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Ditopic ligand based on 1,4,7-triazacyclononane
Kačmarčík, Jaroslav ; Kubíček, Vojtěch (advisor) ; Kotek, Jan (referee)
The radioisotopes 64 Cu and 68 Ga are used in radiomedicine and imaging (PET) due to their properties. The metal ion must be complexed with a suitable ligand forming a stable and kinetically inert complex. The aim of this bachelor thesis was to synthesize polydentate ligand based on the TACN macrocycle, followed by the preparation of its gallium (III) and copper (II) complexes. Based on the dependence of absorbance A on the wavelength λ, d-d transitions in the VIS (λ = 440 - 800 nm) region and CT transitions with transitions on the aromatic cycle in the UV region (λ = 220 - 380 nm) for the [Cu(L)] were also observed. The [Cu(L)] complex was studied by UV-VIS titration. The complex [Ga(L)] was also synthesized, but its further characterization and study of coordination properties were not carried out. Key words: macrocyclic ligands, complexes, stability, radiomedicine, PET
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Nanofiber membranes generating singlet oxygen with magnetic separation
Liška, Vojtěch ; Mosinger, Jiří (advisor) ; Kubíček, Vojtěch (referee)
This thesis focuses on the preparation and study of a new type of photoactive polyurethane nanofiber membrane with encapsulated 5,10,15,20-meso-tetraphenylporphyrin (TPP) photosensitizer and maghemite nanoparticles. The membrane was prepared by electrospinning and shows effective photogeneration of O2 (1 Δg) and photoantibacterial effect on the surface. The membrane can be easily separated by a magnetic field. The magnetic behaviour of the maghemite nanoparticles was studied using Mössbauer spectroscopy. Their size was estimated by DLS. The final nanofiber membrane was characterized by UV-VIS, emission spectroscopy, and by electronic microscopy (SEM). The kinetics of O2 (1 Δg) generation was studied by time-resolved spectroscopy and the relative efficiency of photooxidation was studied using external acceptor of O2 (1 Δg). Significant photoantibacterial properties against bacteria strain Escherichia coli were detected on the surface of the membrane functionalized with TPP photosensitizer.
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Zirconium ternary complexes with fluoride anions
Zach, Kamil - Lukáš ; Kubíček, Vojtěch (advisor) ; Schulz, Jiří (referee)
Modern medicine uses non-invasive imaging methods for diagnostic purposes. Positron emission tomography is one of them. During the examination, the patient is injected with a radiopharmaceutical that is accumulated in tissue abnormalities and emits detectable radiation during its nuclear decay. The world's most commonly used radionuclide for these purposes is the radioisotope 18 F. The biodistribution of the fluoride ion itself is not very specific, so the radioisotope is usually bound to the structure of bioactive molecules. The actual preparation of these molecules is very challenging, so new labeling methods are currently being sought. One of the new possibilities is the preparation of labeled ternary complexes. In this work, the preparation of two polyazamacrocyclic ligands, H3NOTA and H3PCTA, which have acetate arms attached to their skeleton via aliphatic nitrogen atoms, is described. Zirconium complexes were prepared with these ligands. Subsequently, coordination and dissociation studies of fluoride ions to the prepared complexes were carried out. The measurements were monitored with a fluoride ion selective electrode. Both kinetic and thermodynamic aspects of coordination and decoordination were investigated in the measurements. Furthermore, characterization of the prepared ternary...
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Synthesis of chelators for use in diagnostic imaging
Kretschmer, Jan ; Polášek, Miloslav (advisor) ; Kubíček, Vojtěch (referee) ; Hrubý, Martin (referee)
Metals play a crucial role in medicine as a part of therapeutic or diagnostic preparations. However, in the majority of cases, their properties cannot be utilized entirely in free ionic form. Organic molecules capable of chelation are used to open the full potential of the metal. The molecules are called chelators and are the core theme of this thesis. The most important function of these molecules is the chelation and coordination of the metal, but chelators can provide other important functionalities. This work, therefore, focuses on the design, synthesis, and application of such polyfunctional chelators and is divided into two parts: DO3A-Hyp This part of the thesis deals with chelators that can be used as amino acids to incorporate lanthanides into peptides. The developed chelators provide a short and rigid connection of the metal to the peptide chain. Tripeptides containing two units of such chelators with a central amino acid bearing a CF3 group were synthesized to demonstrate the capability of DO3A-Hyp building blocks. Two paramagnetic metals were combined within this tripeptide, and it was shown that such a rigid and locked system could be used for combining their magnetic susceptibility tensors. These magnetic susceptibility tensors were used for manipulation of the 19 F NMR shift of the CF3...
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Trivalent and tetravalent metal complexes for radiodiagnostics
Hacaperková, Eliška ; Kubíček, Vojtěch (advisor) ; Drahoš, Bohuslav (referee) ; Polášek, Miloslav (referee)
Fluorine-18 is the most utilized nucleus for positron emission tomography (PET). In 2009, incorporation of fluorine-18 to the coordination sphere of Al(III) was introduced as a new alternative for commonly employed compounds with F-C bond. Such a radiotracer consists of two parts: a metal complex with a fluoride and a peptide or a small/part of biomolecule. Shortly after that, first clinical studies showed a promising potential of such com- pounds for clinical use. Despite a great number of papers dealing with this issue, the research is mostly application-driven and focused on the peptide part of the molecule responsible for specific accumulation within the organism. Studies oriented on a sta- bility of metal-ligand-fluorine ternary system are rather rare and only very little is known about such a three-component system from a chemical point of view in gen- eral. However, stability of F-Al bond strongly dependents on the chemical structure of other ligands in the coordination sphere. Pendant arms of a hexadentate ligand (usually used for Al(III) complexation, e.g., H3NOTA) can compete with fluoride and cause its release which leads to unspecific radioactivity accumulation. Lower ligand denticity should increase the F-Al bond stability, but can decrease the stability of the whole complex at the...
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Complexes of 1,4,7-triazacyclononane phosphinate derivatives
Lebruška, Viktor ; Kubíček, Vojtěch (advisor) ; Štěpnička, Petr (referee)
Phosphorus pendant arms accelerate the complexation of gallium(III) ions with macrocyclic chelators, which is crucial parameter in labelling by the radioisotope 68 Ga and their use in positron emission tomography (PET). In this thesis, new chelators for the selective complexation of gallium(III) ions were designed. Two chelators derived from the TACN macrocycle were prepared, namely: 1,4,7-triazacyclononane-1-methyl-methylene- bis(phosphinic) acid (H2L1 ) and 1,4,7-triazacyclononane-1-methyl-methylene- bis(phosphinato)-4,7-bis(methyl-phosphinic) (H4L2 ). The acidobase properties of the H2L1 were investigated using potentiometric and NMR titrations. Complexes of H2L1 with Ni(II), Cu(II), Zn(II) and Ga(III) were investigated using potentiometric titrations, which showed the high stability of these complexes. The solid-state structures of the Cu-L1 and Zn-L1 complexes were determined by X-ray diffraction. Complexation of the radioisotope 68 Ga(III) was studied for chelators H2L1 , H4L2 and for several related chelators with phosphorus pendant arms. The complexation study showed that chelators with the methylene-bis(phosphinate) pendant arm and some other phosphorus chelators derived from the TACN macrocycle accelerate complexation of gallium(III) ions. Using Dynamic PET scanning and ex-vivo...
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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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Dimer macrocyclic complexes
Rys, Jan ; Kubíček, Vojtěch (advisor) ; Vojtíšek, Pavel (referee)
This thesis is focused on dimer macrocyclic ligands and their complexes. Two dimer macrocyclic ligands based on ligand DO3A, linked with xylyl linker were prepared (BDO3A-p-X a BDO3A-m-X). Both synthetized ligands were characterized using NMR, MS, EA and in the case of BDO3A-p-X by X-ray crystallography. Data for calculating pseudo-first order reaction rates for complexations with Ce3+ metal ion and their pH dependency were obtained by use of UV/VIS spectrophotometry. Obtained data were compared to structurally close monomer ligand BnDO3A. Dimer ligands display different coordination properties based on proximity and position of coordinating cavities. Both prepared ligands behave differently than structurally close monomer ligand BnDO3A.
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Nanofiber membranes with encapsulated photoactive molecules simultaneously generating NO and 1O2 species
Liška, Vojtěch ; Mosinger, Jiří (advisor) ; Kubíček, Vojtěch (referee)
This thesis focuses on the preparation and study of a new type of photoactive polycaprolactone nanofibrous membrane with encapsulated NO photodonor 4-(N- (aminopropyl)-3-(trifluoromethyl)-4-nitrobenzenamine)-7-nitrobenzofurazan and photosensitizer chlorin e6. The electrospun nanofibrous membrane exhibits efficient photogeneration of NO and singlet oxygen molecules, which initiate facial and space photoantibacterial properties. The structure of the prepared NO photodonor was studied by NMR spectroscopy and UV-VIS absorption spectroscopy measurements. The resulting nanofibrous material was studied by scanning electron microscopy, and the successful encapsulation of both photoactive species was studied by absorption and fluorescence spectroscopy. Photogeneration of the NO molecule was studied by direct amperometric detection of NO and by reaction with a chemical substrate. The photogeneration of singlet oxygen O2( Δg 1 ) was studied by time-resolved spectroscopy and by reaction with a chemical substrate. Significant photoantibacterial properties were demonstrated on the bacterial strain Escherichia coli DH5α. Both antibacterial effects were studied by monitoring the number of colony forming units (CFU) using image analysis, and the facial effect by scanning electron microscopy. Keywords: singlet...
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