|
|
The influence of experimental conditions on chiral separation of borane clusters in capillary electrophoresis
Bodi, Adrián ; Kučera, Radim (advisor) ; Pilařová, Pavla (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of pharmaceutical chemistry and pharmaceutical analysis Candidate: Adrián Bodi Thesis supervisor: doc. PharmDr. Radim Kučera, Ph.D. Consultant: Mgr. Ondřej Horáček Title of thesis: The influence of experimental conditions on chiral separation of borane clusters in capillary electrophoresis Keywords: chiral separation, borane clusters, capillary electrophoresis, cyclodextrins Abstract: Boron compounds also include borane clusters, in which boron atoms form triangular configuration and 30 such sides are presented as a so-called cage. These clusters can be synthetically modified into various forms (open or closed) and can be substitued, for example by carbon atoms. This substitution can lead to the asymmetry of these molecules and thus to their chirality. Currently, their potential is also being studied in medicinal chemistry, where they could contribute to the design of new drugs. For instance, while they are been tested as HIV inhibitors, for boron neutron capture therapy, as CA IX inhibitors, they have also been suitable as part of hydrophobic pharmacophores in the design of drugs targetting the binding sites of various receptors. The task of this thesis is to test the influence of experimental conditions on the chiral separation of...
|
|
|
Quantification of the stabilizing effects of cyclodextrins on volatile biocides using spectral methods
Konovalova, Olga ; Jindřich, Jindřich (advisor) ; Smrček, Stanislav (referee)
This bachelor's thesis deals with monitoring the stability of chlorine dioxide of native and methylated cyclodextrins in the presence of hydrogenating agents. It is believed that using cyclodextrins and carboxymethylcellulose can improve the stability of chlorine dioxide and slow its release from the solution. UV spectroscopy was used to monitor any changes in absorbance over time and to determine the concentration of chlorine dioxide in the solution. When the rate of chlorine dioxide loss from solution was monitored, it was found that the presence of native and permethylated cyclodextrins slowed the loss of chlorine dioxide from solution, with the slowest decomposition observed in the presence of permethylated cyclodextrin. The addition of carboxymethylcellulose to the chlorine dioxide solution slows the rate of chlorine dioxide loss from the open vial the most, by almost three times, compared to ClO2 itself. This study's results can help optimize chlorine dioxide product formulation for various applications and contribute to the development of more stable and effective chlorine dioxide- based products that can be used to control or eliminate harmful microorganisms in different environments. Key words: chlorine dioxide, CDS, cyclodextrins, carboxymethylcellulose, biocides, UV-Vis...
|
|
|
Development of a heterogeneous catalytic system using multiply charged cyclodextrins and proline-based organocatalysts
Zelený, Jan ; Jindřich, Jindřich (advisor) ; Baszczyňski, Ondřej (referee)
Cyclodextrins are a class of organic molecules consisting of a cyclic system of α(1→4) linked glucose units. These compounds possess a range of interesting properties and can be derivatised to suit various industrial and scientific purposes. Among their derivatives are so- called multiply charged cyclodextrins, the development and application of which is an essential part of our group's research interest. These cyclodextrin derivatives are capable of binding electrostatically to different solid sorbents, such as silicagel or alumina. This electrostatic interaction is mediated by an array of permanently positively charged moieties which are covalently attached to the primary rim of a cyclodextrin unit. The free secondary rim then offers the possibility of further derivatisation and functionalisation of this system. The resultant cyclodextrin derivative represents a modular scaffold which can be used to immobilise different functional components. This project focuses on the application of this system to the immobilisation of a Hayashi- Jørgensen-type catalyst for the purposes of heterogeneous catalysis. The work includes the assembly of the of the chosen catalytic system from its precursors and also the synthesis thereof. Furthermore, the resulting supramolecular system is tested for its catalytic...
|
|
|
Synthesis of sulphanylaminoderivatives of cyclodextrines and computational simulations of their complexes formation
Provazníková, Adéla ; Jindřich, Jindřich (advisor) ; Míšek, Jiří (referee)
This master thesis deals with synthesis of 6I -N-monosubstituted β-CD bearing a linear spacer of various lenghts containing disulfidic bond and terminated by amine. Whole series was succesfully prepared by nucleophilic substitution of toluenesulfonyl group on tosyl β-CD by a spacer's amine group. In case of the shortest spacer (cystamine) 35 % yield was achieved. Synthesis of β-CD derivatives using longer and more lipophilic spacer derived from di-, tri- and tetraethylenglycol yielded 66 to 85 %. The oligoethylene spacers were prepared by standard chemical modifications. A separation method using n-butanol elution mixtures was optimized for isolation of β-CD derivatives. To better understand the β-CD derivative behavior in solution, molecular dynamics (MD) computations were used. The synthetized species were intended to be used for fluorescent sensor construction. For the same reason the inclusion of small organic molecules in β-CD cavity was studied with molecular dynamic simulations. MD method for computation of relative binding energy was optimized and gave values of right sign and order of magnitude.
|
|
|
Selectively substituted cyclodextrins for analytical and pharmaceutical applications
Benkovics, Gábor ; Jindřich, Jindřich (advisor) ; Lhoták, Pavel (referee) ; Šindelář, Vladimír (referee)
3 Selectively substituted cyclodextrins for analytical and pharmaceutical applications Abstract This thesis is focused on the selective modification of cyclodextrins, and its primary aim is the preparation and characterization of mono- and persubstituted derivatives of cyclodextrins in a regioselective and straightforward manner. The work is divided into two main parts describing synthetic strategies and applications of modified cyclodextrins with one or several substituents, respectively. The first section deals with the introduction of a single chromophoric moiety on the cyclodextrin scaffold such as cinnamyl, rhodaminyl, fluoresceinyl and eosinyl groups. The complete set of monocinnamyl-α-cyclodextrin regioisomers has been prepared by direct alkylation, and the self-assembling properties of the corresponding regioisomers were thoroughly investigated by dynamic light scattering and NMR experiments. These investigations revealed that the different isomers (mono-6-O-, mono-2-O- and mono-3-O- cinnamyl-α-cyclodextrin) form distinct supramolecular species through intermolecular association. A fast method for the unambiguous identification of the pure regioisomers has also been developed based on a series of 2D NMR measurements. Xanthene-modified β-cyclodextrins, other representatives of monosubstituted...
|
|
|
Synthesis of beta-cyclodextrin derivatives for medicinal applications
Popr, Martin ; Jindřich, Jindřich (advisor) ; Veselý, Jan (referee)
Synthesis of monosubstituted β-cyclodextrin derivatives for medicinal applications Abstract This thesis is focused on preparation of a set of β-cyclodextrin derivatives with potential use as scaffolds for a construction of novel MRI contrast agents. Firstly, the skeleton of native β-CD was selectively persubstituted at possitions 6 and equipped with azide functions. Per-6-azido-β-CD was then monosubstituted on secondary face of the macrocycle. (E)-cinnamylbromide and propargylbromide were chosen as suitable reagents. The monosubstitution reaction afforded two types of regioisomers, substituted at position 2I -O- or 3I -O-. These regioisomers were sucessfully separated via preparative column chromatography after peracetylation of all free hydroxyl groups. 2I -O-, 3I -O-formylmethyl- and 3I -O- karboxymethyl- analogues were prepared by oxidative transformation of cinnamyl group. Finally the usability of the formylmethyl- derivative for covalent binding with suitable substrate via reductive amination was confirmed. Keywords: cyclodextrins, monosubstitution, cinnamyl, propargyl, formylmethyl, carboxymethyl, reductive amination, MRI, contrast agents
|
|
|
Determination of stability constants of charged cyclodextrine complexes by capillary electrophoresis
Beneš, Martin ; Zusková, Iva (advisor) ; Dubský, Pavel (referee)
Martin Beneš Determination of stability constants of charged cyclodextrin comlexes by capillary electrophoresis Abstract Stability constant characterizes binding interaction between an analyte and complexation agent. These interactions play very important role in separation processes of, in other way undistinguishable, compounds, e.g. enantiomers. The most widely used complexation agents are cyclodextrins. Affinity capillary electrophoresis (ACE) belongs to methods suitable for the determination of stability constants. The stability constant is determined from the dependence of the effective mobility of analyte on the increasing concentration of complexation agent in background electrolyte (BGE). If charged CDs are used, the attention must be paid not only to viscosity of the BGE and to the influence of Joule heating on the temperature in the capillary but also to the increasing ionic strength. The thermodynamic stability constants of R,R- and S,S-hydrobenzoin and R- and S-(3-brom- 2-methyl-1-propanol) with cationic modified β-cyclodextrin: 6-monodeoxy-6-mono(3- hydroxy)propylamino-β-cyclodextrin hydrochlorid (PABCD) were determined by affinity capillary electrophoresis. The average temperature (25řC) of the BGE in the capillary was kept constant. This was achieved by decreasing of the cassette temperature...
|
|
|
development of fluorosenzor based on chemically modified electroluminescence diods.
Blažková, Ivona ; Jelínek, Ivan (advisor) ; Dejmková, Hana (referee)
Luminescence sensors based on LED were prepared by modification of LED poly- carbonate surface and following binding of luminescence dyes on this surface. Two methods of modification were utilized. The first one was the oxidation of the surface yielding free carboxylic groups. Such modified LEDs were then covered by cationic cresyl violet dye. The second modification consisted of nitration and consequent reduction to free amino groups followed by binding of anionic sulforhodamine dye. The stability of emission and the stability of dye binding were studied. Then, the response of constructed sensors to toluene as analyte in gas and liquid phase was measured.
|
|
|
Carborane structural blocks in medicinal chemistry
Nekvinda, Jan ; Grüner, Bohumír (advisor) ; Machara, Aleš (referee) ; Janoušek, Zbyněk (referee)
This work deals with carborane and metallacarborane clusters, in terms of their fundamental chemistry and complexation with cyclodextrins, and in the context of emerging pharmacophores applicable in medicinal chemistry. Arguably, the most important part of this work is the preparation of cobalt bis(dicarbollide) sulfamide derivatives. The sulfamido group is attached to the metallacarborane carbon vertex by an alkyl chain that may be modified in its length. This was accomplished by, firstly, the abstraction of the acidic hydrogen, located on the {CH}-vertex from the metallacarborane, by reaction with lithium base, followed by, secondly, reaction with electrophilic agents (PFA, oxirane and oxetane), which leads to a cascade of reactions to give the desired sulfamide derivatives. These compounds were then tested by collaborators in other institutes for in vitro and in vivo activity towards Carbonic Anhydrase IX (CA IX), which is an enzyme associated with tumour growth. In vivo tests on mice have shown that these types of substances are able to effectively reduce tumour size by 30%. The synthetic research continued with the preparation of sulfonamide compounds of the isomers of the carborane series. The reactions began exclusively with propylhydroxy carborane starting materials, which provide optimum...
|
|
|
Synthesis of cyclodextrin derivatives for organocatalysis
Chena Tichá, Iveta
Synthesis of cyclodextrin derivatives for organocatalysis This doctoral thesis examines the preparation of new cyclodextrin (CD) derivatives suitable for organocatalysis. The aim of this work is to prepare monosubstituted and disubstituted CD derivatives as organocatalysts for different types of enantioselective reactions potentially performed in water. In addition, disubstituted CD derivatives require considering the potential mixture of regioisomers and pseudoenantiomers. Thus, this thesis is divided into several sections - preparation of CD precursors and derivatives for organocatalysis, preparation of pure regioisomers and pseudoenantiomers of disubstituted CDs and final application of CD derivatives in enantioselective reactions. Furthermore, this thesis also focuses on the molecular modeling of the prepared CD derivatives and on their catalytic activity in silico. The first section covers the preparation of new disubstituted CD precursors as pure regioisomers for organocatalysts, specifically to develop a new method for the preparation of heterodisubstituted AC regioisomers on the primary rim of α-CD. This section also includes the determination of the regioisomer ratios of common α-CD intermediates disubstituted on the primary rim to evaluate their potential as precursors in organocatalysis....
|
guest ::
