Small, Fluorinated Mn²⁺ Chelate as an Efficient ¹H and ¹⁹F MRI Probe

We explore the potential of fluorine-containing small Mn²⁺ chelates as alternatives to perfluorinated nanoparticles, widely used as ¹⁹F MRI probes. In MnL1, the cyclohexanediamine skeleton and two piperidine rings, involving each a metal-coordinating amide group and an appended CF₃ moiety, provide high rigidity to the complex. This allows for good control of the Mn-F distance (r_MnF=8.2±0.2 Å determined from ¹⁹F relaxation data), as well as for high kinetic inertness (a dissociation half-life of 1285 h is estimated for physiological conditions). The paramagnetic Mn²⁺ leads to a ~150-fold acceleration of the longitudinal ¹⁹F relaxation, with moderate line-broadening effect, resulting in T₂/T₁ ratios of 0.8 (9.4 T). Owing to its inner sphere water molecule, MnL1 is a good ¹H relaxation agent as well (r₁=5.36 mM^-1 s^-1 at 298 K, 20 MHz). MnL1 could be readily visualized in ¹⁹F MRI by using fast acquisition techniques, both in phantom images and living mice following intramuscular injection, with remarkable signal-to-noise ratios and short acquisition times. While applications in targeted imaging or cell therapy monitoring require further optimisation of the molecular structure, these results argue for the potential of such small, monohydrated and fluorinated Mn²⁺ complexes for combined ¹⁹F and ¹H MRI detection.