Fluorinated Mn(III)/(II)-Porphyrin with Redox-Responsive ¹H and ¹⁹F 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 H-1 relaxivity and F-19 NMR response to redox changes. The physical-chemical characterization of both redox states in DMSO-d(6)/H2O evidenced that the H-1 relaxometric and F-19 NMR properties are appropriate for differential redox MRI detection. The Mn(III)-F distance (d(Mn-F)=9.7-10 & ANGS;), as assessed by DFT calculations, is well tailored to allow for adequate paramagnetic effect of Mn(III) on F-19 T-1 and T-2 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 F-19 NMR. The broad H-1 and F-19 NMR signals of Mn(III)-TPP-p-CF3 disappear in the presence of 1 equivalent ascorbate replaced by a shifted and broadened F-19 NMR signal from Mn(II)-TPP-p-CF3. Phantom F-19 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 similar to 24 h. H-1 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.