Tripyridinophane Platform Containing Three Acetate Pendant Arms: An Attractive Structural Entry for the Development of Neutral Eu(III) and Tb(III) Complexes in Aqueous Solution.

We report a detailed characterization of Eu and Tb complexes derived from a tripyridinophane macrocycle bearing three acetate side arms (Htpptac). Tpptac displays an overall basicity (∑ log ) of 24.5, provides the formation of mononuclear ML species, and shows a good binding affinity for Ln (log = 17.5-18.7). These complexes are also thermodynamically stable at physiological pH (pEu = 18.6, pTb = 18.0). It should be noted that the pGd value of Gd-tpptac (18.4) is only slightly lower than that of commercially available MRI contrast agents such as Gd-dota (pGd = 19.2). Moreover, a very good selectivity for these ions over the endogenous cations (log = 14.4, log = 12.9, and log = 9.3) is observed. The X-ray structure of the terbium complex shows the metal coordinated by the nine NO donor set of the ligand and one inner-sphere water molecule. DFT calculations result in two Eu-tpptac structures with similar bond energies (Δ = 0.145 eV): one structure in which the water is coordinated to the metal ion and one structure in which the water molecule is farther away from the ion, bound to the ligand with an OH-π bond. By detailed luminescence experiments, we demonstrate that the europium complex in aqueous solution presents a hydration equilibrium between nine-coordinate, dehydrated [Eu-tpptac] and ten-coordinate, monohydrated [Eu-tpptac(HO)] species. A similar trend is observed for the terbium complex. Despite the presence of this hydration equilibrium, the Htpptac ligand sensitizes Eu and Tb luminescence efficiently in buffered water at physiological pH. Particularly, the terbium complex displays a long excited-state lifetime of 2.24 ms and an overall quantum yield of 33% with a brightness of 3600 M cm. Such features of Ln complexes of Htpptac indicate that this platform appears to be particularly appealing for the further development of luminescent lanthanide labels.