共 84 条
The "somersault" mechanism for the P-450 hydroxylation of hydrocarbons. The intervention of transient inverted metastable hydroperoxides
被引:82
作者:
Bach, RD
[1
]
Dmitrenko, O
[1
]
机构:
[1] Univ Delaware, Dept Chem & Biochem, Newark, DE 19716 USA
关键词:
D O I:
10.1021/ja052111+
中图分类号:
O6 [化学];
学科分类号:
0703 ;
摘要:
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 hydroperoxicle to its inverted isomeric form with a hydroxyl radical hydrogen bonded to the metal oxide (MO-OH -> (MOHO)-H-....). The activation energy for this somersault motion of the FeO-OH group is 20.3 kcal/mol for the P450 model porphyrin iron(Ill) hydroperoxide [Por(SH)Fe(III)-OOH-] to produce the isomeric ferryl oxygen hydrogen bonded to an center dot OH radical [Por(SH)Fe(III)-(OHO-)-H-....]. 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(Ill) 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 center dot 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 (Delta E-double dagger = 19.5 kcal/mol). The overall proposed new mechanism is consistent with a lot of the ancillary experimental data for this enzymatic hydroxylation reaction.
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页码:1474 / 1488
页数:15
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