Deconstructing F430:: quantum chemical perspectives of biological methanogenesis

What stabilizes the unique Ni(I) state of the active form of coenzyme F-430 and of methylcoenzyme M reductase, the enzyme responsible for the last methane-evolving step of biological methanogenesis? A survey of F430 model compounds suggests that the monoanionic nature of the F430 ligand goes a long way toward explaining the stability of Ni(I) F-430. Second, nature appears to have manipulated the stereochemistry of the macrocycle, particularly that of the 12- and 13- substituents, so that the cofactor is sterically constrained against ruffling and forced to adopt a relatively planar conformation with long Ni-N distances. Third, the carbonyl substituent at the 15-meso position electronically stabilizes the Ni(I) state of the cofactor. With regard to the mechanism of methylcoenzyme M reductase, the most reasonable mechanism, in our opinion, involves a Ni(I)-mediated homolytic cleavage of the S-CH3 bond in methylcoenzyme M, followed immediately by the quenching of the methyl radical by coenzyme B (a thiol) to produce methane.