Optimizing the relaxivity at high fields: Systematic variation of the rotational dynamics in polynuclear Gd-complexes based on the AAZTA ligand

A homogeneous series of polynuclear structures containing from 2 to 6 GdAAZTA complexes (AAZTA = 6-amino-6-methylperhydro-1, 4-diazepine tetraacetic acid) were synthesized covering a broad range of molecular weights, ca. 1200-6000 Da. A frequency and temperature dependent 1H and 17O NMR relaxometric study on the Gd(iii) polynuclear complexes clearly highlights a considerable gain of relaxivity (per Gd) passing from the monomer to the hexanuclear complex, with an enhancement of +370% at 1.5 T and 298 K (+470% at 310 K). In particular, the relaxivity of the hexamer reaches a remarkable value of 28.2 mM-1 s-1 at 1.5 T and 298 K (23.8 mM-1 s-1 at 310 K). The NMR study, supported by DFT calculations, allows analysis in detail of the dependence of the rotational dynamics on the size and molecular geometry of the multimers, considering both the global tumbling of the system and the local motions of the monomer units. In addition, T1-weighted phantom MR-images at 1, 3 and 7 T on selected polynuclear complexes highlighted the effective signal enhancement of the new MRI probes at clinically relevant magnetic field strengths in comparison with the clinically approved contrast agent ProHance®. Finally, the results obtained enable us to highlight effective strategies for relaxation enhancement, each suitable for a well-defined range of applied magnetic field strength.