Kinetics of the formation of [Ln(DOTAM)](3+) complexes

The kinetics of the formation of lanthanide(III) complexes of the neutral ligand DOTAM differ considerably from those of DOTA and its derivatives, which contain negatively charged pendant groups. Formation of the complexes [Ln(DOTAM)](3+) occurs upon direct encounter of the Ln(3+) ions and the fully deprotonated ligand in the pH range 4.7-5.8. The formation of a protonated intermediate, which is characteristic of the complexation of DOTA and its derivatives, was not detected. General base catalysis is not valid in the formation reactions of [Ln(DOTAM) ](3+), which also indicates the absence of protonated intermediates. The rates of the proton-exchange reactions for the ligand species H(2)DOTAM(2+) and HDOTAM(+) have been studied by H-1 NMR spectroscopy. Proton ex change was found to be a general base-catalysed process, therefore it cannot play an important role in the formation of these complexes. The second-order rate constants, k(L), which characterize the formation of the complexes [Ln(DOTAM)](3+), are lower than the analogous rate constants reported for the Ln(3+) complexes of open-chain multidentate ligands by three to four orders of magnitude. These low kL values can be interpreted by assuming an early rate-determining step (probably the second or third Ln(3+)-amide bond formation) in the reaction sequence that leads to the (Ln(DOTAM)](3+) complex.