Key Laboratory of Material Chemistry for Energy Conversion and Storage, Ministry of Education, Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Hubei Key Laboratory of Materials Chemistry and Service Failure, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China.
Chem Asian J. 2022 Aug 15;17(16):e202200490. doi: 10.1002/asia.202200490. Epub 2022 Jun 20.
The nonheme diiron toluene/o-xylene monooxygenase (ToMO) is the most studied toluene monooxygenase that mediates an aromatic hydroxylation reaction. In this work, QM/MM calculations were performed to understand the reaction mechanism. It is revealed that the μ-η :η peroxodiferric species is the reactive intermediate after the binding of the O molecule to the reduced diferrous center. Subsequently, both a stepwise and a concerted mechanism involving the critical O-O bond cleavage and C-O bond formation were considered. The latter was calculated to be more favorable, suggesting that the formation of a high-valent diferryl Q intermediate is not needed. The isomeric formation of the phenol product was found very facile. The first step was calculated to be rate-limiting, with a barrier of 17.6 kcal/mol for the ortho-hydroxylation.
非血红素二铁甲苯/邻二甲苯单加氧酶（ToMO）是研究最为广泛的介导芳香族羟化反应的甲苯单加氧酶。在这项工作中，我们进行了量子力学/分子力学计算以理解反应机制。结果表明，μ-η:η过氧二铁物种是 O 分子与还原态二价铁中心结合后形成的反应活性中间体。随后，我们考虑了涉及关键 O-O 键断裂和 C-O 键形成的逐步和协同机制。计算表明，高价二芳基 Q 中间体的形成并非必需。酚产物的异构化过程非常容易发生。我们发现第一步是速率限制步骤，邻位羟化的能垒为 17.6 kcal/mol。
