Kumar Devesh, de Visser Sam P, Shaik Sason
Department of Organic Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
Chemistry. 2005 Apr 22;11(9):2825-35. doi: 10.1002/chem.200401044.
Density functional theoretical calculations are used to elucidate the epoxidation mechanism of styrene with a cytochrome P450 model Compound I, and the formation of side products. The reaction features multistate reactivity (MSR) with different spin states (doublet and quartet) and different electromeric situations having carbon radicals and cations, as well as iron(III) and iron(IV) oxidation states. The mechanisms involve state-specific product formation, as follows: a) The low-spin pathways lead to epoxide formation in effectively concerted mechanisms. b) The high-spin pathways have finite barriers for ring-closure and may have a sufficiently long lifetime to undergo rearrangement and lead to side products. c) The high-spin radical intermediate, (4)2(rad)-IV, has a ring closure barrier as small as the C--C rotation barrier. This intermediate will therefore lose stereochemistry and lead to a mixture of cis and trans epoxides. The barriers for the production of aldehyde and suicidal complexes are too high for this intermediate. d) The high-spin radical intermediate, (4)2(rad)-III, has a substantial ring closure barrier and may survive long enough time to lead to suicidal, phenacetaldehyde and 2-hydroxostyrene side products. e) The phenacetaldehyde and 2-hydroxostyrene products both originate from crossover from the (4)2(rad)-III radical intermediate to the cationic state, (4)2(cat,z(2) ). The process involves an N-protonated porphyrin intermediate that re-shuttles the proton back to the substrate to form either phenacetaldehyde or 2-hydroxostyrene products. This resembles the internally mediated NIH-shift observed during benzene hydroxylation.
密度泛函理论计算被用于阐明细胞色素P450模型化合物I与苯乙烯的环氧化机理以及副产物的形成。该反应具有多态反应性（MSR），涉及不同的自旋态（二重态和四重态）以及具有碳自由基和阳离子以及铁（III）和铁（IV）氧化态的不同电子离域情况。其反应机理包括特定状态的产物形成，具体如下：a）低自旋途径通过有效的协同机理导致环氧化物的形成。b）高自旋途径具有有限的闭环能垒，并且可能具有足够长的寿命以进行重排并导致副产物的形成。c）高自旋自由基中间体(4)2(rad)-IV的闭环能垒与C--C旋转能垒一样小。因此，该中间体将失去立体化学，导致顺式和反式环氧化物的混合物。该中间体生成醛和自杀性复合物的能垒过高。d）高自旋自由基中间体(4)2(rad)-III具有相当大的闭环能垒，并且可能存活足够长的时间以导致自杀性、苯乙酮醛和2-羟基苯乙烯副产物的形成。e）苯乙酮醛和2-羟基苯乙烯产物均源自(4)2(rad)-III自由基中间体向阳离子态(4)2(cat,z(2) )的交叉。该过程涉及一个N-质子化卟啉中间体，该中间体将质子重新穿梭回底物以形成苯乙酮醛或2-羟基苯乙烯产物。这类似于在苯羟基化过程中观察到的内部介导的NIH-迁移。
