Heme FeSO2− intermediates in sulfite reduction: Contrasts with FeOO2− species from oxygen–oxygen bond activating systems

Sulfite reductase (SiR) catalyzes a six electron and six proton reduction of sulfite to sulfide. Similarly to the cytochrome P450 (cytP450) family, the active site in SiR contains a (partially reduced) heme bound axially to a cysteinate ligand—though with an extra Fe4S4 cluster. Fe(III)SO2−, Fe(III)SOH−, and Fe(III)SO(H2) intermediates have been proposed for the catalytic cycle of SiR, leading to a formally Fe(V)S species—akin to the widely accepted reaction mechanism in cytP450. Here, density functional theory (DFT) data is reported for of such FeSO(H2) intermediates. The Fe(III)SO2− models display relatively high energies for homolytic bond breaking compared to their isomeric oxygen‐bound Fe(III)OS2− models, and thus offer a better alternative in terms of avoiding radical side products able to induce enzyme suicide. This could be due to the fact that the (iron‐bound) sulfur is more active from a redox standpoint compared to oxygen, thus permitting the departing oxygen to maintain a redox‐inert state. Di‐protonation of the oxygen is computed to lead to a compound I type Fe(IV)S coupled to a porphyrin radical anion—consistent with an intermediate previously observed by x‐ray crystallography. Sulfite reductase (SiR) catalyzes a six electron and six proton reduction of sulfite to sulfide. Density Fuctional Theory shines a light on the catalytic cycle of SiR, using Fe(III)SO2−, Fe(III)SOH−, and Fe(III)SO(H2) as model systems. Fe(III)SO2− models display relatively high energies for homolytic bond breaking compared to their isomeric oxygen‐bound Fe(III)OS2− models, and thus offering a better alternative to avoid radical side products able to induce enzyme suicide.