Diversifying Metal–Ligand Cooperative Catalysis in Semi‐Synthetic [Mn]‐Hydrogenases

The reconstitution of [Mn]‐hydrogenases using a series of Mn(I) complexes is described. These complexes are designed to have an internal base or pro‐base that may participate in metal–ligand cooperative catalysis or have no internal base or pro‐base. Only Mn(I) complexes with an internal base or pro‐base are active for H(2) activation; only [Mn]‐hydrogenases incorporating such complexes are active for hydrogenase reactions. These results confirm the essential role of metal–ligand cooperation for H(2) activation by the Mn(I) complexes alone and by [Mn]‐hydrogenases. Owing to the nature and position of the internal base or pro‐base, the mode of metal–ligand cooperation in two active [Mn]‐hydrogenases is different from that of the native [Fe]‐hydrogenase. One [Mn]‐hydrogenase has the highest specific activity of semi‐synthetic [Mn]‐ and [Fe]‐hydrogenases. This work demonstrates reconstitution of active artificial hydrogenases using synthetic complexes differing greatly from the native active site.