Tailoring the local environment of Ln³⁺ in pyridine-based complexes: effect on the thermodynamic, kinetic, structural...

The replacement of one or two negatively charged carboxylate functions by neutral pyridine or imidazole pendant groups in pyridine-based polyaminopolycarboxylate ligands was investigated. Four ligands were synthesized and the thermodynamic, kinetic, structural and relaxation properties of their corresponding Ln³⁺ complexes was thoroughly studied. The protonation constants of the ligands as well as the stability constants of the corresponding Ln³⁺ complexes were determined by pH potentiometric measurements. While no strong effect on the stability constants of the Ln³⁺ complexes is observed when one carboxylate is replaced by an imidazole or a pyridine, the replacement of two carboxylate functions is detrimental to the overall stability of the complexes. The dissociation kinetics of GdImPy and GdPyPy, evaluated through Eu³⁺-exchange reactions, predominantly proceed via an acid-catalyzed mechanism, with minimal direct Eu³⁺ attack. The presence of a protonatable function on the imidazole ring leads to more labile complexes. NMR and luminescence studies combined with DFT calculations evidenced the coordination of the imidazole or pyridine pendant arms. The Gd³⁺ complexes exhibit high relaxivity values (r₁ = 8.25 mM^-1 s^-1 and 7.97 mM^-1 s^-1 at 60 MHz and 25 °C for GdImPy and GdPyPy, respectively) in accordance with their bishydrated character, and no aggregation phenomena are observed over a wide range of concentrations. Variable-temperature ¹⁷O NMR and NMRD data analysis of GdImPy and GdPyPy provided insights into the microscopic parameters affecting their relaxation properties. Interestingly, the water exchange rate is strongly accelerated with the imidazole pendant arm compared to the pyridine, which could be related to steric crowding around the Ln³⁺ ion. The two inner-sphere water molecules are not displaced by interactions with biological anions such as citrate and phosphate. However, a relaxivity decrease of ca. 30% is observed in the presence of carbonate, as confirmed by ¹H relaxivity and luminescence lifetime measurements.