Effect of Ligand Chirality and Hyperconjugation on the Thermodynamic Stability of a Tris(aquated) GdIII Complex: Synthesis, Characterization, and T1‐Weighted Phantom MR Image Study

Abstract

The hexadentate chiral alanine‐based ligand, Li3cbda, in a reaction with hydrated GdCl3 at pH ~ 6.5 provided the corresponding nine‐coordinated, neutral GdIII complex (1). The hydration state (q) of complex 1 was 3.1 ± 0.1, as determined by luminescence decay time measurements of TbIII congener in H2O and D2O. Complex 1 exhibited thermodynamic stability, log KGdL = 14.64 in 0.15 m NaCl solution at 25 °C. At 1.41 T, pH ≈ 7.4, and 25 °C, the complex offered longitudinal relaxivity, r1 = 10.95 mm–1 s–1, which was in accordance with three inner‐sphere water molecules. While, the relaxivity value remained unaffected in the pH range of 4.0 to 7.4, under basic conditions (pH ≥ 10) a reduction in the relaxivity value to 6.68 mm–1 s–1 was observed. A similar phenomenon was also realized in the presence of endogenous anions (100 equivalents of F– and HCO3–), which implied the removal of coordinated‐water molecules under the conditions. Phantom MR imaging under the clinical scanner at 1.5 T showed the enhancement in the image intensity with increasing concentration of the complex. As expected, the image intensity of 1 mm complex 1 was about three times compared to 1 mm MultiHance® solution.