Potentiometry and NMR Studies of 1,5,9-Triazacyclododecane-N,N′,N″-triacetic Acid and Its Metal Ion Complexes

A new chelating macrocycle, 1,5,9-triazacyclododecane-N,N′,N″-triacetic acid (DOTRA), has been synthesized, and its complexes with Zn²⁺, Cd²⁺, Ca²⁺, Mg²⁺, and Mn²⁺ have been examined by potentiometry and NMR spectroscopy. The first protonation constant of the free ligand (log K₁ = 12.8) was determined spectrophotometrically, while the remaining were evaluated from potentiometric data (log K₂ = 7.55, log K₃ = 3.65, log K₄ = 2.1). DOTRA forms complexes with Mn²⁺, Mg²⁺, and Ca²⁺ rather slowly but reacts much more rapidly with Zn²⁺ and Cd²⁺. As reported previously for the nine-membered-ring triaza analogue NOTA, DOTRA also forms a more stable complex with Mg²⁺ than with Ca²⁺ (log K_st = 7.1 versus 6.0). High-resolution NMR spectra of the Zn²⁺, Cd²⁺, and Mg²⁺ complexes (log K_st = 19.0, 15.7, and 7.1, respectively) indicate the three six-membered chelate rings are symmetrical and quite rigid in aqueous solution, as evidenced by nonequivalence of all six chelate ring protons.