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 Eu3+ and Tb3+ complexes derived from a tripyridinophane macrocycle bearing three
acetate side arms (H3tpptac). Tpptac3– displays an overall basicity (∑ log KiH) of 24.5, provides the formation of mononuclear
ML species, and shows a good binding affinity for Ln3+ (log KLnL = 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 KCuL = 14.4, log KZnL = 12.9,
and log KCaL = 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.