Intramolecular C-H bond amination catalyzed by myoglobin reconstituted with iron porphycene

Yoshiyuki Kagawa; Koji Oohora; Takashi Hayashi

doi:10.1016/j.jinorgbio.2023.112459

Intramolecular C-H bond amination catalyzed by myoglobin reconstituted with iron porphycene

J Inorg Biochem. 2024 Mar:252:112459. doi: 10.1016/j.jinorgbio.2023.112459. Epub 2023 Dec 21.

Authors

Yoshiyuki Kagawa¹, Koji Oohora², Takashi Hayashi³

Affiliations

¹ Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan.
² Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan; Innovative Catalysis Science Division, Institute for Open and Transdisciplinary Research Initiatives (ICS-OTRI), Osaka University, Suita, Osaka, 565-0871, Japan. Electronic address: oohora@chem.eng.osaka-u.ac.jp.
³ Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan. Electronic address: thayashi@chem.eng.osaka-u.ac.jp.

PMID: 38181613
DOI: 10.1016/j.jinorgbio.2023.112459

Abstract

C-H bond amination is an effective way to obtain nitrogen-containing products. In this work, we demonstrate that myoglobin reconstituted with iron porphycene (rMb(FePc)) catalyzes intramolecular C(sp³)-H bond amination of arylsulfonyl azides to yield corresponding sultam analogs. The total turnover number of rMb(FePc) is up to 5.7 × 10⁴ for the C-H bond amination of 2,4,6-triisopropylbenzenesulfonyl azide. Moreover, rMb(FePc) exhibits higher selectivity for the desired C-H bond amination than the competing azide reduction compared to native myoglobin. Kinetic studies reveal that the k_cat value of rMb(FePc) is 4-fold higher than that of native myoglobin. Furthermore, H64A, H64V and H64I mutants of rMb(FePc) enhance the turnover number (TON) and enantioselectivity for the C-H bond amination of 2,4,6-triethylbenzenesulfonyl azide. The present findings indicate that iron porphycene is an attractive artificial cofactor for myoglobin toward the C-H bond amination reaction.

Keywords: Artificial metalloenzyme; C–H bond functionalization; Iron porphycene; Myoglobin; Nitrene transfer; Sultam synthesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amination
Azides / chemistry
Catalysis
Iron* / chemistry
Kinetics
Myoglobin* / chemistry
Porphyrins*

Substances

porphycene
Iron
Myoglobin
Azides
Porphyrins