On the Mechanism of Catalysis by a Metal‐Free Hydrogenase from Methanogenic Archaea: Enzymatic Transformation of H2 without a Metal and Its Analogy to the Chemistry of Alkanes in Superacidic Solution

Substrate activation by protonation to form a “superelectrophile” could be a new mechanism for enzyme catalysis. The hydrogenation below, catalyzed by an enzyme containing no redox-active transition metal, is very similar to the reaction of carbocations with hydrogen under superacidic conditions. This suggests that in the enzyme-bound state the stable formamidinium ion 1 may also be converted into a highly reactive carbocation, probably through N-protonation and conformational locking.