|
|
Macrocyclic ligands and their complexes with metal ions for utilization in imaging methods
Hrček, Martin ; Hermann, Petr (advisor) ; Kotek, Jan (referee)
Currently, a number of methods, both diagnostic and therapeutic, find use in the field of nuclear medicine. The importance of macrocyclic ligands, capable of coordination of ions of employed metal radionuclides, is rising for both mentioned areas. Great potential lies in the area of the so-called theragnostics, i.e., drugs with both diagnostic and therapeutic functions. This thesis makes the first steps towards the concept of a theranostic ligand containing two macrocyclic coordinating centres, each individually optimised for coordinating radioisotopes of one metal ion. The coordination of Ga(III), currently used in diagnostics, is provided in the studied model system by a nine-membered macrocycle with phosphinate pendant arms. The coordination of Lu(III), currently used for radiotherapy, is provided by a twelve-membered macrocycle with phosphinate pendant arms. The results of the NMR measurements in this thesis show that the studied model system behaves in agreement with requirements placed upon the conceived drug. A macrocyclic ligand L1e, optimised for coordination of Lu(III), was prepared with the intended use in the synthesis of the proposed drug. H-phosphinic acids and a derivative of cyclene were also prepared as precursor compounds for a series of bifunctional ligands L1a - L1e. Keywords...
|
|
|
MRI contrast agents for modern applications
Kotková, Zuzana ; Hermann, Petr (advisor) ; Pinkas, Jiří (referee) ; Drahoš, Bohuslav (referee)
Zuzana Kotková - Ph.D. Thesis: MRI Contrast Agents for Modern Applications 1 Abstract Over the last few decades, Magnetic Resonance Imaging (MRI) has become one of the most powerful medicinal methods for the diagnosis of various diseases (Fig. A1a ). In several types of examinations, contrast agents (CAs) are used to increase the quality of images (Fig. A1b ). These contrast agents are usually based on paramagnetic metal complexes of macrocyclic ligands. In dependence on the measured nuclei, two basic groups of CAs are considered - 1 H MRI CAs and, recently, also 19 F "hot-spot" CAs. The 1 H MRI CAs are based on Gd3+ complexes of macrocyclic ligands with one water molecule coordinated to the central metal ion (Fig. A1c ) and the effect of the CAs is to shorten the relaxation times of water protons. (a) (b) (c) Fig. A1: Illustrative pictures for Magnetic Resonance Imaging (MRI) method; (a) whole body MRI tomograph,* (b) an example of MR head scans with the use of MRI CA** and (c) schematic general structure of a contrast agent based on Gd3+ complex of macrocyclic ligands (for more details see the Thesis, section 1.3.3, Fig. 18). * https://www.ottawaheart.ca/test-procedure/cardiac-mri (Accessed 25 Febr. 2023) ** https://affordablemri.com/mri-explained (Accessed 25 Febr. 2023) The shortening of relaxation...
|
|
|
Electrochemistry of macrocyclic complexes
Kaďorková, Veronika ; Liška, Alan (advisor) ; Kotek, Jan (referee)
The present thesis summarizes fundamental electrochemical properties of copper(II) complexes derived from three cyclame-like macrocyclic ligands. Target application of the studied complexes is radioimaging in medicine. The complexes were studied by means of DC-polarography and cyclic voltammery on mercury hanging drop electrode in buffered media (0.1M sodium acetate, pH 5) upon mixing of the ligand and copper(II) sulfate stock solutions. All three complexes undergo a single two-electron irreversible reduction process yielding free ligand and copper amalgam. The apparent thermodynamic stability of the investigated complexes (expressed as negative shift of the observed reduction potentials relatively to copper(II) sulfate) correlates to structural motifs employed in the individual ligand molecules. Presence of the bridged moiety as well as the carboxylate group seems to enhance the overall stability whereas the phenolic oxygen atoms in role of donor atoms seem to be less efficient.
|
|
|
Dynamics of paramagnetic complexes observed by Nuclear Magnetic Resonance
Blahut, Jan ; Hermann, Petr (advisor) ; Botta, Mauro (referee) ; Dračínský, Martin (referee)
In this Thesis, structure and dynamics of paramagnetic complexes for medical application are studied by Nuclear Magnetic Resonance (NMR). It focuses mainly on development of contrast agents (CA) for Magnetic Resonance Imaging (MRI) which is one of the most effective radiodiagnostic method nowadays. Most of the MRI CAs contains paramagnetic complexes of d- and f-metal ions. The presence of unpaired electron in proximity of NMR active nuclei has two main effects: paramagnetically induced shift and paramagnetically induced relaxa- tion. Both processes can dramatically change the NMR spectrum and often make it unobservable at all. Nevertheless, in many cases, acquisition of such spectra is possible and sometimes even less time-consuming than observation of diamag- netic molecules. Enhanced T1 relaxation allows faster pulse sequence repetition and increased chemical shift dispersion may lead to resolution of originally over- lapped signals. Moreover, the analysis of paramagnetic effects can provide useful information about the structure and dynamics of the studied system. Theoretical background of these effects is described in the Introduction of the Thesis. In the first part of Discussion in the Thesis, a new class of contrast agents for 19F-MRI based on nickel(II) and cobalt(II/III) ions is introduced...
|
|
|
Dynamics of paramagnetic complexes observed by Nuclear Magnetic Resonance
Blahut, Jan
In this Thesis, structure and dynamics of paramagnetic complexes for medical application are studied by Nuclear Magnetic Resonance (NMR). It focuses mainly on development of contrast agents (CA) for Magnetic Resonance Imaging (MRI) which is one of the most effective radiodiagnostic method nowadays. Most of the MRI CAs contains paramagnetic complexes of d- and f-metal ions. The presence of unpaired electron in proximity of NMR active nuclei has two main effects: paramagnetically induced shift and paramagnetically induced relaxa- tion. Both processes can dramatically change the NMR spectrum and often make it unobservable at all. Nevertheless, in many cases, acquisition of such spectra is possible and sometimes even less time-consuming than observation of diamag- netic molecules. Enhanced T1 relaxation allows faster pulse sequence repetition and increased chemical shift dispersion may lead to resolution of originally over- lapped signals. Moreover, the analysis of paramagnetic effects can provide useful information about the structure and dynamics of the studied system. Theoretical background of these effects is described in the Introduction of the Thesis. In the first part of Discussion in the Thesis, a new class of contrast agents for 19F-MRI based on nickel(II) and cobalt(II/III) ions is introduced...
|
|
|
Dynamics of paramagnetic complexes observed by Nuclear Magnetic Resonance
Blahut, Jan
In this Thesis, structure and dynamics of paramagnetic complexes for medical application are studied by Nuclear Magnetic Resonance (NMR). It focuses mainly on development of contrast agents (CA) for Magnetic Resonance Imaging (MRI) which is one of the most effective radiodiagnostic method nowadays. Most of the MRI CAs contains paramagnetic complexes of d- and f-metal ions. The presence of unpaired electron in proximity of NMR active nuclei has two main effects: paramagnetically induced shift and paramagnetically induced relaxa- tion. Both processes can dramatically change the NMR spectrum and often make it unobservable at all. Nevertheless, in many cases, acquisition of such spectra is possible and sometimes even less time-consuming than observation of diamag- netic molecules. Enhanced T1 relaxation allows faster pulse sequence repetition and increased chemical shift dispersion may lead to resolution of originally over- lapped signals. Moreover, the analysis of paramagnetic effects can provide useful information about the structure and dynamics of the studied system. Theoretical background of these effects is described in the Introduction of the Thesis. In the first part of Discussion in the Thesis, a new class of contrast agents for 19F-MRI based on nickel(II) and cobalt(II/III) ions is introduced...
|
|
|
Dynamics of paramagnetic complexes observed by Nuclear Magnetic Resonance
Blahut, Jan ; Hermann, Petr (advisor) ; Botta, Mauro (referee) ; Dračínský, Martin (referee)
In this Thesis, structure and dynamics of paramagnetic complexes for medical application are studied by Nuclear Magnetic Resonance (NMR). It focuses mainly on development of contrast agents (CA) for Magnetic Resonance Imaging (MRI) which is one of the most effective radiodiagnostic method nowadays. Most of the MRI CAs contains paramagnetic complexes of d- and f-metal ions. The presence of unpaired electron in proximity of NMR active nuclei has two main effects: paramagnetically induced shift and paramagnetically induced relaxa- tion. Both processes can dramatically change the NMR spectrum and often make it unobservable at all. Nevertheless, in many cases, acquisition of such spectra is possible and sometimes even less time-consuming than observation of diamag- netic molecules. Enhanced T1 relaxation allows faster pulse sequence repetition and increased chemical shift dispersion may lead to resolution of originally over- lapped signals. Moreover, the analysis of paramagnetic effects can provide useful information about the structure and dynamics of the studied system. Theoretical background of these effects is described in the Introduction of the Thesis. In the first part of Discussion in the Thesis, a new class of contrast agents for 19F-MRI based on nickel(II) and cobalt(II/III) ions is introduced...
|
|
|
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
|
|
|
Ligand systems for zirconium complexation
Hacaperková, Eliška ; Kubíček, Vojtěch (advisor) ; Vojtíšek, Pavel (referee)
The aim of this thesis is to synthesize new kind of macrocyclic ligands for complexation of Zr4+ . Zirconium(IV) complexes have potential as contrast agents in immuno-PET. Three macrocyclic ligands L1, L2 and L3 with dif- ferent pendant arms (HOPO, maltol, hydroxamate) were designed. Despite numerous attempts syntheses of L1 and L2 were unsuccessful. Ligand L3 was synthesized and the protonation constants were determined by poten- tiometric titration. Complexes [Zr4+ (L3)] were studied too. Catechol ligand L4 was prepared and complexes with cations Zn2+ , Ga3+ and Zr4+ were investigated. 1
|
|
|
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.
|
guest ::
