The E2 state of FeMoco: Hydride Formation versus Fe Reduction and a Mechanism for H2 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 (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.

Automated summary

This study explores the energy surface of the E-2 state of FeMoco and identifies two possible contender models: one containing a bridging hydride and an open sulfide-bridge (hydride model), and the other featuring a protonated belt-sulfide and a reduced cofactor without a hydride (non-hydride model).