Water exchange studies of lanthanide complexes and aqua ions

Complexes of lanthanide (III) ions have been used in structural studies of biomolecules and as contrast agents (CA). Clinically approved CAs have only one water molecule in their first coordination sphere. Structure and water exchange rate of these complexes have been very well studied, however, water exchange kinetics of lanthanide complexes with two coordinated water molecules have not been investigated widely. In this regard, in the present work, a comprehensive study of water exchange kinetics of selected Ln3+ complexes with different ligands having two inner-sphere water molecules was conducted. In chapter III, selected lanthanide complexes of DO3A and DTTA-Me as representatives for macrocyclic and acyclic ligands have been studied by 17O NMR spectroscopy and 1H nuclear magnetic relaxation dispersion (NMRD). Water exchange rate constants measured on both complexes show a maximum at dysprosium and are much faster on DTTA-Me complexes than on the DO3A complexes. A change in water exchange mechanism is detected depending on both lanthanide and ligand structure. When analyzing the water exchange rates of [Ln(L)(H2O)2]x complexes, a unique rate constant for the exchange of the two water molecules was considered, however, the individual rate constants can be either very similar or very different. In order to investigate this, in chapter IV, the replacement of coordinated water molecule(s) in [Gd(DTTA-Me)(H2O)2]- by fluoride anions using multinuclear NMR spectroscopy was studied. Variable pressure 17O NMR measurements were also conducted for mechanistic assignment of the exchange reactions. It was found that fluoride binding facilitate the departure of the coordinated water molecule following a dissociative mechanism and accordingly cause a marked acceleration of the water exchange. In chapter V, the water exchange properties of lanthanide complexes of AAZTAPh-NO2 ligand was studied by 1H NMR spectroscopy. Water exchange rate constants were found to change more than two orders of magnitude along the series. Moreover, [Dy(AAZTAPh-NO2)(H2O)2]- was found to potentially be a very effective negative contrast agent for high magnetic fields imaging applications. Chapter VI is dedicated to the water exchange kinetics of selected lanthanide perchlorate and chloride aqua ions at different concentrations of 0.5 m to 2 m in order to establish the extent to which the nature of the counter-ion and the concentration of the Ln3+ change the rate and mechanism of the water exchange. Our results measured on neodymium ion are the first direct experimental proof for the maximum of water exchange rate constant along the lanthanide series as well as the change of the mechanism for water exchange from a dissociative mechanism for aqua ions of the early lanthanides to an associative mechanism for those of the late lanthanides.

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