Explorations of the Hydrogenation of D 2 by Nitrogenase

A non‐physiological substrate of the enzyme nitrogenase, D 2 , is doubly hydrogenated by the enzyme to produce 2HD. This ‘HD reaction’ is in competition with the native function of the enzyme, hydrogenating N 2 to NH 3 . At the active site of the enzyme, a gallery of H atom donors is identified, and the proposed complete cycle mechanism for the N 2 reaction uses these donors eight times to generate the 2NH 3 + H 2 products. Here, the functionality of these H atom donors in hydrogenating D 2 to 2HD is investigated, applying density functional simulations to a 480+ atom model of the active site including all important surrounds. Many possible reaction trajectories were explored, and a revised mechanism for the HD reaction is presented. The mechanisms for hydrogenation of D 2 and of N 2 have common components, accounting for their experimentally known competition. Consideration of ten items of relevant experimental data about the HD reaction shows how the proposed mechanism complies with and interprets these data, although two experimental observations are still to be checked.