Aza- And Oxadithiolates Are Probable Proton Relays In Functional Models For The [fefe]-hydrogenases

摘要

The [FeFe]-hydrogenases are among the very best catalysts known for the reduction of protons to dihydrogen, with turnover frequencies estimated to be ～6000 mol of H_2/mol of enzyme per second operating at nearly Nerstian potentials. The question about why the [FeFe]-hydrogenases are so efficient is topical, and the answer is likely related to the incompletely characterized dithiolate cofactor that bridges the diiron subunit. In 2001, Nicolet et al. proposed that this dithiolate is the azadithiolate (adt, (SCH_2)_2NH), wherein the amine functionality could relay protons to and from the apical site on the distal Fe center. It is known that, unlike typical amine bases, transition metals can be slow to protonate. The adt hypothesis is attractive because it potentially shows how to couple the kinetic facility of amine protonation with the redox abilities of iron hydrides. Indeed, DuBois has demonstrated that amine bases constrained within diphosphine ligands greatly accelerate both H_2 uptake and production for mononuclear iron and nickel phosphine complexes. A recent DFT investigation suggests that the dithiolate cofactor is the oxadithiolate (odt, (SCH_2)_2O), which also merits evaluation since protein crystallography cannot distinguish between C, N, and O.