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

The mechanism for inhibition of [FeFe]-hydrogenases by formaldehyde is examined with model complexes. Key findings: (i) CH 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 Fe(μ-SCH)NH(PMe) (1) react with a mixture of HBF and CHO to give three isomers of [Fe(μ-SCH)NCH(PMe)] ([2]). X-ray crystallography verified the NCHFe 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-CH bond, allowing interchange of all three diastereoisomers. Using CHO, the methylenation begins with formation of [Fe(μ-SCH)NCHOH(PMe)]. Protonation converts this hydroxymethyl derivative to [2], concomitant with C-labelling of all three methylene groups. The Fe-CHN bond in [2] is electrophilic: PPh, hydroxide, and hydride give, respectively, the phosphonium [Fe(μ-SCH)NCHPPh(PMe)], 1, and the methylamine Fe(μ-SCH)NCH(PMe). The reaction of [Fe(μ-SCH)NH(CO)] with CHO/HBF gave [Fe(μ-SCH)NCHCN(CO)] ([4]), the result of reductive elimination from [Fe(μ-SCH)NCH(CO)]. The phosphine derivative [Fe(μ-SCH)NCHCN(CO)(PPh)] ([5]) was characterized crystallographically.