEH-PPV, observa-se que há a coalescência destes núcleos até a formação de uma fase interconectada de uma rede tridimensional. As medidas de difração à altos angulos mostram que há uma preferência de orientação do MEH-PPV ao longo do substrato e nao influencia a isotropia do SAA devido a baixa miscibilidade entre estes polímeros. As unidades de 1-pirenil metila foram utilizadas para avaliar a polaridade do microambiente e o mecanismo de transferencia de energia entre o doador (SAA) e o receptor (MEH-PPV). A dependência do tempo de fluorescência das unidades 1-pirenilmetila com a concentracao do MEH-PPV fornece subsídios para concluir que ocorre interpenetração de cadeias e, portanto uma baixíssima solubilidade entre os dois polímeros. O melhor desempenho de eletroluminescência foi do dispositivo preparado a partir da mistura 50:50 de MEH-PPV:SAA, cuja corrente elétrica foi aumentada em 2,5 vezes e a luminância em 4 vezes se comparado com o dispositivo de MEH-PPV puro. A morfologia de fase interconectada se mostrou importante para um melhor processo de transporte de cargas. O copolímero de SAA permitiu uma melhor injeção de cargas devido aos grupos carboxila presentes das unidades de ácido acrílico / Abstract: The copolymer SAA poly(styrene-co- acrylic acid -co-1-pyrenylmethyl methacrylate) was synthesized by radical emulsion in water and characterized by thermal analyses (DSC, TGA), spectroscopic (NMR 13C and 1:00, UV-VIS, FTIR, stationary and time-resolved fluorescence) and electric (electroluminescence). The blends with poly[2-methoxy-5(2'ethylhexyloxy)-p-phenylenevinylene] (MEH-PPV) were studied from 0. 01; 0. 05; 0.10; 0.50; 1.0; 10.0; 25; 50; 75 and 90 (% in mass) of MEH-PPV in SAA to analyze the morphology evolution by optical, epifluorescence and electronic microscopy. The films were prepared in two thicknesses: one around 70 mm to be analyzed by cryogenic fractures and 70 nm, to be comparable with the device thickness. In low concentrations the domains of MEH-PPV appears dispersed nuclei and accrete when the concentration of MEH-PPV is increased forming an interconnected phase. The diffraction measures (WAXD) show a preference orientation of MEH-PPV along the substrate plane and it do not influences the SAA due the low miscibility between each other. The increase of the MEH-PPV concentration showed a redshift on electroluminescence spectrum due the inner filter and auto-absorption and re-emission effects. The units of 1-pyrenylmethyl were used to evaluate the polarity of the microenvironment and the mechanism of energy transfer of among the donor (SAA) and the acceptor (MEH-PPV). The timedependence of fluorescence with the increase of MEH-PPV concentration show that occurs an chain interpenetration following the fluorescence non-radiative energy transfer model. The best electroluminescent device was prepared using the mixture 50:50 of MEH-PPV:SAA. The interconnected phases are important for a better process of charge transport. The copolymer SAA allowed for a dilution effect avoiding the aggregation process and facilitating the charge injection processes. This technology of polymeric blends gave good results the increase of the luminance intensity and reduction of the voltage operation / Doutorado / Físico-Química / Doutor em Ciências

O presente trabalho teve por objetivo o estudo da viabilidade de utilização de soluções de poli[2-metóxi,5-(2-etil-hexiloxi)-p-fenileno vinileno] (MEH-PPV), em diversos solventes tais como CHCl3 (Clorofórmio), diclorometano (CH2Cl2), bromofórmio (CHBr3), dibromometano (CH2Br2), uma mistura de diclorometano (CH2Cl2) e diiodometano (CH2I2) e tolueno (C6H5CH3), como dosímetros de radiações ionizantes. A novidade está no fato de que estes dosímetros têm como principal característica a variação da cor, proporcionando uma medida visual e direta da radiação recebida. Além disso, a sensibilidade dos dosímetros pode ser ajustada por meio da variação da concentração das soluções do polímero. Neste trabalho, foi utilizada a radiação gama, 60Co, para os estudos de viabilidade deste dosímetro. Quando submetidos a certas doses de radiação gama, o polímero estudado sofre alterações em suas propriedades óticas e em sua estrutura molecular. Para avaliar as alterações óticas, foram utilizadas medidas de espectroscopia de absorção UV-Visível (UV-Vis) e fotoluminescência. Também foram avaliadas as alterações na estrutura molecular, como conseqüência da exposição à radiação gama por meio de técnicas como ressonância magnética nuclear (RMN) e cromatrografia de permeação de gel (GPC). Os Resultados obtidos mostraram que a radiação gama, 60Co, promove, de forma indireta, a diminuição do comprimento efetivo da conjugação do polímero, mais provavelmente em decorrência da quebra da cadeia principal do polímero devido às reações com as espécies reativas, possivelmente nos grupamento vinil. Estas quebras resultam em um deslocamento dos picos máximos dos espectros de absorção para regiões de maior energia (blueshift). Estes deslocamentos dependem não somente da dose de irradiação, mas também do solvente utilizado em da concentração da solução. / The present work aims the study of the viability of using solutions of poly[2-methoxy-5-(2\'-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV), in several solvents such as chloroform (CHCl3), dichloromethane (CH2Cl2), bromoform (CHBr3), dibromomethane (CH2Br2), a mix of dichloromethane (CH2Cl2) and diiodomethane (CH2I2), and toluene (C6H5CH3) as ionizing radiation dosimeters, gamma, in this case. The novelty is in the fact of the dosimeter main characteristic is color change, allowing a visual and direct received radiation measurement. Besides, the sensibility of the dosimeter can be adjusted by the polymer solution concentration variation. In this work, it was used the gamma radiation, 60Co, for the dosimeter viability studies. When exposed to certain doses of this kind of radiation, the studied polymer suffers changes in its optic properties and in its molecular structure. In order to evaluate the optical changes, UV-VIS absorption and photoluminescence spectroscopy measures were performed. Besides, the molecular structure changes, as a consequence of the exposure to gamma radiation, were evaluated by nuclear magnetic resonance (NMR) and Gel Permeation Chromatography (GPC). The results show that the gamma radiation, 60Co, promotes, indirectly, the decrease of the polymer conjugation length probably due the backbone scission caused by reactions with reactive species, probably in the vinyl side groups. These scissions resulted in a blueshift of the absorption spectra maximum peaks. Theses blueshifts depend on the irradiation dose, the used solvent and the solution concentration.

A novel UHV microcalorimeter has been used to study the interaction between calcium and three polymers: MEH-PPV, MEH-PPP and P3HT. All three polymers behave differently in their reaction kinetics with calcium. On MEH-PPV we measure 45 μJ/cm² of heat generated in excess of the heat of bulk metal growth, 120 μJ/cm² for MEH-PPP, and 100 μJ/cm² for P3HT. Comparison of the MEH-PPV and MEHPPP data indicate that the initial reaction of calcium with MEH-PPV occurs at the vinylene group. We propose, based on hypothetical models, that calcium reacts with the vinylene groups of MEH-PPV with a reaction heat of 360 kJ/mol and at a projected surface density of 1.7 sites/nm², while it reacts with the phenylene groups of MEH-PPP in a two-step process with reaction heats of 200 and 360 kJ/mol respectively, at a projected surface density of 3.5 sites/nm². Optical absorption experiments, using either a 1.85 eV diode laser or a xenon lamp coupled to a scanning monochromator, have also been performed using the same calorimeter sensor. In the case of MEH-PPV, using the laser we find an optical absorption cross-section of 3E-¹⁷ cm² per incident calcium atom at low coverages. The change in absorptance at higher coverages correlates perfectly with the population of reacted Ca atoms determined calorimetrically. The size of the absorbance cross-section, and its position just within the band gap of the polymer, are consistent with the reaction being one of polaron formation. Calcium does not appear to dope P3HT, while the photon energy range of 1.5 to 3.75 eV used in these experiments is likely too small for probing polaronic energy states in MEH-PPP.

A novel UHV microcalorimeter has been used to study the interaction between calcium and three polymers: MEH-PPV, MEH-PPP and P3HT. All three polymers behave differently in their reaction kinetics with calcium. On MEH-PPV we measure 45 μJ/cm² of heat generated in excess of the heat of bulk metal growth, 120 μJ/cm² for MEH-PPP, and 100 μJ/cm² for P3HT. Comparison of the MEH-PPV and MEHPPP data indicate that the initial reaction of calcium with MEH-PPV occurs at the vinylene group. We propose, based on hypothetical models, that calcium reacts with the vinylene groups of MEH-PPV with a reaction heat of 360 kJ/mol and at a projected surface density of 1.7 sites/nm², while it reacts with the phenylene groups of MEH-PPP in a two-step process with reaction heats of 200 and 360 kJ/mol respectively, at a projected surface density of 3.5 sites/nm². Optical absorption experiments, using either a 1.85 eV diode laser or a xenon lamp coupled to a scanning monochromator, have also been performed using the same calorimeter sensor. In the case of MEH-PPV, using the laser we find an optical absorption cross-section of 3E-¹⁷ cm² per incident calcium atom at low coverages. The change in absorptance at higher coverages correlates perfectly with the population of reacted Ca atoms determined calorimetrically. The size of the absorbance cross-section, and its position just within the band gap of the polymer, are consistent with the reaction being one of polaron formation. Calcium does not appear to dope P3HT, while the photon energy range of 1.5 to 3.75 eV used in these experiments is likely too small for probing polaronic energy states in MEH-PPP.

O presente trabalho teve por objetivo o estudo da viabilidade de utilização de soluções de poli[2-metóxi,5-(2-etil-hexiloxi)-p-fenileno vinileno] (MEH-PPV), em diversos solventes tais como CHCl3 (Clorofórmio), diclorometano (CH2Cl2), bromofórmio (CHBr3), dibromometano (CH2Br2), uma mistura de diclorometano (CH2Cl2) e diiodometano (CH2I2) e tolueno (C6H5CH3), como dosímetros de radiações ionizantes. A novidade está no fato de que estes dosímetros têm como principal característica a variação da cor, proporcionando uma medida visual e direta da radiação recebida. Além disso, a sensibilidade dos dosímetros pode ser ajustada por meio da variação da concentração das soluções do polímero. Neste trabalho, foi utilizada a radiação gama, 60Co, para os estudos de viabilidade deste dosímetro. Quando submetidos a certas doses de radiação gama, o polímero estudado sofre alterações em suas propriedades óticas e em sua estrutura molecular. Para avaliar as alterações óticas, foram utilizadas medidas de espectroscopia de absorção UV-Visível (UV-Vis) e fotoluminescência. Também foram avaliadas as alterações na estrutura molecular, como conseqüência da exposição à radiação gama por meio de técnicas como ressonância magnética nuclear (RMN) e cromatrografia de permeação de gel (GPC). Os Resultados obtidos mostraram que a radiação gama, 60Co, promove, de forma indireta, a diminuição do comprimento efetivo da conjugação do polímero, mais provavelmente em decorrência da quebra da cadeia principal do polímero devido às reações com as espécies reativas, possivelmente nos grupamento vinil. Estas quebras resultam em um deslocamento dos picos máximos dos espectros de absorção para regiões de maior energia (blueshift). Estes deslocamentos dependem não somente da dose de irradiação, mas também do solvente utilizado em da concentração da solução. / The present work aims the study of the viability of using solutions of poly[2-methoxy-5-(2\'-ethyl-hexyloxy)-1,4-phenylene vinylene] (MEH-PPV), in several solvents such as chloroform (CHCl3), dichloromethane (CH2Cl2), bromoform (CHBr3), dibromomethane (CH2Br2), a mix of dichloromethane (CH2Cl2) and diiodomethane (CH2I2), and toluene (C6H5CH3) as ionizing radiation dosimeters, gamma, in this case. The novelty is in the fact of the dosimeter main characteristic is color change, allowing a visual and direct received radiation measurement. Besides, the sensibility of the dosimeter can be adjusted by the polymer solution concentration variation. In this work, it was used the gamma radiation, 60Co, for the dosimeter viability studies. When exposed to certain doses of this kind of radiation, the studied polymer suffers changes in its optic properties and in its molecular structure. In order to evaluate the optical changes, UV-VIS absorption and photoluminescence spectroscopy measures were performed. Besides, the molecular structure changes, as a consequence of the exposure to gamma radiation, were evaluated by nuclear magnetic resonance (NMR) and Gel Permeation Chromatography (GPC). The results show that the gamma radiation, 60Co, promotes, indirectly, the decrease of the polymer conjugation length probably due the backbone scission caused by reactions with reactive species, probably in the vinyl side groups. These scissions resulted in a blueshift of the absorption spectra maximum peaks. Theses blueshifts depend on the irradiation dose, the used solvent and the solution concentration.

A novel UHV microcalorimeter has been used to study the interaction between calcium and three polymers: MEH-PPV, MEH-PPP and P3HT. All three polymers behave differently in their reaction kinetics with calcium. On MEH-PPV we measure 45 μJ/cm² of heat generated in excess of the heat of bulk metal growth, 120 μJ/cm² for MEH-PPP, and 100 μJ/cm² for P3HT. Comparison of the MEH-PPV and MEHPPP data indicate that the initial reaction of calcium with MEH-PPV occurs at the vinylene group. We propose, based on hypothetical models, that calcium reacts with the vinylene groups of MEH-PPV with a reaction heat of 360 kJ/mol and at a projected surface density of 1.7 sites/nm², while it reacts with the phenylene groups of MEH-PPP in a two-step process with reaction heats of 200 and 360 kJ/mol respectively, at a projected surface density of 3.5 sites/nm². Optical absorption experiments, using either a 1.85 eV diode laser or a xenon lamp coupled to a scanning monochromator, have also been performed using the same calorimeter sensor. In the case of MEH-PPV, using the laser we find an optical absorption cross-section of 3E-¹⁷ cm² per incident calcium atom at low coverages. The change in absorptance at higher coverages correlates perfectly with the population of reacted Ca atoms determined calorimetrically. The size of the absorbance cross-section, and its position just within the band gap of the polymer, are consistent with the reaction being one of polaron formation. Calcium does not appear to dope P3HT, while the photon energy range of 1.5 to 3.75 eV used in these experiments is likely too small for probing polaronic energy states in MEH-PPP. / Science, Faculty of / Chemistry, Department of / Graduate

O objetivo deste trabalho foi de estudar processos de transporte eletrônico em dispositivos a base de semicondutores orgânicos através de técnicas avançadas, como ressonância magnética detectada eletricamente (RMDE) e espectroscopia de impedância elétrica em corrente alternada. Além destas, medidas de ressonância paramagnética eletrônica (RPE) convencional também foram realizadas de forma a complementar as medidas de RMDE. Os dispositivos e materiais estudados foram: (hole-only e PLED) de MEH-PPV, polianilina e OLED multicamadas de Alq3 e -NPD. A técnica de RMDE mede a variação de condutividade da amostra na condição de ressonância magnética, permitindo relacionar processos microscópicos com os seus efeitos nos processos de transporte eletrônico. Os estudos de RPE e RMDE em polianilina mostraram uma transição entre os tipos de spin observados em função da temperatura. Os resultados obtidos indicam que o sinal de RPE se deve principalmente a estados de superfície, enquanto a técnica de RMDE permite observarmos também estados do volume, dependendo da forma de preparação dos dispositivos e dos parâmetros utilizados nas medidas. O sinal de RMDE foi atribuído ao hopping de pólarons intercadeias poliméricas. Nos dispositivos de MEH-PPV, o sinal de RMDE apresenta duas componentes, uma foi atribuída à fusão de pólarons negativos para formar bipólarons negativos e a outra foi atribuída à fusão de pólarons positivos. A deficiência na emissão de luz de alguns dos PLEDs estudados foi atribuída ao desbalanceamento de injeção de cargas, que pode ser observado pela diferença de intensidade entre as componentes do sinal. Nos OLEDs a base de Alq3, medidas de espectroscopia de impedância elétrica em função da voltagem dc (Vdc) mostraram um acúmulo de cargas nas interfaces internas do dispositivo, em baixas tensões. Entretanto, para valores mais altos de Vdc, quando começa o processo de recombinação, foi observado um fenômeno pouco estudado na literatura, conhecido como capacitância negativa. Possíveis abordagens a este problema foram propostas / The subject of this work is the investigation of electronic transport processes in organic semiconductors based devices using advanced techniques, such as electrically detected magnetic resonance (EDMR) and ac electrical impedance spectroscopy. Electron Paramagnetic Resonance (EPR) measurements were also carried out to complement the EDMR results. The studied devices and materials were: MEH-PPV hole-only devices and PLEDs, polyaniline and multilayer Alq3 and -NPD based OLEDs. EDMR measures the sample conductivity variation during magnetic resonance condition, which allows relating microscopic processes to its effects on electronic transport processes. EPR and EDMR investigations on polyaniline showed a transition between two kinds of observed spins as a function of temperature. The results indicate that EPR probes especially surface paramagnetic states, while EDMR allows observing both surface and bulk paramagnetic states, depending on how devices are prepared and on some measurement parameters. The EDMR signal was assigned to interchain hopping of pólarons. On MEH-PPV devices, the EDMR signal was composed of two lines, one was attributed to negative pólarons fusion to form negative bipólarons and the other was assigned to positive pólarons fusion. The light emitting deficiency presented by some of the PLEDs investigated was assigned to a misbalanced charge injection, what could be observed by the difference between the intensity of the two components. Impedance spectroscopy measurements on Alq3 based OLEDs as a function of the dc voltage (Vdc) showed charge accumulation at the inner interfaces of the device at low Vdc values. However, at higher Vdc values, when recombination starts to take place, a strange phenomenon, usually called negative capacitance, was observed. Possible approaches were proposed

O objetivo deste trabalho foi de estudar processos de transporte eletrônico em dispositivos a base de semicondutores orgânicos através de técnicas avançadas, como ressonância magnética detectada eletricamente (RMDE) e espectroscopia de impedância elétrica em corrente alternada. Além destas, medidas de ressonância paramagnética eletrônica (RPE) convencional também foram realizadas de forma a complementar as medidas de RMDE. Os dispositivos e materiais estudados foram: (hole-only e PLED) de MEH-PPV, polianilina e OLED multicamadas de Alq3 e -NPD. A técnica de RMDE mede a variação de condutividade da amostra na condição de ressonância magnética, permitindo relacionar processos microscópicos com os seus efeitos nos processos de transporte eletrônico. Os estudos de RPE e RMDE em polianilina mostraram uma transição entre os tipos de spin observados em função da temperatura. Os resultados obtidos indicam que o sinal de RPE se deve principalmente a estados de superfície, enquanto a técnica de RMDE permite observarmos também estados do volume, dependendo da forma de preparação dos dispositivos e dos parâmetros utilizados nas medidas. O sinal de RMDE foi atribuído ao hopping de pólarons intercadeias poliméricas. Nos dispositivos de MEH-PPV, o sinal de RMDE apresenta duas componentes, uma foi atribuída à fusão de pólarons negativos para formar bipólarons negativos e a outra foi atribuída à fusão de pólarons positivos. A deficiência na emissão de luz de alguns dos PLEDs estudados foi atribuída ao desbalanceamento de injeção de cargas, que pode ser observado pela diferença de intensidade entre as componentes do sinal. Nos OLEDs a base de Alq3, medidas de espectroscopia de impedância elétrica em função da voltagem dc (Vdc) mostraram um acúmulo de cargas nas interfaces internas do dispositivo, em baixas tensões. Entretanto, para valores mais altos de Vdc, quando começa o processo de recombinação, foi observado um fenômeno pouco estudado na literatura, conhecido como capacitância negativa. Possíveis abordagens a este problema foram propostas / The subject of this work is the investigation of electronic transport processes in organic semiconductors based devices using advanced techniques, such as electrically detected magnetic resonance (EDMR) and ac electrical impedance spectroscopy. Electron Paramagnetic Resonance (EPR) measurements were also carried out to complement the EDMR results. The studied devices and materials were: MEH-PPV hole-only devices and PLEDs, polyaniline and multilayer Alq3 and -NPD based OLEDs. EDMR measures the sample conductivity variation during magnetic resonance condition, which allows relating microscopic processes to its effects on electronic transport processes. EPR and EDMR investigations on polyaniline showed a transition between two kinds of observed spins as a function of temperature. The results indicate that EPR probes especially surface paramagnetic states, while EDMR allows observing both surface and bulk paramagnetic states, depending on how devices are prepared and on some measurement parameters. The EDMR signal was assigned to interchain hopping of pólarons. On MEH-PPV devices, the EDMR signal was composed of two lines, one was attributed to negative pólarons fusion to form negative bipólarons and the other was assigned to positive pólarons fusion. The light emitting deficiency presented by some of the PLEDs investigated was assigned to a misbalanced charge injection, what could be observed by the difference between the intensity of the two components. Impedance spectroscopy measurements on Alq3 based OLEDs as a function of the dc voltage (Vdc) showed charge accumulation at the inner interfaces of the device at low Vdc values. However, at higher Vdc values, when recombination starts to take place, a strange phenomenon, usually called negative capacitance, was observed. Possible approaches were proposed