Gadolinium(III)-Based Dual ¹ H/ ¹⁹ F Magnetic Resonance Imaging Probes

We present two novel octadentate cyclen-based ligands bearing one (L ¹ ) or two (L ² ) phenylacetamide pendants with two CF ₃ groups either at positions 3 and 5 (L ¹ ) or 4 (L ² ). The corresponding Gd ³⁺ complexes possess one coordinated water molecule, as confirmed by luminescence lifetime measurements on the Eu ^III and Tb ^III analogues. A detailed ¹ H and ¹⁷ O relaxometric characterization has revealed the parameters that govern the relaxivities of these complexes. The water-exchange rate of the mono-amide derivative GdL ¹ (k _ex ²⁹⁸ =1.52×10 ⁶ s ⁻¹ ) is faster than that determined for the bis-amide complex GdL ² (k _ex ²⁹⁸ =0.73×10 ⁶ s ⁻¹ ). ¹ H and ¹⁹ F NMR studies have indicated that the complexes are present in solution almost exclusively as the square-antiprismatic (SAP) isomers. ¹⁹ F NMR relaxation studies indicated Gd⋅⋅⋅F distances of 7.4±0.1 and 9.1±0.1 Å for GdL ¹ and GdL ² , respectively. Phantom MRI studies revealed the favorable properties of GdL ² as a dual ¹ H/ ¹⁹ F magnetic resonance imaging (MRI) probe, whereas the shorter Gd⋅⋅⋅F distance of GdL ¹ reduces the signal-to-noise ratio due to the very short transverse relaxation time of the ¹⁹ F NMR signal.