Thermodynamic, kinetic and NMR relaxometric studies of Mn(II) complexes as MRI probes

The main goal of this thesis is the characterization in aqueous solutions of new Mn(II) complexes as MRI probes. Our investigation included thermodynamic, kinetic and detailed 1H and 17O NMR relaxometric measurements. We have taken into account Mn-complexes belonging to two different main types of structural units. One encompasses the Mn(II) complexes containing the pentadentate coordinating units 6,6-((methylazanediyl)bis(methylene))dipicolinic acid. We considered several derivatives of the monomeric DPAMA ligand, including mono-, bi- and trinuclear bis-hydrated complexes (Chapter 4). In addition, we investigated a number of derivatives featuring different side arms and a couple of lipophilic derivatives (Chapter 5). All these complexes represent a fairly homogeneous series that has allowed us to obtain useful information on the relationship between the molecular structure, the thermodynamic stability and the relaxation parameters. The other class of complexes are those containing the macrocyclic unit cyclen and two coordinating pendant arms. These macrocyclic derivatives have been studied in detail, considering the chemical nature of the pendant arms, their relative position (cis/trans), the possible presence of isomers with different states of hydration, the kinetic and thermodynamic stability of the complexes and their relaxometric properties (Chapter 6). The synthesis of two novel derivatives bearing hydrophobic pendant groups enabled the investigation of the binding association with human serum albumin (Chapter 7). The global set of experimental results has allowed us to deepen our understanding of the chemistry of Mn(II) complexes as potential MRI probes. We are confident that the new information gained will help in the future design and development of more effective and safer MRI contrast enhancing agents.