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

Abstract

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 Fe 4 S 4 cluster. Fe(III) SO 2− , Fe(III) SOH − , and Fe(III) SO(H 2 ) 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(H 2 ) intermediates. The Fe(III) SO 2− models display relatively high energies for homolytic bond breaking compared to their isomeric oxygen-bound Fe(III) OS 2− 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. K E Y W O R D S cytP450, heme, peroxide, sulfite reductase, sulfur oxide

Side-On OMoF2(η2-SO) and OWF2(η2-SO) Complexes Featuring Peroxo-Like Sulfur Monoxide Ligand

“…The side-on (η 2 -SO) coordination fashion was corroborated for the group 4 and 5 metal complexes, , and the group 5 metal complexes can be considered as (OMF 2 ) + (SO) − based on the S–O stretching vibrational frequency and bond length . The existence of SO – in the SO complexes of group 5 metals raises the question of whether SO can be further reduced upon coordination to transition metals with richer electrons, since O 2 , which is isoelectronic to SO, ,, undergoes stepwise activation to form superoxo and peroxo complexes upon coordination to metal centers. − There has been a comparison focusing on the Fe–SO 2– and Fe–O 2 2– intermediates from the theoretical point of view, but experimental evidence that clearly demonstrates the existence of a peroxo-like sulfur monoxide (SO 2– ) complex of transition metal is limited.…”

Intermediates involved in the reduction of SO2: insight into the mechanism of sulfite reductases

“…1B). [11][12][13][14][15][16][17] Protons are provided by conserved arginine and lysine residues present in the active site. 15 In addition, a sulfur monoxide (SO)-bound siroheme intermediate was proposed based on the crystal structure obtained by the oxidation of an S 2À -bound siroheme-Fe 4 S 4 site (Fig.…”

Reactivity of Small Oxoacids of Sulfur

“…The last steps of the cycle include the formation of Fe-SO adducts, proposed to be a critical step in this cycle [101]. Linkage isomerism is possible in Fe-SO models and Fe 2+ -SO 0 can shift to its OS form [102,103]. This FeOS intermediate would lead to a possible alternative route.…”