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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 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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Methods of insect body and food marking and their utilization in bees (Anthophila)
Macháčková, Lenka ; Straka, Jakub (advisor) ; Bogusch, Petr (referee) ; Hanus, Robert (referee)
Marking methods represent often an essential part of many studies which target on insect biology. These marking techniques sometimes represent the only possible way to obtain new and important informations. In the first part of the thesis I deal with individual insect labeling, which was used for marking of solitary bees and their nests as a tool of obtaining informations about nesting bee dynamics in aggregation. Our study show that nest owner replacements are very common in all four species. However, a large percentage of the nests were abandoned by the female owners before owner change. Only a part of all the nests were trully usurped on the nesting site. The true usurpations thus represent rather minor part of observed nest owner replacement situations. The bees surprisingly often abandon their nests and found the new ones. The frequent contacts of the females on a nesting site occur as a result of common nest owner replacements. High tolerance of bees to each other together with tolerance of usurpations and low level of aggression may thus represent one of the possible ways towards communality and other types of social behaviour. In the second part of the thesis I focus on the possibilities of food marking in bees. Effectivity of sugar and pollen utilization are not yet fully understood in...
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Synthesis of unsymmetric DOTA derivatives and study of their complexes
Obuch, Jakub ; Hermann, Petr (advisor) ; Drahoš, Bohuslav (referee)
Lanthanide(III) complexes are compounds with both diagnostic and therapeutic applications. For diagnostic applications, they are used as contrast agents for imaging techniques such as MRI, PET or SPECT. In therapy, complexes of beta or alpha particle- emitting radionuclides are used. If the complexes contain protonable groups, their behaviour is dependent on pH of the solution. Protonation of these groups should occur close to the physiological pH. If the efficiency (relaxivity) of the MRI contrast agent is dependent on protonation state, this method can be used for determination of pH of tissues in vivo. For radiopharmaceuticals, fast complexation of short-lived metal radionuclides is important and protonation might significantly accelerate the complex formation. For therapeutic applications, possibility of labelling at low temperatures when heat-sensitive biovectors (e.g. antibodies) do not decompose. To assess the effect of protonation of amino group in the vicinity of the metal ion, amino-bis(phosphinate) pendant arm was proposed, where the dissociation constant of the amino group below the physiological pH can be expected. Three ligands containing this group and DO3A fragment were prepared and their complexes were studied to assess aforementioned possible uses in medicine. Their structure and...
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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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Lanthanide complexes of DOTA-"trans"-diamide
Obuch, Jakub ; Hermann, Petr (advisor) ; Kotek, Jan (referee)
Macrocyclic complexes are of great interest due to their utilization in many medic- inal applications, such as MRI contrast agents and radiopharmaceuticals. These com- plexes overcome the toxicity of free heavy metal ions and, thus, enable their use in vivo. In this Thesis, diamide derivative of DOTA (tDODAM) and its lanthanide(III) complexes were prepared and characterised in solution and in the solid state. For cerium(III) com- plex, formation and dissociation kinetics were studied. Structure and dynamics of eu- ropium(III) complex were investigated by multinuclear NMR spectroscopy and various 2D NMR techniques. Similarly to Ln(III)-DOTA complexes, the complexes form square- antiprismatic (SA) and twisted-square-antiprismatic (TSA) isomers and their ratio in solution was determined across the lanthanide series. Structures of 7 lanthanide(III) complexes in the solid state were determined. Thermodynamic data were obtained for Cu(II), Zn(II), Pb(II), Ce(III), Eu(III) and Lu(III) complexes by potentiometric titration. 1
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17O NMR study of LnIIIcomplexes of H4do3apOEt ligand
Svítok, Adam ; Hermann, Petr (advisor) ; Dračínský, Martin (referee)
Macrocyclic complexes of H4dota-like ligands are used in various fields, mainly in medicine. e. g. as MRI contrast agents or luminescent probes. Their applications are greatly influenced by stereochemistry. Stereoisomers of these complexes mostly interconvert with each other in solution. This interconversion can be studied by NMR spectroscopy This work is intended to test 17 O NMR spectroscopy as a tool for monitoring dynamic processes where phosphonate group in the complexes of methylphosphonate derivatives of H4dota is involved. To this end, ligand H4do3apOEt and his LnIII -complexes (Ln ≠ Pm) containing 17 O-labeled phosphonate group were synthesized. Next, 17 O NMR spectra of these complexes were measured and analysed. In an analogy with H4dota complexes, signals of both non-coordinated and coordinated oxygen atoms (except GdIII ) in the complexes could be detected. Fraction of TSA (twisted square-antiprism) and SA (square-antiprism) isomers was determined from the acquired 17 O NMR spectrum for each complex. The determined values were compared with those obtained by analysing 1 H and 31 P NMR spectra of the complexes, which were also measured. The TbIII , DyIII and YbIII complexes (because of high resolution of their 17 O NMR spectra) and CeIII complex (because of anomalous properties of its...
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Evaluation of negative stains for single particle analysis in electron microscopy
ĎURINOVÁ, Eva
Four negative stains, hafnium chloride and europium, samarium and gadolinium nitrates, were tested in single particle electron microscopy as potential alternatives to uranyl acetate, which is recently being widely restricted for its toxicity. The new stains were applied to a structurally well-described plant photosystem I, visualized by a transmission electron microscope and classified in a single particle analysis. The quality of the stains was evaluated by the obtained resolution and ability to provide reliable structural information.
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