title: The "somersault" mechanism for the p-450 hydroxylation of hydrocarbons. The intervention of transient inverted metastable hydroperoxides.
abstract: A series of model theoretical calculations are described that suggest a new mechanism for the oxidation step in enzymatic cytochrome P450 hydroxylation of saturated hydrocarbons. A new class of metastable metal hydroperoxides is described that involves the rearrangement of the ground-state metal hydroperoxide to its inverted isomeric form with a hydroxyl radical hydrogen bonded to the metal oxide (MO-OH --> MO....HO). The activation energy for this somersault motion of the FeO-OH group is 20.3 kcal/mol for the P450 model porphyrin iron(III) hydroperoxide [Por(SH)Fe(III)-OOH(-)] to produce the isomeric ferryl oxygen hydrogen bonded to an *OH radical [Por(SH)Fe(III)-O....HO(-)]. This isomeric metastable hydroperoxide, the proposed primary oxidant in the P450 hydroxylation reaction, is calculated to be 17.8 kcal/mol higher in energy than the ground-state iron(III) hydroperoxide Cpd 0. The first step of the proposed mechanism for isobutane oxidation is abstraction of a hydrogen atom from the C-H bond of isobutane by the hydrogen-bonded hydroxyl radical to produce a water molecule strongly hydrogen bonded to anionic Cpd II. The hydroxylation step involves a concerted but nonsynchronous transfer of a hydrogen atom from this newly formed, bound, water molecule to the ferryl oxygen with a concomitant rebound of the incipient *OH radical to the carbon radical of isobutane to produce the C-O bond of the final product, tert-butyl alcohol. The TS for the oxygen rebound step is 2 kcal/mol lower in energy than the hydrogen abstraction TS (DeltaE() = 19.5 kcal/mol). The overall proposed new mechanism is consistent with a lot of the ancillary experimental data for this enzymatic hydroxylation reaction.
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA. rbach@udel.edu
authors.forename: Robert D
authors.initials: RD
authors.lastname: Bach
authors.forename: Olga
authors.initials: O
authors.lastname: Dmitrenko
mesh_terms: D002073:Butanes / Q000737:chemistry / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism*; D005290:Ferric Compounds / Q000737:chemistry; D006838:Hydrocarbons / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D006861:Hydrogen Peroxide / Q000737:chemistry*; D006900:Hydroxylation; D008665:Metalloporphyrins / Q000737:chemistry; D008697:Methane / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D013816:Thermodynamics
chemical_list: D002073:Butanes; D005290:Ferric Compounds; D006838:Hydrocarbons; D008665:Metalloporphyrins; D003577:Cytochrome P-450 Enzyme System; D006861:Hydrogen Peroxide; D008697:Methane