Nucleophiles react with the α-acetoxy derivative of α-hydroxybenzylbenzylnitrosamine at the carbonyl carbon of the acetoxy moiety followed by fragmentation to the very same intermediates formed by oxidative metabolism. Since α-acetoxybenzylbenzylnitrosamine has been shown to be able to acylate nucleophiles and since the nucleic acids are nucleophiles, then it is possible that this compound may cause mutations by an acylation pathway instead of or in addition to the more common alkylation pathway. The data in Part I of this dissertation should be considered in any further biological investigations of N,N-dialkylnitrosamine induced mutagenesis or carcinogenesis. The study of the synthesis, reactions, mutagenicity, and the possible correlation to compound liposolubility of cyclic N-nitrosamines was also investigated.

N-Nitrosodimethylamine (NDMA), which is a carcinogenic and toxic N-nitrosamine, can be found in water resources associated with a multitude of processes in various industrial facilities or merely as a by-product of water or wastewater treatment. Therefore, the removal of NDMA from drinking water represents an important human safety and public health concern. The present paper presents a density functional theory study of NDMA adsorption in all-silica MFI, Na-ZSM-5 and H-ZSM-5 zeolites. The stability of NDMA inside the zeolite pores was investigated by calculating the amount of energy released during adsorption. Various configurations of adsorbed NDMA to the zeolites were investigated, predominantly at the intersection of straight and sinusoidal channels. The strength of the adsorption energies followed the order H-ZSM5 > Na-ZSM-5 > all-silica MFI. NDMA has a dipole moment and the strongest binding of NDMA occurred through the interactions of the negatively charged O atom of the molecule to positive atoms of the zeolite. Similar calculations were performed for water adsorption in these three zeolites. The adsorption energy of water to these three structures followed the order Na-ZSM5 > H-ZSM-5 > all-silica MFI. We also incorporated van der Waals corrections in the simulations, which had the effect of stabilizing NDMA within the zeolite channels, but did not significantly change the relative stability of the different adsorption geometries. It was concluded that H-ZSM-5 is the best choice to remove NDMA because it is strong enough to adsorb NDMA and it is not too strong in adsorption of water molecules.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22057号 / 工博第4638号 / 新制||工||1723(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 田中 宏明, 教授 伊藤 禎彦, 講師 中田 典秀 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(工学) / 甲第16387号 / 工博第3468号 / 新制||工||1524(附属図書館) / 29018 / 京都大学大学院工学研究科都市環境工学専攻 / (主査)教授 田中 宏明, 教授 清水 芳久, 教授 伊藤 禎彦 / 学位規則第4条第1項該当

Orientador: Susanne Rath / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-18T12:46:57Z (GMT). No. of bitstreams: 1 Canaes_LarissadeSouza_D.pdf: 2777887 bytes, checksum: 4eff3d6893f034649d50087cfb9d903b (MD5) Previous issue date: 2011 / Resumo: As N-nitrosaminas (NA) são compostos N-nitrosos, que mostraram ser carcinogênicas para uma grande variedade de animais experimentais. Além disso, elas apresentam atividade teratogênica e mutagênica. As NA foram encontradas, durante as últimas três décadas, em uma variedade de produtos de consumo, incluindo cosméticos e produtos de higiene e suas matérias-primas. As NA mais comumente encontradas em cosméticos são a N-nitrosodietanolamina (NDELA), N-nitrosomorfolina (NMOR) e N-nitrosodimetilamina (NDMA), em concentrações que variam desde mg kg até mg kg. Os objetivos deste trabalho foram a avaliação do comportamento eletroquímico de NA sobre eletrodo de diamante dopado com boro e construção de uma célula amperométrica para ser associada ao cromatógrafo líquido de alta eficiência (HPLC), assim como o desenvolvimento e validação de métodos para a determinação de NA em xampu, usando a cromatografia líquida, associada ao detector eletroquímico desenvolvido, arranjo por fotodiodos e espectrometria de massas. O comportamento eletroquímico das NA foi estudado usando voltametria cíclica e voltametria de onda quadrada; foram avaliados composição, concentração e pH do eletrólito suporte. A separação da NA foi realizada em uma coluna C18 XBridge¿ e uma fase móvel composta de água/acetonitrila e eluição por gradiente. No preparo de amostras foram avaliadas a extração líquido-líquido, extração em fase sólida (C18 e sílica) e a dispersão da matriz em fase sólida. A performance dos diferentes sistemas de detecção associadas ao HPLC foram comparados na determinação de NA em xampu. Finalmente, o método de cromatografia líquida-espectrometria de massas foi validado para a determinação de NMOR e NDMA em xampu, mediante avaliação dos seguintes parâmetros: faixa linear, linearidade, precisão intra-dia e inter-dia, seletividade, limite de detecção, limite de quantificação e exatidão. O método foi aplicado na determinação de NA em amostras de xampu / Abstract: N-nitrosamines (NA) are N-nitroso compounds, showed to be carcinogenic in a wide variety of experimental animals. In addition, they also present mutagenic and teratogenic activities. N-nitrosamines have been found during the last three decades in a variety of consumer products, including cosmetic and personal care products, and their raw materials. The most common NA detected in cosmetics were N-nitrosodiethanolamine (NDELA), N-nitrosomorpholine (NMOR) and Nnitrosodimethylamine (NDMA), in concentrations varying from mg kg to mg kg. The aims of this work were the evaluation of the electrochemical behavior of NA on a boron doped diamond electrode and construction of an amperometric cell to be coupled to high performance liquid chromatography (HPLC), as well as the development and validation of methods for determination of NA in shampoo, using liquid chromatography coupled to the developed electrochemical cell, photodiode array and mass spectrometry detectors. The electrochemical behavior of NA was studied using cyclic voltammetry and square wave voltammetry; composition, concentration and pH of the electrolyte were evaluated. The separation of NA was achieved using a C18 XBridge¿ column and mobile phase of water and acetonitri le under gradient elution. For sample preparation liquid-liquid extraction, solid phase extraction (C18 and silica) and matrix solid phase dispersion were evaluated. The performance of the different detectors coupled to liquid chromatography to the NA determination in shampoo was compared. Finally, a liquid-chromatography-mass spectrometry method was validated to the determination of NMOR and NDMA in shampoo, thorough the following parameters: linear range, linearity, intra-day and inter-day precision, selectivity, limit of detection, limit of quantification and accuracy. The method was applied to the determination of NA in shampoo samples / Doutorado / Quimica Analitica / Doutor em Ciências

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第21308号 / 工博第4506号 / 新制||工||1701(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 田中 宏明, 教授 清水 芳久, 教授 伊藤 禎彦 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

S'ha desenvolupat una nova estratègia per la síntesi ràpida i eficient de L-[metil-11C]metionina basada en el captive solvent method. La reacció de L-homocisteína (dissolució bàsica en aigua/etanol 1:1) amb [11C]CH3I en un loop de HPLC va permetre la formació del radiotraçador desitjat amb elevat rendiment radioquímic (38.4 ± 4.1%) en un temps curt (< 12 min). Tots el paràmetres analítics compleixen les especificacions requerides per la versió actual de la Farmacopea Espanyola, tot i que els valors d'activitat específica obtinguts van ser relativament baixos. Degut a això, es van estudiar i quantificar les principals fonts que contribueixen a la contaminació de carboni-12 durant les síntesis de [11C]CH3I efectuades segons el "wet" method. Es va observar que la principal font de contaminació de CO2 no radioactiu (contribució>90%) és el propi procés de bombardeig, probablement degut a la combustió (causada per les altes temperatures i pressions assolides durant la irradiació) dels compostos que contenen carboni i que es troben al gas irradiat (o a l'interior del blanc). Es van establir procediments generals per realitzar abans, durant i després de la radiosíntesi per prevenir la contaminació exterior i, d'aquesta manera, augmentar l'activitat específica dels radiotraçadors sintetitzats.En quant al marcatge amb nitrogen-13, s'ha desenvolupat un procés totalment automàtic per a la producció de [13N]NO2- a partir de [13N]NO3- generat en el ciclotró. El precursor radioactiu [13N]NO2- s'ha utilitzat per la radiosíntesi de compostos amb interès biològic com ara S-nitrosotiols (donadors de NO.), N-nitrosamines (molècules amb potencials efectes carcinogènics) i azo compostos (amb possible aplicació com a radiotraçadors per a la detecció in vivo de plaques de &#946;-amiloide). En tots els casos es van obtenir excel·lents conversions radioquímiques (48.7% - 74.5% per S-[13N]nitrosotiols, 45.6% - 53.4% per N-[13N]nitrosamines i 40.0% - 58.3% per 13N-azo compostos) i bons rendiments radioquímics (33.8% - 60.6% per S-[13N]nitrosotiols, 34.0% - 37.8% per N-[13N]nitrosamines i 20.4% - 47.2% per 13N-azo compostos). A més a més, s'ha dissenyat i implementat un mòdul automàtic amb control remot pel marcatge de molècules amb 13N. / Se ha desarrollado una nueva estrategia para la síntesis rápida y eficiente de L-[metil-11C]metionina basada en el captive solvent method. La reacción de L-homocisteína (disolución básica en agua/etanol 1:1) con [11C]CH3I en un loop de HPLC permitió la formación del radiotrazador deseado con elevado rendimiento radioquímico (38.4 ± 4.1%) en un tiempo corto (< 12 min). Todos los parámetros analíticos cumplían las especificaciones requeridas por la versión actual de la Farmacopea Española, aunque los valores de actividad específica obtenidos fueron relativamente bajos. Por ello, se estudiaron y cuantificaron las principales fuentes que contribuyen a la contaminación de carbono-12 durante las síntesis de [11C]CH3I efectuadas según el "wet" method. Se observó que la principal fuente de contaminación de CO2 no radiactivo (contribución>90%) es el propio proceso de bombardeo, probablemente debido a la combustión (causada por las altas temperaturas y presiones alcanzadas durante la irradiación) de los compuestos que contienen carbono y que se encuentran presentes en el gas irradiado (o en el mismo cuerpo del blanco). Se establecieron procedimientos generales para realizar antes, durante y con posterioridad a la radiosíntesis para prevenir la contaminación exterior y, de esta manera, aumentar la actividad específica de los radiotrazadores sintetizados.Respecto al marcaje con nitrógeno-13, se ha desarrollado un proceso totalmente automático para la producción de [13N]NO2- a partir del [13N]NO3- generado en el ciclotrón. El precursor radiactivo [13N]NO2- se ha utilizado para la radiosíntesis de compuestos con interés biológico tales como S-nitrosotioles (donadores de NO.), N-nitrosaminas (moléculas con potenciales efectos carcinogénicos) y azo compuestos (con posible aplicación como radiotrazadores para la detección in vivo de placas de &#946;-amiloide). En todos los casos se obtuvieron excelentes conversiones radioquímicas (48.7% - 74.5% para S-[13N]nitrosotioles, 45.6% - 53.4% para N-[13N]nitrosaminas y 40.0% - 58.3% para 13N-azo compuestos) y buenos rendimientos radioquímicos (33.8% - 60.6% para S-[13N]nitrosotioles, 34.0% - 37.8% para N-[13N]nitrosaminas y 20.4% - 47.2% para 13N-azo compuestos). Además, se ha diseñado e implementado un módulo automático con control remoto para el marcaje de moléculas con 13N. / A new strategy for the fast and efficient synthesis of L-[methyl-11C]methionine based on the captive solvent method has been developed. The in loop reaction of a basic water/ethanol 1:1 solution of L-homocysteine with [11C]CH3I led to the formation of the desired radiotracer with high radiochemical yield (38.4 ± 4.1%) in short production time (< 12 min). All analytical parameters were within the specifications of the current version of the Spanish Pharmacopoeia, although specific radioactivity values were relatively low. Thus, the main sources of carbon-12 during the synthesis of [11C]CH3I by the "wet" method were studied and the contribution attributable to each individual source was quantified. The most relevant contamination of non-radioactive CO2 (contribution>90%) was shown to be generated during the bombardment process, probably due to the combustion (caused by high temperature and pressure during irradiation) of carbon carrier compounds present in the irradiated gas (or target body). General procedures to be performed before, during and after the radiosynthesis were established to prevent external contamination and to improve the specific radioactivity of 11C-labeled radiotracers synthesized from [11C]CH3I produced via the "wet" method. Concerning 13N-labeling, a fully automatic process for the production of [13N]NO2- from cyclotron generated [13N]NO3- has been developed. The radioactive precursor [13N]NO2- has been used for the synthesis of biologically interesting 13N-labeled compounds such as S-nitrosothiols (well-known NO. donors), N-nitrosamines (molecules with potent carcinogenic effects) and azo compounds (with putative application as imaging probes for in vivo detection of &#946;-amyloid plaques). In all cases, excellent radiochemical conversion (48.7% - 74.5% for S-[13N]nitrosothiols, 45.6% - 53.4% for N-[13N]nitrosamines and 40.0% - 58.3% for 13N-labeled azo compounds) and good radiochemical yields (33.8% - 60.6% for S-[13N]nitrosothiols, 34.0% - 37.8% for N-[13N]nitrosamines and 20.4% - 47.2% for 13N-labeled azo compounds) were achieved. An automatic remote controlled synthesis module for the preparation of 13N-labeled structures has been designed and implemented.

The aim of diploma thesis has been development and optimization of method determination of N- nitrososarcosine and N-nitrosoproline in malt by gas chromatography with chemiluminiscence detector. Optimization of extraction method has been performed by response surface method. Quantification has been performed by internal standard method (N-nitrosopipecolic acid, in which matrix effects has been studied. These has been verified in münchen and pilsen malt, therefore matrix-matched calibration has been constructed. The developed method has been aplicated on wheat, münchen and pilsen malt. N- nitrosoproline was detected only in münchen malt and in other cases has been under limit of detection (LOD=4,0 µg/kg). N-nitrososarcosine was in all cases under limit of detection (LOD=3,7 µg/kg). The matrix-matched calibration has been constructed for experimental münchen malt with N-nitrosoproline concentration at 13,2 ± 2,9 µg/kg. Powered by TCPDF (www.tcpdf.org)