Importance of outer-sphere and aggregation phenomena in the relaxation properties of phosphonated gadolinium...

A series composed of a tetra-, a tris- and a bisphosphonated ligand based on a pyridine scaffold (L(4) , L(3) and L(2) , respectively) was studied within the frame of lanthanide (Ln) coordination. The stability constants of the complexes formed with lanthanide cations (Ln=La, Nd, Eu, Gd, Tb, Er and Lu) were determined by potentiometry in aqueous solutions (25.0 °C, 0.1 M NaClO4 ), showing that the tetraphosphonated complexes are among the most stable Ln(III) complexes reported in the literature. The complexation of L(4) was further studied by different titration experiments using mass spectrometry and various spectroscopic techniques including UV/Vis absorption, and steady state and time-resolved luminescence (Ln=Eu and Tb). Titration experiments confirmed the formation of highly stable [LnL(4) ] complexes. (31) P NMR experiments of the LuL(4) complex revealed an intramolecular interconversion process which was studied at different temperatures and was rationalized by DFT modelling. The relaxivity properties of the Gd(III) complexes were studied by recording their (1) H NMRD profiles at various temperatures, by temperature dependent (17) O NMR experiments (GdL(4) ) and by pH dependent relaxivity measurements at 0.47 T (GdL(3) and GdL(2) ). In addition to the high relaxivity values observed for all complexes, the results showed an important second-sphere contribution to relaxivity and pH dependent variations associated with the formation of aggregates for GdL(2) and GdL(3) . Finally, intravenous injection of GdL(4) to a mouse was followed by dynamic MRI imaging at 1.5 T, which showed that the complex can be immediately found in the blood stream and rapidly eliminated through the liver and in large part through the kidneys.