Normal vs. Inverted Ordering of Reduction Potentials in [FeFe]-Hydrogenases Biomimetics: Effect of the Dithiolate Bulk.

Three hexacarbonyl diiron dithiolate complexes [Fe2 (CO)6 (µ-(SCH2 )2 X)] with different substituted bridgeheads (X=CH2 , CEt2 , CBn2 (Bn=CH2 C6 H5 )), have been studied under the same experimental conditions by cyclic voltammetry in dichloromethane [NBu4 ][PF6 ] 0.2 M. DFT calculations were performed to rationalize the mechanism of reduction of these compounds. The three complexes undergo a two-electron transfer whose the mechanism depends on the bulkiness of the dithiolate bridge, which involves a different timing of the structural changes (Fe-S bond cleavage, inversion of conformation and CO bridging) vs redox steps. The introduction of a bulky group in the dithiolate linker has obviously an effect on normally ordered (as for propanedithiolate (pdt)) or inverted (pdtEt2 , pdtBn2 ) reduction potentials. Et→Bn replacement is not theoretically predicted to alter the geometry and energy of the most stable mono-reduced and bi-reduced forms but such a replacement alters the kinetics of the electron transfer vs the structural changes.

C-Cl Bond Activation at Rotated vs Unrotated Dinuclear Site Related to [FeFe]-Hydrogenases.

The novel dinuclear complex related to the [FeFe]-hydrogenases active site, [Fe2(µ-pdt)(κ2-dmpe)2(CO)2] (1), is highly reactive toward chlorinated compounds CHxCl4-x (x = 1, 2) affording selectively terminal or bridging chloro diiron isomers through a C-Cl bond activation. DFT calculations suggest a cooperative mechanism involving a formal concerted regioselective chloronium transfer depending on the unrotated or rotated conformation of two isomers of 1.

Synthesis, Spectroscopy, and Structure of [FeRu(µ-dithiolate)(CN)2(CO)4]2.

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(C2H4)(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]- ([H1]-), 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 (pdtH2). 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 [Fe2(µ-pdt)(CN)2(CO)4]2- ([4]2-). The pathway from [3]2- to Fe2 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. 57Fe Mössbauer spectral parameters are very similar for rotated [5]2- and unrotated Fe2 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 E1/2 ∼ -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 Hox state of the [FeFe] hydrogenases. Density functional theory (DFT) studies reproduce the structure, 1H 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).

Recent Theoretical Insights into the Oxidative Degradation of Biopolymers and Plastics by Metalloenzymes.

Molecular modeling techniques have become indispensable in many fields of molecular sciences in which the details related to mechanisms and reactivity need to be studied at an atomistic level. This review article provides a collection of computational modeling works on a topic of enormous interest and urgent relevance: the properties of metalloenzymes involved in the degradation and valorization of natural biopolymers and synthetic plastics on the basis of both circular biofuel production and bioremediation strategies. In particular, we will focus on lytic polysaccharide monooxygenase, laccases, and various heme peroxidases involved in the processing of polysaccharides, lignins, rubbers, and some synthetic polymers. Special attention will be dedicated to the interaction between these enzymes and their substrate studied at different levels of theory, starting from classical molecular docking and molecular dynamics techniques up to techniques based on quantum chemistry.

Assessing the Performance of Non-Equilibrium Thermodynamic Integration in Flavodoxin Redox Potential Estimation.

Flavodoxins are enzymes that contain the redox-active flavin mononucleotide (FMN) cofactor and play a crucial role in numerous biological processes, including energy conversion and electron transfer. Since the redox characteristics of flavodoxins are significantly impacted by the molecular environment of the FMN cofactor, the evaluation of the interplay between the redox properties of the flavin cofactor and its molecular surroundings in flavoproteins is a critical area of investigation for both fundamental research and technological advancements, as the electrochemical tuning of flavoproteins is necessary for optimal interaction with redox acceptor or donor molecules. In order to facilitate the rational design of biomolecular devices, it is imperative to have access to computational tools that can accurately predict the redox potential of both natural and artificial flavoproteins. In this study, we have investigated the feasibility of using non-equilibrium thermodynamic integration protocols to reliably predict the redox potential of flavodoxins. Using as a test set the wild-type flavodoxin from Clostridium Beijerinckii and eight experimentally characterized single-point mutants, we have computed their redox potential. Our results show that 75% (6 out of 8) of the calculated reaction free energies are within 1 kcal/mol of the experimental values, and none exceed an error of 2 kcal/mol, confirming that non-equilibrium thermodynamic integration is a trustworthy tool for the quantitative estimation of the redox potential of this biologically and technologically significant class of enzymes.

The MRX complex regulates Exo1 resection activity by altering DNA end structure.

Homologous recombination is triggered by nucleolytic degradation (resection) of DNA double-strand breaks (DSBs). DSB resection requires the Mre11-Rad50-Xrs2 (MRX) complex, which promotes the activity of Exo1 nuclease through a poorly understood mechanism. Here, we describe the Mre11-R10T mutant variant that accelerates DSB resection compared to wild-type Mre11 by potentiating Exo1-mediated processing. This increased Exo1 resection activity leads to a decreased association of the Ku complex to DSBs and an enhanced DSB resection in G1, indicating that Exo1 has a direct function in preventing Ku association with DSBs. Molecular dynamics simulations show that rotation of the Mre11 capping domains is able to induce unwinding of double-strand DNA (dsDNA). The R10T substitution causes altered orientation of the Mre11 capping domain that leads to persistent melting of the dsDNA end. We propose that MRX creates a specific DNA end structure that promotes Exo1 resection activity by facilitating the persistence of this nuclease on the DSB ends, uncovering a novel MRX function in DSB resection.

DNA binding modes influence Rap1 activity in the regulation of telomere length and MRX functions at DNA ends.

The cellular response to DNA double-strand breaks (DSBs) is initiated by the Mre11-Rad50-Xrs2 (MRX) complex that has structural and catalytic functions. MRX association at DSBs is counteracted by Rif2, which is known to interact with Rap1 that binds telomeric DNA through two tandem Myb-like domains. Whether and how Rap1 acts at DSBs is unknown. Here we show that Rif2 inhibits MRX association to DSBs in a manner dependent on Rap1, which binds to DSBs and promotes Rif2 association to them. Rap1 in turn can negatively regulate MRX function at DNA ends also independently of Rif2. In fact, a characterization of Rap1 mutant variants shows that Rap1 binding to DNA through both Myb-like domains results in formation of Rap1-DNA complexes that control MRX functions at both DSBs and telomeres primarily through Rif2. By contrast, Rap1 binding to DNA through a single Myb-like domain results in formation of high stoichiometry complexes that act at DNA ends mostly in a Rif2-independent manner. Altogether these findings indicate that the DNA binding modes of Rap1 influence its functional properties, thus highlighting the structural plasticity of this protein.

Insights into Triazolylidene Ligands Behaviour at a Di-Iron Site Related to [FeFe]-Hydrogenases.

The behaviour of triazolylidene ligands coordinated at a {Fe2(CO)5(µ-dithiolate)} core related to the active site of [FeFe]-hydrogenases have been considered to determine whether such carbenes may act as redox electron-reservoirs, with innocent or non-innocent properties. A novel complex featuring a mesoionic carbene (MIC) [Fe2(CO)5(Pmpt)(µ-pdt)] (1; Pmpt = 1-phenyl-3-methyl-4-phenyl-1,2,3-triazol-5-ylidene; pdt = propanedithiolate) was synthesized and characterized by IR, 1H, 13C{1H} NMR spectroscopies, elemental analyses, X-ray diffraction ,and cyclic voltammetry. Comparison with the spectroscopic characteristics of its analogue [Fe2(CO)5(Pmbt)(µ-pdt)] (2; Pmbt = 1-phenyl-3-methyl-4-butyl-1,2,3-triazol-5-ylidene) showed the effect of the replacement of a n-butyl by a phenyl group in the 1,2,3-triazole heterocycle. A DFT study was performed to rationalize the electronic behaviour of 1, 2 upon the transfer of two electrons and showed that such carbenes do not behave as redox ligands. With highly perfluorinated carbenes, electronic communication between the di-iron site and the triazole cycle is still limited, suggesting low redox properties of MIC ligands used in this study. Finally, although the catalytic performances of 2 towards proton reduction are weak, the protonation process after a two-electron reduction of 2 was examined by DFT and revealed that the protonation process is favoured by S-protonation but the stabilized diprotonated intermediate featuring a {Fe-H⋯H-S} interaction does not facilitate the release of H2 and may explain low efficiency towards HER (Hydrogen Evolution Reaction).

Computational and Experimental Investigations of the Fe2(µ-S2)/Fe2(µ-S)2 Equilibrium.

Density functional theory (DFT) calculations on Fe2S2(CO)6-2n(PMe3)2n 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 FeII2(S)2 and FeI2(S2) valence isomers is symmetry-forbidden. Related electron-rich diiron complexes [Fe2S2(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 Fe2(µ-S2)(CO)6 (1) are described. First, salts of iron persulfido cyanides [Fe2(µ-S2)(CO)5(CN)]- and [Fe2(µ-S2)(CN)(CO)4(PPh3)]- were prepared by the reactions of NaN(tms)2 with 1 and Fe2(µ-S2)(CO)5(PPh3), respectively. Alternative approaches to electron-rich diiron disulfides targeted Fe2(µ-S2)(CO)4(diphosphine). Whereas the preparation of Fe2(µ-S2)(CO)4(dppbz) was straightforward, that of Fe2(µ-S2)(CO)4(dppv) required an indirect route involving the oxidation of Fe2(µ-SH)2(CO)4(dppv) (dppbz = C6H4-1,2-(PPh2)2, dppv = cis-C2H2(PPh2)2). DFT calculations indicate that the oxidation of Fe2(µ-SH)2(CO)4(dppv) produces singlet diferrous disulfide Fe2(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 Fe2(µ-SCH=CHPPh2)(µ-SPPh2)(CO)5, implicating a S-centered reaction.

The ATP-bound conformation of the Mre11-Rad50 complex is essential for Tel1/ATM activation.

Activation of the checkpoint protein Tel1 requires the Mre11-Rad50-Xrs2 (MRX) complex, which recruits Tel1 at DNA double-strand breaks (DSBs) through direct interaction between Tel1 and Xrs2. However, in vitro Tel1 activation by MRX requires ATP binding to Rad50, suggesting a role also for the MR subcomplex in Tel1 activation. Here we describe two separation-of-functions alleles, mre11-S499P and rad50-A78T, which we show to specifically affect Tel1 activation without impairing MRX functions in DSB repair. Both Mre11-S499P and Rad50-A78T reduce Tel1-MRX interaction leading to poor Tel1 association at DSBs and consequent loss of Tel1 activation. The Mre11-S499P variant reduces Mre11-Rad50 interaction, suggesting an important role for MR complex formation in Tel1 activation. Molecular dynamics simulations show that the wild type MR subcomplex bound to ATP lingers in a tightly 'closed' conformation, while ADP presence leads to the destabilization of Rad50 dimer and of Mre11-Rad50 association, both events being required for MR conformational transition to an open state. By contrast, MRA78T undertakes complex opening even if Rad50 is bound to ATP, indicating that defective Tel1 activation caused by MRA78T results from destabilization of the ATP-bound conformational state.

Insights into the Two-Electron Reductive Process of [FeFe]H2 ase Biomimetics: Cyclic Voltammetry and DFT Investigation on Chelate Control of Redox Properties of [Fe2 (CO)4 (κ2 -Chelate)(µ-Dithiolate)].

The electrochemical reduction of complexes [Fe2 (CO)4 (κ2 -phen)(µ-xdt)] (phen=1,10-phenanthroline; xdt=pdt (1), adtiPr (2)) in MeCN-[Bu4 N][PF6 ] 0.2 m is described as a two-reduction process. DFT calculations show that 1 and its monoreduced form 1- display metal- and phenanthroline-centered frontier orbitals (LUMO and SOMO) indicating the non-innocence of the phenanthroline ligand. Two energetically close geometries were found for the doubly reduced species suggesting an intriguing influence of the phenanthroline ligand leading to the cleavage of a Fe-S bond as proposed generally for this type of complex or retaining the electron density and avoiding Fe-S cleavage. Extension of calculations to other complexes with edt, adtiPr bridge and even virtual species [Fe2 (CO)4 (κ2 -phen)(µ-adtR )] (R=CH(CF3 )2 , H) or [Fe2 (CO)4 (κ2 -phen)(µ-pdtR )] (R=CH(CF3 )2 , iPr) showed that the relative stability between both two-electron-reduced isomers depends on the nature of the bridge and the possibility to establish a remote anagostic interaction between the iron center {Fe(CO)3 } and the group carried by the bridged-head atom of the dithiolate group.

Rational Design of Fe2 (µ-PR2 )2 (L)6 Coordination Compounds Featuring Tailored Potential Inversion.

It was recently discovered that some redox proteins can thermodynamically and spatially split two incoming electrons towards different pathways, resulting in the one-electron reduction of two different substrates, featuring reduction potential respectively higher and lower than the parent reductant. This energy conversion process, referred to as electron bifurcation, is relevant not only from a biochemical perspective, but also for the ground-breaking applications that electron-bifurcating molecular devices could have in the field of energy conversion. Natural electron-bifurcating systems contain a two-electron redox centre featuring potential inversion (PI), i. e. with second reduction easier than the first. With the aim of revealing key factors to tailor the span between first and second redox potentials, we performed a systematic density functional study of a 26-molecule set of models with the general formula Fe2 (µ-PR2 )2 (L)6 . It turned out that specific features such as i) a Fe-Fe antibonding character of the LUMO, ii) presence of electron-donor groups and iii) low steric congestion in the Fe's coordination sphere, are key ingredients for PI. In particular, the synergic effects of i)-iii) can lead to a span between first and second redox potentials larger than 700 mV. More generally, the "molecular recipes" herein described are expected to inspire the synthesis of Fe2 P2 systems with tailored PI, of primary relevance to the design of electron-bifurcating molecular devices.

Structurally distinct Mre11 domains mediate MRX functions in resection, end-tethering and DNA damage resistance.

Sae2 cooperates with the Mre11-Rad50-Xrs2 (MRX) complex to initiate resection of DNA double-strand breaks (DSBs) and to maintain the DSB ends in close proximity to allow their repair. How these diverse MRX-Sae2 functions contribute to DNA damage resistance is not known. Here, we describe mre11 alleles that suppress the hypersensitivity of sae2Δ cells to genotoxic agents. By assessing the impact of these mutations at the cellular and structural levels, we found that all the mre11 alleles that restore sae2Δ resistance to both camptothecin and phleomycin affect the Mre11 N-terminus and suppress the resection defect of sae2Δ cells by lowering MRX and Tel1 association to DSBs. As a consequence, the diminished Tel1 persistence potentiates Sgs1-Dna2 resection activity by decreasing Rad9 association to DSBs. By contrast, the mre11 mutations restoring sae2Δ resistance only to phleomycin are located in Mre11 C-terminus and bypass Sae2 function in end-tethering but not in DSB resection, possibly by destabilizing the Mre11-Rad50 open conformation. These findings unmask the existence of structurally distinct Mre11 domains that support resistance to genotoxic agents by mediating different processes.

Synthesis, Molecular Modeling and Biological Evaluation of Metabolically Stable Analogues of the Endogenous Fatty Acid Amide Palmitoylethanolamide.

Palmitoylethanolamide (PEA) belongs to the class of N-acylethanolamine and is an endogenous lipid potentially useful in a wide range of therapeutic areas; products containing PEA are licensed for use in humans as a nutraceutical, a food supplement, or food for medical purposes for its analgesic and anti-inflammatory properties demonstrating efficacy and tolerability. However, the exogenously administered PEA is rapidly inactivated; in this process, fatty acid amide hydrolase (FAAH) plays a key role both in hepatic metabolism and in intracellular degradation. So, the aim of the present study was the design and synthesis of PEA analogues that are more resistant to FAAH-mediated hydrolysis. A small library of PEA analogues was designed and tested by molecular docking and density functional theory calculations to find the more stable analogue. The computational investigation identified RePEA as the best candidate in terms of both synthetic accessibility and metabolic stability to FAAH-mediated hydrolysis. The selected compound was synthesized and assayed ex vivo to monitor FAAH-mediated hydrolysis and to confirm its anti-inflammatory properties. 1H-NMR spectroscopy performed on membrane samples containing FAAH in integral membrane protein demonstrated that RePEA is not processed by FAAH, in contrast with PEA. Moreover, RePEA retains PEA's ability to inhibit LPS-induced cytokine release in both murine N9 microglial cells and human PMA-THP-1 cells.

H2 Activation in [FeFe]-Hydrogenase Cofactor Versus Diiron Dithiolate Models: Factors Underlying the Catalytic Success of Nature and Implications for an Improved Biomimicry.

Catalytic H2 oxidation has been dissected by means of DFT into the key steps common to the Fe2 unit of both the [FeFe]-hydrogenase cofactor and selected biomimics. The aim was to elucidate the molecular details underlying the very different performances of the two systems. We found that the better enzyme performance is based on a single iron atom that is maintained electron-poor, favoring H2 binding, although embedded within a highly electron-rich cofactor, ensuring a facile oxidation of the Fe2 -H2 adduct. This is due to 1) CN- coordinating to both iron atoms, due to their amphipathic Lewis acid/base properties, and 2) the 4Fe4S subunit further withdrawing electrons from the Fe2 core. Preserving a moderate electron deficiency at a single iron also helps the cofactor preserve hydride affinity, which favors H2 cleavage. Such valuable characteristics allow the biocatalyst to turnover close to equilibrium conditions. All previous biomimicry has shown, in contrast, the impossibility to properly balance the two apparently contrasting aforementioned requisites, although evident progress has been made by the H2 -ase community. Disclosure of the differences identified could inspire the design of novel biomimics, for instance, reconsidering the use of CN- in the catalyst architecture. Indeed, in the presence of bases normally employed in oxidative catalysis, undesired stable protonation at coordinated CN- , which affects the opposite process (proton reduction), could be overcome.

Synthetic Designs and Structural Investigations of Biomimetic Ni-Fe Thiolates.

Described are the syntheses of several Ni(µ-SR)2Fe 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(PS3)- and Ni(NS3)- (PS33- = tris(phenyl-2-thiolato)phosphine, NS33- = 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(C6F5)2. The following new nickel precursor complexes were characterized: PPh4[Ni(NS3)] and the dimeric imino/amino-phosphine complexes [NiCl2(PCH═NAn)]2 and [NiCl2(PCH2NHAn)]2 (P = Ph2PC6H4-2-). The iron(II) reagents include [CpFe(CO)2(thf)]BF4, [Cp*Fe(CO)(MeCN)2]BF4, FeI2(CO)4, FeCl2(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(NS3), [Cp(CO)Fe(µ-pdt)Ni(dppbz)]BF4, [( R,R-DIPAMP)Ni(µ-pdt)(H)Fe(CO)3]BArF4, [(PCH═NAn)Ni(µ-pdt)(Cl)Fe(dppbz)(CO)]BF4, [(PCH2NHAn)Ni(µ-pdt)(Cl)Fe(dppbz)(CO)]BF4, [(PCH═NAn)Ni(µ-pdt)(H)Fe(dppbz)(CO)]BF4, [(dppv)(CO)Fe(µ-pdt)]2Ni, {H[(dppv)(CO)Fe(µ-pdt)]2Ni]}BF4, and (C6F5)2Ni(µ-pdt)Fe(CO)2(dppv) (DIPAMP = (CH2P(C6H4-2-OMe)2)2; BArF4- = [B(C6H3-3,5-(CF3)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)]2Ni}+, 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.

Electrochemical and Theoretical Investigations of the Oxidatively Induced Reactivity of the Complex [Fe2 (CO)4 (κ2 -dmpe)(µ-adtBn )] Related to the Active Site of [FeFe] Hydrogenases.

Electrochemical oxidation of the complex [Fe2 (CO)4 (κ2 -dmpe)(µ-adtBn )] (adtBn =(SCH2 )2 NCH2 C6 H5 , dmpe=Me2 PCH2 CH2 PMe2 ) (1) has been studied by cyclic voltammetry (CV) in acetonitrile and in dichloromethane in the presence of various substrates L (L=MeCN, trimethylphosphite, isocyanide). The oxidized species, [1-MeCN](PF6 )2 , [1-(P(OMe)3 )2 ](PF6 )2 and [1-(RNC)4 ](PF6 )2 (R=tert-butyl, xylyl), have been prepared and characterized by IR and NMR spectroscopies and, except [1-MeCN](PF6 )2 , by X-ray diffraction analysis. The crystallographic structures of the new FeII FeII complexes reveal that the association of one additional ligand (P(OMe)3 or RNC) occurs and, according to the nature of the substrates, further substitutions of one or three carbonyl groups, by P(OMe)3 or RNC, respectively, arise. Density functional theory (DFT) calculations have been performed to elucidate and discriminate, in each case, the mechanisms leading to the corresponding oxidized species. Moreover, the different degree of ligand substitution in the diiron core has been theoretically rationalized.

Electron-Rich, Diiron Bis(monothiolato) Carbonyls: C-S Bond Homolysis in a Mixed Valence Diiron Dithiolate.

The synthesis and redox properties are presented for the electron-rich bis(monothiolate)s Fe2(SR)2(CO)2(dppv)2 for R = Me ([1]0), Ph ([2]0), CH2Ph ([3]0). Whereas related derivatives adopt C2-symmetric Fe2(CO)2P4 cores, [1]0-[3]0 have Cs 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 [Fe2(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 [Fe2(SR)2L6]+ derivatives, [3]+ undergoes C-S bond homolysis, affording the diferrous sulfido-thiolate [Fe2(SCH2Ph)(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-CH2Ph. DFT calculations predict that the homolysis of a C-S bond is exergonic for [Fe2(SCH2Ph)2(CO)2(PR3)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 [Fe2(SCH2Ph)(S)(CO)4(dppv)2]+ ([5]+), which adopts a bioctahedral structure.

Influence of the Dithiolate Bridge on the Oxidative Processes of Diiron Models Related to the Active Site of [FeFe] Hydrogenases.

Electrochemical studies of [Fe2 (CO)4 (κ2 -dmpe)(µ-dithiolate)] (dithiolate=adtBn , pdt) and density functional theory (DFT) calculations reveal the striking influence of an amine functionality in the dithiolate bridge on their oxidative properties. [Fe2 (CO)4 (κ2 -dmpe)(µ-adtBn )] (1) undergoes two one-electron oxidation steps, with the first being partially reversible and the second irreversible. When the adtBn bridge is replaced with pdt, a shift of 60 mV towards more positive potentials is observed for the first oxidation whereas 290 mV separate the oxidation potentials of the two cations. Under CO, oxidation of azadithiolate compound 1 occurs according to an ECE process whereas an EC mechanism takes place for the propanedithiolate species 2. The dication species [1-CO]2+ resulting from the two-electron oxidation of 1 has been spectroscopically and structurally characterized. The molecular details underlying the reactivity of oxidized species have been explored by DFT calculations. The differences in the behaviors of 1 and 2 are mainly due to the presence, or not, of favored interactions between the dithiolate bridge and the diiron site depending on the redox states, FeI FeII or FeII FeII , of the complexes.

Photocatalytic Hydrogen Evolution Driven by [FeFe] Hydrogenase Models Tethered to Fluorene and Silafluorene Sensitizers.

It is successfully shown that photocatalytic proton reduction to dihydrogen in the presence of a sacrificial electron donor, such as trimethylamine (TEA) and ascorbate, can be driven by compact sensitizer-catalyst dyads, that is, dithiolate-bridged [FeFe] hydrogenase models tethered to organic sensitizers, such as fluorenes and silafluorenes (1 a-4 a). The sensitizer-catalyst dyads 1 a-4 a show remarkable and promising catalytic activities as well as enhanced stabilities during photocatalysis performed under UV-light irradiation. The photocatalysis was carried out both in non-aqueous and aqueous media. The latter experiments were performed by solubilizing the photocatalysts within micelles formed by either sodium dodecyl sulfate (SDS) or cetyltrimethylammonium bromide (CTAB). In this study a turnover number of 539 (7 h) is achieved under optimized conditions, which corresponds to an exceptionally high turnover frequency of 77 h-1 . Theoretical investigations as well as emission decay experiments were performed to understand the observed phenomena together with the mechanisms of photocatalytic H2 generation.