Evaluation of structurally related acyclic ligands OBETA, EHDTA, and EGTA for stable Mn2+ complex formation†

Abstract

In recent years, significant research efforts have been dedicated to finding efficient and safe alternatives to the currently used gadolinium (Gd)-based MRI contrast agents. Among the most explored alternatives are paramagnetic chelates of the Earth-abundant Mn²⁺, which form a prominent class of metal complexes. The design of Mn²⁺ complexes with enhanced relaxation properties and improved safety profiles hinges on a delicate balance between thermodynamic and kinetic stability, as well as the presence of coordinated water molecules. In this study, we present a comprehensive investigation into the coordination chemistry of three structurally related polyetheraminocarboxylic chelating agents. Our aim is to elucidate the structural features, paramagnetic properties, and thermodynamic and kinetic inertness of the corresponding Mn²⁺ complexes. The most significant finding is the considerable difference in the dissociation rates of the complexes, with the octadentate EGTA complex being the most labile. The observed dissociation rates correlate well with the nitrogen inversion dynamics, as assessed through NMR spectral analysis of the analogous Zn²⁺ complexes.