Kinetics of formation and dissociation of lanthanide(iii) complexes with the 13-membered macrocyclic ligand TRITA4−

Abstract

The tetraazamacrocyclic ligand TRITA⁴⁻ is intermediate in size between the widely studied and medically used 12-membered DOTA⁴⁻ and the 14-membered TETA⁴⁻. 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 (k₀ = (4.2 ± 0.5) × 10⁻⁷ s⁻¹; k′ = (3.5 ± 0.3) × 10⁻¹ M⁻¹s⁻¹, k″ = (1.4 ± 0.4) × 10³ M⁻²s⁻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 GdTRITAEu²⁺ species. At physiological pH, the kinetic inertness of GdTRITA⁻ is considerably lower than that of GdDOTA⁻ (t_1/2 = 444 h (25 °C) vs. 3.8 × 10⁵ h (37 °C), respectively). However, GdTRITA⁻ is still kinetically more inert than GdDTPA²⁻, 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 LnH₂TRITA* intermediates (log K_LnH2L* = 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.