PAPER www.rsc.org/dalton | Dalton Transactions

Electrocatalytic dihydrogen evolution mechanism of[Fe2(CO)4(j2-Ph2PCH2CH2PPh2)(l-S(CH2)3S)] and related models of the[FeFe]-hydrogenases active site: a DFT investigation†

Claudio Greco,*a Piercarlo Fantucci,a Luca De Gioia,*a Ricardo Suarez-Bertoa,b Maurizio Bruschi,b

Jean Talarminc and Philippe Schollhammerc

Received 10th December 2009, Accepted 11th May 2010First published as an Advance Article on the web 1st July 2010DOI: 10.1039/b926040d

A DFT study of protonation thermodynamics in H2-evolving biomimetic catalysts related to[FeFe]-hydrogenases active site is presented here. Taking as a reference system the electrocatalyticdihydrogen evolution mechanism recently proposed for the synthetic assembly[Fe2(CO)4(k2-Ph2PCH2CH2PPh2)(m-S(CH2)3S)] (a, which is able to release H2 after having undergonemonoelectron reduction steps and three sequential protonation reactions), we show how the reductionof model complexes to oxidation states lower than those observed in [FeFe]-hydrogenases cofactorleads to a protonation regiochemistry that has no counterpart in the enzymatic mechanism of H2

production. In particular, double protonation of the metal centers turned out to be disfavored in a byup to 12.5 kcal mol-1 with respect to alternative protonation paths; as for the regiochemistry of tripleprotonation, the formation of h2-H2 adducts is disfavored by at least ~25 kcal mol-1. Structural analysisof the theoretical models also revealed that over-reduction of synthetic complexes, though necessary forobserving H2 evolution from the currently available biomimetic electrocatalysts, can generally impairtheir structural integrity. Possible approaches for the modulation of protonation regiochemistry arethen proposed; in particular, it turned out that a targeted use of s-donating ligands showing lowbasicity can favor double protonation of iron centers.

Introduction

Molecular hydrogen (H2) is a key intermediate in several funda-mental industrial productions,1 such as Haber–Bosch process forNH3 evolution from N2 and H2 and hydrogenation of unsaturatedfats; moreover, H2 represents a promising ecological alternative tomineral fuels, since its combustion would give place to pure waterat the point of end use. However, current approaches for molecularhydrogen production are mainly based on steam reforming ofnatural gas, a process that favors greenhouse effect as it has CO2

as its final byproduct.1 On the other hand, H2 production basedon electrolysis of water or electrocatalytic reduction of protons inacidic solutions is a valuable alternative that lacks any pollutingby-products, but the implementation of such process at industriallevel requires the development of new generation catalysts thatare at the same time efficient, cheap and eco-compatible. In thiscontext, nature offers a notable paradigm: a class of enzymes,

aDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2 20126-Milan, Italy. E-mail: luca.degioia@unimib.it, claudio.greco@unimib.it; Tel: +390264483463, +390264483473bDepartment of Environmental Science, University of Milano-Bicocca,Piazza della Scienza 1 20126-Milan, ItalycUMR CNRS 6521, Chimie, Electrochimie Moleculaires et Chimie Analy-tique, Universite de Bretagne Occidentale, 6 Av. V. Le Gorgeu, CS 93837,29238, Brest Cedex 3, France† Electronic supplementary information (ESI) available: Optimized ge-ometries of variously substituted monoprotonated complexes (Fig. S1,S2 and S3); optimized geometries of diprotonated cationic (Fig. S4),neutral (Fig. S5) and anionic complexes (Fig. S6); optimized geometries oftriprotonated cationic (Fig. S7) and neutral (Fig. S8) complexes. See DOI:10.1039/b926040d

generally termed “hydrogenases”, are able to catalyze H2 evolutionfrom protons and electrons by exploiting the properties of ironand/or nickel cations, elements that are widely available on earthlithosphere.

Hydrogenases can be divided in three subclasses: [NiFe]-hydrogenases, [Fe]-hydrogenases and [FeFe]-hydrogenases.2 Thefirst subclass includes both nickel and iron ions of functionalrelevance in the active site,3 while [Fe]-hydrogenases4 and [FeFe]-hydrogenases include only iron as a metal cofactor; in particular,the [Fe]-hydrogenases feature a mononuclear iron complex inthe active site,5,6 while the latter subclass is characterized by adiiron assembly that is covalently linked to a ferredoxin-like Fe4S4

cubane, thus giving place to a Fe6S6 site (the so called “H-cluster”,see Fig. 1).7–9 In Fig. 1, the structural formulae of the active sites

Fig. 1 Schematic structure of the active sites of [NiFe], [Fe] and[FeFe]-hydrogenases. The coordination environment of the metal in[Fe]-hydrogenases features a pyridone derivative that includes a nucleotideportion, omitted in this figure for clarity. As for [FeFe]-hydrogenases, thenon-cysteine sulfur atoms belonging to the dtma ligand have been markedwith an asterisk.

7320 | Dalton Trans., 2010, 39, 7320–7329 This journal is © The Royal Society of Chemistry 2010

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of all three hydrogenases subclasses are reported; it can be noticedthat the metal ions first coordination spheres always includesulfur atoms that, in the case of [NiFe]-hydrogenases and [Fe]-hydrogenases, invariantly belong to cysteine side chains, while in[FeFe]-hydrogenases an unprecedented dithiolate ligand is presentas well; according to recent results, such low-weight bidentateligand corresponds to a di(thiomethyl)amine residue (dtma).10–12

[FeFe]-hydrogenases express very high rates of H2 evolutionfrom protons and electrons,13 thanks to the peculiar propertiesof the H-cluster binuclear subsite that is directly involved incatalysis.14,15 The two iron atoms of the Fe2S2 subsite are bound toCO and CN groups of functional relevance,16,17 and are labeledproximal – “Fep” – or distal – “Fed” – depending on theirposition with respect to the Fe4S4 cluster. The crucial reactionsunderlying catalysis are thought to take place on the vacantcoordination site on Fed trans to the m-CO group:14,18–20 twosequential proton transfer reactions from the amine group ofthe di(thiomethyl)amine residue to the Fed center, along withconcomitant electron transfer events leading to the H-clusterreduction prelude to H2 formation and evolution; notably, theprotonation of sulfur atoms in the dtma residue is thought to benot involved in catalysis, and also the Fep-bound cysteine sulfur islikely to behave as a spectator during the catalytic process, as it isalready tri-coordinated and very far from the catalytically activeFed center. This represents a major difference between the H2-evolving mechanism of [FeFe]-hydrogenases and those of [NiFe]-hydrogenases and [Fe]-hydrogenases: actually, in the latter twohydrogenases subclasses cysteine residues protonation is thoughtto have a crucial role for catalysis.14,21

Several biomimetic analogs of the H-cluster diiron subsite havebeen obtained so far, with the aim of reproducing not only thestructural features, but also the remarkable catalytic propertiesof [FeFe]-hydrogenases.22–30 One of the main goals of the syntheticchemists working in this field has been to substitute the CO and CNgroups with other ligands that could enhance the stability of thebiomimetic assemblies and the basicity of the iron centers, possiblyfavoring the interaction between the substrates (i.e. protons) andthe metal ions outside the protein environment. In particular,phosphine ligands are commonly used in substitution of CNligands,23–25 as they are neutral groups that, differently from theanionic cyanides, do not compete with the iron centers for protonbinding during the electrocatalytic H2 evolving process; at the sametime, phosphines can quite well reproduce the stereoelectroniceffects of cyanides in the biomimetic assemblies.31,32

It is thus not surprising that the very first example of[FeFe]-hydrogenases biomimetic electrocatalyst is a phosphine-containing complex, synthesized by Rauchfuss and coworkers in2001.33 A large number of variously substituted diiron complexeshave then proved to be able to evolve H2 in cyclic voltammetryexperiments in the presence of acids,23–25 and in a few cases34–36 –including the hexacarbonyl assembly [Fe2(CO)6(m-pdt)] (complex1 in Fig. 2; pdt = S(CH2)3S) – the spectroelectrochemicalobservation of m-CO containing species during proton reductionsuggested the possibility that simple binuclear complexes could beable to reproduce the protonation regiochemistry of the H-clusterat the early stages of the electrocatalytic mechanism. However,experimental insights on the subsequent steps of the H2-evolvingmechanism – including the crucial event of H2 formation on thesynthetic catalyst – could not be gained until very recently, when

Fig. 2 Schematic structure of complexes 1, 2 and [2-H]+{Fe(H)Fe}.

Ezzaher et al. isolated and probed the electrocatalytic propertiesof a species that had already undergone single protonation,i.e. the bridged-hydride species [Fe2(CO)4(k2-dppe)(m-pdt)(m-H)]+

(dppe = Ph2PCH2CH2PPh2, pdt = S(CH2)3S).37 The latter, termed[2-H]+

{Fe(H)Fe} in Fig. 2, is the product obtained by protonationof complex 2, [Fe2(CO)4(k2-dppe)(m-pdt)] (see Fig. 2). Cyclicvoltammetry experiments showed that [2-H]+

{Fe(H)Fe} can undergomonoelectron reduction and a subsequent protonation step,leading to the diprotonated species [2-H2]+. The latter was shownto undergo a monoelectron reduction step, giving place to [2-H2];in turn, [2-H2] was proposed to be further reduced yielding [2-H2]-

(Scheme 1). Both [2-H2] and [2-H2]- can be singly protonated,leading to the formation of the triprotonated species [2-H3]+ and[2-H3]; molecular hydrogen can then form from each of the lattertwo intermediates, thus closing the electrocatalytic cycle (processesA and B in Scheme 1).

Scheme 1 Electrocatalytic mechanism proposed for model 2.37

Experimental structural data for intermediates taking part incatalysis are available only for [2-H]+;37,38 moreover, given thereversibility of the monoelectron reduction step of this m-Hspecies, it has been proposed that complex [2-H] is structurallysimilar to the parent cation, and it should thus retain a hydridegroup in the bridging position between the iron atoms.37 Thestructural characterization of subsequent stages in the H2 evolvingmechanism would provide fundamental data for a better under-standing of the chemistry of Fe2S2 biomimetic complexes and forthe design of novel efficient catalysts. In this context, structuralinsights can be obtained by density functional theory calculations,which have been proved to be reliable tools for the interpretationof electrochemical and spectroelectrochemical data, and for the

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characterization of key intermediate species formed along thecatalytic paths mediated by biomimetic diiron clusters.39–48

In the present paper, we take as a reference the H2 evolvingmechanism previously proposed for complex [2-H]+,37 in order tostudy how protonation regiochemistry and reduction of the clus-ter affects the biomimetic reproduction of [FeFe]-hydrogenasescatalysis in this synthetic diiron model and selected analogs.Particular attention will be devoted to the issue of the relativebasicity of Fe and S centers; in fact, previous studies have shownthat protonation of sulfur atoms in the dithiolate ligand cantake place during the H2 evolving process mediated by syntheticcatalysts;40,43 however, as mentioned above, sulfur protonation isthought not to take place during the [FeFe]-hydrogenases catalyticmechanism,49 suggesting that it should be avoided in efficientbiomimetic catalysts.

Results are presented as follows: for each of the steps in theelectrocatalytic cycle that lead to di- and triprotonated species,we have computed the relative stability of adducts in which theincipient hydrogen atom is bound either to a sulfur atom of thedithiolate, or to the metal centers. This allowed us to evaluate notonly the relative basicity of Fe and S centers, but also to investigatethe effects that sulfur or iron protonation exerts on the structuralproperties of the biomimetic catalyst. In this context, computationof redox potential was used to further corroborate the picture com-ing from relative stabilities computations; moreover, protonationof the metal-bound carbonyl ligands yielding formyl adducts hasalso been considered for the sake of completeness, even thoughit must be remarked that the formation of formyl species hasbeen experimentally observed only as a result of the reactionbetween biomimetic complexes and hydrides.35 Then, the effectsof ligands on the regiochemistry of protonation was investigatedby considering two structural analogs of [2-H] carrying either sixp-acid carbonyls and no phosphine ligands, or five phosphinegroups (see Scheme 2). These two different iron coordinationenvironments were chosen as limit cases in which the basicityof the metal centers is lowered or enhanced, respectively. We areaware that the inclusion of five phosphine ligands is trivial inthe context of theoretical modeling but it would be extremelychallenging at synthetic level. In fact, the possibility to studysynthetically challenging molecules is a bonus associated withDFT calculations in view of the final aim of the present paper, i.e.to unravel general principles underlying the reactivity of [FeFe]-hydrogenase biomimetic complexes.

Scheme 2 Variously substituted structural analogs of [2-H-].

Finally, we also considered additional phosphine-containingmodels in which the sulfur atoms of the pdt moiety weresubstituted by selenium atoms. In fact, biomimetic complexescontaining propanediselenolate (pds) have been synthesized,50–52

and the lower basicity of selenolate as compared to thiolategroups in pdt could be exploited to finely tune the protonationregiochemistry of the electrocatalysts.

Methods

DFT calculations have been carried out using the pure functionalBP8653,54 and an all-electron valence triple-z basis set withpolarization on all atoms (TZVP).55 Calculations have been carriedout with the TURBOMOLE 5.7 suite56 applying the resolution-of-the-identity technique.57,58

Stationary points of the energy hypersurface have been locatedby means of energy gradient techniques, and full vibrational anal-ysis has been carried out to further characterize each stationarypoint. The optimization of transition state structures has beencarried out according to a procedure based on a pseudo-Newton-Raphson method, as previously described.40

Free energy (G) values have been obtained from the electronicSCF energy considering three contributions to the total partitionfunction (Q), namely qtranslational, qrotational, and qvibrational, under theassumption that Q may be written as the product of such terms.59

In order to evaluate enthalpy and entropy contributions, the valuesof temperature, pressure, and scaling factor for the SCF wavenum-bers have been set to 298.15 K, 1 bar, and 0.9,60 respectively.Rotations have been treated classically, and vibrational modeshave been described according to the harmonic approximation.The effect of the solvent (acetonitrile, e = 36.64) has been evaluatedaccording to the COSMO approach.61

Calculations of reduction potentials have been carried out usingthe Nernst equation, DG = -nFE, where n is the number ofelectrons transferred and F is the Faraday constant. The resultingE value is an absolute reduction potential (Eabs); i.e., it is notreferenced to any standard electrode. Therefore, in order to obtainthe calculated reduction potentials (Ecalc’s), the absolute reductionpotential for the ferrocene/ferrocenium reference electrode (5.05V)62,63 has been systematically subtracted from Eabs values. Suchabsolute reduction potential for the ferrocene/ferrocenium coupleis obtained by applying standard electrochemical conversionconstants and previous results by Namazian and Coote,63 whocalculated a reduction potential of 4.67 V for standard calomelelectrode (SCE) in acetonitrile. Notice that the choice of theferrocene/ferrocenium electrode as a reference electrode in thepresent work stems from the fact that all the experimental redoxpotential values for 2 and its reduction/protonation productsreported by Ezzaher et al. are referenced to ferrocene/ferroceniumcouple. All Ecalc values have been obtained by taking into accountsolvation contributions computed by using the COSMO approachas above mentioned.

Results and discussion

Before presenting results, let us point out some details on thenomenclature used in the following for the model complexes.In full analogy with the case of complex [2-H]+

{Fe(H)Fe} (Fig. 2and Scheme 1), the names of mono-, di- and triprotonatedintermediates will be given a curly bracket tag as a subscript,that provides information about the protonation regiochemistryof each species; this regards not only protonated hexacarbonyland dppe-containing complexes, respectively derived from 1 and 2(Fig. 2), but also pentaphosphine complexes formally derived fromcomplex [Fe2(CO)(PH3)5(m-pdt)] (3). Moreover, a lower-case lettertag will be added in round brackets to the name of dppe-containingspecies whose structures have not been crystallographically

7322 | Dalton Trans., 2010, 39, 7320–7329 This journal is © The Royal Society of Chemistry 2010

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Table 1 Computed and experimental redox potential values for selectedredox couples. All values in V

Redox coupleComputedredox potential

Experimentalredox potential

[2-H]+{Fe(H)Fe}/[2-H(a)]{Fe(H)Fe} -1.29 -1.23

[1-H]+{Fe(H)Fe}/[1-H(a)]{Fe(H)Fe} -0.56 —

[3-H]+{Fe(H)Fe}/[3-H(a)]{Fe(H)Fe} -2.20 —

[pds2-H]+{Fe(H)Fe}/[pds2-H(a)]{Fe(H)Fe} -0.91 —

[2-H2(b)]+{Fe(2H)Fe}/[2-H2(h)]{Fe(H)Fe_SH} -0.57 > -1.23a

[2-H2(c)]+{Fe(H)Fe_SH}/[2-H2(h)]{Fe(H)Fe_SH} -0.57 > -1.23a

[2-H2(b)]+{Fe(2H)Fe}/[2-H2(f)]{Fe(2H)Fe} -0.99 > -1.23a

[2-H2(c)]+{Fe(H)Fe_SH}/[2-H2(g)]{Fe(H)Fe_SH} -1.15 > -1.23a

[2-H2(f)]{Fe(2H)Fe}/[2-H2(j)]-{Fe(2H)Fe} -1.83b —

a Lower-bound value assigned, on the basis of experimental data, to the[2-H2]+/[2-H2] couple, see Scheme 1. b The theoretical redox potential forthe [2-H2(f)]{Fe(2H)Fe}/[2-H2(j)]-

{Fe(2H)Fe} couple has been compared, in themain text of the paper, with the experimental redox potential for the [2-H2]/[2-H2]- couple (-1.48 V).

characterized; notice that, for the sake of an easier comparison,models of the 1, 2 or 3 type will be assigned the same lower-case letter tag when they share an analogous protonation pattern.Finally, an additional “pds” superscript will be also added in thecase of propanediselenolate-containing models, while transitionstate structures will be given the “TS” flag.

Monoprotonated species: calculation of redox potentials for the[2-H]+

{Fe(H)Fe}/[2-H(a)]{Fe(H)Fe} couple and structurally relatedcomplexes

The redox properties of the m-hydride cationic complex[2-H]+

{Fe(H)Fe} – see Fig. 3 for the optimized structure of thiscation and the corresponding neutral form, the latter termed[2-H(a)]{Fe(H)Fe} – have been experimentally characterized by meansof cyclic voltammetry measurements, which showed that themonoelectron reduction of this cation takes place at relativelymild conditions, the redox potential being -1.23 V (all the poten-tials here discussed are referenced to the ferrocene/ferroceniumreference electrode – see Methods – and are summarized inTable 1). In the present investigation, the redox potential for the[2-H]+

{Fe(H)Fe}/[2-H(a)]{Fe(H)Fe} couple was computed using an ap-proach that has already proved reliable for the theoretical charac-terization of the redox chemistry of biomimetic diiron complexes.40

Fig. 3 Optimized structures of selected monoprotonated species. Alldistances in A.

Notably, the computed redox potential for the [2-H]+{Fe(H)Fe}/

[2-H(a)]{Fe(H)Fe} couple is -1.29 V, which compares well with the

Table 2 Selected structural parameters in monoprotonated complexes[2-H]+

{Fe(H)Fe} and [2-H(a)]{Fe(H)Fe}. All distances in A

Species Fe–S distances

[2-H]+{Fe(H)Fe} 2.35, 2.32, 2.32, 2.38

[2-H(a)]{Fe(H)Fe} 2.31, 2.28, 2.27, 2.32

above mentioned experimental [2-H]+{Fe(H)Fe} reduction potential

(difference between theory and experiment: 0.06 V). Such agood match is in line with previous evidence indicating that themonoelectron reduction of [2-H]+

{Fe(H)Fe} is not coupled to largestructural changes (see Table 2 and Fig. 3),37 and it confirms thegood quality of redox potentials computed at BP86/TZVP levelusing the COSMO continuum solvent model.40 This enables us totake full advantage of the available experimental E values for adeeper comprehension of the mechanism leading to H2 evolution.Moreover, the computation of redox potentials may allow theprediction of the effect of ligands substitution on E values forkey reduction steps along an electrocatalytic path. In this respect,we computed the redox potentials for the singly protonated hex-acarbonyl, pentaphosphine and propanediselenolate-containingcomplexes corresponding to [2-H]+

{Fe(H)Fe}. The trend of computedEcalc values for the [1-H]+

{Fe(H)Fe}/[1-H(a)]{Fe(H)Fe}, [2-H]+{Fe(H)Fe}/

[2-H(a)]{Fe(H)Fe} and [3-H]+{Fe(H)Fe}/[3-H(a)]{Fe(H)Fe} couples (see Fig. 3

and Fig. S1 and S2 in ESI†) is as follows: -0.56, -1.29, and -2.20 V(Table 1); this outcome shows how carbonyl substitution withphosphine ligands can significantly shift the redox potentials tomore negative values, in agreement with the conclusions previouslydrawn by Roy et al. who calculated the E for a large series ofphosphine-substituted diiron adducts, using a different solvationapproach for DFT diiron models.41

As far as the computed redox potential value for the propanedis-elenolate derivative is taken into account, the Ecalc for the[pds2-H]+

{Fe(H)Fe}/[pds2-H(a)]{Fe(H)Fe} couple (see ESI, Fig. S3†) wascomputed to be -0.91 V, a value ~0.3 V less negative than the onefor the corresponding pdt-containing, [2-H]+

{Fe(H)Fe}/[2-H(a)]{Fe(H)Fe}

couple.

Structural features and reactivity of diprotonated cationic adducts

As anticipated in the introduction, 2 can undergo a protonationstep, and the resulting m-hydride species, [2-H]+

{Fe(H)Fe}, can bereduced to yield [2-H(a)]{Fe(H)Fe} (Scheme 1). The latter has beenproposed to undergo monoprotonation during the electrocatalyticpath; by considering the basicity of the groups composingthe complex, one can assume that two protonation routes of[2-H(a)]{Fe(H)Fe} might be operative, the first one leading to adihydride species, and the second one in which a sulfur atomof the dithiolate is protonated. The schematic structures of theresulting complexes, respectively named [2-H2(b)]+

{Fe(2H)Fe} and[2-H2(c)]+

{Fe(H)Fe_SH}, are reported in Fig. 4 (see also Fig. S4,ESI,† and Table 3 for relevant structural parameters and relativestabilities).

In [2-H2(c)]+{Fe(H)Fe_SH}, sulfur protonation results in cleavage of

one Fe–S bond (corresponding Fe–S distance: 3.28 A); as far asthermodynamics is concerned, such a sulfur-protonated adductis essentially as stable as the alternative isomer [2-H2(b)]+

{Fe(2H)Fe}

(DG = –0.1 kcal mol-1 in favor of [2-H2(b)]+{Fe(2H)Fe}). Both com-

plexes turned out to be ~7 kcal mol-1 more stable than the formyl

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Table 3 Relative stabilities and relevant structural parameters of selected diprotonated cationic complexes. Interatomic distances and energies arereported in A and kcal mol-1, respectively; Fe–S distances larger than 3 A are in italic

Species DG Fe–S distances H–H distances between metal-bound H atoms

Complexes containing dppe [2-H2(b)]+{Fe(2H)Fe} 0.0 2.33; 2.37; 2.36; 2.34 0.87

[2-H2(c)]+{Fe(H)Fe_SH} 0.1 3.28; 2.33; 2.26; 2.27 —

[2-H2(d)]+{Fe(H)Fe_HCO} 7.5 2.30; 2.29; 2.27; 2.35 —

Hexacarbonyl complexes [1-H2(b)]+{Fe(2H)Fe} 0.0 2.33, 2.39, 2.39, 2.33 0.92

[1-H2(c)]+{Fe(H)Fe_SH} -13.6 2.35, 3.36, 2.24, 2.32 —

Pentaphosphine complexes [3-H2(b)]+{Fe(2H)Fe} 0.0 2.31, 2.34, 2.37, 2.31 1.14

[3-H2(c)]+{Fe(H)Fe_SH} -2.3 3.29; 2.30; 2.28; 2.22 —

Fig. 4 Schematic structures of selected diprotonated cationic species. Alldistances in A. In the case of minimum structures, below each iron atomare reported the corresponding Mulliken spin population values.

adduct [2-H2(d)]+{Fe(H)Fe_HCO}, the structure of which is reported in

Fig. 4. [2-H2(b)]+{Fe(2H)Fe} and [2-H2(c)]+

{Fe(H)Fe_SH} were computed tohave the same reduction potential value, i.e. -0.57 V; this result isin agreement with cyclic voltammetry results37 indicating that the[2-H2]+/[2-H2] couple has an E value less negative than -1.23 V.‡

The structural features of [2-H2(b)]+{Fe(2H)Fe} deserve particular

attention; it is an adduct showing an activated H2 molecule non-classically bound to one of the metal centers (H–H distance:0.87 A, Fe–H distances: 1.73, 1.63 and 2.03 A, see Table 3and Fig. S4 in ESI†). The existence of such an adduct hasbeen proposed by Ezzaher et al.,37 who also hypothesized thepossibility of H2 release from complex [2-H2(b)]+

{Fe(2H)Fe} during

‡ The redox couples considered for E calculations are [2-H2(b)]+{Fe(2H)Fe}/

[2-H2(h)]{Fe(H)Fe_SH} and [2-H2(c)]+{Fe(H)Fe_SH}/[2-H2(h)]{Fe(H)Fe_SH} (see Fig. 5 for

the structures of the neutral adducts). The neutral species belongingto both couples is the lowest energy diprotonated neutral isomer takeninto account in the present study. However, the computed reductionpotential is less negative than -1.23 V also in the case of [2-H2(b)]+

{Fe(2H)Fe}/[2-H2(f)]{Fe(2H)Fe} and [2-H2(c)]+

{Fe(H)Fe_SH}/[2-H2(g)]{Fe(H)Fe_SH} couples (Ecalc =-0.99 and -1.15 V, respectively), in which the reduction product has notundergone large structural rearrangements with respect to the cationiccounterpart.

electrocatalysis; however, release of H2 at the [2-H2]+ stage turnedout to be inconsistent with the experimental observations. Infact, it was not possible to detect the presence of complex 2when the electrochemical cell was supplied with one equivalentacid; in this context, notice that 2 should necessarily form alonga electrocatalytic path involving H2 release from [2-H2]+. Suchobservations led Ezzaher et al. to suggest that the H2 moleculecould split on [2-H2(b)]+

{Fe(2H)Fe}, thus giving place to a more stableand unreactive dihydride species (adduct [2-H2(e)]+

{Fe(2H)Fe}, seeScheme 3).37

Scheme 3 Schematic structure of the hypothetical dihydride cationicadduct [2-H2(e)]+.

In view of the above mentioned results, we evaluated both thereactivity of [2-H2(b)]+

{Fe(2H)Fe} in terms of H2 evolution, and theconsequences of a possible isomerization reaction leading to H2

splitting on the complex. The transition state for H2 release from[2-H2(b)]+

{Fe(2H)Fe} was individuated (TS-[2-H2(b)]+{Fe(2H)Fe}, Fig. 4),

and it turned out that the reaction barrier is rather low, DG# =7.2 kcal mol-1; at the same time, the dihydride geometry shownin Scheme 3 was found not to correspond to a stationary pointon the PES, thus showing that H2 splitting on the catalyst cannotaccount for the above mentioned electrochemical results. However,theoretical and experimental results can be well reconciled if weadmit that protonation of the hydride ligand of [2-H] is fastenough for [2-H2]+ to be formed in the vicinity of the electrodeand immediately reduced to [2-H2].

Notwithstanding the actual nature of [2-H2]+, the h2-H2 species[2-H2(b)]+

{Fe(2H)Fe} is able to easily release H2; thus, we evaluatedthe possibility of favoring proton attachment to the iron center asopposed to sulfur protonation, by means of a targeted modulationof the donor/acceptor properties of the metal-bound ligands.To this end, we compared the relative stabilities of structuralanalogs of [2-H2(b)]+

{Fe(2H)Fe} and [2-H2(c)]+{Fe(H)Fe_SH}, carrying either

five s-donor PH3 groups, or six p-acid carbonyls. It turnedout that the energy difference between dihydride and sulfur-protonated isomers varies by more than 13 kcal mol-1 as a functionof ligands nature: actually, the free energy difference valuesbetween the dihydride adduct and the sulfur-protonated isomeris DG = 13.6 kcal mol-1 in favor of the latter when the hexacar-bonyl complexes are concerned (complexes [1-H2(b)]+

{Fe(2H)Fe} and[1-H2(c)]+

{Fe(H)Fe_SH}, see Fig. 4).

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Table 4 Relative stabilities and relevant structural parameters of selected diprotonated neutral complexes. Interatomic distances and energies are reportedin A and kcal mol-1, respectively; Fe–S distances larger than 3 A are in italic

Species DG Fe–S distances H–H distances between metal-bound H atoms

Complexes containing dppe [2-H2(f)]{Fe(2H)Fe} 0.0 2.37, 2.35, 2.34, 2.37 1.83[2-H2(g)]{Fe(H)Fe_SH} 3.8 3.12, 2.32, 2.30, 2.25 —[2-H2(h)]{Fe(H)Fe_SH} -9.4 2.41, 4.09, 2.30, 2.32 —[2-H2(i)]{Fe(H)Fe_HCO} -10.3 2.36, 2.32, 2.29, 2.31 —

Hexacarbonyl complexes [1-H2(f)]{Fe(2H)Fe} 0.0 2.37, 2.36, 2.36, 2.37 1.76[1-H2(h)]{Fe(H)Fe_SH} -13.9 2.40, 4.12, 2.32, 2.32 —

Pentaphosphine complexes [3-H2(f)]{Fe(2H)Fe} 0.0 2.35, 2.33, 2.33, 2.35 1.93[3-H2(h)]{Fe(H)Fe_SH} -3.3 2.32, 4.23, 2.29, 2.28 —

Pentaphosphine complexes including pds [pds3-H2(f)]{Fe(2H)Fe} 0.0 — 2.02[pds3-H2(h)]{Fe(H)Fe_SeH} 1.8 — —

We also evaluated the influence of the nature of metal ligandson the barrier for H2 release from the H2 bound complex. To thisend, the transition state for H2 detachment from [1-H2(b)]+

{Fe(2H)Fe}

was calculated, and it turned out that the barrier is as low as4.4 kcal mol-1. Such value is close to the DG# computed for thephosphine-containing complex (DG# = 7.2 kcal mol-1, see above),thus showing that the inclusion of good s-donors in the syntheticcomplex has small impact on the H2 evolution kinetics.

Finally, we evaluated whether substitution of five carbonylgroups with PH3 ligands (complexes [3-H2(b)]+

{Fe(2H)Fe} and[3-H2(c)]+

{Fe(H)Fe_SH}, see Fig. 4) is sufficient to invert the stabil-ity order, thus favoring the dihydride adduct over the sulfur-protonated one. It turned out that [3-H2(b)]+

{Fe(2H)Fe} is closeto [3-H2(c)]+

{Fe(H)Fe_SH} in terms of stability, even if the latteris still thermodynamically favored by 2.3 kcal mol-1. Notably,when pdt is substituted by pds (models [pds3-H2(b)]+

{Fe(2H)Fe} and[pds3-H2(c)]+

{Fe(H)Fe_SeH}, structures shown in ESI†) the dihydridespecies is slightly stabilized over the selenium-protonated complex(DG = –0.7 kcal mol-1) as a consequence of the lower basicity ofR-Se- groups as compared to R-S-; an even more pronounced sta-bilization of the dihydride species was observed when sulfur atomswere substituted with selenium atoms in the dppe-containing com-plexes ([pds2-H2(b)]+

{Fe(2H)Fe} and [pds2-H2(c)]+{Fe(H)Fe_SeH}; structures

shown in ESI†); in fact, in this case the selenium-protonatedspecies turned out to be 4.4 kcal mol-1 lower in energy than thecorresponding dihydride isomer.

Scheme 4 Schematic structure of the hypothetical h2-H2 form of [2-H2].

Structural features and relative stabilities of diprotonated neutralspecies

Complex [2-H2]+ undergoes a monoelectron reduction step inthe H2 evolving cycle reported in Scheme 1; in the presentinvestigation, we have optimized plausible isomers of the reductionproduct [2-H2], namely the dihydride species [2-H2(f)]{Fe(2H)Fe}, them-hydride species [2-H2(g)]{Fe(H)Fe_SH} and [2-H2(h)]{Fe(H)Fe_SH}, andthe formyl species [2-H2(i)]{Fe(H)Fe_HCO} (geometries and relevantstructural parameters reported in Fig. 5 and Table 4). Notably,no minima corresponding to h2-H2 species were found on the PES

Fig. 5 Schematic structures of selected diprotonated neutral species. Alldistances in A.

of the neutral diprotonated compound, in analogy with a previousstudy regarding the complex [Fe2(CO)6(m-pdt)H2]:40 in fact, all theoptimizations started from h2-H2 geometries similar to the oneshown in Scheme 4 ended up on the [2-H2(f)]{Fe(2H)Fe} isomer. Thelatter is a dihydride species showing a H–H interatomic distanceof 1.83 A; and is 3.8 kcal mol-1 lower in energy than the sulfur-protonated complex [2-H2(g)]{Fe(H)Fe_SH}. However, [2-H2(f)]{Fe(2H)Fe}

is significantly less stable than both [2-H2(h)]{Fe(H)Fe_SH} and[2-H2(i)]{Fe(H)Fe_HCO} (DG = 9.4 and 10.3 kcal mol-1, respectively).The former is a m-H, m-CO species in which one of the sulfuratoms of pdt has detached from the phosphine-bound ironcenter, while the latter is a formyl-containing adduct. Thus, onecan conclude that the reduction of [2-H2]+ – as well as thesubsequent monoelectron reduction step [2-H2] → [2-H2]-, videinfra – can favor intramolecular proton transfer reactions and/orlarge structural reorganization of the cluster. Such a conclu-sion is corroborated by the observation that the redox couple[2-H2(f)]{Fe(2H)Fe}/[2-H2(j)]-

{Fe(2H)Fe} – the sole couple among thevarious possible ones, in which diprotonated species, both neutraland monoanionic, retain ligands disposition close to that observed

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in the enzyme binuclear subsite – has a computed redox potentialof -1.83 V, a value significantly more negative than the potentialproposed from CV experiments for the [2-H2]/[2-H2]- reduction(Eexp = -1.48 V).37

As already done for the cationic species in the previous section,we now evaluate the possibility of stabilizing the dihydride adduct[2-H2(f)]{Fe(2H)Fe} by means of a targeted modulation of the ironcoordination environment. To this end, we optimized the pen-taphosphine species [3-H2(f)]{Fe(2H)Fe} and [3-H2(h)]{Fe(H)Fe_SH}, andthe hexacarbonyl species [1-H2(f)]{Fe(2H)Fe} and [1-H2(h)]{Fe(H)Fe_SH}

(see Fig. 5), in order to calculate the relative stabilities of thesulfur-protonated and dihydride isomers. Similarly to the case ofthe cationic diprotonated adduct, the DG values vary by more than10 kcal mol-1 as a function of ligands nature. In fact, the sulfurprotonated species turns out to be almost 14 kcal mol-1 morestable than the dihydride adduct when hexacarbonyl complexes areconcerned, but the free energy difference reduces to 3.3 kcal mol-1

in the case of pentaphosphine complexes. However, to observethe inversion of the stability order in favor of the dihydridecomplex, the substitution of sulfur atoms with selenium atomsin the bidentate ligand is needed: in fact, model [pds3-H2(f)]{Fe(2H)Fe}

turned out to be more stable than [pds3-H2(h)]{Fe(H)Fe_SeH} (structuresnot shown) by 1.8 kcal mol-1.

Structural features and relative stabilities of diprotonated anionicspecies

For the diprotonated anionic species involved in catalysis,four possible isomers have been considered: the dihydridespecies [2-H2(j)]-

{Fe(2H)Fe}, the m-H adducts [2-H2(k)]-{Fe(H)Fe_SH} and

[2-H2(l)]-{Fe(H)Fe_SH}, and the formyl species [2-H2(m)]-

{Fe(H)Fe_HCO}

(Fig. 6).[2-H2(j)]-

{Fe(2H)Fe} is a dihydride adduct in which one of thesulfur atoms is detached from the iron center not coordinatedby the phosphine ligand. The H–H interatomic distance in [2-H2(j)]-

{Fe(2H)Fe} (2.65 A) is larger than the corresponding distancein the neutral dihydride adduct [2-H2(f)]{Fe(2H)Fe} (see Table 5and 4). More importantly, [2-H2(j)]-

{Fe(2H)Fe} is very close to[2-H2(k)]-

{Fe(H)Fe_SH} in terms of stability (DG = -1.0 kcal mol-1

in favor of [2-H2(j)]-{Fe(2H)Fe}), but it is thermodynamically much

less stable than [2-H2(m)]-{Fe(H)Fe_HCO} (DG = 7.1 kcal mol-1) and

[2-H2(l)]-{Fe(H)Fe_SH} (DG = 12.3 kcal mol-1). The latter is a species

in which the protonated sulfur atom has completely detachedfrom both metal centers. This result shows how over-reductionof the protonated dinuclear complex can impair the integrity ofthe synthetic cluster, with consequent failure in the reproductionof the structural features of the H-cluster binuclear subsite.

Fig. 6 Schematic structures of selected diprotonated anionic species. Alldistances in A. Below each iron atom, are reported the correspondingMulliken spin population values.

Although the free energy difference between [2-H2(j)]-{Fe(2H)Fe}

and [2-H2(l)]-{Fe(H)Fe_SH} is very large, our results suggest that it is

possible to invert the stability order between the sulfur-protonatedand the dihydride species by means of the introduction of extras-donor ligands in the iron coordination sphere. In fact, thepentaphosphine species [3-H2(j)]-

{Fe(2H)Fe} (see Fig. 6) is more stablethan m-H complexes [3-H2(k)]-

{Fe(H)Fe_SH} and [3-H2(l)]-{Fe(H)Fe_SH} by

10.2 and 3.6 kcal mol-1, respectively; we also evaluated the stabilitydifference between [3-H2(j)]-

{Fe(2H)Fe} and the formyl-containingisomer [3-H2(m)]-

{Fe(H)Fe_HCO}; the former turned out to be muchmore stable (DG = -9.4 kcal mol-1). Similar conclusions canbe drawn for the corresponding selenium-containing models(optimized geometries reported in ESI†): in particular, model[pds3-H2(j)]-

{Fe(2H)Fe} is more stable than the selenium-protonatedisomer [pds3-H2(l)]-

{Fe(H)Fe_SeH} by 9.8 kcal mol-1.As far as the structural features of [3-H2(j)]-

{Fe(2H)Fe} and[pds3-H2(j)]-

{Fe(2H)Fe} are concerned, very large interatomic distancesare observed between the metal bound hydrogen atoms (2.76and 2.84 A, respectively) and between one of the sulfur or

Table 5 Relative stabilities and relevant structural parameters of selected diprotonated anionic complexes. Interatomic distances and energies arereported in A and kcal mol-1, respectively; Fe–S distances larger than 3 A are in italic

Species DG Fe–S distances H–H distances between metal-bound H atoms

Complexes containing dppe [2-H2(j)]-{Fe(2H)Fe} 0.0 4.37, 2.37, 2.35, 2.26 2.65

[2-H2(k)]-{Fe(H)Fe_SH} 1.0 2.43, 4.16, 2.37, 2.49 —

[2-H2(l)]-{Fe(H)Fe_SH} -7.1 6.36, 5.64, 2.26, 2.28 —

[2-H2(m)]-{Fe(H)Fe_HCO} -12.3 2.40, 2.33, 2.34, 2.39 —

Pentaphosphine complexes [3-H2(j)]-{Fe(2H)Fe} 0.0 2.26, 2.36, 2.36, 4.61 2.76

[3-H2(k)]-{Fe(H)Fe_SH} 10.2 2.30, 4.34, 2.44, 2.39 —

[3-H2(l)]-{Fe(H)Fe_SH} 3.6 6.02, 6.32, 2.24, 2.22 —

[3-H2(m)]-{Fe(H)Fe_HCO} 9.4 2.24, 2.32, 2.37, 3.46 —

7326 | Dalton Trans., 2010, 39, 7320–7329 This journal is © The Royal Society of Chemistry 2010

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Table 6 Relative stabilities and relevant structural parameters of selected triprotonated cationic complexes. Interatomic distances and energies arereported in A and kcal mol-1, respectively; Fe–S distances larger than 3 A are in italic

Species DG Fe–S distances H–H distances between metal-bound H atomsa

Complexes containing dppe [2-H3(n)]+{Fe(3H)Fe} 0.0 2.38, 2.37, 2.36, 2.38 0.84

[2-H3(o)]+{Fe(2H)Fe_SH} 7.3 2.32, 2.26, 2.39, 2.40 1.94

[2-H3(p)]+{Fe(2H)Fe_SH} 27.4 6.70, 5.77, 2.15, 2.16 2.23

[2-H3(q)]+{Fe(H)Fe_SH_HCO} 4.7 2.27, 4.71, 2.32, 2.31 —

[2-H3(r)]+{Fe(2H)Fe_SH} -7.5 6.50, 5.69, 2.25, 2.30 2.05

a In the case of complexes showing three metal-bound hydrogen atoms, only the H–H distance between hydrogen atoms bound to the same metal centersis reported

selenium atoms and the carbonyl-bound metal center (4.61 and4.76 A, respectively); notably, such values are even larger than thecorresponding ones computed for [2-H2(j)]-

{Fe(2H)Fe}.

Triple protonation of synthetic model complexes

Further protonation of [2-H2] and [2-H2]- has been proposed tolead to species capable to release H2, which might correspond toadducts featuring a terminal hydride ligand and an H2 moleculenon-classically bound to one of the metal centers (see Scheme 1);37

as far as the monocationic triprotonated state of the catalyst isconcerned, such an arrangement of ligands is observed in complex[2-H3(n)]+

{Fe(3H)Fe} (Fig. 7), which is a genuine h2-H2 adduct with aH–H distance of 0.83 A between the hydrogen atoms of the metal-bound H2 molecule. Exchanging the H2 and hydride position onthe iron centers gives place to an isomer (structure not shown)which is only 0.4 kcal mol-1 higher in energy.

Fig. 7 Schematic structures of selected triprotonated cationic species. Alldistances in A.

[2-H3(n)]+{Fe(3H)Fe} has been compared with three other plausible

isomers, i.e. the sulfur protonated species [2-H3(o)]+{Fe(2H)Fe_SH}

and [2-H3(p)]+{Fe(2H)Fe_SH}, as well as the formyl species

[2-H3(q)]+{Fe(H)Fe_SH_HCO} (see Fig. 7).§ It turned out that

[2-H3(n)]+{Fe(3H)Fe} is the most stable isomer, with free energy

§ The possible protonation of the m-CO, m-H species [2-H2(g)]{Fe(H)Fe_SH}was also considered in the present investigation; however, the optimizedgeometry of the product turned out to correspond to a saddle point onthe PES (TS-[2-H3(p)]+

{Fe(2H)Fe_SH}, see ESI†), with an imaginary frequencyof 64.0i cm-1. Following the associated eigenmode, we obtained an adductclose to [2-H3(p)]+

{Fe(2H)Fe_SH} in terms of both geometrical features andstability.

differences as large as -7.3, -27.4, and -4.7 kcal mol-1 whencompared to [2-H3(o)]+

{Fe(2H)Fe_SH}, [2-H3(p)]+{Fe(2H)Fe_SH} and [2-

H3(q)]+{Fe(H)Fe_SH_HCO}, respectively (Table 6). The latter three adducts

have geometries not far from what one would expect as aresult of direct protonation of complex [2-H2] (see above for theplausible geometries of the parent diprotonated neutral species);however, it should be noted that several possible dispositions ofprotons in the triprotonated complex are conceivable. In fact, arough sampling of the PES allowed to characterize species whichare significantly more stable than [2-H3(n)]+

{Fe(3H)Fe}, and showunprecedented structural features (see for example complex [2-H3(r)]+

{Fe(2H)Fe_SH} in Fig. 7, which is 7.5 kcal mol-1 more stable than[2-H3(n)]+

{Fe(3H)Fe}, and features a protonated sulfur atom and twohydrides bridging the metal centers).

Then, we evaluated monoelectron reduction of the triprotonatedcation, a reaction that should take place as the final step ofprocess B, before H2 release (see Scheme 1): to this end, weoptimized the neutral complex [2-H3(s)]{Fe(3H)Fe}, the geometry ofwhich is reported in Fig. 8. Differently from the case of the cationicspecies [2-H3(n)]+

{Fe(3H)Fe}, in [2-H3(s)]{Fe(3H)Fe} the bond between theH2 bound iron atom and a sulfur atom of pdt is cleaved (Fe–Sdistance: 3.04 A). Other relevant differences between the cationicand the neutral species are evidenced after the calculation ofrelative stabilities among isomers: in fact, [2-H3(s)]{Fe(3H)Fe} is lessstable than both the formyl-containing adduct [2-H3(v)]{Fe(2H)Fe_HCO}

(DG = 5.4 kcal mol-1, see also Table 7) and the sulfur-protonatedisomers [2-H3(t)]{Fe(2H)Fe_SH} and [2-H3(u)]{Fe(2H)Fe_SH} (DG = 15.7and 26.3 kcal mol-1, respectively; see Fig. 8). Favoring iron vs.

Fig. 8 Schematic structures of selected triprotonated neutral species. Alldistances in A. Below each iron atom, are reported the correspondingMulliken spin population values.

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Table 7 Relative stabilities and relevant structural parameters of selected triprotonated neutral complexes. Interatomic distances and energies arereported in A and kcal mol-1, respectively; Fe–S distances larger than 3 A are in italic

Species DG Fe–S distances H–H distances between metal-bound H atomsa

Complexes containing dppe [2-H3(s)]{Fe(3H)Fe} 0.0 2.39, 2.37, 3.04, 2.38 0.83[2-H3(t)]{Fe(2H)Fe_SH} -15.7 3.88, 2.30, 2.37, 2.29 2.56[2-H3(u)]{Fe(2H)Fe_SH} -26.3 6.23, 6.71, 2.25, 2.27 —[2-H3(v)]{Fe(2H)Fe_HCO} -5.4 2.37, 4.23, 2.31, 2.33 —

Pentaphosphine complexes [3-H3(s)]{Fe(3H)Fe} 0.0 2.35, 2.97, 2.36, 2.35 0.88[3-H3(t)]{Fe(2H)Fe_SH} -7.6 4.21, 2.26, 2.38, 2.24 2.80

a In the case of complexes showing three metal-bound hydrogen atoms, only the H–H distance between hydrogen atoms bound to the same metal centersis reported.

sulfur protonation by introducing an excess of phosphine ligandsaround the metal centers appears not to be feasible in thiscase; in fact, the pentaphosphine complex [3-H3(s)]{Fe(3H)Fe} (seeFig. 8) is 7.6 kcal mol-1 less stable than the dihydride isomer[3-H3(t)]{Fe(2H)Fe_SH}.

Conclusions

In the present contribution, key aspects of protonation thermo-dynamics in H2-evolving biomimetic catalysts related to [FeFe]-hydrogenases active site have been investigated, by taking as areference system the electrocatalytic dihydrogen evolution mech-anism recently proposed for the synthetic assembly [Fe2(CO)4(k2-Ph2PCH2CH2PPh2)(m-S(CH2)3S)].37 This is a species that, apartfrom the dianionic propanedithiolate residue, includes only neutralligands in the metal coordination sphere. The use of neutral ligands(mainly phosphine groups) in place of the naturally occurringCN groups has represented a common synthetic approach overthe last years, and our theoretical analysis on diiron complexescharacterized by various arrangements of CO and phosphinegroups might result helpful for a better interpretation of theirelectrocatalytic properties, as well as for the design of novelbiomimetic assemblies.

We show that the protonation of sulfur atoms in thepropanedithiolate residue is favored with respect to metal pro-tonation, as far as doubly protonated species are concerned. Asthe complex becomes more and more reduced, the energy gapbetween sulfur-protonated and dihydride species becomes largerand larger (the free energy difference value is close to 0 kcal mol-1

for the [2-H2(b)]+{Fe(2H)Fe} → [2-H2(c)]+

{Fe(H)Fe_SH} isomerization, andit becomes as large as 9.4 and 12.3 kcal mol-1 for the [2-H2(f)]{Fe(2H)Fe}

→ [2-H2(h)]{Fe(H)Fe_SH} and [2-H2(j)]-{Fe(2H)Fe} → [2-H2(l)]-

{Fe(H)Fe_SH}

isomerization reactions, respectively). Protonation of sulfur atomsis still favored in the case of neutral triprotonated adducts.

Notably, DFT calculations showed that sulfur protonationusually couples with Fe–S bond breaking; this leads the ironcenter(s) to be coordinatively unsaturated in these intermediates,which are thus expected to be short-lived and to feature a complexand hardly predictable reactivity. However, the relative stabilityof sulfur- and iron-protonated complexes can be modulated bymore than 10 kcal mol-1, by means of targeted modifications ofthe iron atoms coordination environment. In particular, at thelevel of diprotonated monoanionic adducts, the inclusion of anexcess of phosphine ligands in the iron first coordination sphereresults in the stabilization of the dihydride species by 3 kcal mol-1

over the sulfur protonated isomer. As for the monocationic andneutral diprotonated models, the inversion of the stability orderwas observed when the sulfur atoms of pdt in the pentaphosphinespecies were substituted by selenium atoms.

A comparison between the redox properties of the syntheticcatalyst and of the enzyme puts in evidence the following: in[FeFe]-hydrogenases, the binuclear subsite is thought to span theFe(I)Fe(I), Fe(I)Fe(II) and Fe(II)Fe(II) redox states, while zero-valent iron is thought to be irrelevant for the enzyme chemistry;in particular, the second proton transfer reaction in the enzymaticprocess takes place at the formally Fe(I)Fe(II) state, and it hasbeen proposed to be immediately followed by H2 detachment fromthe binuclear subsite.60,64 However, in the biomimetic assembly thesecond proton transfer step is followed by either one or two mono-electron reductions (Scheme 1, processes A and B, respectively);such over-reduction of the electrocatalyst favors proton transferreactions to the metal-bound sulfur atoms, a fact that eventuallyleads to structural reorganization of the cluster which have nocounterpart in the chemistry of the enzyme; similar considerationshold true when coordination geometries of models presenting theFe(I)Fe(0) formal oxidation states, such as [2-H3(v)]{Fe(2H)Fe_HCO}, areconcerned. These observations, along with previous experimentalresults on the structural features of Fe(I)Fe(0) and Fe(0)Fe(0)unprotonated diiron complexes,42,47,65 give us a clue to disclosethe reason why the over-reduction of the H-cluster is avoided in[FeFe]-hydrogenases, and poses new challenges to the biomimeticchemists. In particular, given the current difficulties in obtaininga H2-evolving route without reaching very low oxidation numbersat the iron centers, it is tempting to suggest that sulfur atomsprotection with bulky ligands could be useful to kinetically hinderprotonation of the dithiolate residue, thus favoring an iron-basedH2-evolving mechanism more closely resembling the enzymaticpath of proton reduction.

Substitution of the sulfur atoms with selenium atoms in thebidentate ligand, along with the inclusion of good s-donorsin the iron coordination sphere could also help in preservingthe integrity of the biomimetic complex; the latter considerationholds particularly true in the case of diprotonated monocationiccomplexes, which attain relatively high oxidation states at the ironcenters and are predicted to release H2 with remarkable efficiency.Moreover, calculation of redox potentials indicates that theinclusion of propanediselenolate in place of propanedithiolate iscompatible with a relatively mild reduction chemistry of syntheticcomplexes, a fact that is expected to be helpful for the design ofnovel and efficient bioinspired electrocatalysts.

7328 | Dalton Trans., 2010, 39, 7320–7329 This journal is © The Royal Society of Chemistry 2010

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Acknowledgements

C. G. acknowledges support of the Humboldt Foundation.

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