Recent advances in the area of nanotechnology have led to interesting applications of nanomaterials in medicine, especially in the areas of imaging and treatment. This thesis presents the development of two molecularly imprinted polymers (MIPs) based on the same fluorescent functional monomer. One MIP, prepared in the bulk format, is investigated for its ability to detect tamoxifen and its metabolites. The other MIP synthesised in the nanogel format, holds the potential to be used as pH-responsive drug delivery system. Four objectives were identified within this project. The first was the design and synthesis of fluorescent functional monomer. Two coumarin derivatives carrying a polymerisable unit, for covalent bonding within the polymer, and a carboxylic moiety, for interaction site with the template, were synthesised and characterised. However, only one of them (the VCC: 6-vynilcoumarin-4-carboxylic acid) showed high fluorescent yield and was selected as functional monomer. The second objective involved the development of a detection system based on bulk MIP containing the VCC fluorescent monomer. This system proved effective in generating a detectable signal upon binding the analytes. The signal was observed as a quenching of the polymer fluorescence and it was proportional to the amount of target molecules detected. The third objective was the preparation of tamoxifen-imprinted nanogels for potential application in the drug delivery field. The optimisation of the procedure gave a set of NIP/MIP with the desired solubility, particle size and fluorescence emission. These nanogels were then employed in the last objective, which involved the toxicity study and evaluation of the drug loading on of transgenic line of zebrafish. The nanogels were non-toxic at the tested concentrations and the presence of tamoxifen was confirmed.

<p>In the present work, molecular dynamics simulations were used to evaluate the molecular interactions in prepolymerization mixtures, as occurring during production of molecularly imprinted polymers. The systems simulated were produced based on earlier studies for reference of results. Four systems were simulated in order to investigate the effect on molecular interactions based upon the choice of porogen (acetonitrile or chloroform) and proton transfers. The systems consisted of phenylalanine anilide as template, methacrylic acid as functional monomer, ethylene glycol dimethacrylate as crosslinker and 2,2’-azobis-(2-methylpropionitrile) as radical initiator, with either acetonitrile or chloroform as porogen. Trajectories from the simulations were evaluated through radial distribution function analysis, grid density analysis and hydrogen bond analysis to investigate molecular interactions and complex formations in the simulated complete prepolymerization mixtures. Focus was on functional monomer-template, crosslinker-template and template-template complex formations. The results showed that the porogen influences molecular interactions in complete prepolymerization mixtures. Formation of higher order complexes was confirmed in all of the systems involving all of the investigated molecular species in the prepolymerization mixtures. The results could also confirm the presence of previously observed complexes between functional monomer and template (2:1 and 1:1 stoichiometry) and the prevalence of template dimerization, as well as a high involvement of crosslinker in complex formation.</p>

Biosensors monitor physiological activities for diagnosis and treatment of disease. Molecularly imprinted polymers (MIPs) are a viable synthetic approach for molecular recognition in biosensing. For biosensing purposes, the most important properties in MIP optimization are sensitivity and selectivity towards a desired analyte. This study aims to optimize MIP sensitivity and selectivity by varying the amount and type of cross-linker used in the synthesis of cortisol and melatonin. The four cross-linkers tested were trimethylpropane trimethacrylate (TRIM), ethyleneglycodimethacrylate (EGDMA), divinylbenzene (DVB), and pentaerythritol triacrylate (PETRA). Based on literature, the following ratios were used for the template molecule to functional monomer to cross-linker in MIP synthesis: for EGDMA cross-linked polymers, 1:6:30; for TRIM and PETRA cross-linked polymers, 1:8:8, 1:6:3, and 1:8:35; for DVB cross-linked polymers, 1:6:30, 1:4:16, and 4:1:60. The polymers were ground and washed, then suspended in a polyvinyl matrix which was spin-coated onto an organic electrochemical transducer (OECT). The device performance was evaluated using electrochemical impedance spectroscopy. For each device, the impedance was measured in electrolyte solutions containing target molecules in concentrations ranging from 1 pM to 100 uM. The impedance was plotted against the analyte concentration to give the sensing slope, which is a measurement for the binding affinity of the polymer. For a device to be considered sensitive, its sensing slope should be greater than its non-imprinted counterpart by a factor above the error margin (+/- 1.79). Of the devices tested, CM1835T (highly cross-linked with TRIM) showed sensitivity towards cortisol, but lacks selectivity towards cortisol over its structural analog, estradiol. Of the melatonin selective polymers, MM163T (low cross-linking with TRIM), MM1630D, and MM4160D (both highly cross-linked with DVB) all showed promising results in sensitivity to melatonin. Overall, the results indicate that high degrees of cross-linking in MIPs improve sensitivity for large, rigid, non-aromatic molecules such as cortisol; however there is no correlation between selectivity and the degree of cross-linking. Meanwhile, divinylbenzene as a cross-linker improves sensitivity and selectivity towards aromatic analytes such as melatonin and estradiol. This study could be improved upon by further characterization of imprinted and non-imprinted polymers, investigation of molecular dynamics, and optimization of devices.

京都大学 / 新制・課程博士 / 博士(工学) / 甲第24234号 / 工博第5062号 / 新制||工||1790(附属図書館) / 京都大学大学院工学研究科材料化学専攻 / (主査)教授 大塚 浩二, 教授 沼田 圭司, 教授 大内 誠 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

The synthesis of materials with molecular recognition properties has become a topic of great technological and scientific interest. Molecular imprinting is one of the most effective strategies in preparing highly selective synthetic receptors. The technique of molecular imprinting involves the copolymerization of functional and cross-linking monomers in the presence of a molecular template. Following polymerization and subsequent removal of the template, the molecularly imprinted polymer (MIP) retains a “molecular memory” of the template. During rebinding, the resultant polymer shows higher affinity and selectivity towards the molecular template when compared to other structural analogs. Ease of preparation and high thermal and chemical stability of this class of materials offers a broad range of potential applications. Promising areas of application include separation, chromatography, catalysis, sensors, antibody mimics, and drug delivery etc. The thesis entitled “Molecularly Imprinted Polymers based on Fluorescent and Template binding Cross-linker” deals with the design and synthesis of several molecularly imprinted polymers (MIPs) using different functional and cross-linking monomers, the main focus being use of preformed template-monomer complex, use of fluorescent cross-linker and development of functional group containing cross-linker. Chapter 1: An Introduction to Molecularly Imprinted Polymers. The first chapter provides an introduction to the field of molecularly imprinted polymers. It presents an overview of molecular imprinting process including a brief history of its discovery and its evolution to the present form. This chapter further elaborates on the principle of molecular imprinting with an emphasis on different parameters that directly affect their performance. It also provides a brief review of the applications of molecularly imprinted polymers. Chapter 2: Highly Cross-linked Metal Ion Imprinted Polymers. The second chapter deals with the synthesis of series of highly cross-linked metal-ion imprinted polymers. The process of metal ion-imprinting usually involves carrying out the polymerization and cross-linking directly in presence of the appropriate metal ion. In the present study, chemical-immobilization method was adopted which involves the use of preformed metal complexes with polymerizable group for the imprinting. Acrylate complexes of various metal-ions, such as Cu2+, Zn2+, Co2+, Ni2+, Pb2+ and Cr3+, were synthesized prior to polymerization. These pre-assembled complexes were then used to prepare MIPs, in the anticipation that this would lead to enhanced selectivity. Ethyleneglycol dimethacrylate (EGDMA) was used as the cross-linking monomer. As a control, the respective non-imprinted polymers (NIPs) were also made in absence of the template metal ion. Following polymerization, the template metal ion was extracted from the resultant metal ion-imprinted polymer. The selectivity of the metal ion-imprinted polymers was examined by a batch process using analytical tools, such as, Atomic Absorption Spectroscopy (AAS) and Inductively Coupled Plasma Spectroscopy (ICP). The spectroscopic studies revealed significant selectivity of all the MIPs towards the template metal ion. Among all six metal ion-imprinted polymers, Pb2+ and Cr3+ ion-imprinted polymer showed remarkable selectivity, followed by Cu2+ and Zn2+ ion-imprinted polymers. The Co2+ and Ni2+ ion-imprinted polymers exhibited comparatively poor selectivity. Representative plots depicting the selectivity exhibited by Pb2+ and Cr3+ ion-imprinted polymers are shown in Figure 1. These observations were rationalized based on the size and geometric preferences imposed by the imprinted site on the ion that binds to it. Figure 1. Selectivity study for (a) Pb2+ ion-imprinted polymer, (b) Cr3+ ion-imprinted polymer. Chapter 3. Molecularly Imprinted Fluorescent Chemosensor for Copper (II). Cu(II) is a source of important pollutant and therefore, the development of sensors that can detect Cu(II) selectively as well as remove Cu(II) from contaminated samples is an important objective. The use of molecular imprinting technique is an appealing approach in this regard. For this, a fluorophore containing cross-linker, namely 9,10-bis-(acryloyloxymethyl)anthracene (BAMA) was synthesized. This fluorescent cross-linker was used along with the standard cross-linker, EGDMA, for preparing Cu2+ ion-imprinted polymer. The complex of copper methacrylate (Cu-MAA) was prepared prior to polymerization used for the preparation of MIP. The resultant imprinted polymer exhibited quenching of the fluorescence in presence of Cu2+ ion, both in organic and aqueous medium. The efficiency of quenching of NIP (prepared in absence of Cu2+ ion) was significantly lower than that of MIP. A typical stack spectra showing the quenching process, along with a comparison of the quenching efficiency of MIP and NIP is shown in Figure 2. The imprinted polymers showed significant selectivity over other non-template metal ions, thereby reaffirming the importance of the imprinting process. The sensitivity of the fluorescence detection could be enhanced by increasing the level of the fluorophore incorporation. The increased sensitivity in detecting Cu2+ ion, demonstrated by the MIP suggests that a statistically random incorporation of the fluorophore into MIP matrices could be a useful approach for imparting a sensing element to MIPs. Figure 2. Fluorescence spectra of the (a) imprinted (MIP-1) and (b) non-imprinted (NIP-1) polymers in the presence of various concentration of Cu(OAc)2 in methanol. (c) Comparison of quenching efficiency of MIP-1 and NIP-1. Data were collected 3 h after addition of copper solution. I0 and I are the fluorescence intensities at 399 nm of the polymers in the absence presence of copper respectively. Two individual runs are presented in (c). Chapter 4. Molecularly Imprinted Turn-Off-On Sensor. This chapter describes the design and synthesis of molecularly imprinted fluorescent turn-off-on sensor utilizing the same fluorescent cross-linker, BAMA. Combining the process of fluorescence resonance energy transfer (FRET) with molecular imprinting technique, a novel turn-off-on sensor was developed. A molecularly imprinted polymer was prepared using a fluorescent template Coumarin-30 (C-30). C-30 was chosen as the template to ensure a significant overlap of the emission spectra of BAMA and the absorption spectra of C-30, thereby optimizing for FRET. Figure 3. Structures of relevant molecules. The C-30 imprinted polymer exhibited simultaneous quenching in fluorescence (turn-off) of BAMA and enhancement in fluorescence (turn-on) of C-30 (Figure 4). The imprinted polymer showed significantly better performance over the non-imprinted polymer (NIP). Figure 4. Fluorescence spectra of the (a) imprinted (MIP) and (b) non-imprinted (NIP) polymers with increasing concentration of the template Coumarine-30 in methanol. The UV-vis studies revealed that the more effective quenching is indeed due to the affinity for C-30 exhibited by the higher binding imprinted polymer. The imprinted polymer also showed significant selectivity over structurally analogous molecules. Therefore, both high sensitivity and selectivity were realized in such novel off-on sensor. Extension of this concept to other biologically relevant fluorescent templates could lead to potentially useful applications. Chapter 5. Design of New Template Binding Cross-linker. In molecularly imprinted polymers (MIP), high cross-linking density (~80 to 90 mole percent) is essential to ensure high selectivity, which limits the functional (binding) monomer to about 10-20 mole percent. Methacrylic acid (MAA) and ethyleneglycol dimethacrylate (EGDMA) are the most common combination of functional monomer and cross-linker, respectively, used in molecular imprinting. Generally a molecularly imprinted polymer made with this combination, contains only 10-20% binding sites. This limitation of binding site density is an aspect that has largely been overlooked. In order to improve the efficiency of MIP materials by enhancing the number of binding sites, a new cross-linking monomer (CYDI, 1) with two carboxylic acid groups was designed and synthesized by coupling itaconic anhydride with cyclohexane dimethanol (Figure 5). Figure 5. Structures of relevant molecules. The new functional group bearing cross-linking monomer (1) Itaconate ester of cyclohexanedimethanol (CYDI), the template (2) theophylline (Theop) and the structural analogue of template (3) caffeine (Caff). This new cross-linking monomer was then employed for preparing molecularly imprinted polymer using a drug molecule, theophylline (Theop 2, a bronchodilator) as the template. Seven molecularly imprinted polymers were synthesized with different ratios of CYDI and EGDMA, keeping the cross-linking density constant. The binding efficiency and the selectivity of these imprinted polymers were thoroughly investigated. It was seen that while saturation binding values for theophylline increased continuously with functional cross-linker (CYDI) content, the optimum selectivity with respect to analogous substrate, caffeine, was attained at 40 mol% CYDI. These studies suggest that the approach of using functional group containing cross-linkers could lead to improved MIP performance.

Orientadores: Susanne Rath, Rogério Custódio / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-27T17:08:24Z (GMT). No. of bitstreams: 1 Barros_LeonardoAugustode_D.pdf: 4314419 bytes, checksum: 93a1b964e0a2949ef6a2379990e2f089 (MD5) Previous issue date: 2014 / Resumo: Esse trabalho teve como objetivo principal otimizar e sintetizar polímeros de impressão molecular (MIP) para serem empregados em processos de extração em fase sólida (SPE), visando a determinação de diuréticos tiazídicos em urina. Cálculos teóricos de modelagem molecular, usando o programa computacional Gaussian 09 e os métodos DFT e PCM, no nível B3LYP e conjunto de base 6-31G(d), foram realizados para selecionar o monômero funcional (MF) e o solvente porogênico mais adequados para serem utilizados na síntese dos MIP. Para o desenvolvimento dos MIP compatíveis com água, foi utilizado hidroclorotiazida, clorotiazida ou hidroflumetiazida como molde, acrilamida como MF, etilenoglicol dimetacrilato como reagente de ligação cruzada (RLC) e tetraidrofurano como solvente porogênico. Foram avaliados alguns parâmetros que afetam a eficiência do polímero de impressão, tais como a quantidade de MF e a natureza do RLC. Foram construídas as isotermas de adsorção para cada um dos polímeros sintetizados e foi avaliada a seletividade dos MIP frente a análogos estruturais dos moldes. Os polímeros foram caracterizados por infravermelho com transformada de Fourier, 13C RMN, microscopia eletrônica de varredura, porosimetria de sorção de nitrogênio e análise termogravimétrica. Os MIP foram empregados como fase estacionária em SPE para a determinação de diuréticos tiazídicos em urina por cromatografia líquida de alta eficiência e os mesmos apresentaram seletividade cruzada em relação aos análogos estruturais / Abstract: This work aimed to optimize and synthesize molecularly imprinted polymers (MIP) to be employed in processes of solid phase extraction (SPE), for the determination of thiazide diuretics in urine. Theoretical calculations of molecular modeling, using the Gaussian 09 software and the density functional theory and PCM methods, at the B3LYP/6-31G(d) level, were performed to select a the most appropriate functional monomer (FM) and porogenic solvent for the synthesis of the molecularly imprinted polymers (MIP). For the development of a water-compatible MIP chlorothiazide, hydrochlorothiazide or hydrfoflumethiazide were used as template, acrylamide as FM, ethyleneglycol dimethacrylate as cross-linker and tetrahydrofuran as porogenic solvent. Parameters that affect thepolymer efficiency, such as the amount of the monomer and nature of the cross-linker were evaluated. The adsorption isotherms for each of the synthesized polymers were constructed and the selectivities of the MIPs in relation to structural analogues of the templates were evaluated. The polymers were characterized by Fourier transform infrared, 13C NMR, scanning electron microscopy, nitrogen sorption porosimetry and thermogravimetric analysis. The MIPs were employed as stationary phase in SPE for the determination of thiazide diuretics in urine by high performance liquid chromatography and they showed cross-selectivity in relation to their structural analogues / Doutorado / Quimica Analitica / Doutor em Ciências

Bacterial infections are an increasing problem for human health. In fact, an increasing number of infections are caused by bacteria that are resistant to most antibiotics and their combinations. A new solution to fight bacteria and infectious diseases, without promoting antimicrobial resistance, is required. A promise strategy is the disruption or attenuation of bacterial Quorum Sensing (QS), a refined system that bacteria use to communicate. In a QS event, bacteria produce and release specific small chemicals, signal molecules - autoinducers (AIs) - into the environment. AIs regulate gene expression as a function of cell population density. Phenotypes mediated by QS (QS- phenotypes) include virulence factors, toxin production, antibiotic resistance and biofilm formation. In this work, two polymeric materials (linear polymers and molecularly imprinted nanoparticles) were developed and their ability to attenuate QS was evaluated. Both types of polymers should be able to adsorb bacterial signal molecules, limiting their availability in the extracellular environment, with expected disruption of QS. Linear polymers were composed by methyl methacrylate as backbone and itaconic acid or methacrylic acid as functional monomer. IA and MAA monomers were identified by computer modelling to have strong interactions with the AIs produced by Gram-negative bacteria. Cont/d.

As sulfonamidas são antibióticos amplamente utilizados na medicina humana e animal. Por apresentarem um custo relativamente baixo, além de seu uso medicinal são comumente utilizadas como aditivos nos alimentos para promover o crescimento de animais. O alto consumo das sulfonamidas é preocupante, pois grandes quantidades desses compostos são descartadas no ambiente por meio de excreções humanas, excreções animais e por águas residuárias industriais e hospitalares. A presença de sulfonamidas no ambiente, mesmo em níveis de traços, pode gerar uma toxicidade direta nas espécies expostas bem como a proliferação seletiva de bactérias resistentes, que podem transferir os genes de resistência para outras espécies bacterianas. O impacto ambiental negativo ocasionado por esse tipo de composto exige o monitoramento adequado e o consequentemente desenvolvimento de técnicas e métodos de análise e de preparo de amostra que consigam atingir suficientes intervalos e limites de detecção. Na atualidade a SPE é uma técnica bastante utilizada para extração de analitos em amostras ambientais, pois permite trabalhar com um consumo de solvente reduzido, sua reprodutibilidade é alta, o tempo de preparo de amostra é curto e permite a automatização. No formato automatizado on-line a fase extratora é empacotada em uma pré-coluna e ligada ao sistema cromatográfico geralmente por meio de uma válvula de seis pórticos. Dentre as possíveis fases para a SPE os polímeros molecularmente impressos (MIP) têm tornado-se atrativos por causa de sua alta seletividade em comparação com as fases extratoras tradicionais; além disso, permitem, mediante procedimentos simples, associar a tecnologia MIP com a tecnologia de materiais de acesso restrito - RAM (do inglês: restricted access media) obtendo assim os materiais RAM-MIP. Nesse trabalho foi sintetizado e avaliado o desempenho de um polímero de impressão molecular (MIP), e três polímeros de impressão molecular restritos à ligação de macromoléculas (RAM-MIP, BSA-MIP e RAM-MIP-BSA) para a pré-concentração seletiva de sete sulfonamidas (SNs) em amostras complexas para análise em sistema HPLC-bidimensional. Os materiais obtidos foram avaliados em termos de fator de retenção, seletividade, seletividade competitiva e capacidade de eliminação de macromoléculas. O polímero BSA-MIP apresentou os melhores resultados, demonstrando-se muito mais seletivo para sulfonamidas do que para alguns interferentes como fluoroquinolonas, cafeína, ácido acetilsalicílico entre outros, também demonstrou uma capacidade de exclusão de macromoléculas de 97,63% ao ser testado com uma solução de 44 mg mL-1 de BSA. / Sulfonamides are antibiotics widely used in human and veterinary medicine. Due to their relatively low cost and their therapeutic effects, they are frequently employed as growth promoting additive in animal food. This high consumption causes that high amounts of them are being ejected to the environment through the animal and human excrements or industrial and hospital wastewater. Even in trace amount, these compounds can produce direct toxicity in several species and the selective spread of the antibiotic resistant bacteria that can transfer the resistance genes to others bacteria species. This negative impact has to be adequately monitored and, thus, there is a claim to the development of analytical and sample preparation techniques and methods that permit reaching to very low detection limits and intervals. Currently solid phase extraction (SPE) is the technique commonly used for isolation of analytes from environmental samples, since it allows working with smaller volumes of solvent, shorter sample preparation times, achieving high reproducibility and allowing automation. In automated on-line SPE the extracted phase is packed into a precolumn and linked to the chromatographic system, generally by a 6-port valve. Among the possible phases for SPE the molecular imprinted polymer (MIP) has become interesting because it is more selective than traditional extraction; moreover, through simple procedure it can be associated with the restricted acess media (RAM) producing the RAM-MIP and the MIP-BSA materials. Here we synthesized and evaluated the performance of one MIP and three molecular imprinted polymers linked to macromolecules (RAM-MIP, BSA-MIP e RAM-MIP-BSA) for a selective preconcentration of seven sulfonamides in complex samples for two-dimensional HPLC analysis. The synthesized materials was evaluated regarding the retention factor, competitive selectivity and elimination capacity of macromolecules. The BSA-MIP option showed the best results, achieving high selectivity for sulfonamides against others interferences such as fluoroquinolone, caffeine and acetylsalicylic acid; additionally presenting an exclusion capacity of 97,63% of macromolecules when was tested with a BSA solution at 44 mg ml-1.

A fotocatálise heterogênea é um processo que apresenta baixa seletividade de degradação. Nesse sentido, a síntese de materiais dotados de impressão molecular (IM) deve ajudar a contornar este problema. Os fotocatalisadores dotados de IM foram sintetizados de acordo com duas classes: uma inorgância (via diferentes rotas sol-gel e TEOS como percursor de sílica) e outra orgânica (via impressão não-covalente por precipitação e ácido metacrílico como monômero). No caso da primeira, a impressão molecular foi investigada através do uso de corante (rodamina B) e diferentes fármacos como template (substrato molde). No caso da matriz orgânica, o fármaco diclofenaco foi usado como molécula template. Os materiais foram caracterizados por análises texturais, estruturais e morfológicas. Com respeito à matriz à base de sílica, os sistemas com maiores valores de área específica foram observados pela rota ácida. Como efeito da rota, foi observado que a rota ácida apresentou um fator de seletividade 47% maior que a rota não-hidrolítica em testes de adsorção seletiva. Os resultados obtidos por análise de isotermas também convergem no sentido de revelarem que a rota ácida apresentou a maior capacidade de adsorção (997,9 mg/g) dentre as diferentes rotas de síntese pelo método sol-gel. Nos ensaios de fotocatálise (rodamina como template), foi conseguido um aumento de seletividade e competitividade na fotodegradação da rodamina de até 187% e 290%, respectivamente, comparado ao P25 (amostra comercial de TiO2). Quanto ao uso de fármacos como template em matriz inorgânica, os fotocatalisadores com impressão molecular obtiveram um aumento na adsorção e fotodegradação de até 751 e 427%, respectivamente, em comparação ao P25. Os materiais baseados em matriz orgânica também apresentaram seletividade em comparação ao P25. O valor médio do coeficiente de seletividade (estimado a partir da degradação de moléculas não-alvo, a fluxetina e o paracetamol) foi estimado em 2,8 – portanto sugerindo que a presença de cavidades tridimensionais é um dos principais fatores da seletividade observada. Com o objetivo de explorar o potencial de adsorção das cavidades de impressão molecular, os estudos dos fotocatalisadores seletivos com adição de P25 foram conduzidos de maneira a manter baixa a concentração de TiO2 (de 7 a 44 mg/L em cada teste fotocatalítico). Estudos de reuso do fotocatalisador (com e sem regeneração) também foram conduzidos. Tanto os materiais de matriz inorgânica como orgânica mantiveram em pelo menos 60% da eficiência fotocatalítica original após vários ciclos. / Heterogeneous photocatalysis is a process that has a low selectivity for degradation. In this sense, the synthesis of materials with molecularly imprinting (MI) should help to overcome this problem. The photocatalyst containing MI was synthesized according to two classes: An inorganic one (via different sol-gel routes and TEOS as silica precursor) and an organic one (via non-covalent imprinting by precipitation having methacrylic acid as monomer). In the first case, MI was investigated by use of the dye (rhodamine B) and several pharmaceutical compounds as template. In case the organic matrix, diclofenac was used as the template molecule. The samples were extensively characterized by textural, structural and morphological analysis. With respect to the silica-based matrix, the systems with larger surface area values were obtained by acid route. As effect of the route, it was observed that the acid route showed a selectivity factor 47% higher than that of the non-hydrolytic route in selective adsorption tests. Among the different synthesis routes prepared by sol-gel method, the isotherms analysis showed that acid route has the highest adsorption capacity (997.9 mg/g). Compared to the P25 (commercial sample of TiO2), the photocatalysis assays (rhodamine as the template) have shown an increase in selectivity and competitiveness up to 187% and 290%, respectively. Regarding the use of pharmaceutical as template in the inorganic matrix, the imprinted photocatalyst had an increase in adsorption and photodegradation up to 751 and 427%, respectively. The systems based on the organic matrix have also showed selectivity compared to the P25. The mean value of selectivity coefficient for degradation (estimated from the non-target molecules, such as fluoxetine and paracetamol) was estimated to be 2.8 – thus, suggesting that the presence of three-dimensional cavities is a major factor in the observed selectivity. In order to explore the full potential of adsorption from the MI cavities, the photocatalyst containing P25 were prepared with the low concentration of TiO2 (from 7 to 44 mg/L in each photocatalytic test). The reuse of photocatalysts (with and without regeneration) was also studied. Both inorganic and organic matrix retained at least 60% of the original efficiency after several cycles.

As sulfonamidas são antibióticos amplamente utilizados na medicina humana e animal. Por apresentarem um custo relativamente baixo, além de seu uso medicinal são comumente utilizadas como aditivos nos alimentos para promover o crescimento de animais. O alto consumo das sulfonamidas é preocupante, pois grandes quantidades desses compostos são descartadas no ambiente por meio de excreções humanas, excreções animais e por águas residuárias industriais e hospitalares. A presença de sulfonamidas no ambiente, mesmo em níveis de traços, pode gerar uma toxicidade direta nas espécies expostas bem como a proliferação seletiva de bactérias resistentes, que podem transferir os genes de resistência para outras espécies bacterianas. O impacto ambiental negativo ocasionado por esse tipo de composto exige o monitoramento adequado e o consequentemente desenvolvimento de técnicas e métodos de análise e de preparo de amostra que consigam atingir suficientes intervalos e limites de detecção. Na atualidade a SPE é uma técnica bastante utilizada para extração de analitos em amostras ambientais, pois permite trabalhar com um consumo de solvente reduzido, sua reprodutibilidade é alta, o tempo de preparo de amostra é curto e permite a automatização. No formato automatizado on-line a fase extratora é empacotada em uma pré-coluna e ligada ao sistema cromatográfico geralmente por meio de uma válvula de seis pórticos. Dentre as possíveis fases para a SPE os polímeros molecularmente impressos (MIP) têm tornado-se atrativos por causa de sua alta seletividade em comparação com as fases extratoras tradicionais; além disso, permitem, mediante procedimentos simples, associar a tecnologia MIP com a tecnologia de materiais de acesso restrito - RAM (do inglês: restricted access media) obtendo assim os materiais RAM-MIP. Nesse trabalho foi sintetizado e avaliado o desempenho de um polímero de impressão molecular (MIP), e três polímeros de impressão molecular restritos à ligação de macromoléculas (RAM-MIP, BSA-MIP e RAM-MIP-BSA) para a pré-concentração seletiva de sete sulfonamidas (SNs) em amostras complexas para análise em sistema HPLC-bidimensional. Os materiais obtidos foram avaliados em termos de fator de retenção, seletividade, seletividade competitiva e capacidade de eliminação de macromoléculas. O polímero BSA-MIP apresentou os melhores resultados, demonstrando-se muito mais seletivo para sulfonamidas do que para alguns interferentes como fluoroquinolonas, cafeína, ácido acetilsalicílico entre outros, também demonstrou uma capacidade de exclusão de macromoléculas de 97,63% ao ser testado com uma solução de 44 mg mL-1 de BSA. / Sulfonamides are antibiotics widely used in human and veterinary medicine. Due to their relatively low cost and their therapeutic effects, they are frequently employed as growth promoting additive in animal food. This high consumption causes that high amounts of them are being ejected to the environment through the animal and human excrements or industrial and hospital wastewater. Even in trace amount, these compounds can produce direct toxicity in several species and the selective spread of the antibiotic resistant bacteria that can transfer the resistance genes to others bacteria species. This negative impact has to be adequately monitored and, thus, there is a claim to the development of analytical and sample preparation techniques and methods that permit reaching to very low detection limits and intervals. Currently solid phase extraction (SPE) is the technique commonly used for isolation of analytes from environmental samples, since it allows working with smaller volumes of solvent, shorter sample preparation times, achieving high reproducibility and allowing automation. In automated on-line SPE the extracted phase is packed into a precolumn and linked to the chromatographic system, generally by a 6-port valve. Among the possible phases for SPE the molecular imprinted polymer (MIP) has become interesting because it is more selective than traditional extraction; moreover, through simple procedure it can be associated with the restricted acess media (RAM) producing the RAM-MIP and the MIP-BSA materials. Here we synthesized and evaluated the performance of one MIP and three molecular imprinted polymers linked to macromolecules (RAM-MIP, BSA-MIP e RAM-MIP-BSA) for a selective preconcentration of seven sulfonamides in complex samples for two-dimensional HPLC analysis. The synthesized materials was evaluated regarding the retention factor, competitive selectivity and elimination capacity of macromolecules. The BSA-MIP option showed the best results, achieving high selectivity for sulfonamides against others interferences such as fluoroquinolone, caffeine and acetylsalicylic acid; additionally presenting an exclusion capacity of 97,63% of macromolecules when was tested with a BSA solution at 44 mg ml-1.