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 [(GdL5)₃(H₂O)₃]³⁺ entities in which the monomeric units are joined by μ₂-η¹:η¹-carboxylate groups. However, the ¹H and ⁸⁹Y 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 [TbL5]⁺. The luminescence lifetimes recorded in H₂O and D₂O solutions indicate the presence of a water molecule coordinated to the metal ion, as also evidenced by the ¹H relaxivities measured for the Gd(III) analogues. The Gd(III) complexes present very different exchange rates of the coordinated water molecule (k_ex²⁹⁸ = 87.1 × 10⁶ and 1.06 × 10⁶ s^-1 for [GdL5]⁺ and [GdL6]⁺, respectively). The very high water exchange rate of [GdL5]⁺ 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 [GdL5]⁺ and [GdL6]⁺, respectively). Furthermore, these complexes are remarkably inert with respect to their acid-assisted dissociation, in particular the complex of L5.