Fluorinated Mn(III)/(II)-Porphyrin with Redox-Responsive ¹ H and ¹⁹ F Relaxation Properties

A new fluorinated manganese porphyrin, (Mn-TPP-p-CF₃ ) is reported capable of providing, based on the Mn(III)/Mn(II) equilibrium, dual ¹ H relaxivity and ¹⁹ F NMR response to redox changes. The physical-chemical characterization of both redox states in DMSO-d₆ /H₂ O evidenced that the ¹ H relaxometric and ¹⁹ F NMR properties are appropriate for differential redox MRI detection. The Mn(III)-F distance (d_Mn-F =9.7-10 Å), as assessed by DFT calculations, is well tailored to allow for adequate paramagnetic effect of Mn(III) on ¹⁹ F T₁ and T₂ relaxation times. Mn-TPP-p-CF₃ has a reversible Mn(II)/Mn(III) redox potential of 0.574 V vs. NHE in deoxygenated aqueous HEPES/ THF solution. The reduction of Mn(III)-TPP-p-CF₃ in the presence of ascorbic acid is slowly, but fully reversed in the presence of air oxygen, as monitored by UV-Vis spectrometry and ¹⁹ F NMR. The broad ¹ H and ¹⁹ F NMR signals of Mn(III)-TPP-p-CF₃ disappear in the presence of 1 equivalent ascorbate replaced by a shifted and broadened ¹⁹ F NMR signal from Mn(II)-TPP-p-CF₃ . Phantom ¹⁹ F MR images in DMSO show a MRI signal intensity decrease upon reduction of Mn(III)-TPP-p-CF₃ , retrieved upon complete reoxidation in air within ~24 h. ¹ H NMRD curves of the Mn(III)/(II)-TPP-p-CF₃ chelates in mixed DMSO/water solvent have the typical shape of Mn(II)/Mn(III) porphyrins.