Redox-Dependent 1H and 19F Relaxation of a Fluorinated Mn–Diimidazolyl Porphyrin Complex

Complexes of redox active, paramagnetic transition metal ions, such as manganese, are under scrutiny as potential magnetic resonance imaging (MRI) probes for the assessment of the tissue redox state, and the use of fluorinated ligands can afford dual 1H and 19F MRI detection. While porphyrins are excellent chelators for both oxidized Mn(III) and reduced Mn(II) states, the low aqueous solubility of the complexes often limits application, especially for fluorinated derivatives. To improve hydrosolubility, we have introduced two quaternized methylimidazole functions on the porphyrin complex Mn(III)-6 bearing two CF3 groups. Mn(III)-6 can be reduced by ascorbic acid (AA) or carboxylate-protected cysteine, and Mn(II)-6 is reoxidized by air oxygen. In DMSO/H2O mixtures, both reduction and oxidation reactions are strongly affected by the solvent composition, likely related to the different reducing power of ascorbate and to different Mn-porphyrin aggregation states. The reduction from Mn(III)-6 to Mn(II)-6 is accompanied by important variation in the proton relaxivities with the exception of 30 and 400 MHz, where the nuclear magnetic relaxation dispersion (NMRD) curves of the complexes intersect. The 19F relaxation times become shorter upon reduction (∼ 30% decrease for T1 and 70% for T2; 9.4 T, 25 °C). The 19F MRI signal recorded by a FLASH sequence can be detected for the Mn(III)-6 form with a good signal-to-noise ratio, which is proportional to the Mn(III)-6 concentration. Upon reduction with ascorbic acid, the progressive decrease of the 19F MRI signal is directly reporting on the reaction progress.