Lanthanide Complexes with ¹H paraCEST and ¹⁹F Response for Magnetic Resonance Imaging Applications

We present a detailed study of the lanthanide(III) complexes with cyclen-based ligands containing phenylacetamide pendants that incorporate CF₃ group(s) at different distances from the metal ion. The complexes exhibit square-antiprismatic coordination in solution, as demonstrated by analysis of the Yb³⁺-induced paramagnetic shifts and the X-ray structure of the [YbL³] complex. Luminescence lifetime measurements and a detailed ¹H and ¹⁷O relaxometric characterization confirmed the presence of an inner-sphere H₂O molecule. The Tm³⁺ complexes provide chemical-exchange saturation-transfer response upon saturation at the frequency of the amide protons. A ¹⁹F relaxation study provided accurate estimates of the Ln···F distances that were used to rationalize the efficiency of the complexes as ¹⁹F magnetic resonance imaging (MRI) probes, which was tested in vitro using MRI phantom studies.