Equilibrium, kinetic and structural studies of AAZTA complexes with Ga ³⁺, In³⁺ and Cu²⁺

A detailed study of the structures, thermodynamic stabilities and kinetics of the dissociation of Ga³⁺, In³⁺ and Cu²⁺ complexes formed with the heptadentate ligand AAZTA is reported. The stability constants (log K_ML) of the AAZTA complexes of Ga³⁺, In³⁺ and Cu²⁺ are 22.18, 29.58 and 22.27, respectively, which suggests that the seven-membered-ring skeleton is suited to the accommodation of these metal ions. The solid-state structure of [Cu(H ₂AAZTA)]·H₂O shows a distorted octahedral coordination. The equatorial coordination sites of Cu²⁺ are occupied by one of the ring N atoms, a water O atom, one of the carboxylate O atoms and the N atom of the iminodiacetate moiety. The other ring N atom and the carboxylate O atom of the iminodiacetate moiety coordinate to the Cu ²⁺ in the axial positions. In the pH range 4.5-8.5, Ga³⁺ is present in the form of the highly stable [Ga(AAZTA)OH]^2- (log β_GaLH-1 = 17.69) The exchange reactions of [Ga(AAZTA)OH] ^2- with Cu²⁺ and transferrin are very slow and mainly occur through the spontaneous dissociation of the complex close to physiological conditions. The half-life for the dissociation of [Ga(AAZTA)OH]^2- is t_1/2 = 23 h at pH = 7.5 and 25 °C in 0.025 M NaHCO₃ and 0.15 M NaCl. The high conditional stability, fast formation and sufficiently slow dissociation of [Ga(AAZTA)OH]^2- represent promising properties for the complexation and diagnostic applications of radioactive Ga isotopes.