A Bishydrated, Eight–Coordinate Gd(III) Complex with Very Fast Water Exchange: Synthesis, Characterization, and Phantom MR Imaging

We report here the physical‐chemical characterization of a highly water‐soluble Gd(III) complex (complex 1) formed with the asymmetric hexadentate ligand H4bedik (2,2′‐((2‐(bis (carboxymethyl)amino)benzyl)azanediyl)diacetic acid). The number of water molecules directly coordinated to the metal, q=2.2, was assessed by measuring luminescence lifetimes of the Tb(III) analogue (complex 2) in H2O and D2O and it further was confirmed by 17O chemical shift measurements on the Gd(III) complex. The complex has moderate thermodynamic stability and remains insensitive to physiological anions [biphosphate (HPO42−), bicarbonate (HCO3−)] and pH variation (in the range 5–10) of the medium as evidenced by negligible changes in longitudinal relaxivity (r1) at 1.41 T, 25 °C. The Gd(III) complex exhibits very fast water exchange, among the fastest reported for Gd(III) chelates, and high relaxivity at high magnetic fields (r1=7.47 mM–1s–1 at 9.4 T, pH ∼ 7 and 25 °C). Interestingly, the very high positive value of the activation entropy indicates a dissociatively activated water exchange for this eight‐coordinate complex. A highly water‐soluble and bishydrated Gd(III) complex with very fast water exchange and high relaxivity at high magnetic fields (r1=7.47 mM–1s–1 at 9.4 T, pH ∼ 7 and 25 °C) was synthesized. Interestingly, a dissociative water exchange mechanism was indicated for the bishydrated octacoordinate chelate.