RESUMEN
We report the synthesis of a new family of side-bridged pyclen ligands. The incorporation of an ethylene bridge between two adjacent nitrogen atoms was reached from the pyclen-oxalate precursor described previously. Three new side-bridged pyclen macrocycles, Hsb-3-pc1a, sb-3-pc1py, and Hsb-3-pc1pa, were obtained with the aim to assess their coordination properties toward Cu2+ and Zn2+ ions. We also prepared their nonreinforced analogues H3-pc1a, 3-pc1py, and H3-pc1pa as comparative benchmarks. The two series of ligands were characterized and their coordination properties were investigated in detail. The Zn2+ and Cu2+ complexes with the nonside-bridged series H3-pc1a, 3-pc1py, and H3-pc1pa were successfully isolated and their structures were assessed by X-ray diffraction studies. In the case of the side-bridged family, the synthesis of the complexes was far more difficult and, in some cases, unsuccessful. The results of our studies demonstrate that this difficulty is related to the extreme stiffening and basicity of such side-bridged pyclens.
RESUMEN
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 (kex298 = 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 KGdL = 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.
RESUMEN
A family of three picolinate pyclen-based ligands, previously investigated for the complexation of Y3+ and some lanthanide ions (Gd3+, Eu3+), was studied with 161Tb and 177Lu in view of potential radiotherapeutic applications. The set of six Tb3+ and Lu3+ complexes was synthesized and fully characterized. The coordination properties in the solid state and in solution were thoroughly studied. Potentiometric titrations, supported by density functional theory (DFT) calculations, showed the very high stability constants of the Tb3+ and Lu3+ complexes, associated with remarkable kinetic inertness for up to 30 days in 1 M HCl. A complete radiolabeling study performed with both 161Tb and 177Lu radionuclides, including experiments with regard to the stability with and without scavengers and kinetic inertness using challenging agents, proved that the ligands could reasonably compete with the DOTA analogue. To conclude, the potential of using the same ligand for both radiotherapy and optical imaging was highlighted for the first time.
