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Determination of complexation constants of weak electrolyte analytes by Affinity capillary electrophroesis
Ansorge, Martin ; Šteflová, Jana (advisor) ; Ušelová, Kateřina (referee)
Capillary electrophoresis is not only excellent separation technique but it is often advantageously used for determination of physical-chemical parameters of compounds such as complexation constants of analyte and appropriate complexation agent. The most frequently used electrophoretic method for determination of complexation constants is affinity capillary electrophoresis. In the frame of this work the affinity capillary electrophoresis is used for determination of complexation constants of R and S enantiomers of flurbiprofen, particularly both its neutral and fully dissociated form with neutral β- cyclodextrin. For this purpose we utilized classical method introduced in literature, where complexation constants are determined at two pHs, where analyte is fully and partially dissociated, respectively. Simultaneously, the complexation constants were observed by the new method based on multidimensional nonlinear regression, where all data measured at different pHs and β-cyclodextrin concentrations were utilized for evaluation. Results show that classical method can be highly confusing, especially if unsuitable pH is chosen for determination of stability constants of neutral form of analyte. Multidimensional regression method provides substantially more reliable data but with higher error of estimate....
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Spectrophotometric determination of stability constants of cyclodextrin derivatives by phenolphthalein method
Haiklová, Simona ; Dian, Juraj (advisor) ; Červený, Václav (referee)
This bachelor thesis deals with the determination of stability constants of cyclodextrins and their derivatives in the formation of supramolecular complexes with phenolphthalein. Cyclodextrins - macrocyclic oligosaccharides - are characterized by the shape of a truncated cone, whose internal hydrophobic cavity can form, with suitable substances, host-guest inclusion complexes. The formation of these inclusion complexes is accompanied by a change of a number of physicochemical parameters of the included compounds. In this bachelor thesis, the change of optical absorption of phenolphthalein, which has characteristic violet color in the alkaline area, was studied during its interaction with selected CD macrocycles. The formation of a supramolecular complex resulted in a decrease in optical absorption, which was quantified and used to determine stability constant. In the bachelor thesis, the supramolecular interaction of phenolphthalein with six derivatives of cyclodextrins were studied - basic cyclodextrins β-CD a γ-CD and their two derivatives. In the selected derivatives of these CDs the -OH groups in positions 2, 3, and 6 were replaced either by hydroxypropyl groups (hydroxypropyl-β-CD and hydroxypropyl-γ- CD) or (randomly) by methyl groups (RaMe-β-CD and RaMe-γ-CD). For these CD derivatives, the...
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Cyclodextrin-drug conjugates equipped with targeting groups as anticancer agents
Lamačová, Lucie Josefa ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
This diploma thesis deals with the synthesis of conjugates of cyclodextrin with the anticancer drug 5-fluorouracil and folic acid, which works as a targeting group. 5-Fluorouracil is connected to cyclodextrin via an acid-labile linker, which is expected to be cleaved in decreased pH in the proximity of malignant tissue or in the endosome. Malignant tissue also overexpresses receptor for folic acid, and this phenomenon is used for targeted delivery of therapeutic agents. Cyclodextrins are cyclic oligosaccharides, which are known for their ability to complex various compounds into their hydrophobic cavity and increase solubility, stability and bioavailability of these compounds. A synthetic approach for the preparation of conjugate of cyclodextrin with 5-fluorouracil and folic acid was designed and the conjugate was subsequently synthesized. Key words: cyclodextrin, fluorouracil, targeting group, folic acid, drug delivery
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Cyclodextrin derivatives containing covalently bound volatile substances and studies of their release
Palágyi, Attila ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
The main aim of the work was to prepare a series of β-cyclodextrin derivatives containing covalently bound volatile compounds via an imine bond. The used volatile compounds were cinnamaldehyde, cyclamen aldehyde, lilal, benzaldehyde, anisaldehyde, vanillin, hexanal, heptanal, citral and 5-methylfurfural. Subsequently, the rate of the release of the active compound, as a function of the environment, was studied by 1 H NMR spectroscopy and static headspace-gas chromatography. Key words: cyclodextrin, aldehyde, imine, kinetics, controlled release
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Cyclodextrin derivatives for construction of supramolecular dendrimers
Kouřilová, Ema ; Jindřich, Jindřich (advisor) ; Veselý, Jan (referee)
This bachelor thesis deals with the synthesis of derivatives of α-, β- and γ-cyclodextrins which are potentially usable for the supramolecular dendrimers construction. These dendrimers could be used in medicinal chemistry as carriers of drugs or in other areas of chemistry as well. Firstly, the tosyloxy group of mono-6-O-tosylates of cyclodextrins was substituted with cyanoarylphenolates and then the intermediate permethylated at the remaining hydroxy groups. As reactants for monosubstitutions, 4-hydroxybenzonitrile and 4'-hydroxy-[1,1'-biphenyl]-4-carbonitrile were chosen. The reagent used for permethylations was iodomethane. In the last phase, attempts to trimerize the cyano groups of the permethylated derivatives under basic and acidic conditions were made, but the wanted product was not obtained. Key words: cyclodextrin, monosubstitution, dendrimer, nitrile trimerization, supramolecular polymers
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Chiral and achiral separation using in-house coated β-cyclodextrin column, comparison with commercially available β-cyclodextrin column
Procházková, Hana ; Kalíková, Květa (advisor) ; Kozlík, Petr (referee)
The main aim of this work was to prepare a new chiral stationary phase by dynamic coating of an ion-exchange stationary phase by PEMPDA-β-cyclodextrin (N1 , N1 , N3 , N3 , N3 -pentamethylpropane-1,3-diamine-β-cyclodextrin) and to test column selectivity and separation abilities of the newly prepared sorbent for chiral and also achiral sets of analytes and to evaluate stability of the column. Commercial β- cyclodextrin stationary phase (Astec Cyclobond I 2000 column) was used for comparison. The set of chiral analytes contained five structurally different compounds - lorazepam, oxazepam, BNP, HDDP and Cl-HDDP. Six different groups of achiral analytes were used for testing the column selectivity. All measurements were carried out in reversed phase separation mode. Methanol and 10mM ammonium acetate (pH 4.00) were used as mobile phase constituents. Baseline separations of oxazepam enantiomers and five mixtures of achiral analytes were achieved with PEMPDA-β-cyclodextrin stationary phase. Partial separations of two chiral analytes (HDDP and Cl-HDDP) and one mixture of achiral analytes were obtained with this stationary phase. Enantiomers of BNP and oxazepam and four mixtures of achiral analytes were baseline separated on the Astec Cyclobond I 2000 column. Partial separations were obtained for the rest...
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Determination of complexation constants of weak electrolyte analytes by Affinity capillary electrophroesis
Ansorge, Martin ; Šteflová, Jana (advisor) ; Ušelová, Kateřina (referee)
Capillary electrophoresis is not only excellent separation technique but it is often advantageously used for determination of physical-chemical parameters of compounds such as complexation constants of analyte and appropriate complexation agent. The most frequently used electrophoretic method for determination of complexation constants is affinity capillary electrophoresis. In the frame of this work the affinity capillary electrophoresis is used for determination of complexation constants of R and S enantiomers of flurbiprofen, particularly both its neutral and fully dissociated form with neutral β- cyclodextrin. For this purpose we utilized classical method introduced in literature, where complexation constants are determined at two pHs, where analyte is fully and partially dissociated, respectively. Simultaneously, the complexation constants were observed by the new method based on multidimensional nonlinear regression, where all data measured at different pHs and β-cyclodextrin concentrations were utilized for evaluation. Results show that classical method can be highly confusing, especially if unsuitable pH is chosen for determination of stability constants of neutral form of analyte. Multidimensional regression method provides substantially more reliable data but with higher error of estimate....
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Enantioselective separation systems in capillary electrophoresis
Svobodová, Jana ; Gaš, Bohuslav (advisor) ; Foret, František (referee) ; Kenndler, Ernst (referee)
Chiral separation systems in capillary electrophoresis are in the scope of interest of many research groups all over the world. Therefore, the need to develop reliable theoretical models, which would help to explain phenomena connected with chiral separations or optimization of separation conditions, is obvious. In this thesis several mathematical models and approaches that can fulfill these requirements are presented. First part of the thesis deals with the determination of rate constants of interconversion of enantiomers by means of dynamic capillary electrophoresis. We focused on mixtures of chiral selectors and formulated a mathematical model, which enables to determine rate constants of interconversion in such systems. Mixtures of chiral selectors are very popular in separation practice due to their enhanced enantioselectivity. The theoretical model established in the thesis is able to explain the separation mechanisms of multi-chiral selector systems and to propose and verify possible ways of their optimization. In addition, the separation mechanism in systems with simultaneous cyclodextrin and borate complexation was revealed. Finally we present the complete mathematical model of electromigration in systems with complexation agents. The model is implemented into our simulation tool Simul 5...
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