The chemical mechanism of nitrogenase: calculated details of the intramolecular mechanism for hydrogenation of η²-N₂ on FeMo-co to NH₃

Using density functional calculations, a complete chemical mechanism has been developed for the reaction N₂ + 6e⁻ + 6H⁺→ 2NH₃ catalyzed by the Fe₇MoS₉N^c(homocitrate) cofactor (FeMo-co) of the enzyme nitrogenase. The mechanism is based on previous descriptions of the generation of H atoms on FeMo-co by proton relay through a protein path terminating in water molecule 679, and preserves the model (which explains much biochemical data) for vectorial migration of H atoms to two S atoms and two Fe atoms of FeMo-co. After calculation of the energy profiles for the many possible sequences of steps in which these H atoms are transferred to N₂ and its hydrogenated intermediates, a favourable pathway to 2NH₃ was developed. Transition states and activation potential energies for the 21 step mechanism are presented, together with results for some alternative branches. The mechanism develops logically from the η²-coordination of N₂ at the endo position of one Fe atom of prehydrogenated FeMo-co, consistent with the previous kinetic–mechanistic scheme of Thorneley and Lowe, and passes through bound N₂H₂ and N₂H₄ intermediates. This mechanism is different from others in the literature because it uses a single replenishable path for serial supply of protons which become H atoms on FeMo-co, migrating to become S–H and Fe–H donors to N₂ and to the intermediates that follow. The new paradigm for the chemical catalysis is that hydrogenation of N₂ and intermediates is intramolecular and does not involve direct protonation from surrounding residues which appear to be unable to provide a replenishable supply of 6H⁺. Many steps in this intramolecular hydrogenation are expected to be enhanced by H tunneling.