Computational Investigations of the Chemical Mechanism of the Enzyme Nitrogenase

Abstract The chemical mechanism of nitrogenase, catalysing N 2 +8 e+8 H + →2 NH 3 +H 2 , occurs at a large multi‐metal cluster (FeMo‐co) with composition CFe 7 MoS 9 (homocitrate). More than 20 steps are required. Experimental elucidation of this mechanism is elusive, for various reasons, and computational approaches have a valuable role. This review critically surveys recent density functional calculations of the coordination chemistry and relevant reactions of FeMo‐co within the protein surrounds. Topics covered include the accuracies and validation of the density functionals, the treatment of electronic structure, and the chemical models used. The components of mechanism are described, including the input of N 2 , proton supply, the egress of NH 3 , and the roles of surrounding protein. This leads to descriptions and evaluations of the overall mechanistic cycles proposed on the basis of density functional calculations. Finally, I discuss some current issues, and consider the outlook for further work.