Meso-fluorinated cobalamins: insights into synthesis and redox properties

Here, we present the first method of synthesis of cyano- (F-CNCbl) and aqua (F-H₂OCbl) cobalamins, fluorinated at the C10 (meso) position of the corrin ring, and characterization of their redox properties. The reductive decyanation of F-CNCbl by glutathione and the reduction of F-H₂OCbl to Co(II)-form (F-Cbl(II)) by glutathione or reduced nicotinamide adenine dinucleotide proceed more efficiently than the reactions involving unmodified complexes, which may facilitate their intracellular processing, especially in the case of patients with impaired metabolism of CblC-protein. The stability of the C-F bond in fluorinated Cbls displays remarkable stability upon F-Cbl(II) reduction to the Co(I) form is a remarkable finding, in stark contrast to the elimination of the Br atom in meso-brominated cobalamin is eliminated during this process.