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Abstract Engineered heme proteins were developed to possess numerous excellent biocatalytic nitrenoid C−H functionalizations. Computational approaches such as density functional theory (DFT), hybrid quantum mechanics/molecular mechanics (QM/MM), and molecular dynamics (MD) calculations were employed to help understand some important mechanistic aspects of these heme nitrene transfer reactions. This review summarizes advances of computational reaction pathway results of these biocatalytic intramolecular and intermolecular C−H aminations/amidations, focusing on mechanistic origins of reactivity, regioselectivity, enantioselectivity, diastereoselectivity as well as effects of substrate substituent, axial ligand, metal center, and protein environment. Some important common and distinctive mechanistic features of these reactions were also described with brief outlook of future development.
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Biocatalytic Intramolecular C−H aminations via Engineered Heme Proteins: Full Reaction Pathways and Axial Ligand Effects
Abstract Engineered heme protein biocatalysts provide an efficient and sustainable approach to develop amine‐containing compounds through C−H amination. A quantum chemical study to reveal the complete heme catalyzed intramolecular C−H amination pathway and protein axial ligand effect was reported, using reactions of an experimentally used arylsulfonylazide with hemes containing L=none, SH−, MeO−, and MeOH to simulate no axial ligand, negatively charged Cys and Ser ligands, and a neutral ligand for comparison. Nitrene formation was found as the overall rate‐determining step (RDS) and the catalyst with Ser ligand has the best reactivity, consistent with experimental reports. Both RDS and non‐RDS (nitrene transfer) transition states follow the barrier trend of MeO−−
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- PAR ID:
- 10370156
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Chemistry – A European Journal
- Volume:
- 28
- Issue:
- 59
- ISSN:
- 0947-6539
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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