|
|
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...
|
|
|
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
|
guest ::
