v angličtině Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Lucie Pohanová Supervisor: Assoc. Prof.. Přemysl Mladěnka, Pharm.D., Ph.D. Title of Thesis: Chelation of ferrous ions by xanthen-3-one derivatives Iron is an essential element important for proper function of cells. Imbalance of iron levels can lead to serious diseases. Since there is no excretory mechanism, the homeostasis is regulated at the level of absorption in the intestine. The iron overload, which leads to tissue damage due to catalysis of the formation of free radicals, occur because of genetic disorders such as hemochromatosis or owing to frequent administration of transfusions. Rational therapy for iron overload is the administration of the chelators. The aim of this study was to evaluate the ability of derivatives of 2,6,7- trihydroxyxanthen-3-one (synthesized at the University of Sarajevo - Dr. Durić) to chelate iron in 4 (patho) physiologically relevant pH conditions. The ferrozine spectrophotometric method was used to determine the degree of chelation. Measurements showed dependency of the chelating effect on pH: lowering pH resulted in the decrease of the effect. At pH 7.5, most of the substances showed 100% ferrous ion chelation in the stoichiometric ratio of 1...

The presented diploma thesis deals with a targeted modification of the structural properties of hydrogels, which is closely related to the application properties of these materials (eg transport). Due to the desired pharmacological applications of the use of these materials for targeted drug release, hydrogels based on chitosan and polyvinyl alcohol as substances with good biocompatibility were selected for the study. The combination of these polymers ensured swelling (controlled by the presence of chitosan) and viscoelastic (influenced by the presence of polyvinyl alcohol) properties, which were characterized by a wide range of analytical and physicochemical methods (swelling, tensile strength, rheology, atomic force microscopy or specific surface area, etc.). Information on structural properties played a crucial role not only for a detailed description of the studied materials in terms of whether the structural properties can be changed in a targeted manner, but also served as an explanation for the different release of the active substance diclofenac from the hydrogel matrix. With regard to the literature search, the effect of pH and crosslinking was chosen to modify the properties. From the measured results it was found that even a slight change in pH has an effect on the transport or release of the active substance. The results obtained in this work may be useful in the formation of hydrogel matrices with drugs depending on the intended medical applications.

The interaction between protein A and immunoglobulin G (IgG) was studied at a variety of pH values using a surface plasmon resonance (SPR) device, which provides real time kinetic data without labelling or molecular alteration. This study was carried out due to the large scale use of Protein A affinity chromatography for the purification of IgG for pharmaceutical purposes, and is one of the most costly steps in the purification process. The results produced were largely in line with those produced in previous literature with binding remaining strong between pH 7.4 and 5.0, although the association rate decreased as pH decreased. Below pH 5.0, the rate of IgG elution markedly increased, with pH 3.5 showing near full elution seconds after the association phase of the SPR interaction finished. Problems were encountered with non-specific binding between the SPR sensor chip and IgG occurring under a variety of conditions, requiring various remedies. However, no complete interactions were successfully carried out under pH 5.0, so the results obtained below this value were obtained by binding at pH 7.4 and then elution at the desired pH. The data showed binding behaviour that was most successfully explained by a three-site model, each with a binding ratio of 1:1. The binding ratio is questionable given that Protein A and IgG typically bind at a ratio of 1:2 but may be explained by the sites being independent of one another and thus no secondary attachment is observed. A variety of models were fitted to the data but only two- and three-site models fitted the experimental data, with the three-site model being a more accurate and robust fit across pH changes. A multiple site model seems intuitively correct given the six different binding sites that Protein A has for interaction with IgG. The models produced have potential applications in a larger model of Protein A affinity chromatography, although a number of additional factors would need to be taken into account, such as mass transfer effects and the IgG concentration gradient.

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The interaction between the main ions in aquaponics nutrient solutions affects chemical composition and availability of nutrients, and nutrient uptake by plant roots. This study determined the effect of pH on phosphorus (P) speciation and availability in an aquaponics nutrient solution and used Visual MINTEQ to simulate P species and P activity. In both experimental and simulated results, P availability decreased with increase in pH of aquaponics nutrient solutions. According to simulations, P binds to several cations leaving less free phosphate ions available in solution. High pH values resulted in the formation of insoluble calcium phosphate species. The study also demonstrated the importance of organic matter and alkalinity in keeping free phosphate ions in solution at high pH ranges. It is recommended though that pH in aquaponics systems is maintained at a 5.5-7.2 range for optimal availability and uptake by plants. (C) 2016 Elsevier Ltd. All rights reserved.