Shining Light on the Mechanism of Photochemical Alkene Formation in Vitamin B12

While photolysis of adenosylcobalamin in solution typically yields 5'-deoxyadenosyl radicals that undergo intramolecular cyclization forming 5',8-cycloadenosine, the adenosylcobalamin dependent protein CarH generates a Co(I) species and the alkene product 4',5'-anhydroadenosine. Similarly, alkylcobalamins are known to generate alkene products from the photo-dissociated alkyl radicals, but the mechanistic details of these reactions, how they are influenced by the chosen solvent and additives, and whether there is a connection between the resulting cobalamin oxidation state and the organic product is not well understood. In the present study, we utilized time-resolved UV-visible spectroscopy to investigate the photochemistry of different alkylcobalamins in order to address these questions. We demonstrate that in an aqueous environment, photolysis of alkylcobalamins leads to the formation of Co(I), despite Co(II) being known as the initial product at the picosecond timescale. A protein scaffold is not required for Co(I) formation. In addition, we observe predominantly the alkene product. Rather than being unique to the CarH protein, these seem to be fundamental properties of alkylcobalamins when photolyzed in water. In contrast, we find that Co(II) is the primary photolysis product in solvents with hydrogen atom donor properties, such as ethanol, with the alkane as the major product. The solvent environment plays a crucial role in determining the nature of the organic products, as it influences how the alkyl radicals quench. Since we can cleanly generate cob(I)alamin via photolysis without the need for chemical reductant, we were also able to investigate the mechanism of alkylcobalamin formation from the reaction of cob(I)alamin with alkyl bromides (RBr), revealing a branching pathway. We herein discuss the implications of these results for the mechanism of CarH, as well as the potential for cobalamins as photocatalysts for the transformation of alkyl halides into alkenes.