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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.

SUBMITTER: Zhang F

PROVIDER: S-EPMC8653999 | biostudies-literature |

REPOSITORIES: biostudies-literature

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