Stability, Water Exchange, and Anion Binding Studies on Lanthanide(III) Complexes with a Macrocyclic Ligand Based on 1,7-Diaza-12-crown-4: Extremely Fast Water Exchange on the Gd3+ Complex

The picolinate-derivative ligand based on the 1,7-diaza-12-crown-4 platform (bp12c4(2-)) forms stable Ln(3+) complexes with stability constants increasing from the early to the middle lanthanides, then being relatively constant for the rest of the series (logK(LnL) = 16.81(0.06), 18.82(0.01), and 18.08(0.05) for Ln = La, Gd, and Yb, respectively). The complex formation is fast, allowing for direct potentiometric titrations to assess the stability constants. In the presence of Zn2+, the dissociation of [Gd(bp12c4)](+) proceeds both via proton- and metal-assisted pathways, and in this respect, this system is intermediate between DTPA-type and macrocyclic, DOTA-type chelates, for which the dissociation is predominated by metal- or proton-assisted pathways, respectively. The Cu2+ exchange shows an unexpected pH dependency, with the observed rate constants decreasing with increasing proton concentration. The rate of water exchange, assessed by O-17 NMR, is extremely high on the [Gd(bp12c4)(H2O)(q)](+) complex (k(ex)(298) = (2.20 +/- 0.15) X 10(8) s(-1)), and is in the same order of magnitude as for the Gd3+ aqua ion (k(ex)(298) = 8.0 x 10(8) s(-1)). In aqueous solution, the [Gd(bp12c4)(H2O)(q)](+) complex is present in hydration equilibrium between nine-coordinate, monohydrated, and ten-coordinate, bishydrated species. We attribute the fast exchange to the hydration equilibrium and to the flexible nature of the inner coordination sphere. The large negative value of the activation entropy (Delta S-double dagger = -35 +/- 8 J mol(-1) K-1) points to an associative character for the water exchange and suggests that water exchange on the nine-coordinate, monohydrated species is predominant in the overall exchange. Relaxometric and luminescence measurements on the Gd3+ and Eu3+ analogues, respectively, indicate strong binding of endogenous anions such as citrate, hydrogencarbonate, or phosphate to [Ln(bp12c4)](+) complexes (K-aff = 280 +/- 20 M-1, 630 +/- 50 M-1, and 250 +/- 20 M-1, respectively). In the ternary complexes, the inner sphere water molecules are fully replaced by the corresponding anion. Anion binding is favored by the positive charge of the [Ln(bp12c4)](+) complexes and the adjacent position of the two innersphere water molecules. To obtain information about the structure of the ternary complexes, the [Gd(bp12c4)(HCO3)] and [Gd(bp12c4)(H2PO4)] systems were investigated by means of density functional theory calculations (B3LYP model). They show that anion coordination provokes an important lengthening of the distances between the donor atoms and the lanthanide ion. The coordination of phosphate induces a more important distortion of the metal coordination environment than the coordination of hydrogencarbonate, in accordance with a higher binding constant for HCO3- and a more important steric demand of phosphate.