Tripyridinophane Platform Containing Three Acetate Pendant Arms: An Attractive Structural Entry for the Development...

We report a detailed characterization of Eu³⁺ and Tb³⁺ complexes derived from a tripyridinophane macrocycle bearing three acetate side arms (H₃tpptac). Tpptac^3- displays an overall basicity (∑ log K_i^H) of 24.5, provides the formation of mononuclear ML species, and shows a good binding affinity for Ln³⁺ (log K_LnL = 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 K_CuL = 14.4, log K_ZnL = 12.9, and log K_CaL = 9.3) is observed. The X-ray structure of the terbium complex shows the metal coordinated by the nine N₆O₃ donor set of the ligand and one inner-sphere water molecule. DFT calculations result in two Eu-tpptac structures with similar bond energies (ΔE = 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]⁰ and ten-coordinate, monohydrated [Eu-tpptac(H₂O)]⁰ species. A similar trend is observed for the terbium complex. Despite the presence of this hydration equilibrium, the H₃tpptac ligand sensitizes Eu³⁺ and Tb³⁺ 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^-1 cm^-1. Such features of Ln³⁺ complexes of H₃tpptac indicate that this platform appears to be particularly appealing for the further development of luminescent lanthanide labels.