The E(2) state of FeMoco: Hydride Formation versus Fe Reduction and a Mechanism for H(2) Evolution

The iron‐molybdenum cofactor (FeMoco) is responsible for dinitrogen reduction in Mo nitrogenase. Unlike the resting state, E(0), reduced states of FeMoco are much less well characterized. The E(2) state has been proposed to contain a hydride but direct spectroscopic evidence is still lacking. The E(2) state can, however, relax back the E(0) state via a H(2) side‐reaction, implying a hydride intermediate prior to H(2) formation. This E(2)→E(0) pathway is one of the primary mechanisms for H(2) formation under low‐electron flux conditions. In this study we present an exploration of the energy surface of the E(2) state. Utilizing both cluster‐continuum and QM/MM calculations, we explore various classes of E(2) models: including terminal hydrides, bridging hydrides with a closed or open sulfide‐bridge, as well as models without. Importantly, we find the hemilability of a protonated belt‐sulfide to strongly influence the stability of hydrides. Surprisingly, non‐hydride models are found to be almost equally favorable as hydride models. While the cluster‐continuum calculations suggest multiple possibilities, QM/MM suggests only two models as contenders for the E(2) state. These models feature either i) a bridging hydride between Fe(2) and Fe(6) and an open sulfide‐bridge with terminal SH on Fe(6) (E(2)‐hyd) or ii) a double belt‐sulfide protonated, reduced cofactor without a hydride (E(2)‐nonhyd). We suggest both models as contenders for the E(2) redox state and further calculate a mechanism for H(2) evolution. The changes in electronic structure of FeMoco during the proposed redox‐state cycle, E(0)→E(1)→E(2)→E(0), are discussed.