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

We present two novel octadentate cyclen-based ligands bearing one (L¹ ) or two (L² ) phenylacetamide pendants with two CF₃ groups either at positions 3 and 5 (L¹ ) or 4 (L² ). The corresponding Gd³⁺ 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 GdL¹ (k_ex ²⁹⁸ =1.52×10⁶  s^-1 ) is faster than that determined for the bis-amide complex GdL² (k_ex ²⁹⁸ =0.73×10⁶  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 GdL¹ and GdL² , respectively. Phantom MRI studies revealed the favorable properties of GdL² as a dual ¹ H/¹⁹ F magnetic resonance imaging (MRI) probe, whereas the shorter Gd⋅⋅⋅F distance of GdL¹ reduces the signal-to-noise ratio due to the very short transverse relaxation time of the ¹⁹ F NMR signal.