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Responsive Contrast Agents for Magnetic Resonance Imaging (MRI)
Krchová, Tereza
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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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 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 magnetic resonance imaging
Martinisková, Marie ; Kotek, Jan (advisor) ; Škoch, Karel (referee)
The aim of this bachelor thesis is to synthesize and study new kind of macrocyclic ligands for Ln3+ ions containing nuclei 19 F for using as possible contrast agents in 19 F magnetic resonance imaging. Prepared ligands were designed as analogues of already known ligands for Ln3+ ions, which are used in clinical practice. Both designed ligads were successfully prepared. Complexes [LnIII (dotptfe )]− were prepared and their structure in aqueous solution was predicted by NMR studies and luminiscence spectroscopy. T1 relaxation times of nuclei 19 F in complexes [LnIII (dotptfe )]− and ligand DOTPtfe were determined.
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New ligands for magnetic resonance imaging; pH-sensitive probes
Táborská, Zdeňka ; Kotek, Jan (advisor) ; Kubíček, Vojtěch (referee)
TÁBORSKÁ, Z. New ligands for magnetic resonance imaging; pH-sensitive probes. Prague: Charles University in Prague, Faculty of Science, Department of Inorganic Chemistry, 2011, 32 pages. Supervisor: doc. RNDr. Kotek J., Ph.D. Magnetic resonance imaging is a modern method used in diagnostic for assessing morphology and pathology of soft tissues. This thesis briefly outlines the principles of magnetic resonance imaging, including instrumentation. In many cases intravenously administered contrast agents are used, which are used for diagnostic purposes. At present, the most applied are CAs based on Gd(III) complexes. The experimental part of the thesis is focused on preparation of a derivative of DTPA with aminomethylphosphinate pendant group for using as a potential ligand for CAs for the magnetic resonance imaging. KEYWORDS: magnetic resonance imaging, contrast agents, lanthanides, phosphinates
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Macrobicyclic ligands for use in MRI
Pniok, Miroslav ; Kotek, Jan (advisor) ; Veselý, Jan (referee)
4 Title: Macrobicyclic ligands for use in MRI Author: Bc. Miroslav Pniok Department: Department of Inorganic Chemistry, Faculty of Science Supervisor: doc. RNDr. Jan Kotek, Ph.D. Supervisor's e-mail address: modrej@natur.cuni.cz Abstract: The aim of this project is to synthesize new kind of macrobicyclic ligands for Ln3+ ions, especially Gd3+ ion. Gadolinium(III) complexes are widely used in the clinical practice as contrast agents for MR imaging and an improvement of their properties is in the center of interest of many scientific teams. The macrobicyclic ligands have been designed to make possible coordination of two water molecules in the first coordination sphere with fast water exchange. The macrocyclic core (cyclen) is combined with a linking phosphinate chain in N1 ,N4 - and N1 ,N7 -positions forming a cryptand-like structure. The N1 ,N7 -isomer Et2L1 was synthesized in a small amount so only the N1 ,N4 -isomer H2L3 has been studied. The protonation constants have been determined by pH 31 P NMR titration. Keywords: cyclen, chelating agent, cryptand, MRI, phosphinate
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New ligands for applications in medicine
Holá, Kateřina ; Holzhauser, Petr (referee) ; Kotek, Jan (advisor)
The aim of this Thesis was the preparation of macrocyclic ligands (Figure 1) for the complexation of lantanoides 3+ . Their complexes can be used in nuclear medicine (in case of ligand L1) or as MRI contrast agents (in case of ligand L2). Ligand L1 was designed to increase the rate of complexation due to the weakly binding pendant group based on iminodiacetic acid (IDA). The complexation mechanism was spectrophotometrically studied with Ce3+ . Spectrophotometric kinetic measurements proved that ligand L1 not only shown no improvement in the complexation rate but its complexation is rather noticeable slowed. Ligand L2 contains amino group whose protonization/coordination could be influenced by pH or temperature. It can be utilized in determination of physical status of different tissues. However, it is difficult to obtain the ligand L2 in sufficient purity for further studies N N NN COOHHOOC HOOC N COOH COOH P OH O L1 N N NN COOHHOOC HOOC NH2 L2 Figure 1: Ligands prepared in course of this Bc Thesis
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Plasmid DNAs interactions with lanthanoide compounds
Budko, Kateryna ; Horák, Daniel (referee) ; Rittich, Bohuslav (advisor)
Recently much attention is given to lanthanides and their complexes as excellent catalysts for cleavage of nucleic acids. The thesis has been focused on the cleavage of plasmid and bacterial DNA by ions Nd3+ and Y3+ and by different carriers containing the lanthanide compounds. The creation of single-stranded nicks and double-stranded ones in the plasmid DNA molecules was studied by agarose gel electrophoresis. Verification of the cleavage of bacterial DNA was made by polymerase chain reaction using primers specific for the domain Bacteria and genus and species-specific primers. The results will be used in the development of the method that will allow perfect carriers`s coverage verification with the magnetic perovskit nucleus and other carriers with the lanthanide compounds.
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Lanthanidocenes and their Precursors Synthesis
Koporecová, Zuzana ; Pilátová, Ivana (referee) ; Richtera, Lukáš (advisor)
The aim of this work is to summarize the issues spectroscopic techniques useful in organometallic and polymer synthesis, including sample preparation and interpretation of the data, with a focus on NMR spectroscopy, vibrational spectroscopy and X-ray structural analysis. Part of the work deals with the characteristics of lanthanides, lantanidocens and synthesis of some lantanidocene compounds. Next are in this thesis prepared special laboratory techniques, working with Schlenk vessels, glove box and a dry bag.
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