Equilibrium and kinetic studies on complexes of 10-[2,3-dihydroxy-(1-hydroxymethyl)-propyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetate
Résumé
Complexation properties of the ligand 10-[2,3-dihydroxy-(1-hydroxymethyl)-propyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetatic acid (DO3A-B) were studied and compared with those of 10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (HP-DO3A) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The protonation constants of DO3A-B (KiH) and the stability constants (K) of the complexes formed with Ca2+, Sr2+, Ba2+, Zn2+, Cu2+, Fe3+, Ce3+, Nd3+, Eu3+, Gd3+, Dy3+, Tm3+ and Lu3+ were determined in different media (I = 0.1 M; 25°C). The first protonation constants (log K1H) in Me4NCl, KCl and NaCl were found to be 11.75, 11.27 and 9.46, respectively, indicating the formation of Na+ and weaker K+ complexes. The complexes of lanthanides, alkaline earths and Zn2+ form slowly and the complexation equilibria could be studied by means of an out-of-cell technique. The stabilities of the complexes Ln(DO3A-B) increase from La to Eu while the log K values are practically constant for the heavier lanthanides. The stability constants of the DO3A-B complexes of Ce, Gd and Lu are 1–2 orders of magnitude lower than those of the HP-DO3A complexes. The coordinated alcoholic hydroxy groups dissociate at relatively low pH. The dissociation constant (Kd) obtained pH-metrically for Gd(DO3A-B) (pKd=9.48) is about 100 times higher than that for Gd(HP-DO3A) (pKd=11.36), indicating the higher basicity of the alcoholic oxygen in HP-DO3A, which may contribute to the larger stability constants of the complexes formed with HP-DO3A. The kinetic stability of the complexes Gd(DO3A-B) and Gd(HP-DO3A) were studied by spectrophotometry in the pH range 3.2–5.3 by following the exchange reactions between the complexes and Eu3+. The rates of the exchange reactions proved to be linearly proportional to the H+ concentration. This was interpreted in terms of the rate-determining role of the rearrangement and dissociation of the monoprotonated complexes. The rate constants obtained for the proton-assisted dissociation of Gd(DO3A-B) and Gd(HP-DO3A) were (2.8 ± 0.1) × 10−5 and (2.6 ± 0.1) × 10−4 M−1 s−1, respectively.