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 2 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 2 [(μ-SCH 2 ) 2 NH](CO) 4 (PMe 3 ) 2 (1) react with a mixture of HBF 4 and CH 2 O to give three isomers of [Fe 2 [(μ-SCH 2 ) 2 NCH 2 ](CO) 4 (PMe 3 ) 2 ] + ([2] + ). X-ray crystallography verified the NCH 2 Fe 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 2 bond, allowing interchange of all three diastereoisomers. Using 13 CH 2 O, the methylenation begins with formation of [Fe 2 [(μ-SCH 2 ) 2 N 13 CH 2 OH](CO) 4 (PMe 3 ) 2 ] + . Protonation converts this hydroxymethyl derivative to [2] + , concomitant with 13 C-labelling of all three methylene groups. The Fe-CH 2 N bond in [2] + is electrophilic: PPh 3 , hydroxide, and hydride give, respectively, the phosphonium [Fe 2 [(μ-SCH 2 ) 2 NCH 2 PPh 3 ](CO) 4 (PMe 3 ) 2 ] + , 1, and the methylamine Fe 2 [(μ-SCH 2 ) 2 NCH 3 ](CO) 4 (PMe 3 ) 2 . The reaction of [Fe 2 [(μ-SCH 2 ) 2 NH](CN) 2 (CO) 4 ] 2- with CH 2 O/HBF 4 gave [Fe 2 [(μ-SCH 2 ) 2 NCH 2 CN](CN)(CO) 5 ] - ([4] - ), the result of reductive elimination from [Fe 2 [(μ-SCH 2 ) 2 NCH 2 ](CN) 2 (CO) 4 ] - . The phosphine derivative [Fe 2 [(μ-SCH 2 ) 2 NCH 2 CN](CN)(CO) 4 (PPh 3 )] - ([5] - ) was characterized crystallographically.