Nyílt láncú és makrociklusos ligandumokkal képzett lantanida(III) komplexek termodinamikai, kinetikai és relaxometriás vizsgálata

The thesis is focused on the investigation of ligand exchange reactions of currently used MRI contrast agents (GdDTPA, GdBOPTA and Gd(DTPA-BMA)) with TTHA, and the physico-chemical characterization of gadolinium(III) complexes formed with novel macrocyclic polyamino polycarboxylate ligands (bp12c42- and L1= oxa-triaza tris(glicinate)). The ligand exchange reactions take place through the formation of ternary intermediates. The formation of ternary intermediates is related to the intramolecular rearrangements, occurring in the Gd3+ complexes. The rate of the rearrangements is higher in the Gd(DTPA-BMA) and so the rates of the ligand exchange reactions of this complex are about two to three orders of magnitude higher than those of the Gd(DTPA) and Gd(BOPTA). The ligand exchange reactions take place faster in the presence of the endogenous citrate, phosphate and carbonate ions, but the effect of the citrate and phosphate is very low at their physiological concentrations. The picolinate-derivative ligand based on the 1,7-diaza-12-crown-4 platform (bp12c42-) forms stable Ln3+ complexes. In the presence of Zn2+, the dissociation of [Gd(bp12c4)]+ proceeds both via proton- and metal-assisted pathways, in this respect, this system is intermediate between DTPA-type and macrocyclic, DOTA-type chelates. The rate of water exchange is extremely high on the [Gd(bp12c4)(H2O)q]+ complex, and is in the same order of magnitude as for the Gd3+ aqua ion. For the ligand L1 a comprehensive study was performed, including thermodynamic, kinetic, relaxometric, 17O NMR and PARACEST measurements of its lanthanide(III) complexes. Lanthanide ions form stable complexes with L1. Strong ternary complex formation was observed between GdL1 and lactate and carbonate ions. Surprisingly, the most important pathway in the transmetallation reactions is the spontaneous dissociation, which makes the GdL1 complex kinetically much less inert, than Gd(III)-complexes formed with other macrocyclic ligands