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Synthesis of polymer precursors based on isosorbide
Šichnárek, Vojtěch ; Cigánek, Martin (referee) ; Figalla, Silvestr (advisor)
The theoretical part of the thesis deals with the description of reduced hexitols, methods of isosorbide production and its application purpose in polymer materials. It includes a description of the glucose dehydration process, the influence of reaction conditions and the catalysis of the isosorbide production, the polymerization of isosorbide monomers and their properties. The experimental part of the work is focused on the optimization of isosorbide’s laboratory synthesis‘ reaction conditions, the description of its chemical modification to polymerizable isosorbide derivatives and the physical-chemical characterization of the produced molecules. The synthesis of isosorbide is monitored by LC-MS, the product is subjected to various refining methods and a detailed structural characterization. GC was chosen for the monitoring of the preparation of isosorbide dimethacrylate and structural verification of the diester was confirmed by FT-IR, MS and NMR. The physical-chemical characterization of the prepared isosorbide dimethacrylate consists of the description of its rheological properties in mixture with a commercial methacrylated oil and the study of the reactivity of the monomers by DSC. The mixture of methacrylated oil and isosorbide dimethacrylate was used to prepare polymer thermosets which were analyzed by thermo-mechanical methods such as DMA, bending and TGA. The highest isosorbide conversion achieved value of 81.9 % after 5 hours, and it reached 94,1 % for isosorbide dimethacrylate after 8 hours. According to the results, isosorbide dimethacrylate possesses the abilty to reduce the shear viscosity of polymerizable precursors and to increase the glass transition temperature and crosslinking densities of polymer thermoset.
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Development of LC-MS method for determination of selected endocrine disruptors
Chvalkovská, Eliška ; Kučera, Radim (advisor) ; Štěrbová, Petra (referee)
Charles University Phaculty od Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Eliška Chvalkovská Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Consultant: Mgr. Martin Novák Title of thesis: Development of LC-MS method for determination of selected endocrine disruptors The thesis is focused on the development and optimization of LC-MS method for the determination of twelve endocrine disruptors in amniotic fluid of pregnant women in the third trimestr of pregnancy. There is a suspision that premature births are connected with an increased incidence of endocrine disruptors in amniotic fluid. The analytes were extracted by liquid-liqud extraction with 4-methylpentan-2- on. The analytical method is based on using reverse phase high-performance liquid chromatography with Hypersil C4 GOLD column (2.1 × 100 mm, particles 1.9 µm). For analysis the gradient elution with the mobile phase A (0.5% (v/v) formic acid aqueous solution) and B (0.5% (v/v) formic acid solution in acetonitrile) at a flow rate of 0.5 ml/min, injection 5 µl and column oven temperature 35 řC was used. The high- resolution mass spectrometer Orbitrap Q Exative Plus with atmospheric pressure chemical ionization in positive mode was used to identify and determine the response of...
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LC-MS/MS study of phase one in vitro biotransformation of potential drugs against Alzheimer's disease
Kuřátková, Aneta ; Kučera, Radim (advisor) ; Váňová, Nela (referee)
No treatment that would completely stop the progression of Alzheimer's disease has not been found yet. Recently used tacrine showed good results in the treatment of Alzheimer's disease, however long-term use led to chronic hepatotoxicity due to its metabolites. This master thesis deals with the compound 7-phenoxytacrine, one of the promising tacrine derivatives, which is one of the candidates for potential use in the therapy of Alzheimer's disease. Due to the formation of hepatotoxic metabolites of tacrine after the biotransformation in human liver, it appears necessary to identify the emerging metabolites of 7-phenoxytacrine molecule. Within this master's thesis in vitro biotransformation study of 7-phenoxytacrine using human liver microsomes was performed. High performance liquid chromatography with tandem mass spectrometry was used to determine the parent substance and the seventeen 7-phenoxytacrine metabolites. The analytical method showed the formation of six monohydroxylated and eleven dehydroxylated metabolites of 7-phenoxytacrine. Thus, we concluded that hydroxylation is the major metabolic reaction after in vitro microsomal biotransformation. In addition to the identification of metabolites, a quantification and microsomal stability study, including the determination of the amount of...
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Development of LC-MS method for determination of selected endocrine disruptors
Chvalkovská, Eliška ; Kučera, Radim (advisor) ; Štěrbová, Petra (referee)
Charles University Phaculty od Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Eliška Chvalkovská Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Consultant: Mgr. Martin Novák Title of thesis: Development of LC-MS method for determination of selected endocrine disruptors The thesis is focused on the development and optimization of LC-MS method for the determination of twelve endocrine disruptors in amniotic fluid of pregnant women in the third trimestr of pregnancy. There is a suspision that premature births are connected with an increased incidence of endocrine disruptors in amniotic fluid. The analytes were extracted by liquid-liqud extraction with 4-methylpentan-2- on. The analytical method is based on using reverse phase high-performance liquid chromatography with Hypersil C4 GOLD column (2.1 × 100 mm, particles 1.9 µm). For analysis the gradient elution with the mobile phase A (0.5% (v/v) formic acid aqueous solution) and B (0.5% (v/v) formic acid solution in acetonitrile) at a flow rate of 0.5 ml/min, injection 5 µl and column oven temperature 35 řC was used. The high- resolution mass spectrometer Orbitrap Q Exative Plus with atmospheric pressure chemical ionization in positive mode was used to identify and determine the response of...
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Structure and reactivity of anions of aromatic hydrocarbons
Obluková, Michaela ; Čabala, Radomír (advisor) ; Jašík, Juraj (referee)
This bachelor thesis deals with research about negative ions reactivity of aromatic hydrocarbons which occur in Titan's ionosphere - Saturn's moon. As an experimental method there was used tandem mass spectrometry with electrospray ionization technique, quadrupole mass analyzer and collision cell. The aim of this thesis was to contribute to the general understanding of processes in the Titan's ionosphere. Particularly there were performed experimental studies to created isomeric benzyne radical anions (o-, m-, p- C6H4˙- ) which were generated from phthalic, isophthalic and terephthalic acid and subsequently their reactions were explored with selected neutral gases in collision cell (C2H2, HC3N, CH3CN, SO2, O2).
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Metabolipidomic profiling of white adipose tissue by UPLC-MS/MS
Rombaldová, Martina ; Kuda, Ondřej (advisor) ; Šiklová, Michaela (referee) ; Čajka, Tomáš (referee)
Obesity is a serious problem in society today [1,2]. It might seems to have been caused simply by excess consumption of food compared to energy expenditure but obesity is actually a complex metabolic disorder centred on adipose lipid metabolism and cellular signalling systems linked to it [3]. Understanding the biology of adipose tissue (AT) is very important for the identification of novel and potential therapeutic targets in order to prevent and treat obesity-related disorders [4]. We utilized analytical approach liquid chromatography coupled to mass spectrometry (LC-MS) to study adipose tissue metabolism. Also, we were especially interested in the effect of omega-3 polyunsaturated fatty acids (PUFA) on that metabolism. Rodent and cell line experiments were performed and analyses were done of white adipose tissue (WAT), serum/plasma samples or cells as well as milk samples from mothers. At first, we established several ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods for analysis of acylcarnitines (AC), amino acids (AmA) and other metabolites. Importantly, these methods were able to distinguish isobaric species of AC which is not usually possible. Using these approaches we uncovered several acylcarnitines, i.e. long chain AC, carnitine, acylcarnitine C4 and...
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Detection of Sap2 in the secretome of Candida albicans cell wall and secretory mutants
Kollárová, Nikola ; Janďourek, Ondřej (advisor) ; Konečná, Klára (referee)
Candidate: Nikola Kollárová Title of diploma thesis: Detection of Sap2 in the secretome of Candida albicans cell wall and secretory mutants Charles University, Faculty of Pharmacy in Hradec Králové, Department of Biological and Medicinal Sciences Complutense University of Madrid, Faculty of Pharmacy, Department of Microbiology II Study program: Pharmacy Backgound: The aim of this diploma thesis was to search for C. albicans proteins involved in the secretion of the secreted aspartyl proteinase 2 enzyme (Sap2) evaluating the ability to degrade BSA (bovine serum albumin) as a source of nitrogen in several cell wall and secretory mutants of C. albicans. The work was carried out at the Department of Microbiology II, Faculty of Pharmacy, Complutense University of Madrid. Methods: The supernatant samples of several Candida albicans mutants were tested by SDS-PAGE electrophoresis and stained. Bands corresponding to BSA were observed and compared to controls. The other method was counted with 96-well plate. Results: The correlation between optical density and degradation of BSA was observed. Some mutants with disability to degrade BSA were found in a pilot screening of the ability to degrade BSA using 96-well plate method. That fact was confirmed by SDS-PAGE electrophoresis. C. albicans mutants showing...
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Targeted analysis and metabolism of fatty acids in mice and humans
Oseeva, Marina ; Kuda, Ondřej (advisor) ; Cahová, Monika (referee) ; Vrkoslav, Vladimír (referee)
Widespread sedentary lifestyle and unhealthy eating habits in the last few decades have resulted in a dramatic increase of the number of people affected by obesity, type 2 diabetes, and cardiovascular diseases. The study of these pathological conditions revealed that impaired metabolism often causes these disorders. Lipid metabolism research has contributed significantly to determining mechanisms underlying metabolic disorders. Omega-3 fatty acids are an interesting target for lipidomics studies because they were shown to lower risk of cardiovascular diseases and are hypothesized to regulate lipid metabolism. In this work, I optimized lipid extraction and chemical modification methods for analysis of fatty acids profile of tissue samples and biofluids using comprehensive two-dimensional gas chromatography coupled to mass spectrometry (GCxGC-MS). At first, I evaluated the relative amount of omega-3 fatty acids in red blood cells (Omega-3 index) of people living in Czech Republic in either the capital city (n=476) or the rural region (n=388). For this large-scale project, I extracted phospholipids from red blood cell (RBC) membranes, transesterified them into fatty acid methyl esters (FAMEs), and measured their profile by GCxGC-MS. The mean Omega-3 index was 3.56 mol % and I detected no significant...
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LC-MS/MS study of phase one in vitro biotransformation of potential drugs against Alzheimer's disease
Kuřátková, Aneta ; Kučera, Radim (advisor) ; Váňová, Nela (referee)
No treatment that would completely stop the progression of Alzheimer's disease has not been found yet. Recently used tacrine showed good results in the treatment of Alzheimer's disease, however long-term use led to chronic hepatotoxicity due to its metabolites. This master thesis deals with the compound 7-phenoxytacrine, one of the promising tacrine derivatives, which is one of the candidates for potential use in the therapy of Alzheimer's disease. Due to the formation of hepatotoxic metabolites of tacrine after the biotransformation in human liver, it appears necessary to identify the emerging metabolites of 7-phenoxytacrine molecule. Within this master's thesis in vitro biotransformation study of 7-phenoxytacrine using human liver microsomes was performed. High performance liquid chromatography with tandem mass spectrometry was used to determine the parent substance and the seventeen 7-phenoxytacrine metabolites. The analytical method showed the formation of six monohydroxylated and eleven dehydroxylated metabolites of 7-phenoxytacrine. Thus, we concluded that hydroxylation is the major metabolic reaction after in vitro microsomal biotransformation. In addition to the identification of metabolites, a quantification and microsomal stability study, including the determination of the amount of...
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Metabolipidomic profiling of white adipose tissue by UPLC-MS/MS
Rombaldová, Martina
Obesity is a serious problem in society today [1,2]. It might seems to have been caused simply by excess consumption of food compared to energy expenditure but obesity is actually a complex metabolic disorder centred on adipose lipid metabolism and cellular signalling systems linked to it [3]. Understanding the biology of adipose tissue (AT) is very important for the identification of novel and potential therapeutic targets in order to prevent and treat obesity-related disorders [4]. We utilized analytical approach liquid chromatography coupled to mass spectrometry (LC-MS) to study adipose tissue metabolism. Also, we were especially interested in the effect of omega-3 polyunsaturated fatty acids (PUFA) on that metabolism. Rodent and cell line experiments were performed and analyses were done of white adipose tissue (WAT), serum/plasma samples or cells as well as milk samples from mothers. At first, we established several ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods for analysis of acylcarnitines (AC), amino acids (AmA) and other metabolites. Importantly, these methods were able to distinguish isobaric species of AC which is not usually possible. Using these approaches we uncovered several acylcarnitines, i.e. long chain AC, carnitine, acylcarnitine C4 and...
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