Equilibrium and dissociation kinetics of the [Al(NOTA)] complex (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetate)

Abstract

A detailed investigation of the equilibria and dissociation kinetics for the [Al(NOTA)] complex has been carried out. This complex and its derivatives are known as very good carriers for ¹⁸F-isotope in positron emission tomography. The thermodynamic stability of [Al(NOTA)] has been studied by “out of cell” pH-potentiometric technique since the formation rate of the complex is very low in acidic medium. ¹H- and ²⁷Al-NMR spectra have been recorded to check the time course of equilibration and to validate the equilibrium model consisting of [Al(NOTA)] with lgK = 17.9(1) and [Al(HNOTA)]⁺ with lgK ^H = 1.9(3). A metastable mixed hydroxido complex [Al(NOTA)(OH)]⁻ with lgK ^OH_Al(NOTA)  = −12.2(1) was detected in alkaline solution by direct pH-potentiometry, which transforms slowly to [Al(OH)₄]⁻. The decomplexation reactions of [Al(NOTA)] have been investigated in both acidic and basic conditions. The rate of dissociation is extremely low in acidic medium, while in alkaline solution, it can be characterized by the rate law k_obs = k ₀ + k ₁[OH⁻], where k ₀ = (2.0 ± 0.1) × 10⁻⁶ s⁻¹ and k ₁ = (6.8 ± 0.5) × 10⁻⁶ M⁻¹s⁻¹. The formation of the ternary [Al(NOTA)(F)]⁻ complex via direct reaction of [Al(NOTA)] and F⁻ cannot be detected by either fluoride selective electrode or by ¹⁹F-NMR spectroscopy. However, by applying solvent mixture (1:1 ethanol:water) and heating, the ternary [Al(NOTA)(F)]^– complex was found to form quantitatively within 15 minutes.