Direct Electrophilic Attack of Compound I on the Indole Ring in the Peroxygenase Mechanism of Dehaloperoxidase DHP B in Degrading Haloindole: Electron Transfer Promotes the Reaction.

The HO-dependent degradation of haloindole catalyzed by the dehaloperoxidase (DHP) from has been reported to employ the peroxygenase mechanism, and the two oxidized products 5-halo-2-oxindole and 5-halo-3-oxindole have a similar amount. According to a previous experimental study, compound I (Cpd I) was suggested to be responsible for triggering the reaction, and the reaction may undergo three possible intermediates; however, the reaction details are still unclear. To clarify the reaction mechanism of DHP, the computational model was constructed on the basis of the high-resolution crystal structure, and a series of the quantum mechanical/molecular mechanical calculations were performed. Based on our calculation results, it is confirmed that the reaction starts from the direct electrophilic attack of Cpd I on the indole ring of the substrate, and the resulted intermediate contains both a carbocation and an oxygen anion, whereas the common hydrogen abstraction by Cpd I was calculated to correspond to a relatively higher barrier. In addition, a net electron transfer from the substrate to the iron center is observed during the attack of Cpd I on the indole ring; therefore, the carbocation/oxygen anion intermediate can easily undergo an intramolecular hydride transfer to form the product 5-halo-2-oxindole or isomerize to the epoxide intermediate which finally generates another product 5-halo-3-oxindole. It is the zwitterionic characteristic of the intermediate that makes the intermolecular hydride transfer quite easy, and it is the high electron affinity of the iron center that promotes the single-electron oxidation of the reaction intermediate. Our calculations well explain the formation of two oxidized products 5-halo-2-oxindole and 5-halo-3-oxindole.