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Redox Engineering of Myoglobin by Cofactor Substitution to Enhance Cyclopropanation Reactivity.
- Source :
-
Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Sep 02; Vol. 63 (36), pp. e202403485. Date of Electronic Publication: 2024 Jul 04. - Publication Year :
- 2024
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Abstract
- Design of metal cofactor ligands is essential for controlling the reactivity of metalloenzymes. We investigated a carbene transfer reaction catalyzed by myoglobins containing iron porphyrin cofactors with one and two trifluoromethyl groups at peripheral sites (FePorCF <subscript>3</subscript> and FePor(CF <subscript>3</subscript> ) <subscript>2</subscript> , respectively), native heme and iron porphycene (FePc). These four myoglobins show a wide range of Fe(II)/Fe(III) redox potentials in the protein of +147 mV, +87 mV, +42 mV and -198 mV vs. NHE, respectively. Myoglobin reconstituted with FePor(CF <subscript>3</subscript> ) <subscript>2</subscript> has a more positive potential, which enhances the reactivity of a carbene intermediate with alkenes, and demonstrates superior cyclopropanation of inert alkenes, such as aliphatic and internal alkenes. In contrast, engineered myoglobin reconstituted with FePc has a more negative redox potential, which accelerates the formation of the intermediate, but has low reactivity for inert alkenes. Mechanistic studies indicate that myoglobin with FePor(CF <subscript>3</subscript> ) <subscript>2</subscript> generates an undetectable active intermediate with a radical character. In contrast, this reaction catalyzed by myoglobin with FePc includes a detectable iron-carbene species with electrophilic character. This finding highlights the importance of redox-focused design of the iron porphyrinoid cofactor in hemoproteins to tune the reactivity of the carbene transfer reaction.<br /> (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Details
- Language :
- English
- ISSN :
- 1521-3773
- Volume :
- 63
- Issue :
- 36
- Database :
- MEDLINE
- Journal :
- Angewandte Chemie (International ed. in English)
- Publication Type :
- Academic Journal
- Accession number :
- 38780472
- Full Text :
- https://doi.org/10.1002/anie.202403485