The "somersault" mechanism for the p-450 hydroxylation of hydrocarbons. The intervention of transient inverted metastable hydroperoxides
Bach, RD; Dmitrenko, O
| HERO ID | 1071173 |
|---|---|
| In Press | No |
| Year | 2006 |
| Title | The "somersault" mechanism for the p-450 hydroxylation of hydrocarbons. The intervention of transient inverted metastable hydroperoxides |
| Authors | Bach, RD; Dmitrenko, O |
| Journal | Journal of the American Chemical Society |
| Volume | 128 |
| Issue | 5 |
| Page Numbers | 1474-1488 |
| 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. |
| Doi | 10.1021/ja052111+ |
| Pmid | 16448118 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Is Qa | No |