Assessing the Impact of Amide Donor Groups on Stability and NMR Relaxation Efficiency of Monohydrated Fe(III) Complexes

This study aims to understand the impact of the overall charge of Fe(III) chelates on their water exchange kinetics, thermodynamic stability, and kinetic inertia. To this end, we synthesized two CDTA-amide ligands, each characterized by the replacement of one or two carboxyl groups with diethylamide functionalities. These alterations produced Fe(III) complexes with neutral or positively charged characteristics. The rate of water exchange (k_ex) was determined through a combined analysis of ¹H relaxometric data and ¹⁷O NMR chemical shift and transverse relaxation rate data. Additionally, we evaluated the thermodynamic stability and kinetic inertness of the complexes using potentiometry, UV-Vis spectrophotometry, and capillary zone electrophoresis. Our results indicate that altering the charge of the complex slows down k_ex, consistent with previous observations for Gd(III) and Mn(II) chelates. Furthermore, the results indicate that incorporating amide donor groups decreases the stability of the complexes and reduces their kinetic inertia. However, both stability and kinetic inertia remain higher than those of [Fe(EDTA)]⁻. These findings provide some valuable insights for the development of Fe(III)-based MRI probes alternative to those based on Gd(III).