EFFECT OF LIGAND BASICITY ON THE FORMATION AND DISSOCIATION EQUILIBRIA AND KINETICS OF GD3+ COMPLEXES OF MACROCYCLIC POLYAMINO CARBOXYLATES

The effect of nitrogen basicity on the formation and dissociation equilibria and kinetics of Gd(III) complexes of macrocyclic polyamino carboxylates, GdL (L is HE-DO3A = 10-(2-hydroxyethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, HP-DO3A = 10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, and HIP-DO3A = 10-(2-hydroxyisopropyl)- 1,4,7,10-tetraazacyclododecane-1,4,7-triaceticacid), is studied in the present work. The stability constants of the gadolinium complexes (log K(GdL)) have been determined at 25.0 +/- 0.1-degrees-C and at mu = 0.1 ((TMA)Cl) and have the following order: HIP-DO3A > HP-DO3A > HE-DO3A. The formation and dissociation reaction rates of the chelates have been measured at 25.0 +/- 0.1-degrees-C and at mu = 1.0 (NaCl). The proposed mechanism for the formation reactions involves the formation of an intermediate with stability constant, K(Gd(HL))*, and its base-assisted rate constant of reorganization, k(OH). The calculated stability constants of the intermediate, log K(Gd(HL))*, are 8.4 (HE-DO3A), 8.9 (HP-DO3A), and 8.2 (HIP-DO3A). The second-order rate constants for the base-assisted reorganization (log k(OH)) depend on the nitrogen basicity (log K1) with a linear correlation as follows: log k(OH) = -(0.37 +/- 0.05) log K1 + (11.6 +/- 0.6) (r2 = 0.98). The protonation constants of GdL (log K(GdL(H)) and the stability constants (log K(Gd(H2)) of the protonated species of GdL are determined, and the values are as follows: 2.04, 13.3 (HE-DO3A); 2.38, 14.2 (HP-DO3A); 2.23, 13.6 (HIP-DO3A). The rate of the acid-assisted dissociation of the protonated GdL is first-order in the limiting reagent, [GdL]T, and the rate saturates at higher [H+]. The equilibrium constants, K(GdL(H2)) (M-1), for the formation of the diprotonated species, GdL(H-2), and their dissociation rate constants (10(3)k2, s-1) are as follows: 9 +/- 2 and 1.9 +/- 0.2 for HE-DO3A, 0.35 +/- 0.03 and 1.66 +/- 0.09 for Gd(HP-DO3A) and 0.6 +/- 0.1 and 0.64 +/- 0.05 for Gd(HIP-DO3A). Evidence of a direct dissociation pathway for Gd(HIP-DO3A)(H) is also observed with a rate constant, k(d) (s-1), of (0.2 +/- 0.1) X 10(-4). A comparison of the measured first-order rate constants for acid-assisted dissociation of GdL in 0.1 M HCl, 10(5)k(obsd) (s-1), 46.6 (HE-DO3A), 6.4 (HP-DO3A), and 5.8 (HIP-DO3A), suggests that the rate of dissociation depends on the basicity of nitrogen and the stability constant of the chelate.