Dithiomethylether as a Ligand in the Hydrogenase H-Cluster

An X-ray crystallographic refinement of the H-cluster of FeFe-hydrogenase from Clostridium pasteurianum has been carried out to close-to atomic resolution and is the highest resolution FeFe-hydrogenase presented to date. The 1.39 A, anisotropically refined FeFe-hydrogenase structure provides a basis for examining the outstanding issue of the composition of the unique nonprotein dithiolate ligand of the H-cluster. In addition to influencing the electronic structure of the H-cluster, the composition of the ligand has mechanistic implications due to the potential of the bridge-head gamma-group participating in proton transfer during catalysis. In this work, sequential density functional theory optimizations of the dithiolate ligand embedded in a 3.5-3.9 A protein environment provide an unbiased approach to examining the most likely composition of the ligand. Structural, conformational, and energetic considerations indicate a preference for dithiomethylether as an H-cluster ligand and strongly disfavor the dithiomethylammonium as a catalytic base for hydrogen production.