A Mechanism for Nitrogenase Including Loss of a Sulfide

• Published in: Chemistry : a European journal 2022-02, Vol.28 (12), p.e202103745-n/a
• Main Authors: Wei, Wen‐Jie, Siegbahn, Per E. M.
• Format: Article
• Language: English
• Subjects: activation; Binding; Carbides; Catalysis; Chemistry; density functional calculations; Enzymes; mechanisms; Molybdenum; Molybdenum - chemistry; Nitrogen - chemistry; Nitrogenase; Nitrogenase - chemistry; nitrogenases; Oxidation-Reduction; potential surfaces; Protons; Sulfide; Sulfides
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.202103745

Nitrogenase is the only enzyme in nature that can fix N2 from the air. The active cofactor of the leading form of this enzyme contains seven irons and one molybdenum connected by sulfide bridges. In several recent experimental studies, it has been suggested that the cofactor is very flexible, and might lose one of its sulfides during catalysis. In this study, the possible loss of a sulfide has been investigated by model calculations. In previous studies, we have shown that there should be four activation steps before catalysis starts, and this study is based on that finding. It was found here that, after the four reductions in the activation steps, a sulfide will become very loosely bound and can be released in a quite exergonic step with a low barrier. The binding of N2 has no part in that release. In our previous studies, we suggested that the central carbide should be protonated three times after the four activation steps. With the new finding, there will instead be a loss of a sulfide, as the barrier for the loss is much lower than the ones for protonating the carbide. Still, it is suggested here that the carbide will be protonated anyway, but only with one proton, in the E3 to E4 step. A very complicated transition state for H2 formation involving a large structural change was obtained. The combined step, with a loss of H2 and binding of N2, is calculated to be endergonic by +2.3 kcal mol−1; this is in excellent agreement with experiments in which an easily reversible step has been found. Lost property: The possible loss of a sulfide mechanism for the Mo‐nitrogenase has been investigated by hybrid DFT using a cluster model. The calculations show that, after four reductions, a sulfide can be released as a H2S group. After another four reductions, the central carbon is protonated with one proton in E4, from where the loss of H2 and binding of N2 is reversible.