Multifrequency EPR studies of zero field splitting of Gd(III) based MRI contrast agents in solids and liquids
Magnetic Resonance Imaging (MRI) offers an amazing number of ways to probe the human body. It is a wonderful symbiosis of engineering, science and medicine. The power of MRI is its ability to probe a variety of physical mechanisms that can then not only reveal delicate anatomical structures but also discover important information about the physiology of tissue function in normal and diseased states. Paramagnetic metal ions, as a result of their unpaired electrons, act as potent MRI contrast agents. They decrease the T1 and T2 relaxation times of nearby water protons. The mechanism of T1 relaxation is generally a through space dipole-dipole interaction. This interaction is between the unpaired electrons of a paramagnetic ion, such as Gd(III) and the water molecules that are in fast exchange within the ion's inner-coordination sphere. The lanthanide ion Gd(III) is by far the most frequently chosen metal centre in MRI contrast agent, because it has a very high magnetic moment (S = 7/2) and a symmetric electronic ground state, 8S7/2. As it is generally highly toxic, acyclic and macrocyclic polyaminocarboxylates ligands have been synthesized forming thermodynamically and kinetically stable complexes with Gd(III). The coupling of the seven unpaired electrons of the Gd(III) ion with the surrounding water proton spins observed in MRI is crucial for the contrast agent effectiveness, expressed as relaxivity. Therefore, understanding the behavior of the electron spin system can provide valuable information for the development of new compounds. Since this ion has S >1, its spin Hamiltonian includes a significant Zero Field Splitting (ZFS) contribution. This work was devoted to the determination by Electron Paramagnetic Resonance (EPR) spectroscopy of parameters governing the strength of ZFS of Gd(III)-based MRI contrast agents in aqueous solution, frozen solution, and powders. The analysis of multiple frequency and temperature EPR data has been conducted on selected commercial and potential MRI contrast agents. The studied complexes have been designed in the aim to optimise other important parameters which influence the relaxivity, like the rotational diffusion of the complexes and the water residence time in the first coordination shell. This work provides a survey of electron spin relaxation through the determination of the ZFS parameters for Gd(III)-based contrast agents (1) in solution where a rigorous derivation of the relaxation rates was applied to the analysis of the full EPR line shape at multiple frequencies, and (2) in glasses and powders where a direct and straightforward determination of ZFS parameters allowed, for the first time, to establish a correlation between the sign of the axial ZFS parameter and the nature of the chelating ligand in Gd(III) complexes.
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