Pyclen-Based Ligands Bearing Pendant Picolinate Arms for Gadolinium Complexation

We report the synthesis of two pyclen-based regioisomer ligands (pyclen = 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene) functionalized with picolinic acid pendant arms either at positions 3,9-pc2pa ( L5 ) or 3,6-pc2pa ( L6 ) of the macrocyclic fragment. The ligands were prepared by the regiospecific protection of one of the amine nitrogen atoms of the macrocycle using Boc and Alloc protecting groups, respectively. The X-ray structure of the Gd(III) complex of L5 contains trinuclear [(Gd L5 ) 3 (H 2 O) 3 ] 3+ entities in which the monomeric units are joined by μ 2 -η 1:η 1 -carboxylate groups. However, the 1 H and 89 Y NMR spectra of its Y(III) analogue support the formation of monomeric complexes in solution. The Tb(III) complexes are highly luminescent, with emission quantum yields of up to 28% for [Tb L5 ] + . The luminescence lifetimes recorded in H 2 O and D 2 O solutions indicate the presence of a water molecule coordinated to the metal ion, as also evidenced by the 1 H relaxivities measured for the Gd(III) analogues. The Gd(III) complexes present very different exchange rates of the coordinated water molecule ( k ex 298 = 87.1 × 10 6 and 1.06 × 10 6 s –1 for [Gd L5 ] + and [Gd L6 ] +, respectively). The very high water exchange rate of [Gd L5 ] + is associated with the steric hindrance originating from the coordination of the ligand around the water binding site, which favors a dissociatively activated water exchange process. The Gd(III) complexes present rather high thermodynamic stabilities (log K GdL = 20.47 and 19.77 for [Gd L5 ] + and [Gd L6 ] +, respectively). Furthermore, these complexes are remarkably inert with respect to their acid-assisted dissociation, in particular the complex of L5 .