Hydrogenobinamide and nibinamide - Metal-free ligand and Ni(II)-analogue of the vitamin B12 precursor cobinamide

Abstract

The replacement of cobalt in vitamin B[Formula: see text] derivatives by other transition metals is a formal path to non-natural corrins. Here, we describe nibinamide (Nibi), the novel Ni(II)-analogue of the natural B[Formula: see text]-derivative cobinamide (Cbi), and its synthesis from the metal-free ligand of Cbi, hydrogenobinamide (Hbi), both isolated as tetrafluoroborate salts. Aqueous solutions of the metal-free corrin Hbi are strongly fluorescent, whereas its Ni(II)-complex Nibi is non-luminescent. The solution structures of Hbi and of Nibi were characterized by hetero-nuclear NMR-spectroscopy. The Ni(II)-corrin Nibi was deduced to be roughly iso-structural to cob(I)inamide (Cbi[Formula: see text] and to house a diamagnetic d8-metal-ioniso-electronic to Co[Formula: see text] in Cbi[Formula: see text]. The chemically robust Nibi is, thus, a structural mimic of enzyme-activated and reduced biosynthetic precursors of vitamin B[Formula: see text] and a B[Formula: see text]-antimetabolite potentially functioning as a specific inhibitor of B[Formula: see text]-biosynthesis.