A Coordination Chemistry Approach to Fine‐Tune the Physicochemical Parameters of Lanthanide Complexes Relevant to Medical Applications

The geometric features of two pyclen‐based ligands possessing identical donor atoms but different site organization have a profound impact in their complexation properties toward lanthanide ions. The ligand containing two acetate groups and a picolinate arm arranged in a symmetrical fashion (L1) forms a Gd3+ complex being two orders of magnitude less stable than its dissymmetric analogue GdL2. Besides, GdL1 experiences a much faster dissociation following the acid‐catalyzed mechanism than GdL2. On the contrary, GdL1 exhibits a lower exchange rate of the coordinated water molecule compared to GdL2. These very different properties are related to different strengths of the Gd‐ligand bonds associated to steric effects, which hinder the coordination of a water molecule in GdL2 and the binding of acetate groups in GdL1. More than meets the eye: An apparently innocent change in the arrangement of the ligand donor atoms around the central Ln3+ ion has profound consequences in the thermodynamic stability and dissociation and water exchange kinetics of the complexes.