Tris(phosphonomethyl)cyclen Derivatives: Thermodynamic Stability, Kinetics, Solution Structure, and Relaxivity of Ln3+ Complexes

Abstract

AbstractThe lanthanide (Ln3+) 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) (H6do3p), 3‐[4,7,10‐tris(phosphonomethyl)‐1,4,7,10‐tetraazacyclododec‐1‐yl]propanoic acid (H7do3p1pr), and 10‐(3‐hydroxypropyl)‐1,4,7,10‐tetraazacyclododecane‐1,4,7‐triyltris(methylphosphonic acid) (H6do3p1ol). The three macrocyclic ligands form complexes of very high thermodynamic stability with all studied Ln3+ ions. Kinetic studies showed that the acid‐assisted dissociation of Ce3+ complexes of these ligands is much faster than for the complex of the related ligand H8dotp [1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetrayltetrakis(methylphosphonic acid)]. The number of water molecules coordinated to the Eu3+ and Gd3+ 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 1H and 17O relaxometric measurements. The NMR spectroscopic data indicate the existence of a considerable contribution from second‐sphere water molecules to the relaxivity of all the Gd3+ complexes studied. The 1H and 31P NMR spectra of the Eu3+, Yb3+ and Lu3+ 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 Ln3+ 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.