Kinetics of formation and dissociation of lanthanide(III) complexes with the 13-membered macrocyclic ligand TRITA(4-)

The tetraazamacrocyclic ligand TRITA(4-) is intermediate in size between the widely studied and medically used 12-membered DOTA(4-) and the 14-membered TETA(4-). The kinetic inertness of GdTRITA was characterized by the rates of exchange reactions with Zn2+ and Eu3+. In the Zn2+ exchange, a second order [H+] dependence was found for the pseudo-first-order rate constant (k(0) = (4.2 +/- 0.5) x 10(-7) s(-1); k' = (3.5 +/- 0.3) x 10(-1) M-1 s(-1), k = (1.4 +/- 0.4) x 10(3) M-2 s(-1)). In the Eu3+ exchange, at pH < 5 the rate decreases with increasing concentration of the exchanging ion, which can be accounted for by the transitional formation of dinuclear GdTRITAEu(2+) species. At physiological pH, the kinetic inertness of GdTRITA is considerably lower than that of GdDOTA(-) (t(1/2) = 444 h (25 degrees C) vs. 3.8 x 10(5) h (37 degrees C), respectively). However, GdTRITA is still kinetically more inert than GdDTPA 2, the most commonly used MRI contrast agent (t(1/2) = 127 h). The formation reactions of LnTRITA complexes (Ln = Ce, Gd and Yb) proceed via the rapid formation of a diprotonated intermediate and its subsequent deprotonation and rearrangement in a slow, OH- catalyzed process. The stability of the LnH(2)TRITA* intermediates (log K-LnH2I* = 3.1-3.9) is lower than that of the DOTA-analogues. The rate constants of the OH catalyzed step increase with decreasing lanthanide ion size, and are about twice as high as for DOTA-complexes.