Reducing CO2 to HCO2- at Mild Potentials: Lessons from Formate Dehydrogenase.

The catalytic reduction of CO2 to HCO2- requires a formal transfer of a hydride (two electrons, one proton). Synthetic approaches for inorganic molecular catalysts have exclusively relied on classic metal hydrides, where the proton and electrons originate from the metal (via heterolytic cleavage of an M-H bond). An analysis of the scaling relationships that exist in classic metal hydrides reveal that hydride donors sufficiently hydridic to perform CO2 reduction are only accessible at very reducing electrochemical potentials, which is consistent with known synthetic electrocatalysts. By comparison, the formate dehydrogenase enzymes operate at relatively mild potentials. In contrast to reported synthetic catalysts, none of the major mechanistic proposals for hydride transfer in formate dehydrogenase proceed through a classic metal hydride. Instead, they invoke formal hydride transfer from an orthogonal or bidirectional mechanism, where the proton and electrons are not colocated. We discuss the thermodynamic advantages of this approach for favoring CO2 reduction at mild potentials, along with guidelines for replicating this strategy in synthetic systems.