Rhenium complexes coordinated with suitable organic ligand gain increased interest in radiopharmaceutical medicine. Besides suitable radiological properties given by a metal ion itself, detailed knowledge of overall chemical properties of formed complexes, namely their exact structures, chemical stabilities and possible degradation pathways are essential pre-requisites for their clinical application. Selected rhenium complexes with pyrogallol 2,3-dihydroxynaphthalene and catechol as strongly bound ligands were prepared by a reaction of tetrabutylammonium tetrachlorooxorhenate with twofold molar excess of ligand in presence of various amount of triethylamine. The structures of formed complexes and their consequent reaction products were estimated by means of mass spectrometry with electrospray ionization. The kinetics of reactions in course of complex formation and consequent decomposition were primarily followed by UV- Vis absorption spectra measurement, complemented by single or continuous electrospray mass spectrometry analyses. Optimized HPLC and CZE procedures were utilized for monitoring of the composition of reaction mixtures in course of Re complex formation and for purity check of prepared complexes. Semi-preparative HPLC mode was succesfully utilized for isolation and final purification of...

In recent years, copper radioisotopes have been extensively studied for their suitable coordination and physical properties. Nuclides 61 Cu, 64 Cu and 67 Cu are used in nuclear medicine - in diagnostic as well as in therapeutic applications. The aim of the Thesis is a study of the coordination properties of divalent copper as a stepping stone for the next potential applications. The presented Thesis consists of two thematic parts. The first part deals with the synthesis of cyclam derivatives. Sixteen new macrocyclic ligands with different phosphorus acid coordinating pendant arms (phosphinate, phosphonate, germinal P-C-P) were prepared; an analogous ligand endowed by carboxylic acid pendant arm as well as tetramethylcyclam without coordinating arm were prepared for comparison. The influence of the nature of coordinating acid pendant arms on selectivity and on the rate of copper(II) complexation was studied in detail. The protonation constants of the free ligands and the stability constants of the complexes with selected transition metal ions were determined by potentiometric titrations and by 1 H and 31 P NMR spectroscopy. Kinetic properties - i.e. studies of the formation rate and kinetic inertness of the copper(II) complexes - were performed by UV-Vis spectroscopy. The formation kinetics of the selected...

This PhD thesis provides a commented set of four publications. These publications are focused on capillary electrophoresis, liquid chromatography, and UV/Vis spectrometry used to study complexes of rhenium with aromatic ligands. The methods of mass spectrometry with soft ionization techniques, 1 H and 13 C nuclear magnetic resonance, and infrared spectrometry were used for structural characterization of the individual complexes. The complexes were synthetized in reactions of the rhenium precursor tetrabutylammonium tetrachlorooxorhenate with the corresponding ligand under both aerobic and anaerobic conditions. In the course of the research, it was revealed that the prepared complexes (with Re in the oxidation number +V and +VI) are unstable and their oxidation numbers change to another more stable form (Re+VII ). Sub-projects which were successfully implemented during the research were as follows:  Design and successful realization of the process of synthesis of selected rhenium complexes with aromatic ligands 1,2-dihydroxybenzene, 1,2,3-trihydroxybenzene, and 2,3-dihydroxynaphthalene in reactions with and without air access, and their structural characterization by ESI-MS, APPI- MS, LDI-MS, ESI-MS/MS, NMR, and IR.  ESI-MS SRM and UV/Vis time studies of the behaviour of primary rhenium complexes...

The following monoethynylated N-benzylidene-2-hydroxyanilines were prepared: N-(4- ethynylbenzylidene)-2-hydroxyaniline, N-(3-ethynylbenzylidene)-2-hydroxyaniline, N-(4- ethynylbenzylidene)-2-hydroxy-5-nitroaniline and N-(3-ethynylbenzylidene)-2-hydroxy-5- nitroaniline, which differed in the position of the ethynyl group on the benzylidene ring and the substitution of the hydroxyaniline ring. Monoethynylated N-benzylidene-2- hydroxyanilines were used as the monomers for the chain-growth coordination homo- and copolymerization. The homopolymerization resulted in linear polyacetylene homopolymers with N-benzylidene-2-hydroxyaniline substituents. The copolymerization with multiethynylarene-type cross-linkers provided densely cross-linked copolymeric polyacetylene networks. The linear units of the networks carried N-benzylidene-2- hydroxyaniline substituents, the interconnection between the chains of the networks being realized by arene links. The texture parameters of the prepared networks significantly depended on the type of comonomers used. The highest specific surface area values (~530 m2 /g) were achieved with networks prepared by copolymerization of N-(4- ethynylbenzylidene)-2-hydroxyaniline or N-(3-ethynylbenzylidene)-2-hydroxyaniline,with 4,4'-diethynylbiphenyl used as a cross-linker. Selected...

Synthesis of cyclodextrin derivatives for practical applications Abstract The first part of this PhD thesis is focused on the synthesis of a series of monosubstituted tetraalkylammonium cyclodextrin (CD) derivatives. The emphasis was placed on the possible applicability of the synthetic process to multigram or even industrial scale. Monotosylation of the native cyclodextrins (-, -, -) on the primary side of the macrocycle afforded the starting materials. Derivatives with one cationic group were prepared by the reaction with aqueous trimethylamine. The reaction of the mono-Ts-CD with neat N,N,N'-trimethylethane-1,2-diamine or N,N,N'-trimethylpropane-1,3-diamine and subsequent methylation led to derivatives with the substituent bearing two cationic groups (PEMEDA- and PEMPDA-β-CD). Analogs bearing a moiety with three tetraalkylammonium sites were synthesized by reaction of mono-Ts-CD with bis(3-aminopropyl)amine with subsequent methylation. 1,3-Dipolar cycloaddition of mono-6- azido--CD with diaminoacetylenes followed by methylation led to analogs with a avariable distance of the charged substituent from the CD core. Majority of the presented reactions are straightforward, relatively high-yielding and the workup does not require chromatographic steps. The second part of the work is dealing with the...

Ondřej Zemek Organophosphorus derivatives for "click-chemistry" In this diploma thesis two new macrocyclic ligands were synthesized. They have DO3A moiety where metal (lanthanide) ion can be coordinated and terminal acetylenic or azide group connected through the phosphinic acid. Both terminal acetylenic and azide group should serve for connecting to another molecules or partitions by mean of "click chemistry" i.e. [1,3] copperI catalyzed dipolar cycloaddition between azide and acetylene. In this thesis two ligands, its complexes with some lanthanides as well as its precursors were prepared and characterized. Gd3+ complexes will be further used and studied for potential MRI contrast agents applications.

A new type of organometallic polymer networks with a covalent structure of cross-linked substituted polyacetylenes containing Cu2+ or Pd2+ ions (5 to 17 wt%) has been developed. The metal ions were complexed in the networks predominantly with two N-salicylideneaniline ligands covalently bound to two different network monomeric units. Due to the chosen method of complexation, the metal ions have actively participated (as knots of the network) in the formation of cross-linked architecture of the products. For the preparation of organometallic networks two independent methods were used: (i) the direct polymerization of organometallic monomers and (ii) the two-stage method using postpolymerization introduction of metal ions into polyacetylene polymers containing covalently bound N-salicylideneaniline proligands. The starting low-molecular-weight blocks used for the network synthesis were new substances prepared within the framework of the diploma thesis, namely monomers of the mono- and diethynylated N-salicylideneanilines type and diethynylated organometallic monomers in which two molecules of a monoethynylated N-salicylideneaniline complexed one Mt2+ ion. The ethynylated monomers were polymerized to organometallic networks or precursors of these networks via chain-growth coordination polymerization,...

The thesis is focused on the synthesis and characterization of novel Mn2+ complexes as alternative to Gd3+ chelates which are wide-spread contrast agents in Magnetic Resonance Imaging (MRI). In the perspective to find suitable chelators of Mn2+ , three groups of pentadentate ligands with different size of macrocylic cavity, different donor atoms and number of pendant arms containing various functional groups have been investigated. Coordination numbers of 6 or 7 were found in the crystal structure of the Mn2+ complexes enabling binding of one or two water molecules in the first coordination sphere. The direct water coordination causes a decrease in the complex stability and thus, the thermodynamic stability of investigated chelates is lower than that of polyaminocarboxylate complexes and their dissociation is very fast in comparison to [Mn(nota)] and [Mn(dota)]2- . The studied Mn2+ complexes do not undergo oxidation in air except for complexes with 12-membered ligands which are oxidized to Mn3+ species. The proton relaxivities of the bishydrated complexes are two times higher than those for monohydrated complexes and are comparable to those of commercial contrast agents based on Gd3+ complexes. Variable-temperature 17 O NMR data revealed that the water exchange varies from slow to intermediate or...

The main aim of this thesis was the development of conjugation of existing methods for analysis of arsenic-glutathione complexes (As-GS complexes) together with simple arsenic species (iAs, MMAs, DMAs) during simple run. The basic technique for analysis of As-GS complexes was the HPLC-ICP-MS method with a reverse phase separation column (C18). The separation problem of simple species has been overcome by extending of system by postcolumn hydride generation with cryotrapping system (HG-CT). The resulting HPLC/HG-CT-ICP-MS system provides a complex analysis of all the above-mentioned analytes. According to the currently available resources, it is an innovative system, where for the first time all the simple arsenic species (iAs, MMAs, DMAs) and the As-GS complexes were separated. Under the given conditions, the detection limit for the As-GS complexes of 1.9 pg cm-3 in the RP-HPLC-ICP-MS system (a quantification limit of 6.5 pg cm-3 ) was achieved at a sensitivity of 468 CPS s pg-1 . The HG-CT-ICP-MS system provided a detection limit for iAs of 1.2 pg cm-3 at a sensitivity of 1121 CPS s pg-1 , for MMAs of 0.043 pg cm-3 at a sensitivity of 895 CPS s pg-1 and for DMAs of 0.076 pg.cm-3 at a sensitivity of 926 CPS s pg-1 . This method was applied to achieve another aim, studying the pathways of enzymatic...

- 8 - ABSTRACT (EN) The thesis is submitted as a commented set of reviewed publications documenting and depicting the possibilities of mass spectrometry in the field of chemical, biological and pharmaceutical research; namely for the purposes of structure elucidation of selected organometallic complexes, analyses of drugs and their metabolites, monitoring of important biological markers. In course of experimental work, the following objectives were studied and solved:  Proposal and realization of micro-scale preparation of selected rhenium complexes with aromatic ligands, utilizing tetrabutyammonium tetrachlorooxorhenate as a starting material; preparation and structure characterization of oxorhenium(V) complexes with 1,2-dihydroxybenzene, 1,2,3-trihydroxybenzene, and 2,3- dihydroxynaphtalene as ligands by means of ESI/MS, APPI/MS and LDI-MS; ESI/MS and UV/Vis study of kinetic behavior of complexes arising from the reaction of tetrabutylamonnium tetrachlooxorhenate with pyrogallol and catechol as ligands. Special aim was devoted to the study of subsequent chemical transformation of primarily formed Re(V) complexes; structure characterization of selected ferrocene complexes with copper, gold and silver by means of ESI/MS.  Proposal of methodology of structure characterization and quantification of the...