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ConspectusNature's prototypical hydrogen-forming catalysts─hydrogenases─have attracted much attention because they catalyze hydrogen evolution at near zero overpotential and ambient conditions. Beyond any possible applications in the energy sphere, the hydrogenases feature complicated active sites, which implies novel biosynthetic pathways. In terms of the variety of cofactors, the [FeFe]-hydrogenase is among the most complex.For more than a decade, we have worked on the biosynthesis of the active site of [FeFe] hydrogenases. This site, the H-cluster, is a six-iron ensemble consisting of a [4Fe-4S] H cluster linked to a [2Fe] H cluster that is coordinated to CO, cyanide, and a unique organic azadithiolate ligand. Many years ago, three enzymes, namely, HydG, HydE, and HydF, were shown to be required for the biosynthesis and the in vitro maturation of [FeFe] hydrogenases. The structures of the maturases were determined crystallographically, but still little progress was made on the biosynthetic pathway. As described in this Account, the elucidation of the biosynthetic pathway began in earnest with the identification of a molecular iron-cysteinate complex produced within HydG.In this Account, we present our most recent progress toward the molecular mechanism of [2Fe] H biosynthesis using a collaborative approach involving cell-free biosynthesis, isotope and element-sensitive spectroscopies, as well as inorganic synthesis of purported biosynthetic intermediates. Our study starts from the radical SAM enzyme HydG that lyses tyrosine into CO and cyanide and forms an Fe(CO) 2 (CN)-containing species. Crystallographic identification of a unique auxiliary 5Fe-4S cluster in HydG leads to a proposed catalytic cycle in which a free cysteine-chelated "dangler" Fe serves as the platform for the stepwise formation of a [4Fe-4S][Fe(CO)(CN)(cysteinate)] intermediate, which releases the [Fe(CO) 2 (CN)(cysteinate)] product, Complex B. Since Complex B is unstable, we applied synthetic organometallic chemistry to make an analogue, syn-B, and showed that it fully replaces HydG in the in vitro maturation of the H-cluster. Syn-B serves as the substrate for the next radical SAM enzyme HydE, where the low-spin Fe(II) center is activated by 5'-dAdo • to form an adenosylated Fe(I) intermediate. We propose that this Fe(I) species strips the carbon backbone and dimerizes in HydE to form a [Fe 2 (SH) 2 (CO) 4 (CN) 2 ] 2- product. This mechanistic scenario is supported by the use of a synthetic version of this dimer complex, syn-dimer, which allows for the formation of active hydrogenase with only the HydF maturase. Further application of this semisynthesis strategy shows that an [Fe 2 (SCH 2 NH 2 ) 2 (CO) 4 (CN) 2 ] 2- complex can activate the apo hydrogenase, marking it as the last biosynthetic intermediate en route to the H-cluster. This combined enzymatic and semisynthetic approach greatly accelerates our understanding of H-cluster biosynthesis. We anticipate additional mechanistic details regarding H-cluster biosynthesis to be gleaned, and this methodology may be further applied in the study of other complex metallocofactors.

The paper aims to elucidate the final stages in the biosynthesis of the [2Fe] H active site of the [FeFe]-hydrogenases. The recently hypothesized intermediate [Fe 2 (SCH 2 NH 2 ) 2 (CN) 2 (CO) 4 ] 2- ([1] 2- ) was prepared by a multistep route from [Fe 2 (S 2 )(CN)(CO) 5 ] - . The following synthetic intermediates were characterized in order: [Fe 2 (SCH 2 NHFmoc) 2 (CNBEt 3 )(CO) 5 ] - , [Fe 2 (SCH 2 NHFmoc) 2 (CN)-(CO) 5 ] - , and [Fe 2 (SCH 2 NHFmoc) 2 (CN) 2 (CO) 4 ] 2- , where Fmoc is fluorenylmethoxycarbonyl). Derivatives of these anions include [K(18-crown-6)] + , PPh 4 + and PPN + salts as well as the 13 CD 2 -isotopologues. These Fe 2 species exist as a mixture of two isomers attributed to diequatorial (ee) and axial-equatorial (ae) stereochemistry at sulfur. In vitro experiments demonstrate that [1] 2- maturates HydA1 in the presence of HydF and a cocktail of reagents. HydA1 can also be maturated using a highly simplified cocktail, omitting HydF and other proteins. This result is consistent with HydA1 participating in the maturation process and refines the roles of HydF., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

A cluster-ligand is disclosed in the form of [Ru 3 (CN) 3 (CO) 9 ] 3- ([ 1 ] 3- ). Produced by simple reaction of [Ru 3 (CO) 12 ] with cyanide, [ 1 ] 3- serves as a precursor to a series of μ-CN cages. When treated with [Ru 3 (CO) 12 ], it readily forms the prism [Ru 6 (μ-CN) 3 (CO) 18 ] 3- . With 1.5 equiv of [Cu(MeCN) 4 ] + [ 1 ] 3- reacts to give the expanded prism {Cu 3 [Ru 3 (μ-CN) 3 (CO) 9 ] 2 } 3- , which features three two-coordinate Cu(I) centers. Sources of Ni 2+ and Fe 2+ bind two equivalents of [ 1 ] 3- , giving the double cages {M[Ru 3 (μ-CN) 3 (CO) 9 ] 2 } 4- (M = Ni, Fe) wherein the central metal is octahedral. The 1:1 reaction using [Fe(H 2 O) 6 ] 2+ gave the interpenetrated super-tetrahedrane {Fe 4 (μ 4 -O)[Ru 3 (μ-CN) 3 (CO) 9 ] 4 } 4- ., Competing Interests: Conflicts of interest There are no conflicts to declare.

[FeFe]-hydrogenases employ a catalytic H-cluster, consisting of a [4Fe-4S] H cluster linked to a [2Fe] H subcluster with CO, CN - ligands, and an azadithiolate bridge, which mediates the rapid redox interconversion of H + and H 2 . In the biosynthesis of this H-cluster active site, the radical S -adenosyl-l-methionine (radical SAM, RS) enzyme HydG plays the crucial role of generating an organometallic [Fe(II)(CN)(CO) 2 (cysteinate)] - product that is en route to forming the H-cluster. Here, we report direct observation of this diamagnetic organometallic Fe(II) complex through Mössbauer spectroscopy, revealing an isomer shift of δ = 0.10 mm s -1 and quadrupole splitting of Δ E Q = 0.66 mm s -1 . These Mössbauer values are a change from the starting values of δ = 1.15 mm s -1 and Δ E for the ferrous "dangler" Fe in HydG. These values of the observed product complex B are in good agreement with Mössbauer parameters for the low-spin Fe Q = 3.23 mm s -1 Fe Syn-B, which we report here. These results highlight the essential role that HydG plays in converting a resting-state high-spin Fe(II) to a low-spin organometallic Fe(II) product that can be transferred to the downstream maturase enzymes.2+ ions in synthetic analogues, such as 57 Fe Syn-B, which we report here. These results highlight the essential role that HydG plays in converting a resting-state high-spin Fe(II) to a low-spin organometallic Fe(II) product that can be transferred to the downstream maturase enzymes.

The salt [K(18-crown-6)] 2 [Ru(CN) 2 (CO) 3 ] ([K(18-crown-6)] 2 [ 1 ]) was generated by the reaction of Ru(C 2 H 4 )(CO) 4 with [K(18-crown-6)]CN. An initial thermal reaction gives [Ru(CN)(CO) 4 ] - , which, upon ultraviolet (UV) irradiation, reacts with a second equiv of CN - . Protonation of [ 1 ] 2- gave [HRu(CN) 2 (CO) 3 ] - ([H 1 ] - ), which was isolated as a single isomer with mutually trans cyanide ligands. The complex cis,cis,cis -[Ru(pdt)(CN) 2 (CO) 2 ] 2- ([ 2 ] 2- ) was prepared by the UV-induced reaction of [ 1 ] 2- with propanedithiol (pdtH 2 ). The corresponding iron complex cis,cis,cis -[Fe(pdt)(CN) 2 (CO) 2 ] 2- ([ 3 ] 2- ) was prepared similarly. The pdt complexes [ 2 ] 2- and [ 3 ] 2- were treated with Fe(benzylideneacetone)(CO) 3 to give, respectively, [RuFe (μ-pdt)(CN) 2 (CO) 4 ] 2- ([ 5 ] 2- ) and [Fe 2 (μ-pdt)(CN) 2 (CO) 4 ] 2- ([ 4 ] 2- ). The pathway from [ 3 ] 2- to Fe 2 complex [ 4 ] 2- implicates intermetallic migration of CN - . In contrast, the formation of [ 5 ] 2- leaves the Ru(CN) 2 (CO) center intact, as confirmed by X-ray crystallography. The structure of [ 5 ] 2- features a "rotated" square-pyramidal Fe(CO) 2 (μ-CO) site. NMR measurements indicate that the octahedral Ru site is stereochemically rigid, whereas the Fe site dynamically undergoes turnstile rotation. 57 Fe Mössbauer spectral parameters are very similar for rotated [ 5 ] 2- and unrotated Fe 2 complex [ 4 ] 2- , indicating the insensitivity of that technique to both the geometry and the oxidation state of the Fe site. According to cyclic voltammetry, [ 5 ] 2- oxidizes at E 1/2 ∼ -0.8 V vs Fc +/0 . Electron paramagnetic resonance (EPR) measurements show that 1e - oxidation of [ 5 ] 2- gives an S = 1/2 rhombic species, consistent with the formulation Ru(II)Fe(I), related to the H ox state of the [FeFe] hydrogenases. Density functional theory (DFT) studies reproduce the structure, 1 H NMR shifts, and infrared (IR) spectra observed for [ 5 ] 2- . Related homometallic complexes with both cyanides on a single metal are predicted to not adopt rotated structures. These data suggest that [ 5 ] 2- is best described as Ru(II)Fe(0). This conclusion raises the possibility that for some reduced states of the [FeFe]-hydrogenases, the [2Fe] H site may be better described as Fe(II)Fe(0) than Fe(I)Fe(I).

[FeFe] hydrogenases contain a 6-Fe cofactor that serves as the active site for efficient redox interconversion between H 2 and protons. The biosynthesis of the so-called H-cluster involves unusual enzymatic reactions that synthesize organometallic Fe complexes containing azadithiolate, CO, and CN - ligands. We have previously demonstrated that specific synthetic [Fe(CO) x (CN) y ] complexes can be used to functionally replace proposed Fe intermediates in the maturation reaction. Here, we report the results from performing such cluster semisynthesis in the context of a recent fully defined cluster maturation procedure, which eliminates unknown components previously employed from Escherichia coli cell lysate and demonstrate this provides a concise route to H-cluster synthesis. We show that formaldehyde can be used as a simple reagent as the carbon source of the bridging adt ligand of H-cluster in lieu of serine/serine hydroxymethyltransferase. In addition to the actual H-cluster, we observe the formation of several H-cluster-like species, the identities of which are probed by cryogenic photolysis combined with EPR/ENDOR spectroscopy.

Complexes of the type (diphosphine)Ni( μ -SR) 2 Fe(CO) 3 are investigated with azadithiolate (adt, HN(CH 2 S - ) 2 ) as the dithiolate. The resulting complexes are hybrid models for the active sites of the [NiFe]- and [FeFe]-hydrogenases. The key complex (dppv)Ni( μ -adt)Fe(CO) 3 (3) was prepared from the complex Ni[(SCH 2 ) 2 NCbz](dppv), which contains a Cbz-protected adt ligand (Cbz = C( O )OCH 2 Ph, dppv = cis -1,2-(Ph 2 P) 2 C 2 H 2 ). This complex combines with Fe 2 (CO) 9 to give (dppv)Ni[( μ -SCH 2 ) 2 NCbz]Fe(CO) 3 , which is readily deprotected to give 3 . Complex 3 undergoes protonation at both Fe and N to give successively [(dppv)Ni( μ -adt)FeH(CO) 3 ] + ([H 3 ] + ) and [(dppv)Ni( μ -adtH)FeH(CO) 3 ] 2+ ([H3H] 2+ ). The redox properties and dynamics of these complexes resemble previously reported analogues with propanedithiolate. Solutions of [H 3 ] + readily degrade to [(dppv)Ni[( μ -SCH 2 ) 2 NCH 2 ]Fe(CO) 3 ] + ([ 4 ] + ), which features a methylene group linking N and Fe. Complex [ 4 ] + can be made in high yield by reaction of [H 3 ] + with CH 2 O, and this conversion was also demonstrated with 13 CH 2 O. Complex [ 4 ] + undergoes hydrogenolysis by photochemical reaction with H 2 to give [(dppv)Ni[( μ -SCH 2 ) 2 NMe]FeH(CO) 3 ] + , the N -methylated analogue of [ H3 ] + . Upon treatment ith Me 3 O + , [ 4 ] + undergoes quaternization, giving [(dppv)Ni[( μ -SCH 2 ) 2 N(Me)CH 2 ]Fe(CO) 3 ] 2+ . In contrast with the lability of [H 3 ] + , the phosphine-substituted derivative [(dppv)Ni( μ -adt)FeH(CO) 2 (PPh 3 )] + did not degrade. Most complexes were characterized by X-ray crystallography., Competing Interests: The authors declare no competing financial interest.

Elemental chalcogens react with [Fe(CN) 2 (CO) 3 ] 2- to give the following ferrous derivatives: [K(18-crown-6)] 2 [Fe(S 5 )(CN) 2 (CO) 2 ], [K(18-crown-6)] 2 [Fe(S 2 )(CN) 2 (CO) 2 ], [K(18-crown-6)] 2 [Fe(Se 4 )(CN) 2 (CO) 2 ], [K(18-crown-6)] 2 [Fe(Te 2 )(CN) 2 (CO) 2 ], and (NEt 4 ) 2 [Fe(Te 2 )(CN) 2 (CO) 2 ]. While these complex anions crystallized in a single stereochemistry (i.e., trans dicyanides or cis dicyanides), they isomerize in solution upon irradiation. The results are benchmarked by the corresponding studies on benzyl thiolate [K(18-crown-6)] 2 [Fe(SBn) 2 (CN) 2 (CO) 2 ].

The biosynthesis of the active site of the [FeFe]-hydrogenases (HydA1), the H-cluster, is of interest because these enzymes are highly efficient catalysts for the oxidation and production of H 2 . The biosynthesis of the [2Fe] H subcluster of the H-cluster proceeds from simple precursors, which are processed by three maturases: HydG, HydE, and HydF. Previous studies established that HydG produces an Fe(CO) 2 (CN) adduct of cysteine, which is the substrate for HydE. In this work, we show that by using the synthetic cluster [Fe 2 (μ-SH) 2 (CN) 2 (CO) 4 ] 2- active HydA1 can be biosynthesized without maturases HydG and HydE.

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., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

One of the more active areas in bioorganometallic chemistry is the preparation and reactivity studies of active site mimics of the [NiFe]-hydrogenases. One area of particular recent progress involves reactions that interconvert Ni( μ -X)Fe centers for X = OH, H, CO, as described by Song et al. Such reactions illustrate new ways to access intermediates related to the Ni-R and Ni-SI states of the enzyme. Most models are derivatives of the type (diphosphine)Ni(SR) 2 Fe(CO) 3- n (PR' 3 ) n . In recent work, the methodology has been generalized to include Fe II (diphosphine) derivatives of Ni(N2S2), where N2S2 2- is the tetradentate diamine-dithiolate (CH 2 N(CH 3 )CH 2 CH 2 S - ) 2 . Indeed, models based on Ni(N2S2) have proven valuable, but these studies also highlight challenges in working with heterobimetallic complexes, specifically the tendency of some such Ni-Fe complexes to convert to homometalliic Ni-Ni derivatives. This kind of problem is not readily detected by X-ray crystallography. With this caution in mind, we argue that one series of complexes recently described in this journal are almost certainly misassigned.

The H-cluster of [Fe-Fe] hydrogenase consists of a [4Fe] H subcluster linked by the sulfur of a cysteine residue to an organometallic [2Fe] H subcluster that utilizes terminal CO and CN ligands to each Fe along with a bridging CO and a bridging SCH 2 NHCH 2 S azadithiolate (adt) to catalyze proton reduction or hydrogen oxidation. Three Fe-S "maturase" proteins, HydE, HydF, and HydG, are responsible for the biosynthesis of the [2Fe] H subcluster and its incorporation into the hydrogenase enzyme to form this catalytically active H-cluster. We have proposed that HydG is a bifunctional enzyme that uses S -adenosylmethione (SAM) bound to a [4Fe-4S] cluster to lyse tyrosine via a transient 5'-deoxyadenosyl radical to produce CO and CN ligands to a unique cysteine-chelated Fe(II) that is linked to a second [4Fe-4S] cluster via the cysteine sulfur. In this "synthon model", after two cycles of tyrosine lysis, the product of HydG is completed: a [Fe(CN)(CO) 2 (cysteinate)] - organometallic unit that is vectored directly into the synthesis of the [2Fe] H sub-cluster. However our HydG-centric synthon model is not universally accepted, so further validation is important. In this Frontiers article, we discuss recent results using a synthetic "Syn-B" complex that donates [Fe(CN)(CO) 2 (cysteinate)] - units that match our proposed HydG product. Can Syn-B activate hydrogenase in the absence of HydG and its tyrosine substrate? If so, since Syn-B can be synthesized with specific magnetic nuclear isotopes and with chemical substitutions, its use could allow its enzymatic conversions on the route to the H-cluster to be monitored and modeled in fresh detail.

Azadithiolate, a cofactor found in all [FeFe]-hydrogenases, is shown to undergo acid-catalyzed rearrangement. Fe 2 [(SCH 2 ) 2 NH](CO) 6 self-condenses to give Fe 6 [(SCH 2 ) 3 N] 2 (CO) 17 . The reaction, which is driven by loss of NH 4 + , illustrates the exchange of the amine group. X-ray crystallography reveals that three Fe 2 (SR) 2 (CO) x butterfly subunits interconnected by the aminotrithiolate [N(CH 2 S) 3 ] 3- . Mechanistic studies reveal that Fe 2 [(SCH 2 ) 2 NR](CO) 6 participate in a range of amine exchange reactions, enabling new methodologies for modifying the adt cofactor. Ru 2 [(SCH 2 ) 2 NH](CO) 6 also rearranges, but proceeds further to give derivatives with Ru-alkyl bonds Ru 6 [(SCH 2 ) 3 N][(SCH 2 ) 2 NCH 2 ]S(CO) 17 and [Ru 2 [(SCH 2 ) 2 NCH 2 ](CO) 5 ] 2 S., (© 2021 Wiley-VCH GmbH.)

The homoleptic rhodium pyridine complex [Rh(py) 4 ] + ([ 1 ] + ) is prepared from simple precursors. Lacking good π-acceptor ligands but being sterically protected, [ 1 ] + reversibly oxidizes to colorless [Rh(py) 4 (thf) 2 ] 2+ . This monomeric S = 1/2 Rh(II) complex activates H 2 to give [HRh(py) 4 L] 2+ , which can also be generated by protonation of [ 1 ] + . The Rh(III)-H bond is weak, being susceptible to H atom abstraction as well as deprotonation. These results underpin a novel catalytic system for the oxidation of H 2 by ferrocenium.

[FeFe]-hydrogenases use a unique organometallic complex, termed the H cluster, to reversibly convert H 2 into protons and low-potential electrons. It can be best described as a [Fe 4 S 4 ] cluster coupled to a unique [2Fe] H center where the reaction actually takes place. The latter corresponds to two iron atoms, each of which is bound by one CN - ligand and one CO ligand. The two iron atoms are connected by a unique azadithiolate molecule ( - S-CH 2 -NH-CH 2 -S - ) and an additional bridging CO. This [2Fe] H center is built stepwise thanks to the well-orchestrated action of maturating enzymes that belong to the Hyd machinery. Among them, HydG converts l-tyrosine into CO and CN - to produce a unique l-cysteine-Fe(CO) 2 CN species termed complex-B. Very recently, HydE was shown to perform radical-based chemistry using synthetic complex-B as a substrate. Here we report the high-resolution crystal structure that establishes the identity of the complex-B-bound HydE. By triggering the reaction prior to crystallization, we trapped a new five-coordinate Fe species, supporting the proposal that HydE performs complex modifications of complex-B to produce a monomeric "SFe(CO) 2 CN" precursor to the [2Fe] H center. Substrate access, product release, and intermediate transfer are also discussed.

[FeFe] hydrogenases are highly active catalysts for the interconversion of molecular hydrogen with protons and electrons. Here, we use a combination of isotopic labeling, 57 Fe nuclear resonance vibrational spectroscopy (NRVS), and density functional theory (DFT) calculations to observe and characterize the vibrational modes involving motion of the 2-azapropane-1,3-dithiolate (ADT) ligand bridging the two iron sites in the [2Fe] H subcluster. A - 13 C 2 H 2 - ADT labeling in the synthetic diiron precursor of [2Fe] H produced isotope effects observed throughout the NRVS spectrum. The two precursor isotopologues were then used to reconstitute the H-cluster of [FeFe] hydrogenase from Chlamydomonas reinhardtii ( Cr HydA1), and NRVS was measured on samples poised in the catalytically crucial H hyd state containing a terminal hydride at the distal Fe site. The 13 C 2 H isotope effects were observed also in the H hyd spectrum. DFT simulations of the spectra allowed identification of the 57 Fe normal modes coupled to the ADT ligand motions. Particularly, a variety of normal modes involve shortening of the distance between the distal Fe-H hydride and ADT N-H bridgehead hydrogen, which may be relevant to the formation of a transition state on the way to H 2 formation.

The reaction of Fe 2 S 2 (CO) 6 and PPh 3 affords Fe 2 S 2 (CO) 4 (PPh 3 ) 2 by an unprecedented mechanism involving the intermediacy of SPPh 3 and Fe 2 S(CO) 6 (PPh 3 ) 2 .

Density functional theory (DFT) calculations on Fe 2 S 2 (CO) 6-2 n (PMe 3 ) 2 n for n = 0, 1, and 2 reveal that the most electron-rich derivatives ( n = 2) exist as diferrous disulfides lacking an S-S bond. The thermal interconversion of the Fe II 2 (S) 2 and Fe I 2 (S 2 ) valence isomers is symmetry-forbidden. Related electron-rich diiron complexes [Fe 2 S 2 (CN) 2 (CO) 4 ] 2- of an uncertain structure are implicated in the biosynthesis of [FeFe]-hydrogenases. Several efforts to synthesize electron-rich derivatives of Fe 2 (μ-S 2 )(CO) 6 ( 1 ) are described. First, salts of iron persulfido cyanides [Fe 2 (μ-S 2 )(CO) 5 (CN)] - and [Fe 2 (μ-S 2 )(CN)(CO) 4 (PPh 3 )] - were prepared by the reactions of NaN(tms) 2 with 1 and Fe 2 (μ-S 2 )(CO) 5 (PPh 3 ), respectively. Alternative approaches to electron-rich diiron disulfides targeted Fe 2 (μ-S 2 )(CO) 4 (diphosphine). Whereas the preparation of Fe 2 (μ-S 2 )(CO) 4 (dppbz) was straightforward, that of Fe 2 (μ-S 2 )(CO) 4 (dppv) required an indirect route involving the oxidation of Fe 2 (μ-SH) 2 (CO) 4 (dppv) (dppbz = C 6 H 4 -1,2-(PPh 2 ) 2 , dppv = cis -C 2 H 2 (PPh 2 ) 2 ). DFT calculations indicate that the oxidation of Fe 2 (μ-SH) 2 (CO) 4 (dppv) produces singlet diferrous disulfide Fe 2 (μ-S) 2 (CO) 4 (dppv), which is sufficiently long-lived as to be trapped by ethylene. The reaction of 1 and dppv mainly afforded Fe 2 (μ-SCH=CHPPh 2 )(μ-SPPh 2 )(CO) 5 , implicating a S-centered reaction.

Redox reactions, substitutions, and metalations are reported for the iron carbido sulfide [Fe 6 C(CO) 14 (S)] 2- ([ 1 ] 2- ). Dianion [ 1 ] 2- oxidized to [Fe 6 C(CO) 16 (S)] 0 ([ 2 ] 0 ) upon treatment with of [Fe(C 5 H 5 ) 2 ]BF 4 or HBF 4 (H 2 formation) under an atmosphere of CO. Reaction of [ 2 ] 0 with t BuNC gave [Fe 6 C(S)(CO) 13 ( t BuNC) 5 ], consisting of Fe 5 C(CO) 13 and [Fe( t BuNC) 5 ] 2+ subunits linked by a μ 3 -S 2- . The Fe 7 CS cluster [Fe 7 C(CO) 17 (S)] 2- formed upon treatment of (Ph 4 P) 2 [ 1 ] with Fe(benzylideneacetone)(CO) 3 . The Fe 7 species is an edge-fused cluster with [Fe 6 C(CO) 10 (μ-CO) 4 ] and Fe(CO) 3 subunits joined by μ 3 -S and two Fe-Fe bonds. The analogous reaction using Mo(CO) 4 (norbornadiene) gave [MoFe 6 C(CO) 18 (S)] 2- . In this cluster, the Mo center is located in the octahedral subunit. Treatment of [ 1 ] 2- with SO 2 afforded [Fe 6 C(S)(SO 2 )(CO) 13 ] 2- . This cluster features an Fe 6 C core decorated with μ 3 -S and μ 2 -SO 2 ligands. These experiments were undertaken in an effort to connect organometallic clusters to FeMoco.

Numerous redox transformations that are essential to life are catalyzed by metalloenzymes that feature Earth-abundant metals. In contrast, platinum-group metals have been the cornerstone of many industrial catalytic reactions for decades, providing high activity, thermal stability, and tolerance to chemical poisons. We assert that nature's blueprint provides the fundamental principles for vastly expanding the use of abundant metals in catalysis. We highlight the key physical properties of abundant metals that distinguish them from precious metals, and we look to nature to understand how the inherent attributes of abundant metals can be embraced to produce highly efficient catalysts for reactions crucial to the sustainable production and transformation of fuels and chemicals., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The H-cluster of [FeFe]-hydrogenase consists of a [4Fe-4S] H -subcluster linked by a cysteinyl bridge to a unique organometallic [2Fe] H -subcluster assigned as the site of interconversion between protons and molecular hydrogen. This [2Fe] H -subcluster is assembled by a set of Fe-S maturase enzymes HydG, HydE and HydF. Here we show that the HydG product [Fe II (Cys)(CO) 2 (CN)] synthon is the substrate of the radical SAM enzyme HydE, with the generated 5'-deoxyadenosyl radical attacking the cysteine S to form a C5'-S bond concomitant with reduction of the central low-spin Fe(II) to the Fe(I) oxidation state. This leads to the cleavage of the cysteine C3-S bond, producing a mononuclear [Fe I (CO) 2 (CN)S] species that serves as the precursor to the dinuclear Fe(I)Fe(I) center of the [2Fe] H -subcluster. This work unveils the role played by HydE in the enzymatic assembly of the H-cluster and expands the scope of radical SAM enzyme chemistry.

[FeFe] hydrogenases are extremely active H 2 -converting enzymes. Their mechanism remains highly controversial, in particular, the nature of the one-electron and two-electron reduced intermediates called H red H + and H sred H + . In one model, the H red H + and H sred H + states contain a semibridging CO, while in the other model, the bridging CO is replaced by a bridging hydride. Using low-temperature IR spectroscopy and nuclear resonance vibrational spectroscopy, together with density functional theory calculations, we show that the bridging CO is retained in the H sred H + and H red H + states in the [FeFe] hydrogenases from Chlamydomonas reinhardtii and Desulfovibrio desulfuricans , respectively. Furthermore, there is no evidence for a bridging hydride in either state. These results agree with a model of the catalytic cycle in which the H red H + and H sred H + states are integral, catalytically competent components. We conclude that proton-coupled electron transfer between the two subclusters is crucial to catalysis and allows these enzymes to operate in a highly efficient and reversible manner.

[FeFe] hydrogenases are very active enzymes that catalyze the reversible conversion of molecular hydrogen into protons and electrons. Their active site, the H-cluster, contains a unique binuclear iron complex, [2Fe] H , with CN - and CO ligands as well as an aza-propane-dithiolate (ADT) moiety featuring a central amine functionality that mediates proton transfer during catalysis. We present a pulsed 13 C-ENDOR investigation of the H-cluster in which the two methylene carbons of ADT are isotope labeled with 13 C. We observed that the corresponding two 13 C hyperfine interactions are of opposite sign and corroborated this finding using density functional theory calculations. The spin polarization in the ADT ligand is shown to be linked to the asymmetric coordination of the distal iron site with its terminal CN - and CO ligands. We propose that this asymmetry is relevant for the enzyme reactivity and is related to the (optimal) stabilization of the iron-hydride intermediate in the catalytic cycle.

The enzyme [FeFe]-hydrogenase (HydA1) contains a unique 6-iron cofactor, the H-cluster, that has unusual ligands to an Fe-Fe binuclear subcluster: CN - , CO, and an azadithiolate (adt) ligand that provides 2 S bridges between the 2 Fe atoms. In cells, the H-cluster is assembled by a collection of 3 maturases: HydE and HydF, whose roles aren't fully understood, and HydG, which has been shown to construct a [Fe(Cys)(CO) 2 (CN)] organometallic precursor to the binuclear cluster. Here, we report the in vitro assembly of the H-cluster in the absence of HydG, which is functionally replaced by adding a synthetic [Fe(Cys)(CO) 2 (CN)] carrier in the maturation reaction. The synthetic carrier and the HydG-generated analog exhibit similar infrared spectra. The carrier allows HydG-free maturation to HydA1, whose activity matches that of the native enzyme. Maturation with 13 CN-containing carrier affords 13 CN-labeled enzyme as verified by electron paramagnetic resonance (EPR)/electron nuclear double-resonance spectra. This synthetic surrogate approach complements existing biochemical strategies and greatly facilitates the understanding of pathways involved in the assembly of the H-cluster. As an immediate demonstration, we clarify that Cys is not the source of the carbon and nitrogen atoms in the adt ligand using pulse EPR to target the magnetic couplings introduced via a 13 C 3 , 15 N-Cys-labeled synthetic carrier. Parallel mass-spectrometry experiments show that the Cys backbone is converted to pyruvate, consistent with a cysteine role in donating S in forming the adt bridge. This mechanistic scenario is confirmed via maturation with a seleno-Cys carrier to form HydA1-Se, where the incorporation of Se was characterized by extended X-ray absorption fine structure spectroscopy., Competing Interests: The authors declare no competing interest.

Described is the preparation of the first iron carbide-sulfides. The cluster [Fe 6 C(CO) 15 (SO 2 )] 2- ([2] 2- ), which is generated quantitatively from [Fe 6 C(CO) 16 ] 2- ([1] 2- ), was O-methylated to give the sulfinite [2Me] - . Demethoxylation of [2Me] - with BF 3 gave the face-capped octahedral cluster Fe 6 C(CO) 15 (SO) (3). In solution, 3 spontaneously converted to the sulfide Fe 6 C(CO) 16 (S) (4), an edge-fused double cluster with Fe 5 C and Fe 3 S subunits. Although 4 undergoes 1e - reduction reversibly, 2e - reduction (or base hydrolysis) of 4 gives closo-[Fe 6 C(CO) 14 (S)] 2- ([5] 2- ). The synthetic entries into the Fe 6 CS x manifold may underpin the preparation of active-site analogues of the FeMoco and FeVco cofactors.

Described are the syntheses of several Ni(μ-SR) 2 Fe complexes, including hydride derivatives, in a search for improved models for the active site of [NiFe]-hydrogenases. The nickel(II) precursors include (i) nickel with tripodal ligands: Ni(PS 3 ) - and Ni(NS 3 ) - (PS 3 3- = tris(phenyl-2-thiolato)phosphine, NS 3 3- = tris(benzyl-2-thiolato)amine), (ii) traditional diphosphine-dithiolates, including chiral diphosphine R,R-DIPAMP, (iii) cationic Ni(phosphine-imine/amine) complexes, and (iv) organonickel precursors Ni( o-tolyl)Cl(tmeda) and Ni(C 6 F 5 ) 2 . The following new nickel precursor complexes were characterized: PPh 4 [Ni(NS 3 )] and the dimeric imino/amino-phosphine complexes [NiCl 2 (PCH═N An )] 2 and [NiCl 2 (PCH 2 NH An )] 2 (P = Ph 2 PC 6 H 4 -2-). The iron(II) reagents include [CpFe(CO) 2 (thf)]BF 4 , [Cp*Fe(CO)(MeCN) 2 ]BF 4 , FeI 2 (CO) 4 , FeCl 2 (diphos)(CO) 2 , and Fe(pdt)(CO) 2 (diphos) (diphos = chelating diphosphines). Reactions of the nickel and iron complexes gave the following new Ni-Fe compounds: Cp*Fe(CO)Ni(NS 3 ), [Cp(CO)Fe(μ-pdt)Ni(dppbz)]BF 4 , [( R,R-DIPAMP)Ni(μ-pdt)(H)Fe(CO) 3 ]BAr F 4 , [(PCH═N An )Ni(μ-pdt)(Cl)Fe(dppbz)(CO)]BF 4 , [(PCH 2 NH An )Ni(μ-pdt)(Cl)Fe(dppbz)(CO)]BF 4 , [(PCH═N An )Ni(μ-pdt)(H)Fe(dppbz)(CO)]BF 4 , [(dppv)(CO)Fe(μ-pdt)] 2 Ni, {H[(dppv)(CO)Fe(μ-pdt)] 2 Ni]}BF 4 , and (C 6 F 5 ) 2 Ni(μ-pdt)Fe(CO) 2 (dppv) (DIPAMP = (CH 2 P(C 6 H 4 = [B(C 2 ) 2 ; BAr F 4 - = [B(C 6 H 3 -3,5-(CF 3 ) 2 ] 4 - )) Within the context of Ni-(SR) 2 -Fe complexes, these new complexes feature new microenvironments for the nickel center: tetrahedral Ni, chirality, imine, and amine coligands, and Ni-C bonds. In the case of {H[(dppv)(CO)Fe(μ-pdt)] 2 Ni} + , four low-energy isomers are separated by ≤3 kcal/mol, one of which features a biomimetic HNi(SR) 4 site, as supported by density functional theory calculations.

The chemistry of Fe 2 (μ-SH) 2 (CO) 4 (PPh 3 ) 2 (2 HH ) is described with attention to S-S coupling reactions. Produced by the reduction of Fe 2 (μ-S 2 )(CO) 4 (PPh 3 ) 2 (2), 2 HH is an analogue of Fe 2 (μ-SH) 2 (CO) 6 (1 HH ), which exhibits well-behaved S-centered redox. Both 2 HH and the related 2 MeH exist as isomers that differ with respect to the stereochemistry of the μ-SR ligands (R = H, Me). Compounds 2 HH , 2 MeH , and 2 protonate to give rare examples of Fe-SH and Fe-S 2 hydrides. Salts of [H2] + , [H2 HH ] + , and [H2 MeH ] + were characterized crystallographically. Complex 2 HH reduces O 2 , H 2 O 2 , (PhCO 2 ) 2 , and Ph 2 N 2 , giving 2. Related reactions involving 1 HH gave uncharacterizable polymers. The differing behaviors of 2 HH and 1 HH reflect stabilization of the ferrous intermediates by the PPh 3 ligands. When independently generated by the reaction of 2 HH with 2,2,6,6-tetramethyl-1-piperidinyloxy, 2* quantitatively converts to 2 or, in the presence of C 2 H 4 , is trapped as the ethanedithiolate Fe 2 (μ-S 2 C 2 H 4 )(CO) 4 (PPh 3 ) 2 . Evidence is presented that the Hieber-Gruber synthesis of 1 involves polysulfido intermediates [Fe 2 (μ-S n ) 2 (CO) 6 ] 2- ( n > 1). Two relevant experiments are as follows: (i) protonation of [Fe 4 (μ-S) 2 (μ-S 2 )CO) 12 ] 2- gives 1 and 1 HH , and (ii) oxidation of 1 HH by sulfur gives 1.

We report the solution and structural chemistry of nickel(ii) complexes of the phosphine-oxime Ph2PC6H4-2-CH[double bond, length as m-dash]NOH (PCH[double bond, length as m-dash]NOH). PCH[double bond, length as m-dash]NOH invariably binds in a bidentate manner as illustrated by cis-Ni(PCH[double bond, length as m-dash]NOH)2Cl2 and cis-[Ni(PCH[double bond, length as m-dash]NOH)2]2+ (as its BF4- salt). Treatment of PCH[double bond, length as m-dash]NOH with Ni(OAc)2(H2O)4 gave charge-neutral trans-[Ni(PCH[double bond, length as m-dash]NO)2]0. Treatment of trans-[Ni(PCH[double bond, length as m-dash]NO)2]0 with BF3 gave [Ni(PCH[double bond, length as m-dash]NO)2BF2]BF4. The cation features a planar NiP2N2 center wherein the pair of oximate groups are linked by the difluoroboryl center. The 1 : 1 complexes of the oxime and the oximate are illustrated by [Ni(PCH[double bond, length as m-dash]NOH)Cl2]2 and [Ni(C6F5)(PCH[double bond, length as m-dash]NO)]2, which feature five- and four-coordinate Ni(ii) centers, respectively. All complexes in this series hydrolyze to give the trinickel oxo-phosphine-oximate complex [Ni3(PCH[double bond, length as m-dash]NO)3O]+. One feature of the PCH[double bond, length as m-dash]NOH ligand is its wide bite angle combined with its protic OH center. These aspects are manifested in the structures of Ni(PCH[double bond, length as m-dash]NOH)2Cl2 and [Ni(PCH[double bond, length as m-dash]NOH)Cl2]2, which show intramolecular hydrogen bonding to terminal chloride ligands.

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 H 2 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., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The synthesis and redox properties are presented for the electron-rich bis(monothiolate)s Fe 2 (SR) 2 (CO) 2 (dppv) 2 for R = Me ([1] 0 ), Ph ([2] 0 ), CH 2 Ph ([3] 0 ). Whereas related derivatives adopt C 2 -symmetric Fe 2 (CO) 2 P 4 cores, [1] 0 -[3] 0 have C s symmetry resulting from the unsymmetrical steric properties of the axial vs equatorial R groups. Complexes [1] 0 -[3] 0 undergo 1e - oxidation upon treatment with ferrocenium salts to give the mixed valence cations [Fe 2 (SR) 2 (CO) 2 (dppv) 2 ] + . As established crystallographically, [3] + adopts a rotated structure, characteristic of related mixed valence diiron complexes. Unlike [1] + and [2] + and many other [Fe 2 (SR) 2 L 6 ] + derivatives, [3] + undergoes C-S bond homolysis, affording the diferrous sulfido-thiolate [Fe 2 (SCH 2 Ph)(S)(CO) 2 (dppv) 2 ] + ([4] + ). According to X-ray crystallography, the first coordination spheres of [3] + and [4] + are similar, but the Fe-sulfido bonds are short in [4] + . The conversion of [3] + to [4] + follows first-order kinetics, with k = 2.3 × 10 -6 s -1 (30 °C). When the conversion is conducted in THF, the organic products are toluene and dibenzyl. In the presence of TEMPO, the conversion of [3] + to [4] + is accelerated about 10×, the main organic product being TEMPO-CH 2 Ph. DFT calculations predict that the homolysis of a C-S bond is exergonic for [Fe 2 (SCH 2 Ph) 2 (CO) 2 (PR 3 ) 4 ] + but endergonic for the neutral complex as well as less substituted cations. The unsaturated character of [4] + is indicated by its double carbonylation to give [Fe 2 (SCH 2 Ph)(S)(CO) 4 (dppv) 2 ] + ([5] + ), which adopts a bioctahedral structure.

The kinetically robust hydride [t-HFe 2 (Me 2 pdt)(CO) 2 (dppv) 2 ] + ([t-H1] + ) (Me 2 pdt 2- = Me 2 C(CH 2 S - ) 2 ; dppv = cis-1,2-C 2 H 2 (PPh 2 ) 2 ) and related derivatives were prepared with 57 Fe enrichment for characterization by NMR, FT-IR, and NRVS. The experimental results were rationalized using DFT molecular modeling and spectral simulations. The spectroscopic analysis was aimed at supporting assignments of Fe-H vibrational spectra as they relate to recent measurements on [FeFe]-hydrogenase enzymes. The combination of bulky Me 2 pdt 2- and dppv ligands stabilizes the terminal hydride with respect to its isomerization to the 5-16 kcal/mol more stable bridging hydride ([μ-H1] + ) with t 1/2 (313.3 K) = 19.3 min. In agreement with the nOe experiments, the calculations predict that one methyl group in [t-H1] + interacts with the hydride with a computed CH···HFe distance of 1.7 Å. Although [t-H 57 1] + exhibits multiple NRVS features in the 720-800 cm -1 region containing the bending Fe-H modes, the deuterated [t-D 57 1] + sample exhibits a unique Fe-D/CO band at ∼600 cm -1 . In contrast, the NRVS spectra for [μ-H 57 1] + exhibit weaker bands near 670-700 cm -1 produced by the Fe-H-Fe wagging modes coupled to Me 2 pdt 2- and dppv motions.

[FeFe]-hydrogenases are metalloenzymes that reversibly reduce protons to molecular hydrogen at exceptionally high rates. We have characterized the catalytically competent hydride state (H hyd ) in the [FeFe]-hydrogenases from both Chlamydomonas reinhardtii and Desulfovibrio desulfuricans using 57 Fe nuclear resonance vibrational spectroscopy (NRVS) and density functional theory (DFT). H/D exchange identified two Fe-H bending modes originating from the binuclear iron cofactor. DFT calculations show that these spectral features result from an iron-bound terminal hydride, and the Fe-H vibrational frequencies being highly dependent on interactions between the amine base of the catalytic cofactor with both hydride and the conserved cysteine terminating the proton transfer chain to the active site. The results indicate that H hyd is the catalytic state one step prior to H 2 formation. The observed vibrational spectrum, therefore, provides mechanistic insight into the reaction coordinate for H 2 bond formation by [FeFe]-hydrogenases.

The paper describes three methods for the preparation of methoxysiloxide complexes, a rare class of complexes of relevance to room temperature vulcanization (RTV) of polysiloxanes. The salt metathesis reaction involves the use of the recently described reagent NaOSi(OMe) 2 Me with various metal chlorides to give Cp* 2 Ti[OSi(OMe) 2 Me](OMe), ( Me,Me N 2 N)NiOSi(OMe) 2 Me, (IPr)CuOSi(OMe) 2 Me, and (triphos)CoOSi(OMe) 2 Me (Cp* = C 5 Me 5 , triphos = Me(CH 2 PPh 2 ) 3 ). Several attempted reactions gave methoxide complexes instead, a pathway that is attributed to the intermediacy of κ 2 -OSi(OMe) 2 Me species. The diol Cp* 2 Zr(OH) 2 reacts with excess (MeO) 3 SiMe to give Cp* 2 Zr[OSi(OMe) 2 Me] 2 . In contrast the less nucleophilic Cp* 2 Ti(OH) 2 was unreactive. The third route to methoxysiloxide complexes involves the reaction of Cp* 2 M(O)(py) with (MeO) 3 SiMe to give Cp* 2 M[OSi(OMe) 2 Me](OMe) in nearly quantitative yield (M = Ti, Zr). The structures of Cp* 2 Ti[OSi(OMe) 2 Me](OMe), Cp* 2 Zr[OSi(OMe) 2 Me](OMe), (IPr)CuOSi(OMe) 2 Me, and (triphos)CoOSi(OMe) 2 Me were confirmed by single crystal X-ray diffraction.

The reaction of Fe 2 (pdt)(CO) 6 with two equivalents of Ph 2 PC 6 H 4 NH 2 (PNH 2 ) affords the amido hydride HFe 2 (pdt)(CO) 2 (PNH 2 )(PNH) {[H 1 H] 0 , pdt 2- = CH 2 (CH 2 S - ) 2 }. Isolated intermediates in this conversion include Fe 2 (pdt)(CO) 5 -(κ 1 -PNH 2 ) and Fe 2 (pdt)(CO) 4 (κ 2 -PNH 2 ). X-ray crystallographic analysis of [H 1 H] 0 shows that the chelating amino/amido-phosphine ligands occupy trans -dibasal positions. The 31 P NMR spectrum indicates that [H 1 H] 0 undergoes rapid proton exchange between the amido and amine centers. No exchange was observed for the hydride. Protonation of [H 1 H] 0 gives [HFe 2 (pdt)(CO) 2 (PNH 2 ) 2 ] + ([H 2 1 H] + ), which contains two equivalent amino-phosphine ligands. Single-crystal X-ray crystallographic analysis of [H 2 1 H] + also reveals hydrogen bonds between the exo amine protons with a THF molecule and BF 4 . Deprotonation of [H 1 H] 0 with potassium tert -butoxide gave [HFe 2 (pdt)(CO) 2 (PNH) 2 ] - ([ 1 H] - ), which was characterized spectroscopically. The complex has time-averaged C 2 symmetry with two amido-phosphine ligands. FTIR spectroscopic measurements show that υ CO shifts by approximately 20 cm -1 in the series [ 1 H] - , [H 1 H] 0 , and [H 2 1 H] + . These shifts are comparable to those seen for the S-protonation of the (NC) 2 (CO)Fe-(μ-Scys) 2 Ni(Scys) 2 site in the [NiFe]-hydrogenases. [1] .

This study describes the structural, spectroscopic, and electrochemical properties of electronically unsymmetrical diiron hydrides. The terminal hydride Cp*Fe(pdt)Fe(dppe)(CO)H ([ 1 ( t -H)] 0 , Cp* - = Me 5 C 5 - , pdt 2- = CH 2 (CH 2 S - ) 2 , dppe = Ph 2 PC 2 H 4 PPh 2 ) was prepared by hydride reduction of [Cp*Fe(pdt)Fe(dppe)(CO)(NCMe)] + . As established by X-ray crystallography, [ 1 ( t -H)] 0 features a terminal hydride ligand. Unlike previous examples of terminal diiron hydrides, [ 1 ( t -H)] 0 does not isomerize to the bridging hydride [ 1 ( μ -H)] 0 . Oxidation of [ 1 ( t -H)] 0 gives [ 1 ( t -H)] + , which was also characterized crystallographically as its BF 4 - salt. Density functional theory (DFT) calculations indicate that [ 1 ( t -H)] + is best described as containing an Cp*Fe III center. In solution, [ 1 ( t -H)] + isomerizes to [ 1 ( μ -H)] + , as anticipated by DFT. Reduction of [ 1 ( μ -H)] + by Cp 2 Co afforded the diferrous bridging hydride [ 1 ( μ -H)] 0 . Electrochemical measurements and DFT calculations indicate that the couples [ 1 ( t -H)] +/0 and [ 1 ( μ -H)] +/0 differ by 210 mV. Qualitative measurements indicate that [ 1 ( t -H)] 0 and [ 1 ( μ -H)] 0 are close in free energy. Protonation of [ 1 ( t -H)] 0 in MeCN solution affords H 2 even with weak acids via hydride transfer. In contrast, protonation of [ 1 ( μ -H)] 0 yields 0.5 equiv of H 2 by a proposed protonation-induced electron transfer process. Isotopic labeling indicates that μ -H/D ligands are inert.

The azadithiolate complex Fe 2 [(SCH 2 ) 26 NMe](CO) 6 reacts with borane to give an initial 1:1 adduct, which spontaneously decarbonylates to give Fe 2 [(SCH 2 ) 2 NMeBH 3 ](CO) 5 . Featuring a Fe-H-B three-center, two-electron interaction, the pentacarbonyl complex is a structural model for H 2 complexes invoked in the [FeFe]-hydrogenases. The pentacarbonyl compound is a " σ complex", where a B-H σ bond serves as a ligand for iron. The structure of this σ complex was characterized by variable-temperature NMR spectroscopy and X-ray crystallography. Complementary to the 1:1 borane adduct is the quaternary ammonium complex [Fe 2 ](SCH 2 ) 2 NMe 2 ](CO) 6 ] + , which was also characterized. It represents a kinetically robust analogue of the N-protonated amine cofactor, as indicated by its mild reduction potential.

The nickel-iron hydrogenase enzymes efficiently and reversibly interconvert protons, electrons, and dihydrogen. These redox proteins feature iron-sulfur clusters that relay electrons to and from their active sites. Reported here are synthetic models for nickel-iron hydrogenase featuring redox-active auxiliaries that mimic the iron-sulfur cofactors. The complexes prepared are Ni II (μ-H)Fe II Fe II species of formula [(diphosphine)Ni(dithiolate)(μ-H)Fe(CO) 2 (ferrocenylphosphine)] + or Ni II Fe I Fe II complexes [(diphosphine)Ni(dithiolate)Fe(CO) 2 (ferrocenylphosphine)] + (diphosphine = Ph 2 P(CH 2 ) 2 PPh 2 or Cy 2 P(CH 2 ) 2 PCy 2 ; dithiolate = - S(CH 2 ) 3 S - ; ferrocenylphosphine = diphenylphosphinoferrocene, diphenylphosphinomethyl(nonamethylferrocene) or 1,1'-bis(diphenylphosphino)ferrocene). The hydride species is a catalyst for hydrogen evolution, while the latter hydride-free complexes can exist in four redox states - a feature made possible by the incorporation of the ferrocenyl groups. Mixed-valent complexes of 1,1'-bis(diphenylphosphino)ferrocene have one of the phosphine groups unbound, with these species representing advanced structural models with both a redox-active moiety (the ferrocene group) and a potential proton relay (the free phosphine) proximal to a nickel-iron dithiolate.

[FeFe]-hydrogenases catalyze the reversible reduction of protons to molecular hydrogen with extremely high efficiency. The active site ("H-cluster") consists of a [4Fe-4S] H cluster linked through a bridging cysteine to a [2Fe] H subsite coordinated by CN - and CO ligands featuring a dithiol-amine moiety that serves as proton shuttle between the protein proton channel and the catalytic distal iron site (Fe d ). Although there is broad consensus that an iron-bound terminal hydride species must occur in the catalytic mechanism, such a species has never been directly observed experimentally. Here, we present FTIR and nuclear resonance vibrational spectroscopy (NRVS) experiments in conjunction with density functional theory (DFT) calculations on an [FeFe]-hydrogenase variant lacking the amine proton shuttle which is stabilizing a putative hydride state. The NRVS spectra unequivocally show the bending modes of the terminal Fe-H species fully consistent with widely accepted models of the catalytic cycle.

Hydrogenase enzymes efficiently process H2 and protons at organometallic FeFe, NiFe, or Fe active sites. Synthetic modeling of the many H2ase states has provided insight into H2ase structure and mechanism, as well as afforded catalysts for the H2 energy vector. Particularly important are hydride-bearing states, with synthetic hydride analogues now known for each hydrogenase class. These hydrides are typically prepared by protonation of low-valent cores. Examples of FeFe and NiFe hydrides derived from H2 have also been prepared. Such chemistry is more developed than mimicry of the redox-inactive monoFe enzyme, although functional models of the latter are now emerging. Advances in physical and theoretical characterization of H2ase enzymes and synthetic models have proven key to the study of hydrides in particular, and will guide modeling efforts toward more robust and active species optimized for practical applications., Competing Interests: Notes The authors declare no competing financial interest.

The intermediacy of a reduced nickel-iron hydride in hydrogen evolution catalyzed by Ni-Fe complexes was verified experimentally and computationally. In addition to catalyzing hydrogen evolution, the highly basic and bulky (dppv)Ni(μ-pdt)Fe(CO)(dppv) ([1](0); dppv = cis-C2H2(PPh2)2) and its hydride derivatives have yielded to detailed characterization in terms of spectroscopy, bonding, and reactivity. The protonation of [1](0) initially produces unsym-[H1](+), which converts by a first-order pathway to sym-[H1](+). These species have C1 (unsym) and Cs (sym) symmetries, respectively, depending on the stereochemistry of the octahedral Fe site. Both experimental and computational studies show that [H1](+) protonates at sulfur. The S = 1/2 hydride [H1](0) was generated by reduction of [H1](+) with Cp*2Co. Density functional theory (DFT) calculations indicate that [H1](0) is best described as a Ni(I)-Fe(II) derivative with significant spin density on Ni and some delocalization on S and Fe. EPR spectroscopy reveals both kinetic and thermodynamic isomers of [H1](0). Whereas [H1](+) does not evolve H2 upon protonation, treatment of [H1](0) with acids gives H2. The redox state of the "remote" metal (Ni) modulates the hydridic character of the Fe(II)-H center. As supported by DFT calculations, H2 evolution proceeds either directly from [H1](0) and external acid or from protonation of the Fe-H bond in [H1](0) to give a labile dihydrogen complex. Stoichiometric tests indicate that protonation-induced hydrogen evolution from [H1](0) initially produces [1](+), which is reduced by [H1](0). Our results reconcile the required reductive activation of a metal hydride and the resistance of metal hydrides toward reduction. This dichotomy is resolved by reduction of the remote (non-hydride) metal of the bimetallic unit., Competing Interests: Notes The authors declare no competing financial interest.

Virtually all organosulfur compounds react with Fe(0) carbonyls to give the title complexes. These reactions are reviewed in light of major advances over the past few decades, spurred by interest in Fe2(μ-SR)2(CO)x centers at the active sites of the [FeFe]-hydrogenase enzymes. The most useful synthetic route to Fe2(μ-SR)2(CO)6 involves the reaction of thiols with Fe2(CO)9 and Fe3(CO)12. Such reactions can proceed via mono-, di-, and triiron intermediates. The reactivity of Fe(0) carbonyls toward thiols is highly chemoselective, and the resulting dithiolato complexes are fairly rugged. Thus, many complexes tolerate further synthetic elaboration directed at the organic substituents. A second major route involves alkylation of Fe2(μ-S2)(CO)6, Fe2(μ-SH)2(CO)6, and Li2Fe2(μ-S)2(CO)6. This approach is especially useful for azadithiolates Fe2[(μ-SCH2)2NR](CO)6. Elaborate complexes arise via addition of the FeSH group to electrophilic alkenes, alkynes, and carbonyls. Although the first example of Fe2(μ-SR)2(CO)6 was prepared from ferrous reagents, ferrous compounds are infrequently used, although the Fe(II)(SR)2 + Fe(0) condensation reaction is promising. Almost invariably low-yielding, the reaction of Fe3(CO)12, S8, and a variety of unsaturated substrates results in C-H activation, affording otherwise inaccessible derivatives. Thiones and related C═S-containing reagents are highly reactive toward Fe(0), often giving complexes derived from substituted methanedithiolates and C-H activation.

The commercially practiced conversion of trimethoxymethylsilane (MTM) to [OSi(OMe)Me)]n polymers and resins is assumed to proceed via the silanol (MeO)2MeSiOH. Access to this crucial silanol is gained via the synthesis of (MeO)2MeSiONa, the first methoxysilanoate to be crystallographically characterized. Mild protonation of this silanoate gives (MeO)2MeSiOH, which is shown to condense with (MeO)2MeSiOH but not with MTM. Condensation generates reactive disiloxanols but does not produce symmetric disiloxanes. Parallel results were obtained with (MeO)2PhSiOH.

The photochemical reaction of Fe 2 (S 2 )(CO) 6 and Ph 2 CS affords the perthiolate Fe 2 (S 3 CPh 2 )(CO) 6 ( 1 ) in good yield. As confirmed crystallographically, 1 contains a previously elusive perthiolate ligand. The related reaction of Fe 2 (S 2 )(CO) 5 -(PPh 3 ) and Ph 2 CS gave Fe 2 (S 3 CPh 2 )(CO) 5 (PPh 3 ). Although Fe 3 S 2 (CO) 9 and Ph 2 CS failed to efficiently give Fe 2 (S 2 CPh 2 )(CO) 6 , this compound could be prepared by desulfurization of 1 using PPh 3 .

The complexes Fe2(pdt)(CNR)6 (pdt(2-) = CH2(CH2S(-))2) were prepared by thermal substitution of the hexacarbonyl complex with the isocyanides RNC for R = C6H4-4-OMe (1), C6H4-4-Cl (2), Me (3). These complexes represent electron-rich analogues of the parent Fe2(pdt)(CO)6. Unlike most substituted derivatives of Fe2(pdt)(CO)6, these isocyanide complexes are sterically unencumbered and have the same idealized symmetry as the parent hexacarbonyl derivatives. Like the hexacarbonyls, the stereodynamics of 1-3 involve both turnstile rotation of the Fe(CNR)3 as well as the inversion of the chair conformation of the pdt ligand. Structural studies indicate that the basal isocyanide has nonlinear CNC bonds and short Fe-C distances, indicating that they engage in stronger Fe-C π-backbonding than the apical ligands. Cyclic voltammetry reveals that these new complexes are far more reducing than the hexacarbonyls, although the redox behavior is complex. Estimated reduction potentials are E1/2 ≈ -0.6 ([2](+/0)), -0.7 ([1](+/0)), and -1.25 ([3](+/0)). According to DFT calculations, the rotated isomer of 3 is only 2.2 kcal/mol higher in energy than the crystallographically observed unrotated structure. The effects of rotated versus unrotated structure and of solvent coordination (THF, MeCN) on redox potentials were assessed computationally. These factors shift the redox couple by as much as 0.25 V, usually less. Compounds 1 and 2 protonate with strong acids to give the expected μ-hydrides [H1](+) and [H2](+). In contrast, 3 protonates with [HNEt3]BAr(F)4 (pKa(MeCN) = 18.7) to give the aminocarbyne [Fe2(pdt)(CNMe)5(μ-CN(H)Me)](+) ([3H](+)). According to NMR measurements and DFT calculations, this species adopts an unsymmetrical, rotated structure. DFT calculations further indicate that the previously described carbyne complex [Fe2(SMe)2(CO)3(PMe3)2(CCF3)](+) also adopts a rotated structure with a bridging carbyne ligand. Complex [3H](+) reversibly adds MeNC to give [Fe2(pdt)(CNR)6(μ-CN(H)Me)](+) ([3H(CNMe)](+)). Near room temperature, [3H](+) isomerizes to the hydride [(μ-H)Fe2(pdt)(CNMe)6](+) ([H3](+)) via a first-order pathway.

A new class of synthetic models for the active site of [NiFe]-hydrogenases are described. The Ni(I/II)(SCys)2 and Fe(II)(CN)2CO sites are represented with (RC5H4)Ni(I/II) and Fe(II)(diphos)(CO) modules, where diphos = 1,2-C2H4(PPh2)2(dppe) or cis-1,2-C2H2(PPh2)2(dppv). The two bridging thiolate ligands are represented by CH2(CH2S)2(2-) (pdt(2-)), Me2C(CH2S)2(2-) (Me2pdt(2-)), and (C6H5S)2(2-). The reaction of Fe(pdt)(CO)2(dppe) and [(C5H5)3Ni2]BF4 affords [(C5H5)Ni(pdt)Fe(dppe)(CO)]BF4 ([1a]BF4). Monocarbonyl [1a]BF4 features an S = 0 Ni(II)Fe(II) center with five-coordinated iron, as proposed for the Ni-SIa state of the enzyme. One-electron reduction of [1a](+) affords the S = 1/2 derivative [1a](0), which, according to density functional theory (DFT) calculations and electron paramagnetic resonance and Mössbauer spectroscopies, is best described as a Ni(I)Fe(II) compound. The Ni(I)Fe(II) assignment matches that for the Ni-L state in [NiFe]-hydrogenase, unlike recently reported Ni(II)Fe(I)-based models. Compound [1a](0) reacts with strong acids to liberate 0.5 equiv of H2 and regenerate [1a](+), indicating that H2 evolution is catalyzed by [1a](0). DFT calculations were used to investigate the pathway for H2 evolution and revealed that the mechanism can proceed through two isomers of [1a](0) that differ in the stereochemistry of the Fe(dppe)CO center. Calculations suggest that protonation of [1a](0) (both isomers) affords Ni(III)-H-Fe(II) intermediates, which represent mimics of the Ni-C state of the enzyme.

The title complex, [Fe2(C8H12S3)(CO)6] or [{Fe(CO)3}2(μ-L)] [L = 3,3-dimethyl-4-(propan-2-yl-idene)thietane-2,2-bis-(thiol-ato)], consists of two Fe(CO)3 moieties double-bridged by a di-thiol-ate ligand. Each of the two Fe(I) atoms has a distorted anti-prismatic coordination environment consisting of three carbonyl groups, two S atoms of the di-thiol-ate ligand and the neighboring Fe(I) atom [Fe-Fe = 2.4921 (4) Å]. Weak C-H⋯O inter-molecular inter-actions result in the formation of dimers. This is the second crystal structure reported with the 3,3-dimethyl-4-(propan-2-yl-idene)thietane-2,2-bis-(thiol-ate) ligand and the first in which it bridges two metal atoms.

The mononuclear title complex, [Fe(CF3O3S)(C5H7O2)2(C4H8O)] or [Fe(acac)2(OTf)(THF)] (acac = acetyl-acetonate; OTf = tri-fluoro-methane-sulfon-ate; THF = tetrahydrofuran), (I), consists of one six-coordinate Fe(3+) atom in a slightly distorted octa-hedral environment [Fe-O bond-length range = 1.9517 (11)-2.0781 (11) Å]. The triflate ligand was found to be disordered over two sets of sites, with a site-occupancy ratio of 0.622 (16):0.378 (16). Weak inter-molecular C-H⋯O and C-H⋯F hydrogen-bonding inter-actions generate a two-dimensional supra-molecular structure lying parallel to (100). This is only the second crystal structure reported of a mononuclear bis-(acetyl-acetonato)iron(III) complex.

The metabolism of many anaerobes relies on [NiFe]-hydrogenases, whose characterization when bound to substrates has proven non-trivial. Presented here is direct evidence for a hydride bridge in the active site of the (57)Fe-labelled fully reduced Ni-R form of Desulfovibrio vulgaris Miyazaki F [NiFe]-hydrogenase. A unique 'wagging' mode involving H(-) motion perpendicular to the Ni(μ-H)(57)Fe plane was studied using (57)Fe-specific nuclear resonance vibrational spectroscopy and density functional theory (DFT) calculations. On Ni(μ-D)(57)Fe deuteride substitution, this wagging causes a characteristic perturbation of Fe-CO/CN bands. Spectra have been interpreted by comparison with Ni(μ-H/D)(57)Fe enzyme mimics [(dppe)Ni(μ-pdt)(μ-H/D)(57)Fe(CO)3](+) and DFT calculations, which collectively indicate a low-spin Ni(II)(μ-H)Fe(II) core for Ni-R, with H(-) binding Ni more tightly than Fe. The present methodology is also relevant to characterizing Fe-H moieties in other important natural and synthetic catalysts.

The title complex, [Fe4(C5H7O2)4(CH3O)6Cl2] or [Fe4(acac)4(μ2-OMe)4(μ3-OMe)2Cl2] (acac = acetyl-acetonate), crystallizes in the ortho-rhom-bic Pbca space group with one half of the mol-ecule per asymmetric unit, the other half being completed by inversion symmetry. The core structure consists of a face-sharing double pseudo-cubane entity with two opposite corners missing. Weak C-H⋯Cl inter-molecular inter-actions result in a two-dimensional layered structure parallel to the ac plane.

The dinuclear title complex, [Co2(C5H7O2)4(μ-OH)2] or [Co(acac)2(μ-OH)]2, where acac is acetyl-acetonate, is centrosymmetric with half of the mol-ecule per asymmetric unit. The mol-ecular structure is a dimer of octa-hedrally coordinated Co(III) atoms with four O atoms from two chelating acac ligands and two O atoms from bridging hydroxide ligands. The crystal packing features weak C-H⋯O inter-actions between neighboring mol-ecules, leading to the formation of chains normal to the ac plane. The hydroxide H atoms are not involved in hydrogen bonding because of the bulky acac ligands. This is the first crystal structure reported of a dimeric transition metal bis-acac complex with OH(-) as the bridging group.