Águas residuárias são continuamente contaminadas por fármacos. Dentre estes fármacos, os antimicrobianos causam grande preocupação pelos impactos sobre o desenvolvimento de resistência bacteriana. As principais fontes de contaminação destes fármacos são efluentes urbanos, hospitalares, de fazendas e de algumas indústrias. A complexidade das matrizes ambientais tais como águas residuárias é uma das principais dificuldades para extrair e detectar fármacos, fazendo-se necessário o uso de técnicas de preparo de amostra para a extração destes compostos de interesse. Técnicas clássicas como a extração líquido-líquido (LLE) e a extração em fase sólida (SPE) são largamente usadas para extração de fármacos nesse tipo de matriz, porém estas técnicas não atendem amplamente aos princípios da química verde. Dessa forma, novas técnicas, mais alinhadas à responsabilidade ambiental, têm sido desenvolvidas. Neste âmbito apresenta-se o desenvolvimento e a validação de um método de microextração líquido-líquido para extração e detecção de sulfonamidas e o desenvolvimento e otimização de um método utilizando planejamento experimental para a extração de fluoroquinolonas em águas residuárias. Foi possível obter-se o limite de detecção de 0,2 ng mL-1 para as sulfonamidas analisadas, este LD é relativamente baixo considerando que o detector que foi utilizado não possuía a possibilidade de fazer análises no modo MS/MS, o que certamente reduziria ainda mais o LD. Com os desenvolvimentos desse trabalho tornou-se possível a utilização de apenas 1 mL de solvente orgânico para a pré-concentração off-line, Esta etapa, adicionada a uma outra pré-concentração online (column switching) permitiu a extração dos analitos com a obtenção de um LD relativamente baixo, a partir de apenas 7 mL de amostra. / Drugs are continuously contaminating wastewater. Among these drugs antimicrobials cause great concern for the impacts on the development of bacterial resistance. The main sources of contamination by these drugs are urban effluents, hospitals, farms and some industries. The complexity of the environmental matrices such as wastewater is one of the main difficulties in extracting and detecting drugs, bringing up the need to use sample preparation techniques for the extraction of the interest compounds. Classical techniques such as liquid-liquid extraction (LLE) and solid phase extraction (SPE) are widely used for drug extraction in this type of matrix, but these techniques do not largely meet the principles of green chemistry. In this way, new techniques, more aligned with environmental responsibility, have been developed. In this context, this thesis presents the development and validation of a liquid-liquid microextraction method for sulfonamide extraction and detection and the development and optimization of a method using experimental design for the extraction of fluoroquinolones presented in wastewater. It was possible to obtain a limit of detection (LD) of 0.2 ng mL-1 for the sulfonamides analyzed, this LD is relatively low considering that the detector that was used did not have the possibility to perform analyzes in the MS/MS mode, which certainly would further reduce the LD. With the development of this thesis, it became possible to use only 1 mL of organic solvent for the off-line preconcentration of the analytes. This step, added to another online preconcentration (column switching) allowed the extraction of the analytes obtaining relatively low LDs, from just 7 mL of the sample.

As Sulfonamidas (SAs) são antibióticos de uso muito comum na medicina veterinária, sendo também aplicadas na medicina humana. Os resíduos dessas substâncias, ou dos seus metabolitos na carne e outros alimentos, podem causar efeitos adversos para a saúde dos consumidores como, por exemplo, resistências a antibióticos e alergias. Este trabalho apresenta o desenvolvimento e aplicação de métodos modernos de preparo de amostra para determinação de multiresíduo de sulfonamidas em alimentos por cromatografia líquida acoplada a espectrometria de massas e ultravioleta visível. Dentre os métodos de preparo de amostra, aplicou-se o método de extração QuEChERS (Quicky, Easy, Cheap. Effective, Rugged, Safe) modificado, em combinação com a cromatografia liquida acoplada a espectrometria de massas, para a análise de dez sulfonamidas em amostras de músculo de frango e bovino. No segundo estudo, seguindo a tendência de miniaturização, sintetizou-se um polímero molecularmente impresso (Sulfadimetoxina-MIP) para uso como sorbente em dispositivos de Microextração com Sorbentes Empacotado (MEPS). O método, denominado SDM-MIP-MEPS, foi otimizado e aplicado em amostras de músculo de frango usando a cromatografia liquida com detecção por ultravioleta-visivel. Embora o uso do polímero molecularmente impresso (MIP) como sorbente seletivo para o MEPS já tenha sido reportada em dois trabalhos, pela primeira vez é descrito a aplicação de um MIP impresso com sulfdimetoxina (SDM), usando MEPS para extração de sulfonamidas em músculo de frango. Portanto, a novidade neste caso, é o uso da nova técnica extração miniaturizada (MEPS) com o polímero sintetizado sulfadimetoxina-MIP como sorbente de empacotamento. As metodologias foram validadas com sucesso de acordo com as diretrizes 657/2002/EU. / Sulfonamides are widely used in veterinary and human medicine. Residues of these compounds, or their metabolites in animal meats and other foods, are toxic and can cause side effects in human\'s health, such as resistance to antibiotics and allergic reactions. This study describes the development and application of a modern sample preparation approach for sulfonamides multiresidue determination in food by chromatographic methods coupled to mass spectrometry and ultraviolet-visible spectroscopy. Among those sample preparation methods, the modified QuEChERS extraction in combination with liquid chromatography in tandem with mass spectrometric detection was applied to the analysis of residues of 10 sulfonamides in chiken and cattle muscle. In the second study, following the miniaturization trends, it was synthesized a molecularly imprinted polymer (Sulfadimethoxine-MIP), for application as sorbent in Microextraction by Packed Sorbents (MEPS). The extraction method was optimized and successfully applied to chicken muscle samples in combination with highperformance liquid chromatography by ultraviolet-visible detection. Although the use of MIPs as selective packing materials for MEPS has already been reported in two papers, is first time that application of a MIP imprinted with Sulfadimethoxine is evaluated for the extraction of sulfonamides in chicken muscle. Therefore the novelty of the present work is the use of this new miniaturization extraction technique with synthesized sulfadimethoxine-MIP polymer as packing sorbent. The methods were successfully validated according to the 2002/657/EC guidelines.

The diploma thesis is focused on the determination of tetracyclines, sulfonamides and fluoroquinolones from soil. Antibiotics such as tetracycline, chlortetracycline, oxytetracycline. ciprofloxacin, trimethoprim, sulfamethaxazole and sulfadiazin were selected due to frequent use in veterinary medicine. Due to the fact that the soil is a complex matrix and contains many components that can interfere with the detection signal of analytes, it was necessary to use the MAX column in the SPE method, which removes fulvic aned humic acid from analytes and the HLB column Final analysis of the analytes was performed by liquid chromatography with mass detesction (LC-MS). The method was also used for real soil samples, which were delivered from ÚKZUS.

Constantly increasing consumption of drugs leads to the increase of the concentration of residues in various environmental compartments. For this reason the drug residues are nowadays classified as significant environmental contaminants. The drug residues enter the soil along with the application of sewage sludge either as a fertilizer or during fertilizing by animal excrements excreted after drug administration, eventually by direct contamination from treated grazing animals. The presence of these substances in soil has got negative impact on the sensitive soil ecosystem. The diploma thesis aims to evaluation of possible soil contamination with selected drugs through ecotoxicity tests. For this purpose sulfonamide chemotherapeutic agents, which are often used in veterinary medicine, were chosen, specifically sulfamethoxazole and sulfamethazin. Eartworms (Lumbricus) were selected as suitable test representative soil organism. In the experimantal part of this work the avoidance test according to ISO 17512-1 and modified bioaccumulation test according to OECD 317 methodology were performed. Bioaccumulation substances in oligochaetes, for which the artificial soil was prepared according to OECD 207 methodology, which was subsequently contaminated with above specified drugs. Although according to the results of determination of these substances there is no significant bioaccumulation in eartworms‘ tissue, these organisms are very responsive to the presence of contaminants in the soil environment. This is evident from the results of avoidance tests.

Sulfonamides are antibiotics that are frequently used both in human and veterinary medicine. The combinations of abundant use of these antibiotics and their natural resistance to decay leads often to long term persistence in the environment. This accumulation, especially in living organisms, may lead to subsequent toxicosis. Also, presence of these antibiotic in nature poses problems with regard to the spread of genes for antibiotic resistance between potential pathogens. These facts led to an increase interest in studying the sulfonamide biodegradation and subsequent sulfonamide removal from the environment. In this work it was possible to isolate and characterize the microorganism Acinetobacter sp. strain 49. This microorganism was able to biodegrade under right conditions sulfamethoxazole with 80 % efficiency. Sulfamethoxazole is one of the most commonly found sulfonamide in the nature.

The world’s ever-growing energy demand has evoked great interest in exploring renewable energy sources along with sustainable energy storage systems. While inorganic physics of rocking chair mechanism used in Li-ion battery have proven to provide high energy density and high performance, there are problems yet to be overcome in terms of sustainability and recyclability. This is why research in organic batteries has been on the rise, yet the diversity of organic battery frameworks remains limited and requires overcoming multiple obstacles that restrain the performance of an all-organic battery system. A recent advance in the design of organic electrode material by Wang et al. has shown the possibility of a new stable and tunable class of conjugated sulfonamides (CSA) with an experimental voltage range between 2.85V and 3.45V [5]. A theoretical approach to study these organic materials is taken in this thesis research where the effects of such compounds on the redox potential, physics of ion insertion, and other thermodynamical properties are examined. Density Functional Theory (DFT) is employed in this investigation along with an evolutionary algorithm to generate information about the crystal structure of mentioned systems, their density of states (DOS), and charge distribution in pristine form and after lithiation. Quinone systems with oxygen groups were investigated in a previous research project that complements this thesis which looks into a quinone system with sulfonamide compounds where a comparison between the two could offer more understanding of the electrochemistry of such systems for their application in batteries as high performing organic cathode materials on a par with other inorganic materials.

No description available.

Les travaux décrits dans ce manuscrit de thèse ont porté d'une part sur le développement de nouvelles méthodes de spirocyclisation de céto-ynamides et d'autre part sur la réactivité de spiroénamides tertiaires. Les céto-sulfonamides en présence de bromoalcynes et de carbonate de césium conduisent à la formation de spiro-énamides par réaction de spirocyclisation via un intermédiaire céto-ynamide activé. Une grande variété de cycloalcanones et de bromoalcynes électroattracteurs sont tolérés.Les céto-ynamides conduisent à la formation de dérivés spiro-énamides par traitement avec du Triton B. La spirocyclisation tolère de nombreuses cycloalcanones et différents substituants aryles sur l'ynamide, et opère avec un bon stéréocontrôle de l'énamide. Une version en milieu micellaire aqueux de cette spirocyclisation a également été développée. Deux réactions dominos assistées par l'énamide tertiaire spirocyclique ont ensuite été développées. En présence de tétrachlorure de zirconium, la réaction domino permet d'obtenir des tétracycles de façon diastéréosélective tandis qu'avec le tétrachlorure de titane des pentacycles sont obtenus à partir du spiro-énamide avec un excellent régio- et diastéréocontrôle. / The work described in this manuscript involved the development of new spirocyclization methods starting from keto-ynamides, and the reactivity of tertiary spiro-enamides.Keto-sulfonamides led to spiro-enamides in the presence of cesium carbonate by spirocyclization reaction via an activated keto-ynamide intermediate. A wide range of cycloalkanones and electronwithdrawing bromoalkynes are tolerated. The spirocyclization reaction starting from keto-ynamides afforded spiro-enamide by treatment with Triton B. Various cycloalkanones, as well as a wide range of aryl substituents on the ynamide moiety, were suitable and provided good stereocontrol of the enamide formed. The spirocyclization reaction was also studied in aqueous micellar media. Two domino reactions assisted by the spirocyclic tertiary enamide were next developed. In the presence of zirconium tetrachloride, the domino reaction provided tetracyclic fused ring systems in a diastereoselective manner, whereas in the case of titanium tetrachloride, pentacyclic systems were obtained starting from the spiro-enamide with excellent regio- and diastereocontrol.

Frente a crescente necessidade de se monitorar diferentes contaminantes em matrizes complexas se faz necessário utilizar uma etapa de preparo de amostras eficiente e que esteja aliada à técnicas analíticas de elevada sensibilidade. Consequentemente, vem se aprimorando e desenvolvendo novos materiais sorventes utilizados para aumentar o desempenho do preparo de amostras e de fases estacionárias para cromatografia líquida de alta eficiência. Atualmente, materiais sorventes seletivos como líquidos iônicos, polímeros impressos molecularmente, grafeno, entre outros, vêm se destacando para extrair diferentes contaminantes. Diante desse contexto, esta tese teve como objetivo desenvolver diferentes materiais extratores para serem utilizados na microtécnica de extração in-tube SPME acoplada on-line com UPLC-MS/MS na análise de triazinas e sulfonamidas em matrizes complexas. O material que apresentou maior seletividade pelas classes dos compostos de interesse foi caracterizado por microscopia eletrônica de varredura e espectroscopia vibracional na região do infravermelho. Tanto para as triazinas quanto para as sulfonamidas o polímero impresso molecularmente apresentou maior afinidade e foi utilizado como fase extratora para extrair e pré-concentrar os analitos utilizando a microténica in-tube SPME UPLC-MS/MS. Além disso, para as triazinas utilizou-se também como fase de extração óxido de grafeno ancorado em sílica. As metodologias desenvolvidas nessa tese foram todas otimizadas e posteriormente validadas para analisar as matrizes de interesse que foram: uva, suco de uva integral, leite e água. Após à validação, as amostras foram analisadas com seus respectivos métodos validados, sendo que nenhum dos analitos foram encontrados considerando-se os limites das metodologias desenvolvidas, as quais se mostraram eficientes quando aplicadas nas análises das triazinas e sulfonamidas em suas respectivas amostras fortificadas. Outra abordagem explorada nesse trabalho foi o desenvolvimento de colunas tubulares abertas do tipo PLOT para serem utilizadas como colunas de extração em sistemas automatizados na cromatografia líquida. Colunas de sílica fundida foram preparadas para avaliar a formação da fase e sua aderência na parede do tubo. Para as colunas PS-DVB, os melhores resultados foram obtidos com duas horas de polimerização em banho de água. No entanto, para as colunas ODS a polimerização foi feita utilizando forno, e a fase não aderiu corretamente na parede do tubo para as colunas de 250 μm de diâmetro interno, requerendo estudos mais aprofundados para o preparo adequado destas colunas. / In view of the increasing need to monitor different contaminants in complex matrices, it is necessary to use efficient sample preparation techniques combined with highly sensitive analytical techniques. Consequently, new sorbent materials have been improved and developed to be used aiming to increase the performance of sample preparation and stationary phases for high performance liquid chromatography. Currently, selective sorbents such as ionic liquids, molecularly imprinted polymers, graphene, among others, have been emphasized to extract different contaminants. In this context, this thesis aimed to develop different extractive materials to be used in in-tube solid phase microextraction coupled on-line with UPLC-MS/MS in the analysis of triazines and sulfonamides in complex matrices. The material that presented greater selectivity for the classes of the compounds of interest was characterized by scanning electron microscopy and vibrational spectroscopy in the infrared region. For triazines and sulfonamides the molecularly imprinted polymer had higher affinity and was used as the extractive phase to extract and preconcentrate the analytes using the in-tube SPME UPLC-MS/MS. In addition, another extraction phase - graphene oxide anchored in silica - was also used. The methodologies developed in this thesis were all optimized and later validated to analyze the target compounds in the following matrices: grape, grape juice, milk and water. After the validation, the samples were analyzed with their respective validated methods and none of the analytes were found considering the limits of the methodologies developed, which were efficient when applied in the analysis of the triazines and sulfonamides in their respective fortified samples. Another approach explored in this work was the development of open tubular columns (PLOT) to be used as extraction columns in automated sample preparation - liquid chromatography systems. Silica columns were prepared in order to evaluate the formation of the phase and its adhesion to the tube wall. For the PS-DVB columns the best results were obtained with two hours of water-bath polymerization. However, for the ODS columns the polymerization done using an oven the phase did not adhere correctly in the tube wall the columns with 250 μm internal diameter. These results suggest that further experiments are required in order to better understand the preparation of these columns.

Frente a crescente necessidade de se monitorar diferentes contaminantes em matrizes complexas se faz necessário utilizar uma etapa de preparo de amostras eficiente e que esteja aliada à técnicas analíticas de elevada sensibilidade. Consequentemente, vem se aprimorando e desenvolvendo novos materiais sorventes utilizados para aumentar o desempenho do preparo de amostras e de fases estacionárias para cromatografia líquida de alta eficiência. Atualmente, materiais sorventes seletivos como líquidos iônicos, polímeros impressos molecularmente, grafeno, entre outros, vêm se destacando para extrair diferentes contaminantes. Diante desse contexto, esta tese teve como objetivo desenvolver diferentes materiais extratores para serem utilizados na microtécnica de extração in-tube SPME acoplada on-line com UPLC-MS/MS na análise de triazinas e sulfonamidas em matrizes complexas. O material que apresentou maior seletividade pelas classes dos compostos de interesse foi caracterizado por microscopia eletrônica de varredura e espectroscopia vibracional na região do infravermelho. Tanto para as triazinas quanto para as sulfonamidas o polímero impresso molecularmente apresentou maior afinidade e foi utilizado como fase extratora para extrair e pré-concentrar os analitos utilizando a microténica in-tube SPME UPLC-MS/MS. Além disso, para as triazinas utilizou-se também como fase de extração óxido de grafeno ancorado em sílica. As metodologias desenvolvidas nessa tese foram todas otimizadas e posteriormente validadas para analisar as matrizes de interesse que foram: uva, suco de uva integral, leite e água. Após à validação, as amostras foram analisadas com seus respectivos métodos validados, sendo que nenhum dos analitos foram encontrados considerando-se os limites das metodologias desenvolvidas, as quais se mostraram eficientes quando aplicadas nas análises das triazinas e sulfonamidas em suas respectivas amostras fortificadas. Outra abordagem explorada nesse trabalho foi o desenvolvimento de colunas tubulares abertas do tipo PLOT para serem utilizadas como colunas de extração em sistemas automatizados na cromatografia líquida. Colunas de sílica fundida foram preparadas para avaliar a formação da fase e sua aderência na parede do tubo. Para as colunas PS-DVB, os melhores resultados foram obtidos com duas horas de polimerização em banho de água. No entanto, para as colunas ODS a polimerização foi feita utilizando forno, e a fase não aderiu corretamente na parede do tubo para as colunas de 250 μm de diâmetro interno, requerendo estudos mais aprofundados para o preparo adequado destas colunas. / In view of the increasing need to monitor different contaminants in complex matrices, it is necessary to use efficient sample preparation techniques combined with highly sensitive analytical techniques. Consequently, new sorbent materials have been improved and developed to be used aiming to increase the performance of sample preparation and stationary phases for high performance liquid chromatography. Currently, selective sorbents such as ionic liquids, molecularly imprinted polymers, graphene, among others, have been emphasized to extract different contaminants. In this context, this thesis aimed to develop different extractive materials to be used in in-tube solid phase microextraction coupled on-line with UPLC-MS/MS in the analysis of triazines and sulfonamides in complex matrices. The material that presented greater selectivity for the classes of the compounds of interest was characterized by scanning electron microscopy and vibrational spectroscopy in the infrared region. For triazines and sulfonamides the molecularly imprinted polymer had higher affinity and was used as the extractive phase to extract and preconcentrate the analytes using the in-tube SPME UPLC-MS/MS. In addition, another extraction phase - graphene oxide anchored in silica - was also used. The methodologies developed in this thesis were all optimized and later validated to analyze the target compounds in the following matrices: grape, grape juice, milk and water. After the validation, the samples were analyzed with their respective validated methods and none of the analytes were found considering the limits of the methodologies developed, which were efficient when applied in the analysis of the triazines and sulfonamides in their respective fortified samples. Another approach explored in this work was the development of open tubular columns (PLOT) to be used as extraction columns in automated sample preparation - liquid chromatography systems. Silica columns were prepared in order to evaluate the formation of the phase and its adhesion to the tube wall. For the PS-DVB columns the best results were obtained with two hours of water-bath polymerization. However, for the ODS columns the polymerization done using an oven the phase did not adhere correctly in the tube wall the columns with 250 μm internal diameter. These results suggest that further experiments are required in order to better understand the preparation of these columns.