High kinetic inertness of a bis-hydrated Gd-complex with a constrained AAZTA-like ligand

Abstract

Kinetic inertness is a key property for a Gd-based contrast agent. The Gd^III complex of a cyclohexyl-fused AAZTA derivative shows the highest kinetic inertness for non-macrocyclic bis hydrated (q = 2) Gd^III-complexes with a dissociation half-life of 91 years under physiological conditions, very close to that of macrocyclic clinically approved contrast agents. It also shows optimal relaxometric performance (r₁ = 8.3 mM⁻¹ s⁻¹ at 20 MHz and 25 °C) due to the presence of two inner sphere water molecules in fast exchange with bulk water and not displaced by endogenous anions.