Thermodynamic and kinetic studies of lanthanide(III) complexes with H5do3ap (1,4,7,10-tetraazacyclododecane-1,4,7-triacetic-10-(methylphosphonic acid)), a monophosphonate analogue of H4dota

Solution properties of complexes of a new H(4)dota-like ligand containing three acetate and one methylphosphonate pendant arms (H(5)do3ap, H5L) were studied. The ligand exhibits a high last dissociation constant (pK(A) = 13.83) as a consequence of the presence of phosphonate moiety. In solution, successive attachment of protons leads to several reorganizations of protonation sites and the neutral zwitterionic species H(5)do3ap has the same solution structure as in the solid state, where the nitrogen atom binding methylphosphonate and the opposite nitrogen atoms are protonated. Stability constants with Na+ and trivalent lanthanide ions (La3+, Ce3+, Eu3+, Gd3+, Lu3+) and Y3+ have been determined. The constants are comparable or higher than those of H(4)dota due to the higher overall basicity of H5do3ap. Formation of the stable protonated complexes, as well as complexes with the L: M = 1: 2 stoichiometry, was proved. Formation and decomplexation kinetics of the Ce3+ and Gd3+ complexes were investigated. The mechanism of formation of the H5do3ap complexes is similar to that observed for H4dota complexes and the complex species with mono- or diprotonated ligand on the cyclen ring are considered as the reaction intermediates. Acid-assisted decomplexation of H(5)do3ap complexes is faster in comparison with those of H(4)dota. This is caused by higher basicity of the phosphonate pendant arm and the ring nitrogen atoms, which facilitates the proton transfer from the bulk solution to the nitrogen atoms of cyclen ring.