Iron(III)-complexes as MRI Contrast Agents

In Magnetic Resonance Imaging (MRI), Gd(III)-based contrast agents (GBCAs) have proven to be ofgreat help for the diagnosis of various pathologies and for improving image quality. Although suchcompounds are generally considered safe, in response to concerns about patients who cannot toleratesome Gd(III) contrast agents as well as more recent reports of Gd(III) retention in the body, there hasbeen a renewed interest in finding alternatives to using Gd(III) for MR contrast. In this regard,complexes based on endogenous ions such as Fe(III) and Mn(II) may be a viable option. Some recentresults indicate that Fe(III) chelates administered at higher doses than GBCAs have achieved similarresults in typical clinical applications. Despite these important initial contributions, the mechanismsresponsible for the increase in water proton relaxation induced by Fe(III) complexes and therelationships between the molecular parameters governing their efficacy and chemical structure havenot yet been well elucidated, thus preventing the development of systems with optimal propertiesthrough rational ligand design. This dissertation reports the combined 1H and 17O NMR relaxometricstudy of a series of Fe(III)-based complexes in order to evaluate their effectiveness as reliablecandidates for designing potentially safer MRI contrast agents, particularly for use at the highmagnetic fields of modern clinical scanners. These measurements are also supported by DFTcalculation. Furthermore, the thermodynamic stabilities and kinetic inertias of these complexes arealso evaluated by potentiometry and UV-Vis spectrophotometry. The combined application of thesetechniques allows to thoroughly characterize these compounds so that the design of this emergingclass of contrast agents can be optimized.