The roles of long-range proton-coupled electron transfer in the directionality and efficiency of [FeFe]-hydrogenases

Significance Activation of hydrogen in biology is achieved by enzymes rivalling the platinum metals in catalytic activity. Attached to an electrode, hydrogenases display electrocatalytic reversibility—just the tiniest potential bias from the equilibrium value drives oxidation or production of H 2 at significant rates. Hydrogenases activate H 2 heterolytically; hence, reversibility, an extreme marker for evolved efficiency, is expected to depend on electron and proton transfer processes occurring in concert. Experiments in which the long-range proton-transfer pathway in two [FeFe]-hydrogenases has been mildly disrupted without affecting the electron transfer pathway show that electrocatalytic reversibility fades as electron and proton transfers become temporally decoupled. These subtlest of observations demonstrate how evolution responded to the need for concerted electron–proton transfer in optimizing catalytic efficiency.