The activating capture of N2 at the active site of Mo–nitrogenase

Abstract

Dinitrogen is inherently inert. This report describes detailed density functional calculations (with a 485+ atom model) of mechanistic steps by which the enzyme nitrogenase activates unreactive N₂ at the intact active site FeMo-co, to form a key intermediate with bound HNNH. This mechanism does not bind N₂ first and then add H atoms, but rather captures N₂ (‘N2-ready’) that diffuses in through the substrate channel and enters a strategic gallery of H atom donors in the reaction zone, between Fe2 and Fe6. This occurs at the E4 stage of the complete mechanism. Exploration of possible reactions of N₂ in this space leads to the conclusion that the first reaction step is transfer of H on Fe7 to one end of N2-ready, soon followed by Fe–N bond formation, and then a second H transfer from bridging S2BH to the other N. Two H–N bonds and one or two N–Fe bonds are formed, in some cases with a single transition state. The variable positions and orientations of N2-ready lead to various reaction trajectories and products. The favourable products resulting from this capture, judged by the criteria of reaction energies, reaction barriers, and mechanistic competence for further hydrogenation reactions in the nitrogenase cycle, have Fe2–NH–NH bonding. The trajectory of one N₂ capture reaction is described in detail, and calculations that separate the H atom component and the ‘heavy atom’ components of the classical activation energy are described, in the context of possible H atom tunneling in the activation of N2-ready. I present arguments for the activation of N₂ by the pathway of concerted hydrogenation and binding of N2-ready, alternative to the commonly assumed pathway of binding N₂ first, with subsequent hydrogenation. The active site of nitrogenase is well primed for the thermodynamic and kinetic advantages of N₂ capture.