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Macrocyclic ligands and their complexes
Buziková, Michaela ; Hermann, Petr (advisor) ; Kotek, Jan (referee)
Macrocyclic ligands are very efficient agents for complexation of paramagnetic metal ions in complexes possessing high kinetic inertness and thermodynamic stability. These properties are very useful for medical applications. The aim of this work is to prepare ligand cis- DO2A2P using a new synthetic approach. Cis-DO2A2P is the last ligand in the series of DOTA derivatives with mixed carboxylate and phosphonate pendant arms which does not have its complexes fully described. This thesis includes basic information known on the ligands from this series, about the structure and properties of their complexes, and synthesis of the cis-DO2A2P. Key words: macrocycles, polydentate ligands, lanthanides, transition metals, organophosphorus acids
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Responsive Contrast Agents for Magnetic Resonance Imaging (MRI)
Krchová, Tereza ; Kotek, Jan (advisor) ; Marek, Radek (referee) ; Platas-Iglesias, Carlos (referee)
ABSTRACT This work is focused on the synthesis of a family of new macrocyclic ligands with exchangeable protons on coordinating groups that could potentially serve (after complexation with suitable paramagnetic lanthanide(III) ions) as responsive contrast agents (CAs) for magnetic resonance imaging (MRI). It is expected that measurement of extracellular pH should bring information for tumorous disease diagnoses and/or for suggesting the most efficient treatment. Therefore, our attention was focused on pH-dependent CAs based on a PARAmagnetic Chemical Exchange Saturation Transfer (PARACEST) mechanism capable of reporting pH changes in tissue. The PARACEST-related properties of a series of Ln(III) complexes with the CEST effect caused by amino groups coordinated to the central Ln(III) metal ions were investigated. Such a kind of PARACEST CA is new and has had no precedent in the literature. It was shown that these Ln(III) complexes produce a pH-sensitive PARACEST effect in the pH region relevant for living systems. The study brings proof-of-principle for utilization of complexes with a linear diamine pendant arm, i.e. complexes with two exchanging proton pools, for ratiometric pH determination by MRI independently on the probe concentration. In addition, to ensure a higher kinetic inertness of the...
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Contrast agents for 19F MRI
Koucký, Filip ; Kotek, Jan (advisor) ; Vojtíšek, Pavel (referee)
For 19 F MRI the fluorinated contrast agents should be endowed by short relaxation times. Paramagnetic metal ions make relaxation times shorter and this effect depends on the distance between the metal ion and 19 F nuclei. The aim of this thesis is the synthesis of suitable ligand containing fluorine atoms, and a preparation of its Ni2+ and Cu2+ complexes. Macrocyclic 1,4,8,11- tetraazacyclotetradecane (cyclam) was selected as a starting material as it has optimal ring-size for complexation of the selected ions. The parent macrocycle was substituted by fluorine-containing coordinating pendant arms. Key words: Cyclam; Contrast agents; Phosphonic acids, 19 F MRI, Paramagnetic relaxation, d-metals
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Contrast agents for 19F magnetic resonance imaging
Martinisková, Marie ; Kotek, Jan (advisor) ; Vojtíšek, Pavel (referee)
The aim of this Master Thesis is to synthesize and study new macrocyclic ligands containing fluorine atoms for use as potencial contrast agents in 19 F magnetic resonance imaging. New ligands were designed as analogues of ligands used in contrast agents already utilized in clinical practice - macrocyclic ligand for complexation of trivalent lanthanide ions based on DOTA skeleton and series of macrocyclic ligands for complexation of divalent nickel ion based on cyclam skeleton. All designed ligands were synthesized a characterized. The complexes [LnIII (dotptfe )]− were tested in vitro and in vivo to study 19 F NMR relaxation times enhancements.
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Contrast Agents for 19F-MRI
Špánek, Jiří ; Kotek, Jan (advisor) ; Hrubý, Martin (referee)
Noninvasive imaging methods, such as MRI, are one of the most used methods in today's medicine. New MRI techniques that are being developed focus on measuring 19 F nuclei or saturation transfer between 1 H nuclei signals of contrast agent (CA) and water molecule. For these purposes, it is advantageous to use complexes of paramagnetic metal ions, whose magnetic properties cause increased rate of relaxation and thus reducing acquisition time. In this bachelor thesis two new ligands L1 and L2 are prepared, whose complexes with metal ions, such as Cu2+ and Ni2+ , could find a potencial use as CAs in methods mentioned above.
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Design and synthesis of ligands for selective copper(II) separation
Beliš, Marek ; Kotek, Jan (advisor) ; Smrček, Stanislav (referee)
Radioisotopes of copper are used in nuclear medicine for their physical properties. One step in process of preparing copper-containing radiopharmaceuticals is separation of copper radionuclides from other elements, especially zinc and nickel. The target of this Thesis is preparation of ligands based on linear tetraamine skeleton, which should be able of selective complexation and decomplexation of copper depending on pH of the solution. The Thesis contains synthesis of ligands, their NMR study and measurement of dissociation kinetics of their Cu-complexes. Powered by TCPDF (www.tcpdf.org)
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MRI contrast agents for angiography
Urbanovský, Peter ; Kotek, Jan (advisor) ; Vojtíšek, Pavel (referee)
Modern diagnostic method magnetic resonance imaging (MRI) usually uses contrast agents T1-type, which are based on Gd3+ complexes. Due to severe toxicity of free Gd3+ , it is desired to have thermodynamically stable and kinetically inert complexes with fast elimination from the body. This work summarizes information about a novel contrast agent based on ligand DO3AP (1,4,7,10-tetraazacyclododecane-1-methyl(alkyl)phosphinic-4,7,10- triacetic acid) with pendant hydrophobic dibenzylamino group which is able to interact hydrophobically with the macromolecule of serum albumin. The stability of supracomplex is dependent on pH value, i.e. on the protonation of the pendant amino group of the complex (pKA = 5.6) and this interaction was confirmed from 1 H-NMRD profile and fluorescent analysis. The compound was tested for its angiographic properties in vivo on rat model. Furthermore, other complexes of the ligand with trivalent lanthanides (Nd3+ , Eu3+ , Tb3+ , Dy3+ , Er3+ ) were characterized by various methods (XRD, luminescence, UV-VIS, 1 H-, 17 O- and 31 P-NMR). The cleavage of the benzyl groups affords ligand whose Ln3+ complexes possess pH dependent PARACEST effect. These complexes were characterized by XRD, luminescence and 1 H- and 31 P-NMR. Moreover, the novel ligands with modified length of pendant...
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Hydrosolubilization of BODIPY for optical labelling of biomolecules
Bartoň, Jan ; Kotek, Jan (advisor) ; Vrábel, Milan (referee)
1 Abstract This work aims at showing synthesis and potential use of water-soluble fluorescent probes based on BODIPY. The preparation of probes containing bioorthogonal mono- and heterobifunctional functional groups was demonstrated. Ground work was done at the optimisation of reliable, scalable and fast sulfonation of BODIPY in 2,6-positions. A protocol for handling sulfonated BODIPY has been established; especially for the exchange of counterions. In counterion se- lection, their relation to synthetic pathway and biocompatibility were taken into consideration. The second part of the work shows series of water-soluble fluorescent probes, into which can be easily introduced bioactive or bioorthogonal functional groups. This can be used for click chemistry in connection with turn off/on probes or fluorescent sensing of molecules or ions. All this can be done in aqueous solution without organic solvents, which is relevant for biochemical, analytical and imaging applications. Keywords BODIPY, bifunctional, water-soluble, fluorescent probe, solubilization, biocompa- tible probes, bioorthogonal reaction, BODIPY sulfonation
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