Synthesis and NMR studies of three pyridine-containing triaza macrocyclic triacetate ligands and their complexes with lanthanide ions

The synthesis of three triazamacrocycles containing the pyridine moiety and three acetate pendant arms (PCTA) is reported. The three systems differ due to the number of carbon atoms in the macrocyclic ring forming ligands PCTA-[12], -[13], and -[14], endowed with different coordination capabilities toward lanthanide(III) ions. Microscopic protonation sequences for the three ligands have been investigated by H-1 NMR spectroscopy. Complexes of PCTA-[12], -[13], and -[14] with La(III), Gd(III), and Lu(III) have been prepared. Relaxometric measurements on the aqueous solutions of the paramagnetic Gd(III) complexes in the presence of competitive ligands gave the following stability constants: log K-f = 20.8 for Gd-PCTA-[12], log K-f = 19.3 for GdPCTA-[13], and log K-f = 12.5 for GdPCTA-[14]. The measurement of water relaxation rates indicated a tendency to decrease the degree of hydration upon increasing the ring size. The VT H-1 and C-13-NMR spectra of the diamagnetic La(III) and Lu(III) complexes exhibit a large variability of the solution structures dictated by the matching of the size of the lanthanide ion and the macrocyclic cavity. This results in noticeable differences in their stereochemical nonrigidity, hydration state, and thermodynamic stability. To some extent the changes observed in continuing from the 12-14-membered ring macrocyclic complexes parallels the behaviors shown by the octacoordinated lanthanide(III) complexes with DOTA and TETA. GdPCTA-[12] and -[13] feature promising properties in view of their possible use as contrast agents for magnetic resonance imaging.