Nitrogen reduction by the Fe sites of synthetic [Mo3S4Fe] cubes.

Nitrogen (N2) fixation by nature, which is a crucial process for the supply of bio-available forms of nitrogen, is performed by nitrogenase. This enzyme uses a unique transition-metal-sulfur-carbon cluster as its active-site co-factor ([(R-homocitrate)MoFe7S9C], FeMoco)1,2, and the sulfur-surrounded iron (Fe) atoms have been postulated to capture and reduce N2 (refs. 3-6). Although there are a few examples of synthetic counterparts of the FeMoco, metal-sulfur cluster, which have shown binding of N2 (refs. 7-9), the reduction of N2 by any synthetic metal-sulfur cluster or by the extracted form of FeMoco10 has remained elusive, despite nearly 50 years of research. Here we show that the Fe atoms in our synthetic [Mo3S4Fe] cubes11,12 can capture a N2 molecule and catalyse N2 silylation to form N(SiMe3)3 under treatment with excess sodium and trimethylsilyl chloride. These results exemplify the catalytic silylation of N2 by a synthetic metal-sulfur cluster and demonstrate the N2-reduction capability of Fe atoms in a sulfur-rich environment, which is reminiscent of the ability of FeMoco to bind and activate N2.

Flow-Chemistry-Enabled Synthesis of 5-Diethylboryl-2,3'-bipyridine and Its Self-Assembly Dynamics.

5-Diethylboryl-2,3'-bipyridine (1), which is inaccessible by conventional batch methods, was synthesized by using a flow microreactor. Compound 1 was obtained as an equilibrium mixture of a cyclic trimer and a cyclic tetramer in solution, the latter of which was crystallized in benzene by vapor diffusion of hexane at 7 °C. The dynamic nature of this system was confirmed by solvent- and concentration-dependent experiments. Notably, the dynamics was verified by using flow NMR spectroscopy, which revealed that the time required to reach equilibrium was influenced by the solvent ratio (<18 s, 24-28 s, and 34-42 s in 2 : 1, 1 : 1, and 1 : 2 mixtures of [D6 ]acetone and C6 D6 , respectively). Compound 1 and 3-[4'-(diethylboryl)phenyl]pyridine (2) exhibited different self-assembly behavior in solution and crystals. Density functional theory calculations suggested that this difference was largely due to enhanced planarity between two consecutive aromatic rings.

Incorporation of an Asymmetric Mo-Fe-S Cluster as an Artificial Cofactor into Nitrogenase.

Nitrogenase employs a sophisticated electron transfer system and a Mo-Fe-S-C cofactor, designated the M-cluster [(cit)MoFe7 S9 C]), to reduce atmospheric N2 to bioaccessible NH3 . Previously, we have shown that the cofactor-free form of nitrogenase can be repurposed as a protein scaffold for the incorporation of a synthetic Fe-S cluster [Fe6 S9 (SEt)2 ]4- . Here, we demonstrate the utility of an asymmetric Mo-Fe-S cluster [Cp*MoFe5 S9 (SH)]3- as an alternative artificial cofactor upon incorporation into the cofactor-free nitrogenase scaffold. The resultant semi-artificial enzyme catalytically reduces C2 H2 to C2 H4 , and CN- into short-chain hydrocarbons, yet it is clearly distinct in activity from its [Fe6 S9 (SEt)2 ]4- -reconstituted counterpart, pointing to the possibility to employ molecular design and cluster synthesis strategies to further develop semi-artificial or artificial systems with desired catalytic activities.

Metal-Sulfur Compounds in N2 Reduction and Nitrogenase-Related Chemistry.

Transition metal-sulfur (M-S) compounds are an indispensable means for biological systems to convert N2 into NH3 (biological N2 fixation), and these may have emerged by chemical evolution from a prebiotic N2 fixation system. With a main focus on synthetic species, this article provides a comprehensive review of the chemistry of M-S compounds related to the conversion of N2 and the structures/functions of the nitrogenase cofactors. Three classes of M-S compounds are highlighted here: multinuclear M-S clusters structurally or functionally relevant to the nitrogenase cofactors, mono- and dinuclear transition metal complexes supported by sulfur-containing ligands in N2 and N2Hx (x = 2, 4) chemistry, and metal sulfide-based solid materials employed in the reduction of N2. Fair assessments on these classes of compounds revealed that our understanding is still limited in N2 reduction and related substrate reductions. Our aims of this review are to compile a collection of studies performed at atomic to mesoscopic scales and to present potential opportunities for elucidating the roles of metal and sulfur atoms in the biological N2 fixation that might be helpful for the development of functional materials.

Four-Electron Reduction of Dioxygen on a Metal Surface: Models of Dissociative and Associative Mechanisms in a Homogeneous System.

Two different four-electron reductions of dioxygen (O2) on a metal surface are reproduced in homogeneous systems. The reaction of the highly unsaturated (56-electron) tetraruthenium tetrahydride complex 1 with O2 readily afforded the bis(µ3-oxo) complex 3 via a dissociative mechanism that includes large electronic and geometric changes, i.e., a four-electron oxidation of the metal centers and an increase of 8 in the number of valence electrons. In contrast, the tetraruthenium hexahydride complex 2 induces a smooth H-atom transfer to the incorporated O2 species, and the O-OH bond is cleaved to afford the mono(µ3-oxo) complex 4 via an associative mechanism. Density functional theory calculations suggest that the higher degree of unsaturation in the tetrahydride system induces a significant interaction between the tetraruthenium core and the O2 moiety, enabling the large changes required for the dissociative mechanism.

Synthesis of Dinuclear Mo-Fe Hydride Complexes and Catalytic Silylation of N2.

Two transition-metal atoms bridged by hydrides may represent a useful structural motif for N2 activation by molecular complexes and the enzyme active site. In this study, dinuclear MoIV -FeII complexes with bridging hydrides, CpR Mo(PMe3 )(H)(µ-H)3 FeCp* (2 a; CpR =Cp*=C5 Me5 , 2 b; CpR =C5 Me4 H), were synthesized via deprotonation of CpR Mo(PMe3 )H5 (1 a; CpR =Cp*, 1 b; CpR =C5 Me4 H) by Cp*FeN(SiMe3 )2 , and they were characterized by spectroscopy and crystallography. These Mo-Fe complexes reveal the shortest Mo-Fe distances ever reported (2.4005(3) Šfor 2 a and 2.3952(3) Šfor 2 b), and the Mo-Fe interactions were analyzed by computational studies. Removal of the terminal Mo-H hydride in 2 a-2 b by [Ph3 C]+ in THF led to the formation of cationic THF adducts [CpR Mo(PMe3 )(THF)(µ-H)3 FeCp*]+ (3 a; CpR =Cp*, 3 b; CpR =C5 Me4 H). Further reaction of 3 a with LiPPh2 gave rise to a phosphido-bridged complex Cp*Mo(PMe3 )(µ-H)(µ-PPh2 )FeCp* (4). A series of Mo-Fe complexes were subjected to catalytic silylation of N2 in the presence of Na and Me3 SiCl, furnishing up to 129±20 equiv of N(SiMe3 )3 per molecule of 2 b. Mechanism of the catalytic cycle was analyzed by DFT calculations.

Synthesis of [Mo3S4] Clusters from Half-Sandwich Molybdenum(V) Chlorides and Their Application as Platforms for [Mo3S4Fe] Cubes.

Triangular [Mo3S4] clusters are known to serve as platforms to accommodate a metal atom M, furnishing cubic [Mo3S4M] clusters. In this study, three [Mo3S4] clusters supported by η5-cyclopentadienyl (CpR) ligands, [CpR3Mo3S4]+ (CpR = C5Me4SiMe3, C5Me4SiEt3, and C5Me4H), were synthesized via half-sandwich molybdenum chlorides CpRMoCl4. In the cyclic voltammogram of the [Mo3S4] cluster having C5Me4H ligands, a weak feature appeared in addition to the [CpR3Mo3S4]0/- redox process, indicating the interaction between [CpR3Mo3S4]- and the [NnBu4] cation of the electrolyte, while such a feature was less significant for the C5Me4SiR3 variants. The [Mo3S4] clusters with bulky C5Me4SiR3 ligands were successfully applied as platforms to accommodate an Fe atom to furnish cubic [Mo3S4Fe] clusters. On the other hand, the corresponding reactions of the less bulky C5Me4H analogue gave complex mixtures.

Cubane-Type [Mo3 S4 M] Clusters with First-Row Groups†4-10 Transition-Metal Halides Supported by C5 Me5 Ligands on Molybdenum.

A synthetic protocol was developed for a series of cubane-type [Mo3 S4 M] clusters that incorporate halides of first-row transition metals (M) from Groups 4-10. This protocol is based on the anionic cluster platform [Cp*3 Mo3 S4 ]- ([1]- ; Cp*=η5 -C5 Me5 ), which crystallizes when K(18-crown-6) is used as the counter cation. Treatment of in situ-generated [1]- with such transition-metal halides led to the formation of [Mo3 S4 M] clusters, in which the M/halide ratio gradually changes from 1:2 to 1:1.5 and to 1:1, when moving from early to late transition metals. This trend suggests a tendency for early transition metals to tolerate higher oxidation states and adopt larger ionic radii relative to late transition metals. The properties of the [Mo3 S4 Fe] cluster 6 a were investigated in detail by using 57 Fe Mössbauer spectroscopy and computational methods.

[Fe4] and [Fe6] Hydride Clusters Supported by Phosphines: Synthesis, Characterization, and Application in N2 Reduction.

Multiple iron atoms bridged by hydrides is a common structural feature of the active species that have been postulated in the biological and industrial reduction of N2. In this study, the reactions of an Fe(II) amide complex with pinacolborane in the presence/absence of phosphines afforded a series of hydride-supported [Fe4] and [Fe6] clusters Fe4(µ-H)4(µ3-H)2{N(SiMe3)2}2(PR3)4 (PR3 = PMe3 (2a), PMe2Ph (2b), PEt3 (2c)), Fe6(µ-H)10(µ3-H)2(PMe3)10 (3), and (η6-C7H8)Fe4(µ-H)2{µ-N(SiMe3)2}2{N(SiMe3)2}2 (4), which were characterized crystallographically and spectroscopically. Under ambient conditions, these clusters catalyzed the silylation of N2 to furnish up to 160 ± 13 equiv of N(SiMe3)3 per 2c (40 equiv per Fe atom) and 183 ± 18 equiv per 3 (31 equiv per Fe atom). With regard to the generation of the reactive species, dissociation of phosphine and hydride ligands from the [Fe4] and [Fe6] clusters was indicated, based on the results of the mass spectrometric analysis on the [Fe6] cluster, as well as the formation of a diphenylsilane adduct of the [Fe4] cluster.

Reduction of C1 Substrates to Hydrocarbons by the Homometallic Precursor and Synthetic Mimic of the Nitrogenase Cofactor.

Solvent-extracted nitrogenase cofactors can reduce C1 substrates (CN-, CO and CO2) to hydrocarbons in reactions driven by a strong reductant, SmI2 (E0' = -1.55 V vs SCE). Here we show that a synthetic [Et4N]4[Fe6S9(SEt)2] cluster (designated the Fe6RHH-cluster), which mimics the homometallic [Fe8S9C] core of the nitrogenase cofactor (designated the L-cluster), is capable of conversion of C1 substrates into hydrocarbons in the same reactions. Comparison of the yields and product profiles between these homometallic clusters and their heterometallic counterparts points to possible roles of the heterometal, interstitial carbide and belt sulfur-bridged iron atoms in catalysis. More importantly, the observation that a "simplified", homometallic cofactor mimic can perform Fischer-Tropsch-like hydrocarbon synthesis suggests future biotechnological adaptability of nitrogenase-based biomimetic compounds for recycling C1 substrates into useful chemical and fuel products.

Synthesis and Characterization of Bioinspired [Mo2 Fe2 ]-Hydride Cluster Complexes and Their Application in the Catalytic Silylation of N2.

The hydride-supported [Mo2 Fe2 ] cluster complex {Cp*Mo(PMe3 )}2 {FeN(SiMe3 )2 }2 (H)8 (2 a; Cp*=η5 -C5 Me5 ) and its [Mo2 Mn2 ] congener 2 b were synthesized from the reactions of Cp*Mo(PMe3 )(H)5 (1) with M{N(SiMe3 )2 }2 (M=Fe, Mn). The amide-to-thiolate ligand-exchange reactions of complex 2 a with bulky thiol reagents (HSR; R=2,4,6-iPr3 C6 H2 (Tip), 2,6-(SiMe3 )2 C6 H3 (Btp)) furnished the corresponding hydride-supported [Mo2 Fe2 ](SR)2 cluster complexes. The [Mo2 Fe2 ] clusters served as catalyst precursors for the reductive silylation of N2 and yielded ≈65-69 equivalents of N(SiMe3 )3 relative to the [Mo2 Fe2 ] clusters. Treatment of complexes 2 a and b with an excess of CNtBu resulted in the formation of dinuclear Mo-Fe and Mo-Mn complexes, which indicated that the [Mo2 M2 ] cores (M=Fe, Mn) split into two dinuclear species upon accommodation of substrates.

Self-Assembly of 4-(Diethylboryl)pyridine: Crystal Structures of the Cyclic Pentamer and Hexamer and Their Solvent-Dependent Selective Crystallization.

Two distinct oligomeric structures were obtained by the self-assembly of 4-(diethylboryl)pyridine (1). In the (1)H NMR spectrum of 1 in CDCl3, at least two sets of signals were observed for the pyridyl α- and ß-hydrogen atoms. ESI-MS, VPO, and TLC analysis revealed that 1 assembles mainly into a mixture of cyclic pentamers and hexamers in solution via intermolecular boron-nitrogen coordination bonds. Crystallization of 1 in THF by vapor diffusion of EtOH or in CHCl3 afforded the cyclic hexamer incorporating one THF molecule (16·THF) or 1.5 mol equiv of chloroform molecule (16·CHCl3), respectively. Similarly, a solution of 1 in a mixture of benzene and hexane furnished the cyclic pentamer bearing two benzene molecules (15·C6H6). It seems that the solvent differences affected the crystallization of the two distinct cyclic oligomers of 1, either of which was cocrystallized predominantly with the solvent molecule. Thermogravimetric analysis of the crystals and NMR studies of the solution revealed that the noncovalent interactions between the host and guest are not strong enough to hold the guest molecule in the cavity.

Interconversion between [Fe4S4] and [Fe2S2] Clusters Bearing Amide Ligands.

Structural conversion of [Fe4S4] clusters into [Fe2S2] clusters has been suggested to be a fundamental process for some O2-sensing proteins. While the formation of [Fe2S2] clusters from synthetic [Fe4S4] clusters has been unprecedented, an all-ferric [Fe4S4](4+) cluster Fe4S4{N(SiMe3)2}4 (1) was found to split in the presence of pyridines, giving [Fe2S2] clusters Fe2S2{N(SiMe3)2}2(L)2 (2, L = pyridines). The structural conversion between [Fe4S4] and [Fe2S2] clusters appeared to be reversible, and the thermodynamic parameters for the equilibrium reactions between 1 + L and 2 were determined. Assembly of two [Fe2S2] clusters was also induced by chemical reductions of Fe2S2{N(SiMe3)2}2(Py)2 (Py = pyridine), and the resultant [Fe4S4] clusters [1](-) and [1](2-) were found to split into two [Fe2S2] clusters by oxidation with [Cp2Fe](+) in the presence of pyridine.

Co6 H8 (Pi Pr3 )6 : A Cobalt Octahedron with Face-Capping Hydrides.

A square-planar Co4 amide cluster, Co4 {N(SiMe3 )2 }4 (2), and an octahedral Co6 hydride cluster, Co6 H8 (Pi Pr3 )6 (4), were obtained from metathesis-type amide to hydride exchange reactions of a CoII amide complex with pinacolborane (HBpin) in the absence/presence of Pi Pr3 . The crystal structure of 4 revealed face-capping hydrides on each triangular [Co3 ] face, while the formal CoII2 CoI4 oxidation state of 4 indicated a reduction of the cobalt centers during the assembly process. Cluster 4 catalyzes the hydrosilylation of 2-cyclohexen-1-one favoring the conjugate reduction. Generation of the catalytically reactive Co cluster species was indicated by a trapping experiment with a chiral chelating agent.

Structure and Reactivity of an Asymmetric Synthetic Mimic of Nitrogenase Cofactor.

The Mo nitrogenase catalyzes the ambient reduction of N2 to NH3 at its M-cluster site. A complex metallocofactor with a core composition of [MoFe7 S9 C], the M-cluster, can be extracted from the protein scaffold and used to facilitate the catalytic reduction of CN- , CO, and CO2 into hydrocarbons in the isolated state. Herein, we report the synthesis, structure, and reactivity of an asymmetric M-cluster analogue with a core composition of [MoFe5 S9 ]. This analogue, referred to as the Mo-cluster, is the first synthetic example of an M-cluster mimic with Fe and Mo positioned at opposite ends of the cluster. Moreover, the ability of the Mo-cluster to reduce C1 substrates to hydrocarbons suggests the feasibility of developing nitrogenase-based biomimetic approaches to recycle C1  waste into fuel products.

Combining a Nitrogenase Scaffold and a Synthetic Compound into an Artificial Enzyme.

Nitrogenase catalyzes substrate reduction at its cofactor center ([(Cit)MoFe7S9C](n-); designated M-cluster). Here, we report the formation of an artificial, nitrogenase-mimicking enzyme upon insertion of a synthetic model complex ([Fe6S9(SEt)2](4-); designated Fe6(RHH)) into the catalytic component of nitrogenase (designated NifDK(apo)). Two Fe6(RHH) clusters were inserted into NifDK(apo), rendering the conformation of the resultant protein (designated NifDK(Fe)) similar to the one upon insertion of native M-clusters. NifDK(Fe) can work together with the reductase component of nitrogenase to reduce C2H2 in an ATP-dependent reaction. It can also act as an enzyme on its own in the presence of Eu(II)DTPA, displaying a strong activity in C2H2 reduction while demonstrating an ability to reduce CN(-) to C1-C3 hydrocarbons in an ATP-independent manner. The successful outcome of this work provides the proof of concept and underlying principles for continued search of novel enzymatic activities based on this approach.

Synthesis of V/Fe/S clusters using vanadium(III) thiolate complexes bearing a phenoxide-based tridentate ligand.

Vanadium(III) thiolate complexes carrying a phenoxide-based tridentate ligand were prepared from the reactions of V(NMe2)4 with the protonated forms of tridentate ligands (H2(O,P,O) = bis(3,5-di-tert-butyl-2-hydroxyphenyl)phenylphosphine or H2(O,O,O) = bis(3,5-di-tert-butyl-2-hydroxyphenyl)phenylphosphineoxide) and thiols (HSR; R = mesityl (Mes), 2,4,6-(i)Pr3C6H2 (Tip)). The vanadium-thiolate complexes were subjected to the V/Fe/S cluster synthesis via treatment with an Fe(II) thiolate complex [(TipS)Fe]2(µ-SDmp)2 (4, Dmp = 2,6-(mesityl)2C6H3) and elemental sulfur in toluene, leading to the formation of two new V/Fe/S clusters. One is an edge-bridged double-cubane-type [VFe3S4]-[VFe3S4] cluster [(O,P,O)VFe3S4(SDmp)(HNMe2)]2 (5) having face-capping tridentate (O,P,O) ligands on vanadium atoms. The other is a [VFe3S4-Fe] cluster [(µ-O,O,O)VFe3S4(SDmp)(STip)Fe(µ-SDmp)] (6), the core of which consists of a cubane-type [VFe3S4] unit and an external iron atom. The external iron is bound to an SDmp ligand and two oxygen atoms of the tridentate (O,O,O) ligand. Cluster 6 is structurally relevant to the active site of nickel-dependent CO dehydrogenase, and their common structural features include a cubane-type unit with a heterometal, one more iron atom besides the cubane unit, and a bridging ligand between the external iron and the heterometal of the cubane unit.

A convenient route to synthetic analogues of the oxidized form of high-potential iron-sulfur proteins.

An amide-bound [Fe4S4](3+) cluster, [Fe4S4{N(SiMe3)2}4](-) (1), was found to serve as a convenient precursor for synthetic analogues of the oxidized form of high-potential iron-sulfur proteins. Treatment of 1 with 4 equiv of bulky thiols led to replacement of the amide ligands with thiolates, giving rise to a series of [Fe4S4(SR)4](-) clusters (R = Dmp (2a), Tbt (2b), Eind (2c), Dxp (2d), Dpp (2e); Dmp = 2,6-di(mesityl)phenyl, Tbt = 2,4,6-tris[bis(trimethylsilyl)methyl]phenyl, Eind = 1,1,3,3,5,5,7,7-octaethyl-s-hydrindacen-4-yl, Dxp = 2,6-di(m-xylyl)phenyl, Dpp = 2,6-diphenylphenyl). These clusters were characterized by the mass spectrum, the EPR spectrum, and X-ray crystallography. The redox potentials of the [Fe4S4](3+/2+) couple, -0.82 V (2a), -0.86 V (2b), -0.84 V (2c), -0.74 V (2d), and -0.63 V (2e) vs Ag/Ag(+) in THF, are significantly more negative than that of [Fe4S4(SPh)4](-/2-) (-0.21 V).

Synthetic analogues of [Fe4S4(Cys)3(His)] in hydrogenases and [Fe4S4(Cys)4] in HiPIP derived from all-ferric [Fe4S4{N(SiMe3)2}4].

The all-ferric [Fe(4)S(4)](4+) cluster [Fe(4)S(4){N(SiMe(3))(2)}(4)] 1 and its one-electron reduced form [1](-) serve as convenient precursors for the synthesis of 31-site differentiated [Fe(4)S(4)] clusters and high-potential iron-sulfur protein (HiPIP) model clusters. The reaction of 1 with four equivalents (equiv) of the bulky thiol HSDmp (Dmp = 2,6-(mesityl)(2)C(6)H(3), mesityl = 2,4,6-Me(3)C(6)H(2)) followed by treatment with tetrahydrofuran (THF) resulted in the isolation of [Fe(4)S(4)(SDmp)(3)(THF)(3)] 2. Cluster 2 contains an octahedral iron atom with three THF ligands, and its Fe(S)(3)(O)(3) coordination environment is relevant to that in the active site of substrate-bound aconitase. An analogous reaction of [1](-) with four equiv of HSDmp gave [Fe(4)S(4)(SDmp)(4)](-) 3, which models the oxidized form of HiPIP. The THF ligands in 2 can be replaced by tetramethyl-imidazole (Me(4)Im) to give [Fe(4)S(4)(SDmp)(3)(Me(4)Im)] 4 modeling the [Fe(4)S(4)(Cys)(3)(His)] cluster in hydrogenases, and its one-electron reduced form [4](-) was synthesized from the reaction of 3 with Me(4)Im. The reversible redox couple between 3 and [3](-) was observed at E(1/2) = -820 mV vs. Ag/Ag(+), and the corresponding reversible couple for 4 and [4](-) is positively shifted by +440 mV. The cyclic voltammogram of 3 also exhibited a reversible oxidation couple, which indicates generation of the all-ferric [Fe(4)S(4)](4+) cluster, [Fe(4)S(4)(SDmp)(4)].

Coupling of an N-heterocyclic carbene on iron with alkynes to form η5-cyclopentadienyl-diimine ligands.

A cyclometalated N-heterocyclic carbene ligand in a half-sandwich iron complex was found to couple with alkynes, leading to a unique type of ring opening of the carbene ligand and the formation of ferrocenyl-diimine complexes. An intermediary iron complex obtained from the reaction with phenylacetylene reveals that the ring opening follows the formation of a fused heterocycle consisting of an imidazole ring and two alkynes.