Approaches to efficient molecular catalyst systems for photochemical H2 production using [FeFe]-hydrogenase active site mimics

The research on structural and functional biomimics of the active site of [FeFe]-hydrogenases is in an attempt to elucidate the mechanisms of H(2)-evolution and uptake at the [FeFe]-hydrogenase active site, and to learn from Nature how to create highly efficient H(2)-production catalyst systems. Undoubtedly, it is a challenging, arduous, and long-term work. In this perspective, the progresses in approaches to photochemical H(2) production using mimics of the [FeFe]-hydrogenase active site as catalysts in the last three years are reviewed, with emphasis on adjustment of the redox potentials and hydrophilicity of the [FeFe]-hydrogenase active site mimics to make them efficient catalysts for H(2) production. With gradually increasing understanding of the chemistry of the [FeFe]-hydrogenases and their mimics, more bio-inspired proton reduction catalysts with significantly improved efficiency of H(2) production will be realized in the future.     

A triad [FeFe] hydrogenase system for light-driven hydrogen evolution

A novel molecular triad [FeFe]-H(2)ase 1, and its model complexes 2 and 3 have been successfully constructed. The multistep PET and long-lived Fe(i)Fe(0) species were found to be responsible for the better performance of triad 1 than that of 2 with 3 for light-driven H(2) evolution.     

Terminal pyridine-N ligation at [FeFe] hydrogenase active-site mimic

Diiron model complexes (μ-pdt)Fe₂(CO)₅L with L = pyridine ligands, e.g. py (A), etpy (B), btpy (C), were synthesized as active site analogues of [FeFe] hydrogenase, and characterized by X-ray crystallography and electrochemistry. Pyridine-N ligation was found to be able to tune the redox properties of the diiron centers of model complexes.     

Mechanism of H2 production by the [FeFe]H subcluster of di-iron hydrogenases: implications for abiotic catalysts

To explore the possibility that the active center of the di-iron hydrogenases, the [FeFe] H subcluster, can serve by itself as an efficient hydrogen-producing catalyst, we perform comprehensive calculations of the catalytic properties of the subcluster in vacuo using first principles density functional theory. For completeness, we examine all nine possible geometrical isomers of the Fe(II)Fe(I) active-ready state and report in detail on the relevant ones that lead to the production of H 2. These calculations, carried out at the generalized gradient approximation level, indicate that the most efficient catalytic site in the isolated [FeFe] H subcluster is the Fe d center distal (d) to the [4Fe-4S] H cluster; the other iron center site, the proximal Fe p, also considered in this study, has much higher energy barriers. The pathways with the most favorable kinetics (lowest energy barrier to reaction) proceed along configurations with a CO ligand in a bridging position. The most favorable of these CO-bridging pathways start from isomers where the distal CN (-) ligand is in up position, the vacancy V in down position, and the remaining distal CO is either cis or trans with respect to the proximal CO. These isomers, not observed in the available enzyme X-ray structures, are only marginally less stable than the most stable nonbridging Fe d-CO-terminal isomer. Our calculations indicate that this CO-bridging CN-up isomer has a small barrier to production of H 2 that is compatible with the observed rate for the enzyme. These results suggest that catalysis of H 2 production could proceed on this stereochemically modified [FeFe] H subcluster alone, thus offering a promising target for functional bioinspired catalyst design.     

Photo-induced hydrogen production in a helical peptide incorporating a [FeFe] hydrogenase active site mimic

There is growing interest in the development of hydrogenase mimics for solar fuel production. Here, we present a bioinspired mimic designed by anchoring a diiron hexacarbonyl cluster to a model helical peptide via an artificial dithiol amino acid. The [FeFe]-peptide complex catalyses photo-induced production of hydrogen in water.     

An artificial [FeFe]-hydrogenase mimic with organic chromophore-linked thiolate bridges for the photochemical production of hydrogen

An artificial [FeFe]-hydrogenase ([FeFe]-H₂ase) mimic 3II, consisting of dual organic chromophores covalently assembled to the [Fe₂S₂] active site, was constructed for light-driven hydrogen evolution. The structural conformation of synthetic photocatalyst was characterized crystallographically and spectroscopically. The photo-induced intramolecular electron transfer was evidently demonstrated by the combination of electrochemical, steady-state, and transient absorption spectroscopic studies. Finally, a remarkable activity was obtained in the present photocatalytic system, indicating the covalent incorporation of photosensitizer and catalytic center as a promising strategy to construct inexpensive, easily accessible [FeFe]-H₂ase model photocatalysts.     

Mild redox complementation enables H2 activation by [FeFe]-hydrogenase models

Mild oxidants such as [Fe(C(5)Me(5))(2)](+) accelerate the activation of H(2) by [Fe(2)[(SCH(2))(2)NBn](CO)(3)(dppv)(PMe(3))](+) ([1](+)), despite the fact that the ferrocenium cation is incapable of oxidizing [1](+). The reaction is first-order in [1](+) and [H(2)] but independent of the E(1/2) and concentration of the oxidant. The analogous reaction occurs with D(2) and proceeds with an inverse kinetic isotope effect of 0.75(8). The activation of H(2) is further enhanced with the tetracarbonyl [Fe(2)[(SCH(2))(2)NBn](CO)(4)(dppn)](+) ([2](+)), the first crystallographically characterized model for the H(ox) state of the active site containing an amine cofactor. These studies point to rate-determining binding of H(2) followed by proton-coupled electron transfer. Relative to that by [1](+), the rate of H(2) activation by [2](+)/Fc(+) is enhanced by a factor of 10(4) at 25 °C.     

FeFe]-hydrogenase-catalyzed H2 production in a photoelectrochemical biofuel cell

The Clostridium acetobutylicum [FeFe]-hydrogenase HydA has been investigated as a hydrogen production catalyst in a photoelectrochemical biofuel cell. Hydrogenase was adsorbed to pyrolytic graphite edge and carbon felt electrodes. Cyclic voltammograms of the immobilized hydrogenase films reveal cathodic proton reduction and anodic hydrogen oxidation, with a catalytic bias toward hydrogen evolution. When corrected for the electrochemically active surface area, the cathodic current densities are similar for both carbon electrodes, and approximately 40% of those obtained with a platinum electrode. The high surface area carbon felt/hydrogenase electrode was subsequently used as the cathode in a photoelectrochemical biofuel cell. Under illumination, this device is able to oxidize a biofuel substrate and reduce protons to hydrogen. Similar photocurrents and hydrogen production rates were observed in the photoelectrochemical biofuel cell using either hydrogenase or platinum cathodes.     

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) CH₂ 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 Fe₂[(μ-SCH₂)₂NH](CO)₄(PMe₃)₂ (1) react with a mixture of HBF₄ and CH₂O to give three isomers of [Fe₂[(μ-SCH₂)₂NCH₂](CO)₄(PMe₃)₂]⁺ ([2]⁺). X-ray crystallography verified the NCH₂Fe 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–CH₂ bond, allowing interchange of all three diastereoisomers. Using ¹³CH₂O, the methylenation begins with formation of [Fe₂[(μ-SCH₂)₂N¹³CH₂OH](CO)₄(PMe₃)₂]⁺. Protonation converts this hydroxymethyl derivative to [2]⁺, concomitant with ¹³C-labelling of all three methylene groups. The Fe–CH₂N bond in [2]⁺ is electrophilic: PPh₃, hydroxide, and hydride give, respectively, the phosphonium [Fe₂[(μ-SCH₂)₂NCH₂PPh₃](CO)₄(PMe₃)₂]⁺, 1, and the methylamine Fe₂[(μ-SCH₂)₂NCH₃](CO)₄(PMe₃)₂. The reaction of [Fe₂[(μ-SCH₂)₂NH](CN)₂(CO)₄]²⁻ with CH₂O/HBF₄ gave [Fe₂[(μ-SCH₂)₂NCH₂CN](CN)(CO)₅]⁻ ([4]⁻), the result of reductive elimination from [Fe₂[(μ-SCH₂)₂NCH₂](CN)₂(CO)₄]⁻. The phosphine derivative [Fe₂[(μ-SCH₂)₂NCH₂CN](CN)(CO)₄(PPh₃)]⁻ ([5]⁻) was characterized crystallographically.

The mechanism for inhibition of [FeFe]-hydrogenases by formaldehyde is examined with model complexes.     

Photoswitchable electrochemical behaviour of a [FeFe] hydrogenase model with a dithienylethene derivative

A diiron dithiolate complex 1o with a dithienylethene (DTE) phosphine ligand has been elaborately designed and fully investigated by spectroscopic and DFT computational studies. Upon irradiation with UV light, the DTE moiety in complex 1o undergoes an excellent photocyclization reaction to attain ring-closed state 1c in high yield (>95%), accompanied by a colour change from orange to deep blue. On the other hand, upon irradiation with visible light (>460 nm), ring-closed form 1c in CH(3)CN solution reverts perfectly into ring-open form 1o. Both 1o and 1c were characterised by IR, (1)H, (31)P, (19)F NMR and electrochemical spectroscopy. The electrochemical behaviours of both the open and closed forms were investigated by cyclic voltammetry. Upon photocyclization reaction, a 290 mV (from -2.29 V to -2.00 V) positive shift is induced in the potential of electrochemical catalytic proton reduction, due to the electron-withdrawing effect of the ring-closed DTE moiety. Consequently, complex 1 can reversibly photoswitch the potential of proton reduction on the [FeFe] moiety.     

Electrochemical insights into the mechanisms of proton reduction by [Fe2(CO)6{micro-SCH2N(R)CH2S}] complexes related to the [2Fe](H) subsite of [FeFe]hydrogenase

Electrochemical investigations on a structural analogue of the [2Fe](H) subsite of [FeFe]H(2)ases, namely, [Fe(2)(CO)(6){micro-SCH(2)N(CH(2)CH(2)- OCH(3))CH(2)S}] (1), were conducted in MeCN/NBu(4)PF(6) in the presence of HBF(4)/Et(2)O or HOTs. Two different catalytic proton reduction processes operate, depending on the strength and the concentration of the acid used. The first process, which takes place around -1.2 V for both HBF(4)/Et(2)O and HOTs, is limited by the slow release of H(2) from the product of the {2 H(+)/2 e} pathway, 1-2H. The second catalytic process, which occurs at higher acid concentrations, takes place at different potentials depending on the acid present. We propose that this second mechanism is initiated by protonation of 1-2H when HBF(4)/Et(2)O is used, whereas the reduction of 1-2H is the initial step in the presence of the weaker acid HOTs. The potential of the second process, which occurs around -1.4 V (reduction potential of 1-3H(+)) or around -1.6 V (the reduction potential of 1-2H) is thus dependent on the strength of the available proton source.     

Solution-phase photochemistry of a [FeFe]hydrogenase model compound: evidence of photoinduced isomerisation

The solution-phase photochemistry of the [FeFe] hydrogenase subsite model (μ-S(CH(2))(3)S)Fe(2)(CO)(4)(PMe(3))(2) has been studied using ultrafast time-resolved infrared spectroscopy supported by density functional theory calculations. In three different solvents, n-heptane, methanol, and acetonitrile, relaxation of the tricarbonyl intermediate formed by UV photolysis of a carbonyl ligand leads to geminate recombination with a bias towards a thermodynamically less stable isomeric form, suggesting that facile interconversion of the ligand groups at the Fe center is possible in the unsaturated species. In a polar or hydrogen bonding solvent, this process competes with solvent substitution leading to the formation of stable solvent adduct species. The data provide further insight into the effect of incorporating non-carbonyl ligands on the dynamics and photochemistry of hydrogenase-derived biomimetic compounds.     

Terminal hydride in [FeFe]-hydrogenase model has lower potential for H2 production than the isomeric bridging hydride

Protonation of the symmetrical tetraphosphine complexes Fe2(S2CnH2n)(CO)2(dppv)2 afforded the corresponding terminal hydrides, establishing that even symmetrical diiron(I) dithiolates undergo protonation at terminal sites. The terminal hydride [HFe2(S2C3H6)(CO)2(dppv)2](+) was found to catalyze proton reduction at potentials 200 mV milder than the isomeric bridging hydride, thereby establishing a thermodynamic advantage for catalysis operating via terminal hydride. The azadithiolate protonates to afford, [Fe2[(SCH2)2NH2](CO)2(dppv)2](+), [HFe2[(SCH2)2NH](CO)2(dppv)2](+), and [HFe2[(SCH2)2NH2](CO)2(dppv)2](2+), depending on conditions.     

Hydroxy and ether functionalized dithiolanes: Models for the active site of the [FeFe] hydrogenase

In attempt to synthesize suitable [FeFe] hydrogenase model complexes, 2-methoxypropane-1,3-dithiole and 4-methyl-4-hydroxy-1,2-dithiolane were reacted with Fe₃(CO)₁₂ to give the respective complexes [Fe₂(CO)₆(H₃COCH(CH₂S)₂)] and [Fe₂(CO)₆(HOC(CH₃)(CH₂S)₂)]. The compounds were characterized by ¹H and ¹³C NMR spectroscopy, mass spectrometry and elemental analysis. In addition, their electrochemical properties were investigated by cyclic voltammetry and compared with that of [Fe₂(CO)₆(HOC(CH₂S)₂)] known from literature.     

On the electrochemistry of diiron dithiolate complexes related to the active site of the [FeFe]H2ase

A few recent electrochemical studies of diiron models of the iron-only hydrogenases' active site are summarized. Emphasis is put on the reduction mechanisms of hexacarbonyl complexes and on the different mechanisms of proton reduction that may operate depending on the nature of the complex and the strength of the acid. An attempt is made to discuss the thermodynamic and kinetic limitations of proton reduction processes supported by these compounds.     

Formaldehyde--a rapid and reversible inhibitor of hydrogen production by [FeFe]-hydrogenases

Dihydrogen (H(2)) production by [FeFe]-hydrogenases is strongly inhibited by formaldehyde (methanal) in a reaction that is rapid, reversible, and specific to this type of hydrogenase. This discovery, using three [FeFe]-hydrogenases that are homologous about the active site but otherwise structurally distinct, was made by protein film electrochemistry, which measures the activity (as electrical current) of enzymes immobilized on an electrode; importantly, the inhibitor can be removed after addition. Formaldehyde causes rapid loss of proton reduction activity which is restored when the solution is exchanged. Inhibition is confirmed by conventional solution assays. The effect depends strongly on the direction of catalysis: inhibition of H(2) oxidation is much weaker than for H(2) production, and formaldehyde also protects against CO and O(2) inactivation. By contrast, inhibition of [NiFe]-hydrogenases is weak. The results strongly suggest that formaldehyde binds at, or close to, the active site of [FeFe]-hydrogenases at a site unique to this class of enzyme--highly conserved lysine and cysteine residues, the bridgehead atom of the dithiolate ligand, or the reduced Fe(d) that is the focal center of catalysis.     

Site-selective X-ray spectroscopy on an asymmetric model complex of the [FeFe] hydrogenase active site

The active site for hydrogen production in [FeFe] hydrogenase comprises a diiron unit. Bioinorganic chemistry has modeled important features of this center, aiming at mechanistic understanding and the development of novel catalysts. However, new assays are required for analyzing the effects of ligand variations at the metal ions. By high-resolution X-ray absorption spectroscopy with narrow-band X-ray emission detection (XAS/XES = XAES) and density functional theory (DFT), we studied an asymmetrically coordinated [FeFe] model complex, [(CO)(3)Fe(I)1-(bdtCl(2))-Fe(I)2(CO)(Ph(2)P-CH(2)-NCH(3)-CH(2)-PPh(2))] (1, bdt = benzene-1,2-dithiolate), in comparison to iron-carbonyl references. Kβ emission spectra (Kβ(1,3), Kβ') revealed the absence of unpaired spins and the low-spin character for both Fe ions in 1. In a series of low-spin iron compounds, the Kβ(1,3) energy did not reflect the formal iron oxidation state, but it decreases with increasing ligand field strength due to shorter iron-ligand bonds, following the spectrochemical series. The intensity of the valence-to-core transitions (Kβ(2,5)) decreases for increasing Fe-ligand bond length, certain emission peaks allow counting of Fe-CO bonds, and even molecular orbitals (MOs) located on the metal-bridging bdt group of 1 contribute to the spectra. As deduced from 3d → 1s emission and 1s → 3d absorption spectra and supported by DFT, the HOMO-LUMO gap of 1 is about 2.8 eV. Kβ-detected XANES spectra in agreement with DFT revealed considerable electronic asymmetry in 1; the energies and occupancies of Fe-d dominated MOs resemble a square-pyramidal Fe(0) for Fe1 and an octahedral Fe(II) for Fe2. EXAFS spectra for various Kβ emission energies showed considerable site-selectivity; approximate structural parameters similar to the crystal structure could be determined for the two individual iron atoms of 1 in powder samples. These results suggest that metal site- and spin-selective XAES on [FeFe] hydrogenase protein and active site models may provide a powerful tool to study intermediates under reaction conditions.     

Photocatalytic hydrogen evolution by two comparable [FeFe]‐hydrogenase mimics assembled to the surface of ZnS

Two photocatalytic hydrogen evolution systems were constructed by assembling [FeFe]‐hydrogenase mimics, either carboxyl group‐containing ( C1 ) or not ( C2 ), on to the surface of ZnS using triethanolamine as electron donor in DMF‐H₂O (9/1, v/v) solution. Upon irradiation for 30 h, the turnover numbers of hydrogen evolution were 3400 and 4950 for the hybrid system C1 /ZnS and C2 /ZnS, respectively. The photocatalytic activity of the C2 /ZnS system was five times higher than the activity of the pristine ZnS, suggesting that the [FeFe]‐hydrogenase mimics are crucial toward improving the activity of ZnS. On the basis of the spectroscopic studies and analyses, the photogenerated electron transfer from ZnS to the mimics is probably responsible for the activity enhancement of ZnS. The time dependence of hydrogen generation shows that the mimic C2 is more active than C1 . The different hydrogen evolution activity can be attributed to the different adsorption modes of the two [FeFe]‐hydrogenase mimics on the surface of ZnS. Copyright © 2014 John Wiley & Sons, Ltd.