title: Fe-O versus O-O bond cleavage in reactive iron peroxide intermediates of superoxide reductase.
abstract: It is generally accepted that the catalytic cycles of superoxide reductases (SORs) and cytochromes P450 involve a ferric hydroperoxo intermediate at a mononuclear iron center with a coordination sphere consisting of four equatorial nitrogen ligands and one axial cysteine thiolate trans to the hydroperoxide. However, although SORs and P450s have similar intermediates, SORs selectively cleave the Fe-O bond and liberate peroxide, whereas P450s cleave the O-O bond to yield a high-valent iron center. This difference has attracted the interest of researchers, and is further explored here. Meta hybrid DFT (M06-2X) results for the reactivity of the putative peroxo/hydroperoxo reaction intermediates in the catalytic cycle of SORs were found to indicate a high-spin preference in all cases. An exploration of the energy profiles for Fe-O and O-O bond cleavage in all spin states in both ferric and ferrous models revealed that Fe-O bond cleavage always occurs more easily than O-O bond cleavage. While O-O bond cleavage appears to be thermodynamically and kinetically unfeasible in ferric hydrogen peroxide complexes, it could occur as a minor (significantly disfavored) side reaction in the interaction of ferrous SOR with hydrogen peroxide.
authors.affiliation: Department of Chemistry and Chemical Engineering, Babes-Bolyai University, 1 Mihail Kogălniceanu str, 400084 Cluj-Napoca, Romania.
authors.forename: Amr Ali Ahmed Ali
authors.initials: AA
authors.lastname: Attia
authors.forename: Daniela
authors.initials: D
authors.lastname: Cioloboc
authors.forename: Alexandru
authors.initials: A
authors.lastname: Lupan
authors.forename: Radu
authors.initials: R
authors.lastname: Silaghi-Dumitrescu
mesh_terms: D055162:Biocatalysis; D007501:Iron / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D010545:Peroxides / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity; D013482:Superoxide Dismutase / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D010545:Peroxides; D007501:Iron; D013482:Superoxide Dismutase; D010100:Oxygen