Issue 47, 2021

Inhibition of [FeFe]-hydrogenase by formaldehyde: proposed mechanism and reactivity of FeFe alkyl complexes

Abstract

The mechanism for inhibition of [FeFe]-hydrogenases by formaldehyde is examined with model complexes. Key findings: (i) CH2 donated by formaldehyde covalently link Fe and the amine cofactor, blocking the active site and (ii) the resulting Fe-alkyl is a versatile electrophilic alkylating agent. Solutions of Fe2[(μ-SCH2)2NH](CO)4(PMe3)2 (1) react with a mixture of HBF4 and CH2O to give three isomers of [Fe2[(μ-SCH2)2NCH2](CO)4(PMe3)2]+ ([2]+). X-ray crystallography verified the NCH2Fe linkage to an octahedral Fe(II) site. Although [2]+ is stereochemically rigid on the NMR timescale, spin-saturation transfer experiments implicate reversible dissociation of the Fe–CH2 bond, allowing interchange of all three diastereoisomers. Using 13CH2O, the methylenation begins with formation of [Fe2[(μ-SCH2)2N13CH2OH](CO)4(PMe3)2]+. Protonation converts this hydroxymethyl derivative to [2]+, concomitant with 13C-labelling of all three methylene groups. The Fe–CH2N bond in [2]+ is electrophilic: PPh3, hydroxide, and hydride give, respectively, the phosphonium [Fe2[(μ-SCH2)2NCH2PPh3](CO)4(PMe3)2]+, 1, and the methylamine Fe2[(μ-SCH2)2NCH3](CO)4(PMe3)2. The reaction of [Fe2[(μ-SCH2)2NH](CN)2(CO)4]2− with CH2O/HBF4 gave [Fe2[(μ-SCH2)2NCH2CN](CN)(CO)5] ([4]), the result of reductive elimination from [Fe2[(μ-SCH2)2NCH2](CN)2(CO)4]. The phosphine derivative [Fe2[(μ-SCH2)2NCH2CN](CN)(CO)4(PPh3)] ([5]) was characterized crystallographically.

Graphical abstract: Inhibition of [FeFe]-hydrogenase by formaldehyde: proposed mechanism and reactivity of FeFe alkyl complexes

Supplementary files

Article information

Article type
Edge Article
Submitted
21 Oct 2021
Accepted
15 Nov 2021
First published
16 Nov 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 15673-15681

Inhibition of [FeFe]-hydrogenase by formaldehyde: proposed mechanism and reactivity of FeFe alkyl complexes

F. Zhang, T. J. Woods, L. Zhu and T. B. Rauchfuss, Chem. Sci., 2021, 12, 15673 DOI: 10.1039/D1SC05803G

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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