Electron‐Rich Diferrous–Phosphane–Thiolates Relevant to Fe‐only Hydrogenase: Is Cyanide “Nature's Trimethylphosphane”?

The two‐step one‐pot oxidative decarbonylation of [Fe₂(S₂C₂H₄)(CO)₄(PMe₃)₂] ( 1 ) with [FeCp₂]PF₆, followed by addition of phosphane ligands, led to a series of diferrous dithiolato carbonyls 2 – 6 , containing three or four phosphane ligands. In situ measurements indicate efficient formation of 1 ²⁺ as the initial intermediate of the oxidation of 1 , even when a deficiency of the oxidant was employed. Subsequent addition of PR₃ gave rise to [Fe₂(S₂C₂H₄)(μ‐CO)(CO)₃(PMe₃)₃]²⁺ ( 2 ) and [Fe₂(S₂C₂H₄)(μ‐CO)(CO)₂(PMe₃)₂(PR₃)₂]²⁺ (R=Me 3 , OMe 4 ) as principal products. One terminal CO ligand in these complexes was readily substituted by MeCN, and [Fe₂(S₂C₂H₄)(μ‐CO)(CO)₂(PMe₃)₃(MeCN)]²⁺ ( 5 ) and [Fe₂(S₂C₂H₄)(μ‐CO)(CO)(PMe₃)₄(MeCN)]²⁺ ( 6 ) were fully characterized. Relevant to the H_red state of the active site of Fe‐only hydrogenases, the unsymmetrical derivatives 5 and 6 feature a semibridging CO ligand trans to a labile coordination site.     

An S‐Oxygenated [NiFe] Complex Modelling Sulfenate Intermediates of an O2‐Tolerant Hydrogenase

To understand the molecular details of O₂‐tolerant hydrogen cycling by a soluble NAD⁺‐reducing [NiFe] hydrogenase, we herein present the first bioinspired heterobimetallic S‐oxygenated [NiFe] complex as a structural and vibrational spectroscopic model for the oxygen‐inhibited [NiFe] active site. This compound and its non‐S‐oxygenated congener were fully characterized, and their electronic structures were elucidated in a combined experimental and theoretical study with emphasis on the bridging sulfenato moiety. Based on the vibrational spectroscopic properties of these complexes, we also propose novel strategies for exploring S‐oxygenated intermediates in hydrogenases and similar enzymes.     

Heterolytic Cleavage of Hydrogen by an Iron Hydrogenase Model: An Fe‐H⋅⋅⋅H‐N Dihydrogen Bond Characterized by Neutron Diffraction

Hydrogenase enzymes in nature use hydrogen as a fuel, but the heterolytic cleavage of H? H bonds cannot be readily observed in enzymes. Here we show that an iron complex with pendant amines in the diphosphine ligand cleaves hydrogen heterolytically. The product has a strong Fe‐H???H‐N dihydrogen bond. The structure was determined by single‐crystal neutron diffraction, and has a remarkably short H???H distance of 1.489(10) Å between the protic N‐H^δ+ and hydridic Fe‐H^δ? part. The structural data for [CpFe H (P^tBu₂N^tBu₂ H )]⁺ provide a glimpse of how the H? H bond is oxidized or generated in hydrogenase enzymes. These results now provide a full picture for the first time, illustrating structures and reactivity of the dihydrogen complex and the product of the heterolytic cleavage of H₂ in a functional model of the active site of the [FeFe] hydrogenase enzyme.     

Ligand Displacement Reaction Paths in a Diiron Hydrogenase Active Site Model Complex

The mechanism and energetics of CO, 1‐hexene, and 1‐hexyne substitution from the complexes (SBenz)₂[Fe₂(CO)₆] (SBenz=SCH₂Ph) ( 1 ‐CO), (SBenz)₂[Fe₂(CO)₅(η²‐1‐hexene)] ( 1 ‐(η²‐1‐hexene)), and (SBenz)₂[Fe₂(CO)₅(η²‐1‐hexyne)] ( 1 ‐(η²‐1‐hexyne)) were studied by using time‐resolved infrared spectroscopy. Exchange of both CO and 1‐hexyne by P(OEt)₃ and pyridine, respectively, proceeds by a bimolecular mechanism. As similar activation enthalpies are obtained for both reactions, the rate‐determining step in both cases is assumed to be the rotation of the Fe(CO)₂L (L=CO or 1‐hexyne) unit to accommodate the incoming ligand. The kinetic profile for the displacement of 1‐hexene is quite different than that for the alkyne and, in this case, both reaction channels, that is, dissociative (S_N1) and associative (S_N2), were found to be competitive. Because DFT calculations predict similar binding enthalpies of alkene and alkyne to the iron center, the results indicate that the bimolecular pathway in the case of the alkyne is lower in free energy than that of the alkene. In complexes of this type, subtle changes in the departing ligand characteristics and the nature of the mercapto bridge can influence the exchange mechanism, such that more than one reaction pathway is available for ligand substitution. The difference between this and the analogous study of (μ‐pdt)[Fe(CO)₃]₂ (pdt=S(CH₂)₃S) underscores the unique characteristics of a three‐atom S?S linker in the active site of diiron hydrogenases.     

A [RuRu] Analogue of an [FeFe]‐Hydrogenase Traps the Key Hydride Intermediate of the Catalytic Cycle

The active site of the [FeFe]‐hydrogenases features a binuclear [2Fe]_H sub‐cluster that contains a unique bridging amine moiety close to an exposed iron center. Heterolytic splitting of H₂ results in the formation of a transient terminal hydride at this iron site, which, however is difficult to stabilize. We show that the hydride intermediate forms immediately when [2Fe]_H is replaced with [2Ru]_H analogues through artificial maturation. Outside the protein, the [2Ru]_H analogues form bridging hydrides, which rearrange to terminal hydrides after insertion into the apo‐protein. H/D exchange of the hydride only occurs for [2Ru]_H analogues containing the bridging amine moiety.     

Hydrophilic Quaternary Ammonium‐Group‐Containing [FeFe]‐Hydrogenase Models: Synthesis,Structures, and Electrocatalytic Hydrogen Production

The first quaternary ammonium‐group‐containing [FeFe]‐hydrogenase models [(μ‐PDT)Fe₂(CO)₄{κ²‐(Ph₂P)₂N(CH₂)₂NMe₂BzBr}] ( 2 ; PDT=propanedithiolate) and [(μ‐PDT)Fe₂(CO)₄{μ‐(Ph₂P)₂N(CH₂)₂NMe₂BzBr}] ( 4 ) have been prepared by the quaternization of their precursors [(μ‐PDT)Fe₂(CO)₄{κ²‐(Ph₂P)₂N(CH₂)₂NMe₂}] ( 1 ) and [(μ‐PDT)Fe₂(CO)₄{μ‐(Ph₂P)₂N(CH₂)₂NMe₂}] ( 3 ) with benzyl bromide in high yields. Although new complexes 1 – 4 have been fully characterized by spectroscopic and X‐ray crystallographic studies, the chelated complexes 1 and 2 converted into their bridged isomers 3 and 4 at higher temperatures, thus demonstrating that these bridged isomers are thermodynamically favorable. An electrochemical study on hydrophilic models 2 and 4 in MeCN and MeCN/H₂O as solvents indicates that the reduction potentials are shifted to less‐negative potentials as the water content increases. This outcome implies that both 2 and 4 are more easily reduced in the mixed MeCN/H₂O solvent than in MeCN. In addition, hydrophilic models 2 and 4 act as electrocatalysts and achieve higher i_cat/i_p values and turnover numbers (TONs) in MeCN/H₂O as a solvent than in MeCN for the production of hydrogen from the weak acid HOAc.     

Mononuclear Nonheme Iron(III)‐Iodosylarene and High‐Valent Iron‐Oxo Complexes in Olefin Epoxidation Reactions

High‐spin iron(III)‐iodosylarene complexes are highly reactive in the epoxidation of olefins, in which epoxides are formed as the major products with high stereospecificity and enantioselectivity. The reactivity of the iron(III)‐iodosylarene intermediates is much greater than that of the corresponding iron(IV)‐oxo complex in these reactions. The iron(III)‐iodosylarene species—not high‐valent iron(IV)‐oxo and iron(V)‐oxo species—are also shown to be the active oxidants in catalytic olefin epoxidation reactions. The present results are discussed in light of the long‐standing controversy on the one oxidant versus multiple oxidants hypothesis in oxidation reactions.     

[FeFe] Hydrogenase: Protonation of {2Fe3S} Systems and Formation of Super‐reduced Hydride States

The synthesis and crystallographic characterization of a complex possessing a well‐defined {2Fe3S(μ‐H)} core gives access to a paramagnetic bridging hydride with retention of the core geometry. Chemistry of this 35‐electron species within the confines of a thin‐layer FTIR spectro‐electrochemistry cell provides evidence for a unprecedented super‐reduced Fe^I(μ‐H)Fe^I intermediate.     

Identification of HcgC as a SAM‐Dependent Pyridinol Methyltransferase in [Fe]‐Hydrogenase Cofactor Biosynthesis

Previous retrosynthetic and isotope‐labeling studies have indicated that biosynthesis of the iron guanylylpyridinol (FeGP) cofactor of [Fe]‐hydrogenase requires a methyltransferase. This hypothetical enzyme covalently attaches the methyl group at the 3‐position of the pyridinol ring. We describe the identification of HcgC, a gene product of the hcgA‐G cluster responsible for FeGP cofactor biosynthesis. It acts as an S‐adenosylmethionine (SAM)‐dependent methyltransferase, based on the crystal structures of HcgC and the HcgC/SAM and HcgC/S‐adenosylhomocysteine (SAH) complexes. The pyridinol substrate, 6‐carboxymethyl‐5‐methyl‐4‐hydroxy‐2‐pyridinol, was predicted based on properties of the conserved binding pocket and substrate docking simulations. For verification, the assumed substrate was synthesized and used in a kinetic assay. Mass spectrometry and NMR analysis revealed 6‐carboxymethyl‐3,5‐dimethyl‐4‐hydroxy‐2‐pyridinol as the reaction product, which confirmed the function of HcgC.