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Macrocycles and complexation of large metal cations
Faltejsek, Jan ; Hermann, Petr (advisor) ; Drahoš, Bohuslav (referee)
In the last years, radioisotopes of heavy elements from the bottom of the Periodic Table have been increasingly used in nuclear medicine with focus on alpha-therapy. These large metal ions demand ligands fulfilling their special requirements. Complexes of polyazamacrocyclic ligands have been used in radiomedicine for a long time as diagnostic and therapeutic agents. This work aims to con- tribute to understanding of coordination chemistry of large macrocycles toward large metal ions. Thus, this work deals with structural studies, formation and decomplexation kinetics of Ln(III)-H4pyta complexes employing X-ray solid-state and solution NMR/UV-Vis spectroscopic data. The H4pyta is a 18-membered hexaazamacrocycle formed by two pyridine units and four amine groups which are modified with four acetate pendant arms. In the solid state, several isomeric complexes were structu- rally characterized. Large Ln(III) ions form decacoordinated species with two and two acetates on each side of the macrocyclic N6-plane. Small Ln(III) binds the ligand in a nonadentate fashion with one pendant non-coordinated. In the middle of lanthanide series, both isomers were characterized for several Ln(III) ions. Formation of the complexes takes place in a three-step mechanism with fast formation of an out-of-cage intermediate...
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Ternary macrocyclic complexes of metals with fluoride anions
Kuncová, Lucie ; Kubíček, Vojtěch (advisor) ; Schulz, Jiří (referee)
The aim of this thesis was to synthesize three ligands derived from mackrocycle TACN, which were previously investigated in our laboratory group, and subsequently prepare gallium and aluminum complexes with these ligands for the study of coordination properties. The complexes were characterized by NMR, HPLC-MS and EA. For the complexes that were prepared, data on the ability to bind fluoride anions (i.e. the formation of ternary macrocyclic complexes) were measured using fluoride ion-selective electrode. Dissociation equilibria at pH = 8-10 were also studied for the complex [Ga(L1)] that had the highest percentage of bound fluorine anions (~ 95%).
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Lanthanide macrocyclic complexes with phosphonate/phosphinate pendant arms
Procházková, Soňa
Imaging methods have become an integral part of diagnostic and therapeutic procedures in current medicine. Contrast agents based on metal complexes are often used to improve the final image. Complexes contain radioisotopes in nuclear medicine and gadolinium(III) ion in MRI. These complexes have to show high kinetic and thermodynamic stability and their preparation must not be time consuming. H4DOTA and its derivatives are convenient type of ligand for the formation of stable complexes. This work has focused on phosphonate and phosphinate derivatives of the ligand H4DOTA. The studied compounds can be divided into ligands containing only methylphosphinate/phosphonate (H4DO3APH, H5DO3APOH) and ligands with a second coordination center (H6DO3APIDA, H5DO3APPIN, H4DO3APAM, H8DO3APBP a H7DOTAMBP). The work has examined the possibilities of influencing the way and rate of complexation under different conditions. In order to approach the preparation conditions of radio complexes, kinetics measurements were performed not only under the metal ions excess, but also under the ligand excess. The aim was to compare the results of both types of measurements, which often showed to be different. A mechanism for the formation of various types of intermediates formed during complexation has been proposed. The...
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Alluminium complexes for biomedical applications
Beranová, Tereza ; Kubíček, Vojtěch (advisor) ; Havlíček, David (referee)
The aim of this work was to prepare ligands of macrocycle TACN with aminophosphinate pendant arms. Two ligands were prepared and fully characterized. A complex of aluminium ion was synthesized with one of the ligand. The complex was used for studying a fluoride coordination by a fluoride ion selective electrode. Key words: macrocyclic complex, positron emission tomography, phosphinic acid
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TACN derivatives bearing aminophosphinate pendant arms
Beranová, Tereza ; Kubíček, Vojtěch (advisor) ; Němec, Ivan (referee)
The aim of this work was studying of the coordination properties of TACN macrocyclic derivatives with aminophosphinate pendant arms. Two ligands were prepared, one with two pendant arms NODPam and one with three pendant arms NOTPam. Because of degradation of ligand NODPam during its synthesis, only the ligand NOTPam was studied further. Acid-base properties of ligand and termodynamic stability of aluminium and gallium complexes were studied. Formation and disociation studies were performed with the complexes. Coordination of fluoride ions to aluminium complex was studied using ion selective fluoride electrode. Finally coordination of complex AlFx with ligand NOTPam was studied using 19F and 27Al NMR spectroscopy. Selected experiments were made also with ligand NOTA. Key words: macrocyclic complexes, positron emission tomography, phosphinic acids
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Lanthanide macrocyclic complexes with phosphonate/phosphinate pendant arms
Procházková, Soňa ; Kubíček, Vojtěch (advisor) ; Cígler, Petr (referee) ; Řezanka, Pavel (referee)
Imaging methods have become an integral part of diagnostic and therapeutic procedures in current medicine. Contrast agents based on metal complexes are often used to improve the final image. Complexes contain radioisotopes in nuclear medicine and gadolinium(III) ion in MRI. These complexes have to show high kinetic and thermodynamic stability and their preparation must not be time consuming. H4DOTA and its derivatives are convenient type of ligand for the formation of stable complexes. This work has focused on phosphonate and phosphinate derivatives of the ligand H4DOTA. The studied compounds can be divided into ligands containing only methylphosphinate/phosphonate (H4DO3APH, H5DO3APOH) and ligands with a second coordination center (H6DO3APIDA, H5DO3APPIN, H4DO3APAM, H8DO3APBP a H7DOTAMBP). The work has examined the possibilities of influencing the way and rate of complexation under different conditions. In order to approach the preparation conditions of radio complexes, kinetics measurements were performed not only under the metal ions excess, but also under the ligand excess. The aim was to compare the results of both types of measurements, which often showed to be different. A mechanism for the formation of various types of intermediates formed during complexation has been proposed. The...
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Complexes of macrocyclic ligands with phosphonate and phosphinate penant arms for molecular imaging
Pazderová, Lucia ; Kubíček, Vojtěch (advisor) ; Pinkas, Jiří (referee) ; Polášek, Miloslav (referee)
In an effort to increase the thermodynamic stability and the kinetic inertness of the complexes, the five new azamacrobicyclic ligands derived from TACN, cyclen, and cyclam have been prepared. The ligands were decorated with phosphinate or phosphonate pendant arms to maintain fast complexation. Since the ascending importance of targeted diagnostic and therapy, the bone-targeted non-bridged cyclam derivative with phosphinate-bis(phosphonate) pendant arm (H5TE1PBP) has also been synthesized. The ligands were studied with respect to their application. The bridged TACN (H2bpbtacn) and cyclen (H4bpbcen) ligands show high macrocyclic basicity (logK1 = 12.25 and 12.70, respectively). The thermodynamic stability of H2bpbtacn with Cu(II) ion is more than ten orders of magnitude lower than that of the NOTA ligand. The stability constants of H4bpbcen with Cu(II) and Zn(II) ions are comparable to those given for the DOTA. The stability of Ln(III)-bpbcen complexes is 7-10 orders of magnitude lower compared to DOTA complexes. For both ligands, the lower thermodynamic stability of the complexes is attributed to the high rigidity of the ligand structure. The bridged cyclam derivatives with phosphonate (H4TE2P), bis(phosphinate) (H4TE2bpin), or phosphinate (H2TE2PH) pendants are characterized by high stability of...
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Complexes of 1,4,7-triazacyclononane derivatives
Kubinec, Jan ; Kubíček, Vojtěch (advisor) ; Vojtíšek, Pavel (referee)
The aim of this thesis was to prepare monoamide of macrocycle H3NOTA, which was prepared by multiple step synthesis. Ligand was characterized by NMR, MS and X-ray difraction analysis. Acid-base properties were studied by potentiometric titrations. Four protonation constants pKa`s were found and these protonation constants are lower than pKa`s of H3NOTA. Coordination properties with selected metal ions from the first row of transition metal, metal ions of biological interest and with lithium ions were investigated by potentiometric titration. Stability constants show that monoethylamide derivative of macrocycle H3NOTA forms complexes with lower stability than diethylamide derivative of macrocycle H3NOTA. Stability constants for complexes which contains amide group are lower than for H3NOTA complexes. Kinetics of Ga3+ complexation was investigated at different pH by 71 Ga NMR. The rate constants of and half-lives of complexation were determined at pH = 1. The rate constant was higher and the half-life of complexation was shorter than for H3NOTA ligand. Key words: macrocyclic complexes, thermodynamic stability, formation kinetics, radiopharmaceutical
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Macrocyclic complexes with open coordination sphere
Jaroš, Adam ; Kubíček, Vojtěch (advisor) ; Gyepes, Róbert (referee)
The aim of this work was to synthesize and study acid-base and coordination properties of ligands bearing a neutral or negative charge on their pendant arms. Acid-base properties of two ligands and thermodynamic stability of their complexes with gallium, copper, and zinc ions were studied using potentiometry, UV-Vis and NMR. Solid state structure of one of the ligands and its complex with copper ion was studied using RTG structural analysis. Structure of complexes in solution was studied using methods of computational chemistry.
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Synthesis and coordination properties of TACN phosphinate derivatives
Kohúteková, Soňa ; Kubíček, Vojtěch (advisor) ; Gyepes, Róbert (referee)
The aim of this work is preparation and characterization of a ligand for a selective complexation of gallium (III). The ligand is a derivative of macrocycle NOTA with bis(phosphinic) pendant arm. Protonation constants and stability constants with copper (II), nickel (II), zinc (II) and gallium (III) cations were determined by potentiometric titrations. The ligand was also used for studying complexation kinetics with gallium (III) ions and might serve as a potential contrast agent for 68 Ga-PET.
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