Chiral Pyclen-Based Heptadentate Chelates as Highly Stable MRI Contrast Agents.

In recent years, pyclen-based complexes have attracted a great deal of interest as magnetic resonance imaging (MRI) contrast agents (CAs) and luminescent materials, as well as radiopharmaceuticals. Remarkably, gadopiclenol, a Gd(III) bishydrated complex featuring a pyclen-based heptadentate ligand, received approval as a novel contrast agent for clinical MRI application in 2022. To maximize stability and efficiency, two novel chiral pyclen-based chelators and their complexes were developed in this study. showed significant enhancements in both thermodynamic and kinetic stabilities compared to those of the achiral parent derivative . H NMRD profiles reveal that both chiral gadolinium complexes ( and ) have a higher relaxivity than , while variable-temperature O NMR studies show that the two inner-sphere water molecules have distinct residence times τ and τ. Furthermore, imaging demonstrates that enhances the signal in the heart and kidneys of the mice, and the chiral Gd complexes exhibit the ability to distinguish between tumors and normal tissues in a 4T1 mouse model more efficiently than that of the clinical agent gadobutrol. Biodistribution studies show that and are primarily cleared by a renal pathway, with 24 h residues of in the liver and kidney being lower than those of .