Tris(phosphonomethyl)cyclen Derivatives: Thermodynamic Stability, Kinetics, Solution Structure, and Relaxivity of Ln(3+) Complexes
Abstract
The lanthanide (Ln(3+)) complexes of three cyclen-based ligands containing three methylphosphonate pendant arms were studied, the ligands being 1,4,7,10-tetraazacyclododecane-1,4,7-triyltris(methylphosphonic acid) (H(6)do3p), 3-[4,7,10-tris(phosphonomethyl)-1,4,7,10-tetraazacyclododec-1-yl]propanoic acid (H(7)do3p1pr), and 10-(3-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyltris(methylphosphonic acid) (H(6)do3p1ol). The three macrocyclic ligands form complexes of very high thermodynamic stability with all studied Ln(3+) ions.
Kinetic studies showed that the acid-assisted dissociation of Ce(3+) complexes of these ligands is much faster than for the complex of the related ligand H(8)dotp [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayltetrakis(methylphosphonic acid)]. The number of water molecules coordinated to the Eu(3+) and Gd(3+) complexes was estimated to be < 1 for the do3p1ol ligand but ca. 1 for the other two ligands, as obtained by time-resolved luminescence spectroscopy and by (1)H and (17)O relaxometric measurements.
The NMR spectroscopic data indicate the existence of a considerable contribution from second-sphere water molecules to the relaxivity of all the Gd(3+) complexes studied. The (1)H and (31)P NMR spectra of the Eu(3+), Yb(3+) and Lu(3+) complexes showed that the propionate arm in the [Ln(do3p1pr)](4-) complexes and the propanol arm in the [Ln(do3p1ol)](3-) complexes are not bound to the Ln(3+) ion.
The [Ln(do3p)](3-) and [Ln(do3p1pr)](4-) complexes have a clear preference for the TSAP (twisted square antiprismatic) isomer, while both SAP (square antiprismatic) and TSAP isomers are present in solutions of the [Ln(do3p1ol)](3-) complexes.