synthetic [fefe] hydrogenase active site model …173200/...abbreviations adt...

ACTAUNIVERSITATIS

UPSALIENSISUPPSALA

2009

Digital Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Science and Technology 599

Synthetic [FeFe] HydrogenaseActive Site Model Complexes

LENNART SCHWARTZ

ISSN 1651-6214ISBN 978-91-554-7404-1urn:nbn:se:uu:diva-9548

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List of Publications

This thesis is based on the following publications, which are referred to in the text by the Roman numerals I-VI.

I Iron hydrogenase active site mimic holding a proton and a hydride. Schwartz, Lennart; Eilers, Gerriet; Eriksson, Lars; Gogoll, Adolf; Lomoth, Reiner; Ott, Sascha. Chemical Communications, 2006, (5), 520-522.

II Ligand versus metal protonation of an iron hydrogenase actives site mimic. Eilers, Gerriet; Schwartz, Lennart; Stein, Matthias; Zampella, Giuseppe; de Gioia, Luca; Lomoth, Reiner; Ott, Sascha. Chemistry –A European Journal, 2007, (13), 7075-7084.

III Facilitated hydride binding in an Fe-Fe hydrogenase active-site biomimic revealed by X-ray absorption spectroscopy and DFT calculations. Löscher, Simone; Schwartz, Lennart; Ott, Sascha; Haumann, Michael. Inorganic Chemistry, 2007, (46), 11094-11105.

IV Dynamic ligation at the first amine-coordinated iron hydrogenase active site mimic. Schwartz, Lennart; Ekström, Jesper; Lomoth, Reiner; Ott, Sascha. Chemical Communications, 2006, (40), 4206-4208.

V Tuning the electronic properties of Fe2(�-arenedithiolate) (CO)6-n(PMe3)n (n = 0, 2) complexes related to the [FeFe] hydrogenase active site. Schwartz, Lennart; Singh, Pradyumna S.; Eriksson, Lars; Lomoth, Reiner; Ott, Sascha. Comptes Rendus Chemie, 2008, (11), 875-889.

VI Influence of an electron-deficient bridging o-carborane on the electronic

properties of an [FeFe] hydrogenase active site model. Schwartz, Lennart; Eriksson, Lars; Lomoth, Reiner; Teixidor, Francesc; Viñas, Clara; Ott, Sascha. Dalton Transactions, 2008, (18), 2379-2381.

The publications are printed with the kind permission from the publishers.

Contribution Report

Paper I-III Contributed to the formulation of the research problem, performed all synthetic work, contributed to the characterization, prepared samples for the XAS experiments, made contribution to the interpretations of the results and to the writing of the manuscripts.

Paper IV Major contribution to the formulation of the research problem,

made all experimental work (except X-ray crystallography and FTIR-spectroelectrochemistry), made major contribution to the interpretations of the results and to the writing of the manuscript.

Paper V Major contribution to the formulation of the research problem,

made all synthetic work and characterization, made the initial voltammetric studies, performed all of the attempted catalysis experiments, made major contribution to the interpretations of the results and to the writing of the manuscript.

Paper VI Major contribution to the formulation of the research problem,

made all experimental work, made major contribution to the interpretations of the results and contributed to the writing of the manuscript.

Chapter 5 Major contribution to the formulation of the research problem,

made all synthetic work concerning the synthesis of the iron complexes.

Chapter 6 Major contribution to the formulation of the research problem,

majority of the experimental work (synthesis, characterization by NMR and IR, cyclic voltammetry, in situ IR experiments and EPR samples), made major contributions in coordinating a multi-disciplinary project.

Abbreviations

adt 2-azapropane-1,3-dithiolate or azadithiolate AcOH acetic acid bdt benzene-1,2-dithiolate bpy 2,2’-bipyridine cdt carborane-1,2-dithiolate CV Cyclic Voltammetry dba dibenzylideneacetone dqp 2,6-di(8’quinolinylpyridine) DCM dichloromethane DFT Density Functional Theory DPV Differential Pulse Voltammetry ENDOR Electron Nuclear Double Resonance Epa anodic peak potential Epc cathodic peak potential EPR Electron Paramagnetic Resonance edt ethane-1,2-dithiolato EXAFS Extended X-Ray Absorption Fine Structure Fc ferrocene FTIR Fourier Transform Infrared Spectroscopy GC Gas Chromatography H2ases Hydrogenases HBr hydrobromic acid HCl hydrochloric acid HClO4 perchloric acid HOTf triflic acid = trifluoromethanesulfonic acid HOTs p-toluenesulfonic acid HYSCORE Hyperfine Sublevel Correlation Spectroscopy ip,a anodic peak current ip,c cathodic peak current IR Infrared Spectroscopy LUMO Lowest Unoccupied Molecular Orbital Me methyl MeCN acetonitrile NMR Nuclear Magnetic Resonance ORTEP Oak Ridge Thermal Ellipsoid Plot pdt propane-1,3-dithiolate Pr propyl SCE Saturated Calomel Electrode = 380 mV vs. Fc/Fc+ S-Phos 2-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl SEC Spectroelectrochemistry TBA tert-butylamine TEA triethanolamine THF tetrahydrofuran TLC Thin Layer Chromatography TMEDA N,N,N',N'-Tetramethylethylenediamine tpy 2,2’:6’,2,’’-terpyridine XAS X-ray Absorption Spectroscopy XANES X-ray Absorption Near Edge Structure X-phos 2-Dicyclohexylphosphino-2�,4�,6�-triisopropylbiphenyl

Table of Contents

1 Introduction .........................................................................................11 1.1 General........................................................................................11 1.2 The Concept of Artificial Photosynthesis ...................................12

1.2.1 Proton Reduction Catalysts....................................................13 1.3 Hydrogenases..............................................................................14

1.3.1 General...................................................................................14 1.3.2 [FeFe] Hydrogenases .............................................................15

1.4 Synthetic Model Complexes of the [FeFe] Hydrogenase [2Fe]H Subsite.........................................................................................17

1.4.1 General Synthetic Routes.......................................................17 1.4.2 Design of Model Complexes .................................................18

1.5 Experimental Methods ................................................................20 1.5.1 General...................................................................................21 1.5.2 Infrared Spectroscopy ............................................................21 1.5.3 Electrochemistry ....................................................................23

2 Mimicking the Dibasic Properties of the [FeFe] Hydrogenase [2Fe]H Subsite (paper I-III) ............................................................................26

2.1 Introduction.................................................................................26 2.2 Synthesis .....................................................................................27 2.3 Characterization of the Protonation States..................................28 2.4 Electrochemistry and Electrochemical Proton Reduction...........32 2.5 Conclusions.................................................................................33

3 Mimicking the Labile Ligand in the [FeFe] Hydrogenase [2Fe]H Subsite (paper IV)...............................................................................35

3.1 Introduction.................................................................................35 3.2 Synthesis .....................................................................................36 3.3 Electrochemistry and Infrared Spectroscopy ..............................37 3.4 An Analogue Bearing the Azadithiolate Functionality

(Unpublished) .............................................................................41 3.5 Conclusions.................................................................................41

4 Tuning the Electronic Properties of [FeFe] Hydrogenase [2Fe]H Subsite Model Complexes (Papers V and VI) ....................................43

4.1 Introduction.................................................................................43

4.2 Synthesis and Characterization ...................................................44 4.3 Electrochemistry .........................................................................50

4.3.1 Electrochemical Behaviour....................................................50 4.3.2 Electrochemical Proton Reduction ........................................53

4.4 Conclusions.................................................................................55

5 Towards Light-driven Electron Transfer and Hydrogen Generation from an [FeFe] Hydrogenase Active Site Mimic Covalently Linked to a Ruthenium Photosensitizer ..............................................................57

5.1 Introduction.................................................................................57 5.2 Design .........................................................................................58 5.3 Synthetic Progress Towards a Ruthenium-Diiron Dyad.............59 5.4 Conclusions.................................................................................62

6 Isotope-labelled, Mixed-Valent Fe(I)-Fe(II), Model Complexes ........63 6.1 Introduction.................................................................................63 6.2 Synthesis and Characterization ...................................................64 6.3 Generation and Study of the Fe(I)-Fe(II) state............................66 6.4 Conclusions.................................................................................68

7 Concluding Remarks ...........................................................................69

Acknowledgements.......................................................................................71

References.....................................................................................................73

Appendix I ....................................................................................................78

Appendix II ...................................................................................................79

Appendix III..................................................................................................83

Swedish Summary ........................................................................................87

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1 Introduction

1.1 General The demand for more energy has never been greater in our modern civilization. At the same time, Earth is facing an urgent problem as global warming is at its doorstep. In order to decrease the CO2 emission and to be able to maintain our lifestyle, the need for renewable energy is evident. There are a lot of options to satisfy mankind’s energy need1 and probably, like today, the energy of the future will originate from many different sources. Solar energy is still fairly unexplored and almost unused, especially considering its great potential. Sunlight can be captured and converted to electricity using photovoltaic cells. However, the capture of the solar energy by solar cells suffers from one major drawback. Since sunlight has its periodic variations it is vital that one can store the collected energy for night time and short winter days.2 Electricity can be stored in batteries or be converted into mechanical energy where, for instance, the electricity is used for pumping water uphill. These storage alternatives are however not suited for a global energy scheme. The need for a new fuel, i.e. a new carrier of energy in the form of chemical bonds, to substitute oil is apparent. The energy carrier of the future must be formed from abundant inexpensive materials and the ultimate fuel must be possible to be recycled. Hydrogen is often considered to be the ideal fuel since its combustion generates only water. Terms like the hydrogen economy3 or hydrogen society tells something about the expectations and impact that hydrogen might have as the “new” energy carrier of our globe. Of course, such a vision demands a lot of infrastructural work, but the two main questions have always been: how to store hydrogen safely and how to produce it from sustainable energy. Hydrogen (and oxygen) can be produced from water by electrolysis, a procedure which is rather inefficient and that has been very expensive so far. Direct hydrogen production from sunlight could be more advantageous. Mimicking the key steps in photosynthesis could be a way to realize mankind’s dream of a clean fuel from sun and water.

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1.2 The Concept of Artificial Photosynthesis In photosynthesis, solar energy is converted into chemical energy in a very efficient manner. Photosynthesis consists of mainly two reaction schemes: i) the light reaction where sunlight is absorbed, water is oxidized to oxygen and NADP+ is reduced to NADPH and ii) the “dark” reaction (the Calvin cycle) where the reducing power of NADPH is used for the fixation of CO2 into sugars. These processes can be summarized by the following equation:

The light reaction takes place in two protein clusters, namely photosystem I (PSI) and photosystem II (PSII). The reaction starts when a photon is absorbed by photosystem II. From the thereby created high-energy excited state, an electron is ejected from the reaction centre in PSII and a photo-induced charge separation takes place. The expelled electron is transferred to PSI where it will ultimately lead to the reduction of NADP+ to NADPH after a second photon absorption. The photosensitizer in PSII gets oxidized in this process, takes however an electron back from a proximate tyrozine. This tyrozine, in turn, takes an electron from the oxygen evolving complex (OEC) which consists of a tetranmuclear manganese cluster.4 After repeating this sequence four times, the OEC provides sufficient oxidation power to catalyze the oxidation of water. Thus, the reducing power (or electrons) for the reduction of NADP+ comes ultimately from the oxidation of water. The key features in photosynthesis are: i) antenna effects, ii) photo-induced charge separation and iii) the water oxidation.

Figure 1. Schematic presentation of an artificial photosynthetic device.

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A long-term goal has been to construct a supramolecular system that can convert sunlight to a molecular fuel (hydrogen). Many of the key-features described above for the natural photosynthesis have to be mimicked in order to obtain a functional artificial system. The work presented in this thesis is part of this effort to create an artificial photosynthetic system. As depicted in Figure 1, such a supramolecular device has to contain a number of units and is envisaged to be connected in a D–P–A fashion,5,6 where P is a photosensitizer that can absorb a photon and eject an electron from the excited state to an acceptor A. The donor D should be able to donate electrons to the oxidized state of P, creating the charge separated state D+�P�A-. This charge separated state should have a sufficiently long lifetime and appropriate energy so that the catalytic reactions can take place i.e. the water oxidation on the donor and the reduction of protons into molecular hydrogen at the acceptor side. This thesis work is focused on: i) the exploration of biomimetic models of the [FeFe] hydrogenase active site as proton reduction catalysts that can be employed in a supramolecular device as described above and ii) synthetic approaches towards a dyad which consists of a photosensitizer that is covalently linked to a catalytically active [FeFe] hydrogenase active site model complex. Such a dyad would represent the P–A “half cell” of the D–P–A triad.

1.2.1 Proton Reduction Catalysts

There are a few examples of homogenous proton reduction catalysts in the literature.7 One of the most studied systems is based on Co(diglyoxime) complexes, which can catalyze H2 evolution at rather mild potentials of about - 0.50 to -0.26 V vs. SCE depending on the diglyoxime ligand that is used.8-11 Koelle et al. have also reported H2 production catalyzed by other Co-based complexes, namely CpCo(PR3)2

12 and CoCp2 (Cp = cyclopentadienyl).13,14 Moreover, Dubois and co-workers have reported proton reduction catalyzed by [Ni(PPh

2NPh

2)2(CH3CN)](BF4)2 (where PPh2N

Ph2

= 1,3,5,7-tetraphenyl-1,5-diaza-3,7-diphosphacyclooctane) at -0.7 V vs. Fc+/0.15

There are also examples of homogenous light-driven catalytic supra-molecular systems. Rau et al. have synthesized a heterodinuclear Ru-Pd complex which catalyzes proton reduction that is driven by the action of light.16 Fontecave and co-workers have also prepared photocatalytic supramolecular systems where the above-mentioned cobaloxime catalysts are employed together with ruthenium, iridium or rhenium photosensitizers.17,18

We are aiming for inexpensive homogenous catalysts that are based on abundant base metals. One promising alternative is to use biomimetic models of the active site of hydrogenases (See Section 1.3). Therefore, diiron dithiolate model complexes of the [FeFe] hydrogenase active site have

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been explored in this thesis and their potential as functional proton reduction catalysts has been evaluated.

1.3 Hydrogenases

1.3.1 General

Hydrogenases (H2ases) constitute a family of enzymes that can catalyze the reversible reduction of protons into molecular hydrogen by the following heterolytic mechanism:

In certain bacteria and green algae, hydrogenases play a vital role in the anaerobic metabolism as hydrogen can be used either as a source of electrons or, upon evolution of hydrogen, as a way to dispose excess electrons. Three classes of hydrogenases have been recognized that differ in the metal content in their active sites: i) [Fe]-hydrogenases (formerly known as metal-free hydrogenases),19,20 ii) [FeFe]-hydrogenases (formerly known as iron-only hydrogenases) and iii) [NiFe]-hydrogenases.21,22 Although the active sites of [FeFe] hydrogenase and [NiFe] hydrogenase are structurally similar, both enzymes are phylogenetically unrelated.23 Comparison between [FeFe] and [NiFe] hydrogenases has shown that [FeFe] hydrogenases are more involved in hydrogen production while [NiFe] hydrogenases catalyze preferentially the oxidation of hydrogen.23 Moreover, the activity of [NiFe] hydrogenases is lower than that of [FeFe] hydrogenases while the latter seem to be more sensitive towards oxygen and inhibition by carbon monoxide.24 [FeFe] hydrogenases have shown very high rates of hydrogen generation. For example, the [FeFe] hydrogenase of the Desulfovibrio desulfuricans bacteria has a turnover rate of 9 000 moles of hydrogen per mole enzyme and second at 30 °C.25-27 For these reasons and due to the fact that the synthetic chemistry is relatively well established, biomimetic model complexes of [FeFe] hydrogenases have been far more investigated than [NiFe] hydrogenase mimics.

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1.3.2 [FeFe] Hydrogenases

The structures of the [FeFe] hydrogenases from Desulfovibrio desulfuricans and Clostridium pasteurianum have been elucidated by X-ray crystallography.25,27 Their active sites, called H-cluster, consist of a [4Fe4S]H cubane cluster which is linked to a [2Fe2S] subcluster, [2Fe]H, through a cysteine residue (Scheme 1). The connected [4Fe4S] cluster together with several other non-linked cubane clusters provide a pathway for electron transfer from and to the [2Fe2S] subcluster. The iron centres of the [2Fe2S] subcluster are bridged by a dithiolate ligand, -S-CH2-X-CH2-S-, where the atom X has yet to be identified. It has been suggested to be a carbon (propane-1,3-dithiolate = pdt), a nitrogen (2-azapropane-1,3-dithiolate = adt) or even an ether.28 Moreover, the two iron centres are surrounded by CO and CN– ligands which are stabilizing the low oxidation states of the metals. As deduced from the X-ray structure of the enzyme, one carbonyl ligand resides in a semi-bridging position between the two iron centres in at least one oxidation state. Semi-bridged carbonyl ligands provide the possibility for an excessively low-valent metal centre to transfer some of its electron density to a carbonyl ligand on a less negatively charged metal atom.29 While the [4Fe4S] cluster is linked to the “proximal” iron Fep, the “distal” iron centre Fed has a labile ligand site (L). The nature of this labile ligand depends on the oxidation state in the catalytic cycle. Crystallography and IR spectroscopy have shown that the site L is occupied by a CO ligand upon exposure to exogenous carbon monoxide.30 In this CO-inhibited state, the activity of the enzyme is lost and it is therefore suggested that the site L is the putative hydrogen binding site during the catalysis. The labile site is thus vital for the function of the enzyme. A [2Fe]H model complex with such a labile site will be presented in Chapter 3.

Scheme 1. The [FeFe] hydrogenase active site (the H-cluster).

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The catalytic mechanisms of the [FeFe] hydrogenases are still not entirely understood. The most recent model is shown in Scheme 2.31 The activation step is reductive in nature and followed by the loss of either an aqua or a hydroxo ligand, creating an unoccupied coordination site and the active [Fe(II)Fe(I)] oxidation state (Hox). When a CO ligand occupies the free

coordination site, a coordinatively saturated and catalytically inactive Hox-CO state is obtained. A mimic of this state is presented in Chapter 6. The next step in the catalytic cycle is a reduction together with the protonation of a nearby base (represented as X = N in Scheme 2) to form Hred. Then, the proton is transferred to the distal iron centre Fed and thereby reduced to a hydride. As the proton is reduced, the two iron centres are oxidized (oxidative addition) to the [Fe(II)Fe(II)] state. A second proton is then picked up by the basic site and subsequent reduction will reduce the active site to [Fe(II)Fe(I)]. The proton on the basic site will then combine with the terminal hydride to create a dihydrogen ligand which is then liberated to

Scheme 2. Proposed mechanism for the catalytic hydrogen production by [FeFe] hydrogenase (ref 31).

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reform the active [Fe(II)Fe(I)] state and to close the catalytic cycle. An alternative mechanism, rather different from the one described above, has also been proposed.32 This mechanism involves intermediates where the hydride resides at a bridging position between the two iron centres instead of at a terminal position in the [Fe(II)Fe(II)] Hred state. This hypothesis is supported by the high stability of the bridging hydride found in model complexes and from DFT calculations. A model complex that can hold a bridging hydride and a proton on an azadithiolate ligand is presented in Chapter 2. It has however been debated if the bridging hydride is a valid structure of an intermediate in the catalytic cycle of the enzyme. It has been suggested that the possible role of the bridging CO ligand is to prevent the hydride to reside in the bridging position.33 As stated in Section 1.3.1, hydrogenases are bidirectional. Both directions are equally as interesting in future technical applications: H2 production and the development of platinum-free fuel-cells34 where the oxidation of dihydrogen is essential. This work is however only focused on model complexes for proton reduction.

1.4 Synthetic Model Complexes of the [FeFe] Hydrogenase [2Fe]H Subsite

1.4.1 General Synthetic Routes

It has been a decade since the first structure of an [FeFe] hydrogenase was revealed by X-ray crystallography. Many different routes to new model complexes of the active site have been developed since then.35,36 The field is however a lot older as diiron hexacarbonyl disulfide complexes which are close mimics of the active site have already been synthesized eighty years ago. The routes (denoted A–F) to different diiron hexacarbonyl complexes and the chemistry of their precursors are depicted in Scheme 3. In the pioneering work of Reihlen, a diiron hexacarbonyl complex was synthesized from Fe(CO)5 and a thiol (A).37 Other iron(0)carbonyl precursors, namely [Fe3(CO)12] and [Fe2(CO)9], have been used in the same manner. When dithiols are employed, diiron complexes (including [Fe2(�-pdt(CO)6]) with bridging dithiolate ligands can be synthesized (B1 and B2).

38,39 One of the most widely used iron-carbonyl precursor today is [Fe2S2(CO)6].

40,41 It adds to alkenes42 and C60 or C70 fullerenes43 under irradiation in a [2+2] manner (C). Seyferth at al. have shown that [Fe2S2(CO)6] can be converted to the lithium salt, Li2[Fe2S2(CO)6], by treatment with super-hydride (LiEt3BH).44 The dianion can then be alkylated with alkyl halides to form dithiolate bridged [Fe2(�-(S2R)(CO)6] complexes.45 Reacting Li2[Fe2S2(CO)6] with bis(chloromethyl)amines affords complexes with the azadithiolate functionality, [Fe2(�-(SCH2)2NR(CO)6] (D1).

46 Bis(chloromethyl)-amines

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from primary amines, para-formaldehyde and thionyl chloride can in turn be prepared by the procedure of Rauchfuss and co-workers.47 In addition, other routes (D2–D4) to [Fe2(�-(SCH2)2NR(CO)6] have also been developed.48 Moreover, [Fe2(�-(SCH2OCH2S)(CO)6] can be prepared via route E or from Li2[Fe2S2(CO)6] and bis(chloromethyl)ether.49 The analogous complex with a thiodithiolate ligand, [Fe2(�-(SCH2SCH2S)(CO)6] has been prepared from [Fe2(CO)9] and 1,2,4-trithiolane (F).50

1.4.2 Design of Model Complexes

As illustrated in the previous section, it is clear that the synthetic chemist’s tool-box to vary the bridging dithiolate ligand is well equipped. The bridging ligand can be altered to accomplish different goals, and in Chapter 4 we will

Scheme 3. General synthetic routes for [Fe2(�-(S2R)(CO)6] complexes.

19

use certain substituents at aromatic dithiolate ligands to realize proton reduction at low overpotentials. However, also the carbonyl ligands of the hexacarbonyl complexes can be exchanged by other ligands to answer questions about the H-cluster or to design better proton reduction catalysts.

In order to mimic the electron donating cyanide ligands in the [2Fe]H subcluster, strongly electron-donating ligands can be introduced to the hexacarbonyl model complexes. For example, model complexes with ligands such as CN-,51-53 PMe3,

54,55 PPh356, P(OR)3,

57 and diphosphanes36 etc. have been synthesized. It has been shown that diiron complexes with electron donating ligands can be protonated at the Fe-Fe bond.58,59 In Chapter 2, electron donating trimethylphosphine ligands are employed in the design of a model complex with two basic sites.

The metal centres in the complexes described in Scheme 3 are in the Fe(I)Fe(I) state. As discussed in Section 1.3.2, the catalytic cycle of the [FeFe] hydrogenases however involves higher oxidation states. Pickett and co-workers have therefore synthesized a Fe(I)Fe(I) complex, [Fe2(MeSCH2C(Me)(CH2S)2)(CN)2(CO)4]

2-, which can stabilize the Fe(I)Fe(II) state by the dynamic coordination of a pendant thioether arm.60 In Chapter 6, this strategy will be discussed in a preliminary spectroscopic study of similar complexes. Model complexes with higher oxidation states have also been obtained by van der Vlugt et al.61 Due to the stabilization by electron donating PMe3 ligands, a complex with the Fe(II)Fe(II) oxidation state could be generated. When reacting this oxidized complex with a hydride source such as NaBH4, a terminal hydride species was observed.62

The greatest challenge in mimicking the [2Fe]H subunit is probably to find a way to invert the ligand geometry around one iron centre (Scheme 4).63,64

Such a rotated structure will not only contain a bridging CO ligand, but would hopefully also lead the hydride into the more reactive terminal position (instead of the less reactive or inert bridging). This reasoning has led the field into unsymmetrically disubstituted complexes which can favour this rotated structure. Recently, Darensbourg and co-workers and also Rauchfuss and co-workers have reported the structural changes of complexes [Fe2(CO)3(PMe3)(IMes)(�-pdt)] (IMEs = 1,3-bis(2,4,6-trimethylphenyl)-imidazol-2-ylidene)65 and [Fe2(CO)3(PMe3)(�

2-dppv)(�-edt)] (dppv =

Scheme 4. The two rotamers.

20

Ph2PCH=CHPPh2)66 after their one-electron oxidation. The oxidation of both

complexes induces the inversion of the pyramidal geometry around one iron centre and thus leads to a rotated structure with a semi-bridging CO ligand.

The number of reported cases of proton reduction catalyzed by diiron model complexes is steadily increasing.67,68 The first example of catalysis using a hydrogenase model complex was reported by Gloaguen et al. who demonstrated electrochemical proton reduction at -1.2 V vs. Ag/AgCl (corresponding to -1.71 V vs. Fc+/0),69 using the mixed ligand complex [Fe2(�-pdt)(CO)4(PMe3)(CN)]-.70,71 Ott et al. reported electrochemical H2 production at -1.48 V vs. Fc+/0 that was facilitated by the presence of an azadithiolate ligand at the hexacarbonyl model complex [Fe2(�-adt)(CO)6].

69 The azadithiolate functionality which is protonated during the cause of the catalysis shifts the potential required for electrocatalysis by 230 mV to milder potentials compared to the reaction that is catalyzed by [Fe2(�-pdt)(CO)6] with an all-carbon based dithiolate linker. When acids that are too weak to protonate the adt nitrogen are used this difference in catalytic behaviour is lost. The proton reduction catalysis of [Fe2(�-adt)(CO)6] was suggested to follow a PEPE (proton-electron-proton-electron) mechanism, where the second protonation presumably occurs at the Fe-Fe bond. As mentioned above, electron donating ligands can be utilized to promote protonation of the Fe-Fe bond already at the Fe(I)Fe(I) oxidation state. Our work to prepare an azadithiolate diiron complex which can form the �-hydride already before the first reduction step is presented in Chapter 2. Capon et al. have demonstrated that [Fe2(�-bdt)(CO)6] (bdt = benzene-1,2-dithiolate) catalyzes proton reduction at rather mild potentials (-1.3 V vs. Fc+/0) when a strong acid is used.72 Inspired by these reports, we have initiated a project on benzenedithiolate-related complexes which will be presented in Chapter 4.

The most important criteria for a proton reduction catalyst are i) chemical robustness, ii) high turnover frequency and iii) performance at low overpotential. Unfortunately, no catalyst that is based on a model complex of the [FeFe] hydrogenase active site has so far met these criteria satisfactorily.

As stated in section 1.2, our long-term interest lies in supramolecular systems for light-driven proton reduction, using an [FeFe] hydrogenase active site model complex as the catalytic unit. In Chapter 5, the design and synthetic approaches towards such a system are presented.

1.5 Experimental Methods In this work, the synthetic compounds were generally characterized by the standard techniques such as NMR (Nuclear Magnetic Resonance), FTIR (Fourier Transformed Infrared Spectroscopy) and elemental analysis. Single crystals of many of the complexes were obtained and X-ray diffraction

21

analysis was performed. The electrochemical behaviour of selected complexes was studied by CV (cyclic voltammetry), DPV (differential pulse voltammetry), bulk electrolysis and FTIR-SEC (FTIR-spectro-electrochemistry). It has been a pleasure to collaborate with a number of skilled scientists who have explored our compounds by XAS (X-ray Absorption Spectroscopy, EXAFS and XANES to be precise), EPR (Electron Paramagnetic Resonance) spectroscopy (together with ENDOR, Electron Nuclear double Resonance and HYSCORE, Hyperfine Sublevel Correlation Spectroscopy) and DFT (Density Functional Theory) calculations.

1.5.1 General

All synthesized model complexes in this thesis have an initial FeI-FeI oxidation state. Each Fe(I) centre has a d7 configuration and the “unpaired” electron from each Fe centre form the Fe-Fe bond. The complexes are thus diamagnetic compounds and can be studied by NMR spectroscopy.

X-ray diffraction analysis is superior over all other characterization techniques as it unambiguously reveals the structure of a compound. In this thesis, single crystal X-ray diffraction was employed, which requires single crystals of good quality

1.5.2 Infrared Spectroscopy

An IR spectrum arises from the transition of energy between different vibrational modes of a molecule. In order for the vibrational mode to be IR active it must give a change in dipole moment during the vibration. Therefore, polar groups such as carbonyl and cyanide exhibit strong absorptions i.e. high intensity stretching bands in the IR spectrum. The vibrational frequencies for stretching bonds in molecules are related to the strength of the chemical bonds and the masses of the atoms. The C-O vibration (�CO) in free carbon monoxide gas occurs at 2143 cm-1. When coordinated to a metal, the stretching frequency �CO is decreased. There are three metal-CO bonding interactions: i) metal-CO �-bonding, ii) metal to CO

Figure 2. The three metal-CO bond interactions.

22

�-backbonding and iii) CO to metal �-bonding (Figure 2). The lowest unoccupied molecular orbital (LUMO) of CO is an

antibonding �*-orbital and is low enough in energy to function as an acceptor orbital when interacting with filled d-orbitals on metals. This is the reason why coordination to electron rich metal centers shifts the �CO stretching frequency to lower energy as the C-O bond weakens due to the d �* backbonding. Another factor that sets the value of �CO is the

coordination mode of the carbonyl ligand (terminal, bridging or semibridging). The synergic bonding (i.e. �-bonding and �*-backbonding) between the CO ligand and the metal centre renders IR spectroscopy a very powerful tool to probe the electronic environment in metal-carbonyl complexes. This technique will be used extensively to investigate different protonation states of a complex in Chapter 2.

The number of carbonyl bands depends on the number of CO ligands and the symmetry of the metal complex. Secondary effects such as Fermi resonance and overtone interactions can complicate the IR spectra further. The carbonyl stretching frequencies in the IR spectrum of [Fe2(�-pdt)(CO)6] have been assigned by Hall and co-workers (Figure 3).73 C2v symmetric, hexacarbonyl complexes of the [Fe2(�-S2R)(CO)6] type all show similar IR patterns in the CO region, although shifted depending on the electronic properties of the bridging dithiolate ligand (as an example, see chapter 4).

Figure 3. The assignments (most prominent showed) of the CO stretching frequencies of the IR spectra for [Fe2(�-S2R)(CO)6] complexes. The IR spectrum of [Fe2(�-pdt)(CO)6] is shown as an example (ref 73).

23

1.5.3 Electrochemistry

In this thesis, the electrochemical behaviour of the synthesized complexes was studied by cyclic voltammetry, differential pulse voltammetry and bulk electrolysis (controlled potential coulometry).

Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) are both techniques where the potential is varied with time in a preset manner. The timescale of the experiment is determined by the scan rate which is set in the experiment. The difference between the two techniques is that in cyclic voltammetry the potential is continuously swept and cycled through the experiment while in the differential pulse voltammetry experiment the potential is pulsed (Figure 4). The resulting current is measured as a function of the potential where the oxidative (anodic) current is depicted as a positive wave and the reductive (cathodic) current is depicted as a negative wave. CV and DPV are techniques that are widely used to study the formal potential E0’ required for the reduction or the oxidation of an electroactive species. The obtained formal potential values provide information on the molecular orbital energy levels where the reduction potential is related to the LUMO (lowest unoccupied molecular orbital) and the oxidation potential is connected to the HOMO (highest unoccupied molecular orbital).74,75 The formal potential is most accurately determined by differential pulse voltammetry if the process is irreversible. For a reversible process,

Figure 4. The relationship between potential, time and current in cyclic voltammetry (top) and differential pulse voltammetry (bottom). The potential is controlled in their respective preset manners (left) and the followed current responses are shown (right). The i in the DPV is the difference in current sampled before and at the end (set of open and solid circles) of each potential pulse.

24

determination of the formal potential is however made with highest accuracy by cyclic voltammetry. CV also provides the possibility to study the stability of the reduced (or oxidized) species from the reversibility of the voltammetric wave. A reversible electrochemical process should exhibit equal amplitude (peak current ip) for the forward and the backward scan. A non-reversible system indicates that the electrochemically generated species is consumed in a subsequent process. Such processes could be redox-triggered chemical reactions, deposition on the working electrode surface or even complete degradation. In the case of electrochemical proton reduction, irreversible CV-waves are expected as many H2 molecules per catalyst are formed that leave the system. In this context, it is important to emphasize that in CV and DPV experiments the mass transport of substances only occurs by diffusion and that the electrochemical reaction (and subsequent processes) only affect the molecules within the diffusion layer of the electrode. In catalytic proton reduction, increasing concentrations of brønsted acid (HA) will increase the height of the reduction wave. The characteristic shape of the cyclic voltammetric responses depends on the ratio of the rate constant and the experimental timescale together with the ratio of [HA]/[catalyst].76

In this work CV (and DPV) is applied to establish proton reduction catalysis. The focus here is on homogenous catalysis. When evaluating complexes in an electrochemical setup, it may proof difficult to discern if the catalysis is indeed homogenous. It is therefore advisable to study the solution after every electrocatalytic experiment by IR spectroscopy to ensure that the catalyst is still intact and that catalysis is not originating from heterogeneous decomposition products or films on the electrode surface.

For the cyclic and differential pulse voltammetry, a three-compartment cell was used. The working electrode was a glassy carbon disc (3 mm in diameter). A glassy carbon rod in a compartment separated from the bulk solution by a fritted disk (but not always) was used as counter electrode. The reference electrode was a non-aqueous Ag/AgNO3 electrode (10 mM in acetonitrile) with a potential of approximately -0.08 V vs. the ferrocenium/ferrocene (Fc+/0) couple in acetonitrile which was used as an internal standard after every experiment.

In bulk electrolysis (potentiostatic coulometry) the objective is the complete conversion of the electroactive species in the bulk. This is in contrast to CV and DPV where only the solute in the vicinity of the electrode is affected. In coulometry, the current obtained in an experiment is integrated over time and thus provides an exact measure on the number of electrons that are involved per molecule in the given electrochemical process. Bulk electrolysis is also employed to study catalysis over a longer timescale. This is especially useful for systems with low catalytic turnover frequencies. In addition, the hydrogen that is catalytically produced in a bulk electrolysis experiment can be verified and quantified by gas chromatography (GC). The

25

HA,0

H

0HA p

303.2aK

FRTEE −= +

moles of electrons (calculated from the charge) which pass through the system in the bulk electrolysis experiment should then correspond to the moles of produced hydrogen (i.e. high faradaic yield) to assure that no side reactions occur during the course of the electrolysis.

In the evaluation of proton reduction catalysts, it is important to take a few factors into account. A molecular catalyst will always be restricted by the acid strength (pKa) of the proton source since the catalyst has to be protonated during the catalytic cycle. Felton at al. have outlined the aspects for evaluating the catalytic efficiency of proton reduction.77 Overpotential is the potential difference between the potential required by a specific compound to catalyze the reduction of protons and the potential required by platinum (the standard potential for the employed acid) under otherwise identical conditions. The standard potential of the acid, E0

HA, depends on the pKa of the acid and the standard potential for proton reduction E0

H+ for the specific solvent: In this context, it should be noted that the glassy carbon electrode, which is employed in this work, also catalyzes the reduction of protons, however only at very negative potentials.

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2 Mimicking the Dibasic Properties of the [FeFe] Hydrogenase [2Fe]H Subsite (paper I-III)

As mentioned in section 1.3.2, the [FeFe] hydrogenase active site could contain an azadithiolate (adt) cofactor which would most probably function as a proton relay to the iron centres.78 As a result of the electron donating cyanide ligands, the diiron centre in the active site can also be identified as a basic site where the proton can add in an oxidative fashion to form a hydride. The proposed dibasic property of the active site was mimicked in a model complex that is at the heart of the present chapter.

2.1 Introduction Various interesting synthetic [Fe2(�-adt)(CO)6] model complexes have been prepared (See section 1.4.1).46,48 The azadithiolate functionality presents these complexes with a basic site that is not present in the all-carbon pdt bridged analogues. The ability to protonate the adt nitrogen results in milder potentials required for the electrocatalytic production of hydrogen compared to the [Fe2(�-pdt)(CO)6] complex.69

The introduction of trimethylphosphine ligands at the diiron core has been a popular method to mimic the electron donating cyanide ligands in the [FeFe] hydrogenase active site (See section 1.4.2). Using this approach, the electron density at the diiron core is sufficiently increased to allow for the oxidative addition of a proton to the diiron bond to form a bridging hydride (FeII-H-FeII). As the proton reduction in the hydrogenases assuredly follows an ionic mechanism, it may be expected that the enzymatic reaction involves a terminal and not a bridging hydride. However, it has been shown by computational studies that a Fe2(�-H) species may also be a possible intermediate in the catalytic cycle.32 Furthermore, the bridging hydride has been identified in the functionally related [NiFe] hydrogenase.79

Prior to the publication of paper I, there was no example of a model complex in the literature that contains the azadithiolate functionality and an electron rich diiron centre (created by electron donating PMe3 ligands) at the same time. Since we expected that such a complex with two basic sites would have interesting properties, we ventured into the synthesis of complex 1.

27

2.2 Synthesis Complex 3 in Scheme 5 was prepared according to the literature protocol in which complexes with the azadithiolate moiety are prepared from primary amines and Fe2S2(CO)6.

46,48,69 Bis(chloromethyl)amine 2 was added spoon wise without further purification to a solution of freshly prepared [Li2Fe2S2(CO)6] in THF at -78°C under an atmosphere of argon. Purification by column chromatography using hexane/toluene (90/10) as eluent and subsequent recrystallization from hexane gave pure complex 3 in 68% yield. Complex 1 was prepared by the addition of 10 equivalents of PMe3 into a solution of 3 in hexane. After stirring at room temperature under a nitrogen atmosphere for 3 hours, complex 1 is obtained as a dark red precipitate. Complex 1 is fairly oxygen sensitive and purification by column chromatography is difficult due to degradation on the silica gel. Sufficiently

pure samples can however be obtained by washing with cold hexane and recrystallization from toluene-hexane to yield complex 1 in 91% yield. Single crystals suitable for X-ray diffraction analysis were prepared by evaporation of a toluene-hexane solution during the course of 10 min.

The X-ray structure of 1 reveals that the Fe cations are coordinated in an edge-bridged bi-square-pyramidal geometry and that the distance between the two iron centres is 2.55 Å (Figure 5). Moreover, the two PMe3 ligands are positioned in a mixed basal/apical arrangement.

Scheme 5. Synthesis of 1.

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2.3 Characterization of the Protonation States The reactivity of complex 1 towards acids of different strength was studied by a number of different analytical techniques. As a result of our design with the azadithiolate functionality and the electron rich diiron centres, a doubly protonated species [1HHy]2+ can be obtained. Complex 1 is the first [FeFe] hydrogenase active site model complex which can simultaneously carry a proton at the adt nitrogen as well as a bridging hydride at the diiron core. Remarkably, it was found that two singly protonated states can selectively be prepared, one where the adt nitrogen is protonated ([1H]+) and a second which contains a bridging hydride ([1Hy]+). In total, four protonation states can thus be prepared instead of the three states that are usually expected from a diprotic acid. The four protonation states were characterized experimentally by 1H-NMR, 31P-NMR, FTIR and X-ray absorption spectroscopy where structural features of the states were elucidated in detail, and theoretically by DFT calculations.

O1

C31

C32

C1

C21

P1 S2

C6

Fe1

C33

C23

C11

N10

C17

P2

C2

C12

C16

O2

C22

Fe2

C5

S1 C4

C13

C3

C15

O3

O4

C14

Figure 5. ORTEP view (50% probability ellipsoids) of 1.

29

As stated in section 1.5.2, FTIR spectroscopy is a powerful tool to follow chemical transformations in the complexes that are discussed in this thesis. Figure 6 shows the four different protonation states together with their respective IR spectrum. Addition of one equivalent of trifluoromethane sulfonic acid (HOTf) or perchloric acid to a solution of 1 in acetonitrile results in the formation of [1H]+. The IR spectrum of [1H]+ shows that the CO stretching frequencies are shifted by ��CO � 16 cm-1 towards higher energy compared to 1. A similar shift of the CO bands can be found in the

literature upon addition of acid to other model complexes bearing the azadithiolate functionality.46,69 The doubly protonated species [1HHy]2+ is formed in high concentrations of HOTf and the IR spectrum is shifted by another ��CO � 80 cm-1. This major shift is a result of the decreased electron density at the diiron core as expressed by a change of the formal oxidation state of the bridging hydride complex to FeII-FeII. Addition of a nitrogen base such as triethanolamine or triethylamine to a solution of [1HHy]2+ does not produce the unprotonated starting material, but the second singly protonated state [1Hy]+ in which the bridging hydride is still present. This observation proofs that the bridging hydride is inert towards nitrogen bases. Non-protonated complex 1 can however be recovered quantatively by treatment of [1Hy]+ with tetrabutylammonium chloride. The extraordinary finding of

Figure 6. IR spectra of the four protonation states 1, [1H]+, [1Hy]+ and [1HHy]2+. Grey dashed traces show the spectra of the preceding state in clockwise order.

30

the two singly protonation states can be explained by the kinetically slow protonation and deprotonation of the Fe-Fe bond. The pKa values of the different states were determined from deprotonation experiments with appropriate bases in acetonitrile solutions. This study resulted in the conclusion that the [1Hy]+ state is the thermodynamically more stable (pKa = 15) of the two singly protonated species while [1H]+ is a metastable (pKa = 12), kinetically favoured intermediate. It was also found that the tautomerization from [1H]+ to [1Hy]+ is catalyzed by hydrochloric acid. The use of hydrohalic acids seems to facilitate the hydride formation compared to non hydrohalic acids, even if those are stronger. This effect can be explained either by the fact that hydrohalic acids HX are sterically less demanding or by a mechanism where the nucleophilic halide is transiently coordinating to the Fe-Fe centre and thereby promotes the hydride formation.

All protonation states were exhaustively characterized by 1H- and 31P{1H}-NMR (Figure 7). In the 1H-NMR spectrum of 1, the signals of the trimethylphosphine protons reveal (Figure 7a) that complex 1 exists in two isomeric forms in solution. From density functional theory (DFT)

Figure 7. 1H-NMR and 31P-NMR spectra of the four protonation states:1, [1H]+, [1Hy]+ and [1HHy]2+ in CD3CN. a) 1H-NMR spectra of the PMe3 protons. b) 31P-NMR spectra. c) 1H-NMR spectra of the bridging hydride region.

31

calculations it was deduced that the major isomer is the one in which both PMe3 ligands occupy basal positions. Thus, 1 has a different conformation in the solid state than in solution at room temperature. The 1H- and 31P-NMR spectra of [1H]+ and [1HHy]2+ show (Figure 7a, b) clearly that the protonation of the adt nitrogen hinders the inversion of the six atom membered azametalloheterocycle which results in two non-equivalent Fe(CO)2PMe3 units. Consequently, the trimethylphosphine protons in the 1H-NMR spectra of [1H]+ and [1HHy]2+ feature as two doublets due to the coupling to the two non-equivalent phosphorus centres while the 1H-NMR spectra of 1 and [1Hy] + show only one such doublet . In analogy, the 31P-NMR spectra of 1 and [1Hy]+ show one phosphorus signal while the spectra of [1H]+ and [1HHy]2+ show two phosphorus resonances. The bridging hydride can be observed at a very typical chemically shift in the 1H-NMR spectra of [1Hy]+ and [1HHy]2+ (Figure 7c). In the spectrum of [1Hy]+, the hydride features as a triplet since it couples to the two equivalent phosphorus atoms while in the spectrum of [1HHy]2+ the hydride resonance signal yields two doublets as a result of the broken symmetry discussed above. It was confirmed that the hydride resides in the expected bridging position from the 31P-NMR spectra as both of the phosphorus signals in the spectrum of [1HHy]2+ show coupling to the hydride. Further evidence was obtained from a two-dimensional 1H-31P NMR correlation (HMQC) study of [1HHy]2+ which showed that the hydride couples to both phosphorous centres. The basal/basal conformation of the PMe3 ligands in the [1Hy]+ and [1HHy]2+ were deduced from the large JH-P coupling constants (� 21-23 Hz).

The EXAFS experiments gave a slightly shorter Fe-Fe bond distance (~2.53 Å) of complex 1 compared that found in the crystal structure of 1 (2.55 Å). Another interesting finding that was obtained from the EXAFS measurements concerns the Fe-Fe bond distances in the four different

Figure 8. The Fe-Fe bond distances in the four protonation states 1, [1H]+, [1Hy]+ and [1HHy]2+ revealed by EXAFS analysis (solid circles, left y axis) and DFT calculations (open squares, right y axis). See paper III for details.

32

protonation states of 1. The largest prolongation of the Fe-Fe bond is already observed upon protonation of the adt nitrogen of 1 (to form [1H]+) and not as one would probably assume upon the formation of the bridging hydride. Similar results were obtained theoretically from DFT calculations (Figure 8). In the [1Hy]+ and [1HHy]2+ states, a slight decrease of the Fe-Fe distance was observed both in the EXAFS experiments and in the DFT calculations. The relative changes of the Fe-Fe distances observed in the EXAFS experiments are in very good agreement with the values calculated by DFT, recognizing the strength when both techniques are used in parallel.

Summarizing the EXAFS and DFT results, the most prominent structural changes seem to occur already during the transition from 1 to [1H]+. The longer Fe-Fe distance together with a change in the coordination geometry around the Fe centres from a nearly trigonal-bipyramidal iron coordination in 1 to a nearly square pyramidal coordination in [1H]+ renders the Fe-Fe bond more accessible for protonation and may explain the tautomerization from [1H]+ to [1Hy]+.

2.4 Electrochemistry and Electrochemical Proton Reduction

The differential pulse voltammograms (DPV) of 1, [1H]+, [1Hy]+ and [1HHy]2+ are presented in Figure 9. Compared to the hexacarbonyl analogue, 69 the reduction of 1 (Epc = -2.18 V vs. Fc+/0) is shifted by 0.65 V towards more negative potential as a result of the electron donating phosphine ligands. Upon protonation of the azadithiolate nitrogen (from 1 to [1H]+), the reduction potential (Epc = -1.57 V vs. Fc+/0) is shifted by 610 mV to milder potentials. As an effect of the protonation of the Fe-Fe bond, the reduction of the [1Hy]+ state (Epc = -1.10 vs. Fc+/0) is facilitated by 1.08 V. In

Figure 9. Left: Differential pulse voltammograms of 1, [1H]+, [1Hy]+ and [1HHy]2+ in acetonitrile. Right: Cyclic voltammograms (� = 0.100 V/s) in acetonitrile solution of [1H]+: 1 (1 mM) with HClO4 (10, 20, 35, 60, 90 mM).

33

the transition from [1Hy]+ to [1HHy]2+ (Epc = -0.96 V), the reduction potential is shifted by only 150 mV. This small effect caused by the protonation of the azadithiolate nitrogen of [1Hy]+ shows that this second protonation is electronically localized on the adt nitrogen and only weakly communicated to the Fe-Fe core, the electron density of which is already low due to the FeII-(μ-H)-FeII state. However, as an effect of the dibasic property, the reduction of [1HHy]2+ occurs at very mild potential compared to that of other [FeFe] hydrogenase model complexes.

When the mild reduction potential of [1HHy]2+ was observed, it was intriguing to investigate if the [1HHy]2+ state is electrocatalytically active. Unfortunately, no electrocatalytic behavior on the cyclic voltammetry timescale was observed for neither [1HHy]2+ nor [1Hy]+ (at 1.0 V and -1.1 V, respectively). However, for [1H]+, catalytic proton reduction could be demonstrated by cyclic voltammetry (Figure 9) as increasing peak currents around -1.5 V were observed with increasing concentration of HClO4. Bulk electrolysis was carried out in parallel and hydrogen could be detected by gas chromatography (GC). Performing the same experiment under conditions that facilitate the formation of [1HHy]2+, low catalytic turnover (1-2 turnovers) was observed. One interpretation of this result is that the low turnover frequency is caused by the slow formation of the bridging hydride which was found to be below 1 M-1s-1. In contrast to this explanation is the observation that the formation of the hydride is fast with hydrohalic acids, even on the voltammetric timescale, but no significant change in turnover rate was observed in the bulk electrolysis experiments when a mixture of HClO4 and HCl was used. It was thus concluded that the turnover rate is limited by another step in the catalytic cycle.

2.5 Conclusions A model complex of the [FeFe] hydrogenase [2Fe]H subsite with dibasic properties has been synthesized. The four protonation states 1, [1H]+, [1Hy]+ and [1HHy]2+ could be prepared selectively and studied by XAS, IR and NMR spectroscopy. It was found that among the two single protonated states, the hydride [1Hy]+ state is the thermodynamically more stable product while the protonation of the azadithiolate nitrogen to form the metastable [1H]+ is kinetically favored. [1HHy]2+ is the first mimic which can hold a proton and a hydride simultaneously. In the EXAFS experiments it was found that there is a lengthening of the Fe-Fe bond already upon protonation of the adt nitrogen. A similar observation, i.e. a substantial lengthening of the Fe-Fe bond upon exposure to acidic media (or the absence thereof) in the natural [FeFe] hydrogenase [2Fe]H subsite could indicate if the bridging dithiolate consists of an all carbon-based or an azadithiolate cofactor.

34

The low catalytic turnover frequency observed for [1HHy]2+ is presumably not due to slow hydride formation, but the existence of another rate limiting step. This step may be the intramolecular reaction between the proton and the hydride or a slow release of molecular hydrogen from the catalyst. From a mechanistic viewpoint, the presence of the bridging hydride instead of a terminal coordination hinders fast catalysis for two reasons: i) the hydride is too far from the proton on the adt nitrogen to be able to efficiently form a bond intramolecularly and ii) the reactivity of the bridging hydride with protons is decreased compared to that of the terminal one.68 Based on this reasoning, it is assumed that the catalytic proton reduction shown by the [1H]+ state does not involve an intramolecular hydride-proton step but a bimolecular reaction. Such an intermolecular reaction can either occur with protons from the bulk or from the reaction between two catalyst complexes.

35

3 Mimicking the Labile Ligand in the [FeFe] Hydrogenase [2Fe]H Subsite (paper IV)

As stated in section 1.3.2, the labile ligand in the [FeFe] hydrogenase [2Fe]H subsite is crucial for the function of the enzyme. In the present chapter, the synthesis and the characterization of a model complex which contains such a labile ligand is presented.

3.1 Introduction The electrochemical behaviour of the hexacarbonyl model complex [Fe2(�-pdt)(CO)6] has been investigated numerous times and it has been shown that its reduction triggers severe structural rearrangements that ultimately lead to the formation of a tetranuclear complex.80-84 The iron centres in [Fe2(�-pdt)(CO)6] are coordinatively saturated (each Fe having 18 valence electrons) and to be able to bind two-electron ligands such as a hydride or a dihydrogen ligand, one iron centre must first shed a ligand. Further evidence for the importance of the labile/vacant site is the loss of enzyme activity in the presence of exogenous CO.30 It has therefore been suggested in this context that a complex which bears a sacrificial ligand that dissociates upon reduction to create a coordinatively unsaturated complex could be an efficient proton reduction catalysts.35 To some extend, such behaviour would resemble the activation step of the [FeFe] hydrogenase enzyme where it is believed that an aqua ligand dissociates after a one-electron reduction (See section 1.3.2). To construct a complex that mimics this feature is of course difficult as the hemistable ligand is only supposed to leave after reduction, but be stable in the neutral state to allow for the isolation and characterization of the starting complex.

Primary amines such as n-propylamine have been used as decarbonylation agent to facilitate ligand substitution in the synthesis of [2Fe]H subsite model complexes of the general formula [Fe2(�-S2R)(CO)5(L)].85,86 In the search for complexes with labile ligands the idea arose to isolate the decarbonylated “intermediate” of the substitution reaction. This complex will bear a labile ligand, presumably an n-propylamine, which evidently is easily expelled and substituted by other ligands.

36

3.2 Synthesis Complex 5 was prepared from [Fe2(�-pdt)(CO)6]

38 (4) by refluxing the latter in n-propylamine for 6 hours (Scheme 6). Remarkably, the n-propylamine substituted product is fairly stable in non-coordinating solvents and can be isolatated in 43% yield after purification by column chromatography and

recrystallization from hexane. Similar ligand exchange reactions in various mixtures of THF and n-propylamine were performed, produced however lower yields of 5. The structure of complex 5 was confirmed by X-ray diffraction analysis (Figure 10) which shows that an n-propylamine ligand is coordinated to one of the Fe centres in a basal position. This arrangement is different to that of other mono-substituted complexes like [Fe2(�-pdt)(CO)5(CN)]-, for which the lowest energy conformer was calculated to be the one where the cyanide ligand occupies an apical position. The isomer in which the newly introduced ligand coordinates in a basal position as in 5 was found to have the highest energy of all four possible isomers.87 The

orientation of the incoming ligand in monosubstituted [Fe2(�-pdt)(CO)5(L)] complexes thus seems to vary.88 Furthermore, monosubstituted complexes

Scheme 6. Synthesis of complex 5.

Figure 10. ORTEP view (50% probability ellipsoids) of complex 5. Selected bond lengths (Å): Fe1-Fe2 2.5480(6), Fe1-S1 2.2750(9), Fe1-S2 2.2550(7), Fe2-S1 2.2301(9), Fe2-S2 2.2453(7), Fe2-N1 2.067(2).

37

have been suggested to stabilize the highly desired entatic state that arises from the rotation of either the Fe(CO)3 or the Fe(CO)2L unit depending on the donor property of the ligand L.63

The Fe-Fe bond distance in 5 is similar to that in 1 (~2.55 Å) and thus slightly longer than the distance found in the parent hexacarbonyl complex (~2.51 Å).52

3.3 Electrochemistry and Infrared Spectroscopy As mentioned above, complex 5 exhibits a fairly high stability in non-coordinating solvents. In a coordinating solvent such as CH3CN, complex 5 is however expended and a new species 6 is formed. This transformation can

be followed by IR spectroscopy which shows the consumption of 5 during the course of 2 hours when dissolved in acetonitrile (Figure 11). Since the IR spectrum of the new species 6 has a similar CO band pattern as complex 5, it was concluded that no major structural changes occur during the transformation. It was suggested that the n-propylamine ligand is substituted by an acetonitrile solvent molecule. Further proof for this assignment was obtained from an experiment where an IR spectrum identical to that of 6 was obtained when a solution of Fe2(�-pdt)(CO)6 in acetonitrile was reacted with the decarbonylation reagent Me3NO (1 eq.). Complex 5 could be fully recovered by the addition of excess n-propylamine to an acetonitrile solution of 6. It thus seems that there is an equilibrium between 5 and 6 and that this equilibrium is shifted towards species 6 in acetonitrile solution (Scheme 7).

Figure 11. Spectral changes in the carbonyl region upon the transformation of 5 into 6 in acetonitrile solution.

38

Various attempts to isolate complex 6 have been made by us and others89, however without any success. This failure to isolate 6 is presumable not caused by weaker iron-ligand bond strength, but by the reactivity of the coordinated acetonitrile towards nucleophiles. As the IR spectrum of 6 is shifted towards higher energy compared to that of 5 it can be concluded that the n-propylamine has a stronger electron donating effect than the CH3CN ligand. Whereas the �-donor strength of both ligands may be comparable, CH3CN is certainly a better �-acceptor, making it overall a weaker donor ligand. This effect was also observed in the cyclic voltammograms (Figure 12) of 5 and 6 where the reduction of complex 5 (Epc = -1.80 V vs. Fc+/0) occurs at more negative potentials then the reduction of 6 (Epc = -1.68 V vs. Fc+/0). Remarkably, the cyclic voltammograms of both 5 and 6 show

chemical reversibility of the electrochemically triggered processes. In contrast, Fe2(�-pdt)(CO)6 undergoes irreversible structural changes in order to stabilize the lower oxidation states after reduction.81 The re-oxidation of both of the reduced species of 5 and 6 occurs at the same potential

Scheme 7. The equilibrium between 5 and 6.

Figure 12. Cyclic voltammograms (0.100 V/s) of 5 (a, obtained in a presence of n-propylamine and 6 (b) in CH3CN.

39

(Epa = -1.28 vs. Fc+/0), suggesting that the reductions of 5 and 6 lead to the same species.

Further evidence for this hypothesis was obtained from FTIR-spectroelectrochemistry (SEC) (Figure 13) which made it apparent that

Figure 13. IR spectrum of complex 5 (a) and 6 (b) before (dashed line) and after (solid line) electrochemical reduction. Grey traces show the difference spectra during the course of the electrolysis.

Scheme 8. Proposed (electro)chemical transformations upon reduction of 5 and 6.

40

indeed the same species is formed after reduction of 5 and 6. The exact structure of this species is difficult to deduce solely from the FTIR-SEC data. The FTIR-SEC spectra however reveal one certain (and exciting) detail: the FTIR-SEC spectrum of the reduced species shows a weak absorption at 1699 cm-1 which is characteristic for a carbon monoxide ligand that is bridging the two Fe centres. Furthermore, it is plausible to suggest that both complexes (5 or 6) loose the labile ligand after the reduction in order to stabilize the additional electron density. Based on this reasoning and the results from FTIR-SEC and cyclic voltammetry structure 7- was suggested as the structure of the reduced species. (Scheme 8). Structure 7- is a 35 electron, unsaturated complex, where one of the iron centres inevitably has a 17 electron configuration.

More recently, Best and Pickett published a study that focused on the reduction chemistry of [Fe2(�-edt)(CO)5(NCMe)] (edt = ethane-1,2-dithiolate), obtained by treatment of a CH3CN solution of [Fe2(�-pdt)(CO)6] with Me3NO. Not surprisingly, [Fe2(�-edt)(CO)5(NCMe)] shows the same electrochemistry and SEC as 6-. In contrast to our work, however, Pickett and co-workers were able to isolate single crystals of the reduced edt-analogue.90 X-ray diffraction analysis of this reduced complex reveals that a diamagnetic tetranuclear complex with the structure 82- is actually obtained after reduction (Scheme 9). Considering the spectroscopic similarities between 82- and the reduction product of 5 and 6, one has to admit that the proposed structure 7- is incorrect and at best an intermediate towards the final reduced state 82-. In contrast to 7-, structure 82- describes a coordinatively saturated system in which each iron satisfies the 18-electron rule.

Scheme 9. Product obtained from the one electron reduction of [Fe2(�-edt)(CO)5-(NCMe)] (ref 90).

41

3.4 An Analogue Bearing the Azadithiolate Functionality (Unpublished)

From the interesting findings in connection with complex 5, we were intrigued to attempt the synthesis of an azadithiolate analogue of 5, namely [Fe2(�-SCH2N(CH2Ph)CH2S)(CO)5(H2NPr)] (9). Unfortunately, under the same reaction conditions as those employed for the synthesis of 5, the reaction using [Fe2(�-SCH2N(CH2Ph)CH2S)(CO)6] (3) led only to decomposition products. 9 was however prepared with modest success using trimethylamine oxide as decarbonylation reagent followed by the addition of

n-propylamine. Purification by column chromatography and recrystallization gave single crystals of 9 with very low overall yield (~1%). A substantial amount (58%) of the parent hexacarbonyl complex was however recovered. Single crystal X-ray diffraction reveals that the n-propylamine ligand in 9 resides in an apical position (Figure 14). Again, the orientation of the incoming ligand seems difficult to be foreseen. Experimental details are found in Appendix I. Due to the low availability of 9, further characterizations and functional studies were impeded.

3.5 Conclusions Model complex 5 with an in this context unusual amine ligand has been synthesized. In acetonitrile solution, ligand substitution by a solvent molecule (to form 6) illustrates the labile character of the amine ligand. The

S1N1

Fe2

N2

Fe1

S2

Figure 14. ORTEP view (50% probability ellipsoids) of complex 9. Selected bond lengths (Å): Fe1-Fe2 2.522(11), Fe1-S1 2.288(10), Fe1-S2 2.294(13), Fe2-S1 2.304(14), Fe2-S2 2.287(17), Fe2-N1 2.070(16).

42

facile substitution of the n-propylamine ligand makes complex 5 a useful precursor for the synthesis of other asymmetric complexes.

Complexes 5 and 6 show an interesting electrochemical behaviour where the reduction of each compound is associated with the loss of the labile ligands n-propylamine and MeCN, respectively. This process is chemically reversible upon re-oxidation. FTIR-spectroelectrochemistry shows that the reduction products of 5 and 6 are identical and that this species contains a bridging carbonyl ligand. The loss of the labile ligand upon reduction together with the presence of a bridging carbonyl ligand has resemblance to the enzyme active site, although the latter operates in different oxidation states.

43

4 Tuning the Electronic Properties of [FeFe] Hydrogenase [2Fe]H Subsite Model Complexes (Papers V and VI)

This chapter will describe the efforts to tune the electronic properties of model complexes of the [FeFe] hydrogenase [2Fe]H subsite. The work is focused on model complexes with aromatic bridging dithiolate ligands and the hypothesis that electronically different dithiolate ligands should have an impact on the reduction potentials of the corresponding complexes. In one case, the tuning of the ligand by certain substituents resulted in proton reduction catalysis at an overpotential that is lower than that required by the non-substituted parent compound. Furthermore and in analogy to the work described in Chapter 2, electron donating phosphine ligands were introduced into the complexes to make the diiron centres more basic.

4.1 Introduction Complex [Fe2(�-bdt)(CO)6] (bdt = benzene-1,2-dithiolate) (20) has been the subject of several investigations. It has been established that 20 can undergo a reversible two-electron reduction. One Fe-S bond in the thereby produced dianionic species is cleaved and a carbonyl ligand has moved into a bridging position, giving 202- a lower symmetry compared to the mother complex (Scheme 10).91,92 The reduction occurs at a relatively mild potential (E1/2 = -1.31 V vs. Fc+/0).i The mild reduction potential has been explained by the

i Value obtained in our laboratory, Capon et al. have reported E1/2 = -1.27 vs. Fc+/0 (ref. 72) and Felton et al. have reported E1/2 = -1.32 vs. Fc+/0 (ref. 92).

Scheme 10. Proposed structural changes upon reduction of [Fe2(�-bdt)(CO)6].

44

ability of the benzenedithiolate ligand to buffer electronic changes to some extend. This is achieved by the interaction between the sulfur p� orbitals and benzene p� orbitals which minimizes the energy changes upon reduction.93-95 Capon et al. have shown that 20 catalyzes the reduction of p-toluenesulfonic acid (HOTs) at rather mild potentials (ca -1.3 V).72 In addition, Felton et al. have reported the electrocatalytic reduction of weaker acids such as AcOH at mild overpotential.96 Based on these encouraging reports, we embarked on the synthesis of a series of electronically-differentiated dithiolate bridging ligands and their Fe2(CO)6 complexes. In addition, phosphine ligands were introduced during the syntheses of [Fe2(�-S2Ar)(CO)4(PMe3)2] analogues, in order to obtain more basic diiron centres (as described for complex 1 in Chapter 2). [Fe2(�-S2R)(CO)6] model complexes that hold various aromatic bridging dithiolate ligands (R = quinoxaline-2,3-dithiolate, closo-o-carborane-1,2-dithiolate, benzene-1,2-dithiolate, toluene-3,4-dithiolate and 3,6-dichloro-benzene-1,2-dithiolate) were synthesized, together with the dinuclear [Fe2(�-S2R)(CO)4(PMe3)2] and mononuclear [Fe(S2R) (CO)2(PMe3)2] analogue complexes.

4.2 Synthesis and Characterization Quinoxaline-2,3-dione (11) is prepared by a condensation reaction between benzene-1,2-diamine and diethyloxalate following the procedure of Lin97

(Scheme 11). Chlorination with thionyl chloride98 gave 2,3-dichloroquinoxaline (12) in 76% yield. Compound 12 was treated with thiourea and subsequent hydrolysis gave quinoxaline-2,3-dithiol (13) in 80% yield.99

Scheme 11. Synthesis of quinoxaline-2,3-dithiol (13).

45

1,2-(SH2)-closo-C2B10H12 (14)100, kindly provided by the group of C. Viñas and F. Teixidorii is perhaps somewhat unusual in this context since is structurally unrelated to the classical, benzene-derived aromatics 13 and 15-17. It has however the same spatial requirement as a spinning benzene and has electronically been described as a unit that can be regarded as a benzene of strongly electron-deficient character

The Fe2CO6 complexes were synthesized in the usual fashion by separately refluxing 13-17 together with Fe3(CO)12 to give the respective [Fe2(�-S2R)(CO)6] complexes 18, 19, 2091,101, 2139,56 and 22 (Scheme 12). The lower yields obtained in the syntheses of complexes 18, 19 and 22 can

be explained by the electron withdrawing effect of the bridging dithiolate ligand which weakens the Fe-S bonds. All complexation reactions were carefully monitored by TLC and the reactions were immediately stopped when all Fe2(CO)12 starting material had been consumed.

The IR spectra of complexes 18-22 show similar patterns of the CO bands. It is however also evident that the spectra are considerably shifted relative to each other (Figure 15). This shift is entirely a result of the different electronic properties of the bridging arenedithiolate ligands as electronic properties of the ligand will influence the electron density around the diiron centre by charge delocalization. As stated before (Section 1.6.2), the electron density at the diiron centre determines the extent of backbonding into the �* CO-orbitals which affects the CO stretching frequencies in the IR

ii Campus U.A.B., Bellaterra, Barcelona, Spain.

Scheme 12. The synthesis of complexes 18 – 22.

46

spectrum. From the comparison between the IR spectra of complexes 18–22 it can be concluded that the carborane cluster has the most prominent electron-withdrawing character amongst the ligands 13–17, while ligands 15 and 16 are the least electron-withdrawing. The inductive effect of the chlorine substituents of the 3,6-dichloro-benzene-1,2-dithiolate ligand gives rise to a shift of the CO stretching frequencies of 22 by �CO � 6 cm-1 to higher energies compared to those of complex 20. The quinoxaline-2,3-dithiolate ligand showed an additional electron withdrawing effect compared to 3,6-dichloro-benzene-1,2-dithiolate ligand as the corresponding CO bands of complex 18 are shifted to higher energies by �CO � 3 cm-1 compared to the carbonyl stretching frequencies of 22. The complex with the most electron withdrawing ligand of the series is however the carborane complex 19, the IR frequencies of which are shifted by another ~7 cm-1 compared to those of 22.

Complexes 18–22 were characterized by 1H and 13C NMR and the NMR data for 21 and 22 where in agreement with literature. Noteworthy is that the electronic effect of the bridging ligands also affects the resonance frequencies of the carbonyl carbons. The 13C NMR spectra of 19, 18, 22 and 21 showed the carbonyl carbon signal at � = 205.3, 206.4, 206.9 and 207.7 ppm, respectively.

The structures 19 and 22 were determined by single crystal X-ray diffraction analysis (Figure 16). In the comparison of the structures of 19, 20101, 2156 and 22, no significant relationship between the Fe-Fe distance and the electron withdrawing character of the bridging ligand can be found. The Fe–CCO and the C–O bond distances were however shown to be affected by the electronic property of the bridging arenedithiolate ligand. For example the Fe–CCO and C–O bond distances of 20 (daverage � 1.792(8) and daverage � 1.135(8), respectively) can be compared to the ones of complex 19 (daverage � 1.799(17) and daverage � 1.124(11), respectively). This is consistent with the result from the IR spectra of 19 and 20 and the discussion in Section

Figure 15. The IR spectra (carbonyl region) of complexes 18 (dotted), 19 (black solid), 20 (light grey) and 22 (dark grey).

47

1.6.2. Less backbonding into the �* CO orbital leads to higher bond order and shorter bond distance of the CO bond while the Fe–CCO bond order decreases and the bond is lengthened.

Complexes 18, 20, 21 and 22 were treated with PMe3 in a similar fashion as in the synthesis of 1 in Chapter 2 (Scheme 13). Interestingly, not only the expected disubstituted, dinuclear products (23–26) were obtained but also

the corresponding mononuclear by-products 27, 28102, 29, 30. The products were successfully separated by flash column chromatography and purified further by recrystallization from toluene-hexane solutions. From the column chromatography of each reaction mixture, a white solid was obtained that was identical irrespective of the reaction from which it was isolated. Single

SS

Fe

COOC

Me3P PMe3hexane

+ + [Fe(CO)3(PMe3)2]

S S

Fe FeOC

COOC CO CO

COS S

Fe FeOC

COMe3P CO CO

PMe3

N N

Cl Cl

25 (26%)

24 (50%)26 (27%)

23 (30%)

R=

PMe3

N N

Cl Cl

29 (21%)

28 (25%)30 (34%)

27 (27%)

R =

N N

Cl Cl

21

2022

18

R =

Scheme 13. The synthesis of complexes 23 – 30.

Cl1

O4

O6

C8

C4

S1

C6

C9

C7

O2

Fe2

C2

C10

C12

Fe1C5

C11

C1 S2

O5

O1

C3

Cl2

O3

O3

C3

O6

S2

B8

C6

B9

O1C1

C8

Fe1

B2

B7

B6

Fe2

C2

C5

B10

B3

O5

O2

C7

B1

S1

C4

B5

B4

O4

Cl1

O4

O6

C8

C4

S1

C6

C9

C7

O2

Fe2

C2

C10

C12

Fe1C5

C11

C1 S2

O5

O1

C3

Cl2

O3

O3

C3

O6

S2

B8

C6

B9

O1C1

C8

Fe1

B2

B7

B6

Fe2

C2

C5

B10

B3

O5

O2

C7

B1

S1

C4

B5

B4

O4

Figure 16. ORTEP view (50% probability ellipsoids) of complex 19 (left) and 22 (right).

48

crystal X-ray diffraction analysis of this solid revealed that it is [Fe(CO)3(PMe3)2].

Noteworthy is that the ligand substitution reactions went to completion within 10–90 min (10 min in the synthesis of 23 and 27). This is considerably faster then the corresponding reaction of related [Fe2(�-pdt)(CO)6)] (6) and trimethylphosphine where refluxing overnight is required to afford [Fe2(�-pdt)(CO)4(PMe3)2].

55 The dinuclear 23–26 and mononuclear 27–30 complexes were fully

characterized by 1H, 13C and 31P NMR. Every 1H NMR spectrum of 23–26 shows only one doublet for the methyl protons of the PMe3 ligands, thus pointing towards a symmetric coordination of the two phosphine ligands to the diiron site in solution. This assignment is also supported by the corresponding 31P NMR spectra which featured only one signal for the two equivalent phosphines. The 13C NMR spectra of 23–26 exhibit doublets for the carbonyl carbons that arise from the coupling to the phosphorous centers at the same Fe(CO)2(PMe3) subunit. The NMR spectra of the mononuclear complexes 27–30 are somewhat more complicated to elucidate. For example, in the 1H NMR spectra of 27–30, the methyl protons give rise to triplet signals. The triplet signals are explained by the phenomenon called virtual coupling.103-105 This effect arises when the methyl protons of the trimethylphosphine ligand are almost equally strongly coupled to a second phosphorus centre. In other words, it occurs when the 2J (P,P) between two equivalent phosphorus nuclei is large. A large coupling is given in the conformation where the two phosphine ligands are trans to each other. The virtual coupling was not only shown in the 1H NMR spectra but also in the 13C NMR spectra of 27–30 where the PMe3 carbon resonances also appear as virtual triplets. Moreover, the carbonyl carbons feature as triplets in 27, 28 and 30 and as two triplets in 29. The 31P{1H} NMR spectra show singlet resonances for all mononuclear complexes. In summary, the NMR data thus

Figure 17. The IR spectra (carbonyl region) of complexes 23 (black), 26 (dark grey) and 24 (light grey).

49

indicate that the PMe3 ligands are in trans conformation in complexes 27–30.

The IR spectra of the dinuclear complexes 23–26 follow the same trend as those of the hexacarbonyl complexes 18, 20–22. The �-quinoxaline-2,3-dithiolate ligand displays once more the strongest electron withdrawing character of the bridging arenedithiolate ligands as the carbonyl bands in the IR spectrum of 23 are found at highest energy. (Figure 17) The same findings were obtained from the IR spectra of the mononuclear complexes 27–30 (Figure 18).

Solid state structures of several dinuclear and mononuclear complexes, namely of 23, 24, 26, 27 and 28 were obtained by the X-ray diffraction analysis. The X-ray structures of 23 and 24 are shown in Figure 19. The structure of complex 23 reveals a somewhat distorted �-quinoxaline-2,3-

dithiolate moiety which may be explained by the steric demand of the bulky PMe3 ligand in apical position. The X-ray structures of 26, 27 and 28 are

O1

C1

O2

C16

N2

C2

S2

C7

C15

C17

Fe1

O4

C18

C4P1

C14

C6

C12

C11

Fe2

C9

C13

N1

S1

C5

C3

P2

O3

C10

C8

O2

C7

C2

C5

O4

S2

P1

C15

C4

Fe1

C16

C9

C14

C1

C6

Fe2

C11

O1

C13

P2

S1

C12

C3

C8

C10

O3

a) b)

O1

C1

O2

C16

N2

C2

S2

C7

C15

C17

Fe1

O4

C18

C4P1

C14

C6

C12

C11

Fe2

C9

C13

N1

S1

C5

C3

P2

O3

C10

C8

O2

C7

C2

C5

O4

S2

P1

C15

C4

Fe1

C16

C9

C14

C1

C6

Fe2

C11

O1

C13

P2

S1

C12

C3

C8

C10

O3

O1

C1

O2

C16

N2

C2

S2

C7

C15

C17

Fe1

O4

C18

C4P1

C14

C6

C12

C11

Fe2

C9

C13

N1

S1

C5

C3

P2

O3

C10

C8

O2

C7

C2

C5

O4

S2

P1

C15

C4

Fe1

C16

C9

C14

C1

C6

Fe2

C11

O1

C13

P2

S1

C12

C3

C8

C10

O3

a) b)

Figure 19. Thermal ellipsoid representations (50% probability) of the molecular structures of (a) 24 and (b) 23.

Figure 18. The IR spectra (carbonyl region) of complexes 27 (black), 30 (dark grey) and 28 (light grey).

50

shown in Figure 20. The X-ray structure of complex 26 shows the co-crystallization of two isomers. These are treated separately in Figure 20a. The isomers differ mainly in the orientation of the trimethylphosphine ligands. In 26(ap,ap), both phosphine ligands reside in apical positions, whereas in 26(ap,ap), one PMe3 ligand is in a basal orientation. Crystallographic data together with tables of selected bond distances and angles for all solid state structures are presented in Paper VI.

4.3 Electrochemistry

4.3.1 Electrochemical Behaviour

From the IR spectra of complexes 18–22 it was concluded that the closo-o-carborane-1,2-dithiolate, quinoxaline-2,3-dithiolate and 3,6-dichloro-benzene-1,2-dithiolate ligands are more electron withdrawing compared to the benzene-1,2 dithiolate and toluene-3,4-dithiolate ligands. As this effect

C3

O1

S1

N1

C2

C7

C1

P1

C5

C6

C8

C4

Fe1

C4

C6

C8

C5

P1

C1

C2

C7

N1

S1

O1

C3

C5

O2

S2

C2

C3

P1

C13

C7

C14

C12

C4

Fe1 P2

C9

C1

C11

S1 C6

C10

O1C8

Cl2

C5

O2

C7

C2

P1

C15

S2

O4

C14

C16

Fe1

C4

C6 C9

C1

C13

C11

Fe2

O1

C12

S1P2

C3

C10

C8

Cl1

O3

Cl1

O3

C8

C7

C3

C5 C10

S1

C12

P2

P1

C11

C13

Fe2

C6

C9

C4

Fe1

C16

C14

O4

C15

C1 S2

C2

O1

O2

Cl2

a)

b) c)

C3

O1

S1

N1

C2

C7

C1

P1

C5

C6

C8

C4

Fe1

C4

C6

C8

C5

P1

C1

C2

C7

N1

S1

O1

C3

C5

O2

S2

C2

C3

P1

C13

C7

C14

C12

C4

Fe1 P2

C9

C1

C11

S1 C6

C10

O1C8

Cl2

C5

O2

C7

C2

P1

C15

S2

O4

C14

C16

Fe1

C4

C6 C9

C1

C13

C11

Fe2

O1

C12

S1P2

C3

C10

C8

Cl1

O3

Cl1

O3

C8

C7

C3

C5 C10

S1

C12

P2

P1

C11

C13

Fe2

C6

C9

C4

Fe1

C16

C14

O4

C15

C1 S2

C2

O1

O2

Cl2

a)

b) c)

Figure 20. Thermal ellipsoid representations of the molecular structures of (a) the two isomers of 26 (30% probability), 26ap,ba (left) and 26ap,ap (right), (b) 27 (50% probability) and (c) 28 (30% probability).

51

has already been observed by IR spectroscopy, an influence on the reduction potential of the complexes can also be expected. The cyclic voltammograms of 18, 20, 21 and 22 are shown in Figure 21. The cyclic voltammograms show that the reductions of 18 (E1/2 = -1.18 V vs. Fc+/0) and 22 (E1/2 = -1.20 V vs. Fc+/0) are shifted to milder potentials by 130 mV and 110 mV,

respectively, compared to that of 20. This is again a result of the electronically different bridging ligands. Felton et al. have shown that the reduction of 20 is a case of potential inversion which means that the second reduction step is thermodynamically more favourable then the first one.92 From the shape of the cyclic voltammograms, it is likely that the reductions of 18 and 20-22 also follow a similar potential inversion mechanism. Controlled-potential coulometry reveals that the reductions of 18, 21 and 22 are indeed two-electron processes.

The cyclic voltammogram of 19 (Figure 22) is vastly different from that of 18, 20, 21 and 22. Instead of the potential inversion behaviour, complex

Figure 21. Cyclic voltammograms of 18 (cyan trace), 20 (green trace), 21 (red trace) and 22 (navy blue trace).

Figure 22. Cyclic voltammograms of 19 (second scans).

52

19 exhibits two well-resolved one-electron reductions. The cyclic voltammogram features a reversible reduction at E1/2 = -0.88 V vs. Fc+/0 followed by a second wave at Ep

c = -1.13 V vs. Fc+/0. The second reduction is not totally reversible and a shoulder emerges in the re-oxidation scan at -0.6 V vs. Fc+/0. Compared to the CV of 20, the first reduction of 19 is shifted to more positive values by almost 400 mV, reflecting the strong electron-withdrawing character of the closo-o-carborane-1,2-dithiolate ligand. The difference in electrochemical behaviour in the comparison between 19 and 20 is not completely understood. The structural changes upon reduction of 20 that are presented in Scheme 10 do probably not apply for 19. Since the first reduction is a reversible one-electron process, it can be assumed that on the timescale of the voltammetry experiment no structural reorganizations takes place that would enable a second reduction under the same or more positive potential. One possible explanation is that the carborane ligand offers much better electron delocalization so that no structural changes are necessary to stabilize the mono-reduced diiron site.

Similar electrochemical behaviour as exhibited by 19 has also been found in the cyclic voltammograms of a related [Fe2(�-bpdt)(CO)6] (bpdt = biphenyl-2,2’-dithiolate) where two separate one-electron reductions are found in the cathodic scan.106 The cyclic voltammetric data for 18–22 are compiled in Table 1.

Table 1. Cyclic voltammetric data (vs. Fc+/0) for 18, 19, 20, 21 and 22.

18 19a 20 21 22 cpE (V) -1.22 -0.93 -1.36 -1.37 -1.23

apE (V) -1.13 -0.83 -1.27 -1.29 -1.16

redE 2/1 (V) -1.18 -0.88 -1.31 -1.33 -1.20

cp

ap ii / 0.79 0.98 0.96 0.98 0.97

a) First wave

53

Compared to the hexacarbonyl complexes 18, 20, 21, and 22, the reductions of the dinuclear complexes 23–26 are shifted by about 800 mV towards more negative potentials as a result of the electron donating trimethylphosphine ligands (Figure 23). Again, the electron withdrawing character of the �-arenedithiolates in 18 and 22 results into a shift towards milder potentials compared to the reductions of 20 and 21. The electrochemical reversibility seen in 18, 20, 21, and 22 is lost upon the introduction of the phosphine ligands.

4.3.2 Electrochemical Proton Reduction

Proton reduction catalysis by complex 22 was investigated by cyclic voltammetry. It was found that the peak current increases with increasing concentration of trifluoromethanesulfonic acid (HOTf) in acetonitrile, indicating that proton reduction is indeed operating. Further evidence for the catalytic activity of complex 22 was obtained from controlled potentiometry where an acetonitrile solution of 22 and an excess of perchloric acid were electrolyzed at -1.28 V vs. Fc+/0 (Figure 24). The rate of electrolysis decreases after a while as the system is depleted of protons, but can be recovered to some extend by the addition of more perchloric acid. After 2150 seconds, the charge that has passed through the cell is equivalent to circa 40 turnovers. The solution was checked by IR spectroscopy before and after the experiment and it was concluded that more then 40% of complex 22 were still intact after the electrolysis. Hydrogen gas was measured by gas chromatography where the amount of produced hydrogen was calculated to be equivalent to >38 turnovers (>0.23 mmol). The very similar turnover values that were obtained from coulometry and gas chromatography demonstrate that the faradaic yield of the electrocatalysis experiment is very high.

Figure 23. Cyclic voltammograms of 23 (cyan trace), 24 (green trace), 25 (red trace) and 26 (navy blue trace).

54

Unfortunately, no catalysis could be established from the cyclic voltammograms of 26 with increasing concentrations of trifluoro-methanesulfonic acid (HOTf) (Figure 25). Instead, it is believed that the Fe-Fe bond is protonated and it is the reduction of the protonated species that features in the cyclic voltammograms at -1.07 V vs. Fc+/0. The protonation of the Fe-Fe bond by HOTf was confirmed by IR spectroscopy.

Figure24. Coulometry for the bulk electrolysis at -1.28 V vs. Fc+/0 of an acetonitrile solution (containing 0.1 M TBAPF6) of HClO4 (100 mM) at a glassy carbon electrode (A = 0.7 cm2) in the presence (2 mM, solid trace) and absence (dashed trace) of 22. HClO4 was added at 650 and 1500 s with the purpose of recover the initial acid concentration of 100 mM. Solution volume: 3 mL; total cell volume: ~200 mL Unpublished results.

Figure 25. Cyclic voltammograms of 26 (2 mM) in the presence of trifluoromethanesulfonic acid (0–14 mM).

55

The cyclic voltammograms of 19 together with HOTf are shown in Figure 26. From the doubling of the peak current of the first reduction event, it is evident that the mono-reduced species 19– can be protonated once to form 19H. The protonated species is then reduced a second time to 19H– at the same potential as the reduction of 19. Unfortunately, it seems that the double-reduced, mono-protonated 19H– is not basic enough to be protonated a second time. No catalysis could therefore be demonstrated from the cyclic voltammetry experiments of complex 19.

4.4 Conclusions The effects that the electronically different ligands 13–17 exhibit on the corresponding complexes [Fe2(�-S2R)(CO)6] 18–22, [Fe2(�-S2Ar)(CO)4-(PMe3)2] 23–26 and [Fe(�-S2Ar)(CO)2(PMe3)2] 27–30 were studied in detail. The electron withdrawing character of the bridging dithiolate ligands 13, 14 and 17 have a marked influence on the IR and NMR spectra as well as on the X-ray structures and the cyclic voltammograms. In summary, a more electron withdrawing dithiolate ligand results in IR spectra with higher energy CO stretching frequencies, shorter CO bonds, longer Fe–CCO bonds and anodically shifted reduction potentials. All the results are coherent in that the order of electron withdrawing character of the ligands is: closo-o-carborane-1,2-dithiolate > quinoxaline-2,3-dithiolate > 3,6-dichloro-benzene-1,2-dithiolate > benzene-1,2 dithiolate > toluene-3,4-dithiolate.

In more general terms, it became apparent from our study that higher energy CO frequencies in the IR spectrum are associated with milder reduction potentials. A graph which correlates the three wavenumber maxima observed in the CO region of the IR spectra of five [Fe2(�-

Figure 26. Cyclic voltammograms of 19 (3 mM) in the presence of trifluoromethanesulfonic acid (0–12 mM).

56

SRS)(CO)6] complexes with their first reduction potential is presented in Figure 27. From an inspection of Figure 27 it can be concluded that there is a linear relationship between wavenumber of the CO stretching modes and the first reduction potential of the [Fe2(�-SRS)(CO)6] type complexes.

As a result of the inductive effect of the two chlorine substituents on the ligand of 22, the reduction potential and thus the potential for

electrocatalytic proton reduction is shifted by 130 mV towards milder potentials compared to that shown for complex 20. Complex 22 was also shown to be a robust catalyst in controlled electrolysis experiments. Since it catalyzes proton reduction at mild potentials and is fairly easy to synthesize, complex 22 is a good candidate for future molecular assemblies that are aiming towards light-driven hydrogen production (see also Chapter 5).

Figure 27. Correlations between the reduction potential Ep,c and the three wavenumber maxima ( , �, �) observed in the CO region of the IR spectra of five [Fe2(�-SRS)(CO)6] complexes. R = carborane (19), benzene (20), CH2N-(PhBr)CH2,

85 CH2N(CH2PhBr)CH2,69 and propane (5) (in order of increasingly

negative reduction potential). dEp,c/d�max � 25 ( ), 34 (�), 42 (�) mV / cm-1.

57

5 Towards Light-driven Electron Transfer and Hydrogen Generation from an [FeFe] Hydrogenase Active Site Mimic Covalently Linked to a Ruthenium Photosensitizer

As outlined in Section 1.2, our long term goal is to construct a bio-mimetic supramolecular system for light-driven hydrogen production. In this line of work, a functional molecular assembly which consists of an [FeFe] hydrogenase active site mimic and a photosensitizer is highly sought-after. In this chapter we describe our synthetic efforts towards such a ruthenium-diiron dyad. Experimental details are found in Appendix II.

5.1 Introduction There are only a few examples in the literature where a diiron dithiolate model complex is covalently linked to a photosensitizer with the aim to realize the light-driven reduction of protons. These so-called dyads are frequently based on ruthenium photosensitizers ([Ru(bpy)3]

2+ or [Ru(tpy)2]

2+) and diiron complexes with azadithiolate (adt) or propanedithiolate (pdt) ligands.85,107-110 In addition, reports by Song and co-workers have focused on porphyrins as alternative photosensitizers111,112 However, in none of these dyads, electron transfer could convincingly be established, let alone hydrogen production be observed. This failure to be a functional system is mainly caused by the redox properties of the photosensitizer and the diiron complex which are such that the forward electron transfer (ET) reaction is thermodynamically impossible. The driving force for reductive ET from a photosensitizer to an acceptor can be calculated from the Rehm-Weller equation113:

where E0(P+/0) is the oxidation potential of the photosensitizer, E0(A0/-) is the reduction potential of the acceptor and E00 is the energy of the excited state. Although ET in the ruthenium-diiron systems in the literature is impossible from the excited state, the dyads could probably still show electron transfer from the photosensitizer to the acceptor (the diiron complex), albeit by a

00/00/ )()( EAEPEG −−=Δ −+ ��

58

different mechanism. This mechanism makes use of an additional redox reaction that takes place prior to the ET step that involves the photosensitizer and the diiron site. This additional step is the reductive quenching of the excited state of the photosensitizer by an external and often sacrificial donor. The thereby generated photo-reduced sensitizer is a stronger reducing agent than the excited state and is thus capable to transfers its excess electron to the acceptor in a dark reaction. Such a mechanism has recently been used in a bimolecular approach where hydrogen was generated with 4.3 turnovers using a diiron complex as catalyst, Ru(bpy)3 as photosensitizer and ascorbic acid as sacrificial donor.114 In order to obtain better control of the electron transfer rates and in order to prevent potential competing side reactions such as energy transfer (EnT), one should strive for covalently linked systems. For this reason, our ambition is to design and to synthesize covalently linked molecular systems for the reduction of protons. Furthermore, we strive to drive the ET from the excited state of the photosensitizer, omitting the need for a preceding reductive quenching. Employing such a strategy, we also preserve the property of our photosensitizer to provide the oxidation power for the oxidation of water in a complete molecular system as the one described in Section 1.2. We have therefore focused our work on covalently linked dyads where direct electron transfer is feasible.

5.2 Design As stated in Section 4.3.2, complex 22 ([Fe2(�-3,6-dichloro-benzene-1,2-dithiolate)(CO)6] catalyzes the reduction of protons at relatively mild potential and thus fulfills the fundamental requirement to be employed in a potentially functional dyad. In addition, the robustness with which the proton reduction catalysis occurs is another appealing aspect that makes electron-deficient arenedithiolate complexes interesting acceptor unit in a molecular assembly.

In a separate line of work, a new class of photosensitizers, namely Ru(dqp)2

2+(dqp = 2,6-di(8’quinolinylpyridine), with unprecedented long excited state lifetimes (up to 3 �s) and suitable redox properties (E1/2(Ru(dqp-OMe)2

3+/2+ = 0.56 V vs. Fc+/0)115 has recently been prepared in our Department.116,117 According to the Rehm-Weller equation, the electron transfer from the excited-state of Ru(dqp-OMe)2

2+ to 22 is estimated to be favourable by 40 meV. Moreover, the Ru(dqp)2

2+ complexes give isomer-free and rod-like arrays when functionalized in the para positions of the central pyridines. This is a great advantage over the well know [Ru(bpy)3]

2+ (bpy = 2,2’-bipyridine) complexes which give isomeric mixtures when employed as the central unit in covalently linked multi-unit systems. An isomeric mixture of compounds complicates the analysis of the electron transfer kinetics tremendously.118

59

We decided to focus our synthetic work on the assembly of a Ru(dqp-OMe)2

2+ photosensitizer to a diiron benzenedithiolate model complex such as 22. The methoxy- substituents at the dqp ligands were chosen because they provide convenient synthetic handles as well as they render the Ru complex a stronger excited state reducing agent. Having decided on the exact nature of the two redox centres, the bridging unit had to be designed. In general, a somewhat linear and rigid geometry is desirable to avoid complications due to conformational flexibility. In order to electronically decouple the ruthenium from the diiron site and to keep the electronic properties of the Ru photosensitizer undisturbed, the introduction of a saturated methylene group at the oxypyridine seemed desirable. Finally, according to chapter 4.4, it was established that electron-deficient arenedithiolates promote the reduction of protons at mild potential and are thus also essential. Taking all of these considerations into account, we decided on a tetrafluorobenzyl unit as a suitable bridging group. In the following chapter, a number of different synthetic approaches to the resulting target compound 31 are discussed.

5.3 Synthetic Progress Towards a Ruthenium-Diiron Dyad

One obvious synthetic pathway to complex 31 utilizes the chlorine substituents of 22 as a synthetic handle for further functionalization. The linking can potentially be realized by the Suzuki-Miyaura cross-coupling reaction where a aryl-boronic acid is reacted with an aryl-halide under palladium(0) catalysis.119 In this cross-coupling reaction, one chlorine substituent is replaced by the tetrafluorobenzyl bridging unit (Scheme 14). The Suzuki-Miyaura reaction (Route A) requires however somewhat electron rich aryl-boronic acids and/or aryl-halides with more reactive bromide or iodide substituents. The cross-coupling reaction was therefore first tested using complex 22 and pentaflourophenylboronic acid (Scheme 15). Several protocols were employed, including Pd(PPh3)4/Ag2O/K3PO4, Pd(dba)2/K3PO4/S-Phos and Pd(dba)2/K3PO4/X-Phos in a number of different solvents (DMF, THF and toluene).120 The result was however always similarly disappointing since no product was ever obtained. Other palladium mediated reactions like the Negishi cross-coupling protocol121 were also tried using 1,4-dibromotetrafluorobenzene and 22 (n-BuLi/ZnCl2/Pd(dba)2/S-Phos). After an extensive search to finding suitable reaction conditions without any positive results, we changed our focus on alternative strategies for the synthesis of 31.

60

In order to increase the reactivity of the diiron site in cross-coupling reactions, diiron complexes with a bromine or iodine functionalized benzenedithiolate ligand were targeted. Second, another route was identified

where a trimethylsilyl substituted benzenedithiolate diiron complex (32) can potentially be reacted with [Ru(dqpOMe)(dqp-OCH2-C6F5) ](PF6)2 (33) in the presence of CsF or KF (Scheme 14, Route B).

Following Route A, a diiron complex with a bromine or iodine substituted benzenedithiolate ligand had to be synthesized. After many ill-fated attempts, our efforts were finally met with success (Scheme 16). 4-bromo-1,2-diiodobenzene (34) was obtained from 4-bromobenzene-1,2-diamine via

Scheme 14. Retrosynthesis of target complex 31.

Scheme15. The attempted cross-coupling of 22 and pentaflourophenylboronic acid.

61

the Sandmeyer reaction in 11% yield. The palladium-catalyzed synthesis of the silyl-protected benzenedithiol was carried out according to a procedure adopted from Kreis and Bräse.122 In situ deprotection by tetrabutyl-ammonium fluoride and immediate complexation by Fe3(CO)12 gave 36 in 14% yield over three steps. Even though the reactivity of the bromine substituent was envisaged to be much higher than that of the chloride, still no product could be obtained from the reaction of 36 with pentaflourophenylboronic acid, using Pd(dba)2/K3PO4/X-Phos in toluene.

This reaction is currently attempted using other protocols. In an approach towards the target dyad following Route B, the diiron

complex 32 was synthesized according to Scheme 17. Crude 3-(trimethylsilyl)benzene-1,2-dithiol (37) was prepared from 1,2-benzenedithiol according to a slightly modified literature procedure.123 Heating ligand 37 together with Fe3(CO)12 in THF for 25 minutes gave complex 32 in 14% yield over three steps. Route B was tried on a very small scale where a THF solution of complex 32 and 33 together with potassium

H2N NH2 acetic acid

1) NaNO2/H2SO42) KI/H2O

1) 10 mol% Pd(PPh3)4,Cs2CO3, toluene, 100 °C, 24 h2) TBAF, THF, reflux, 1h

Fe3(CO)12

THF, reflux, 30 min

S S

Fe FeOC

COOC CO CO

CO

Br

I I

Br

BrHS SH

Br

HS Si+

34

35

34

36 Scheme 16. Synthesis of bromo-substituted diiron complex 36.

Scheme 17. Synthesis of TMS-substituted diiron complex 32.

62

fluoride (sprayed-dried) and Kryptofix 222 was heated to 80 °C.124 The reaction was followed by LC-MS which clearly showed the molecular mass of a product of type 31 with the usual isotope pattern of a Ru complex. However, due to the small scale of the reaction and the absence of more of the reaction partner 33, further analytical data of the reaction product remained elusive.

5.4 Conclusions Major ground work has been laid towards the synthesis of dyad 31. With the two diiron complexes 32 and 36 together with the ruthenium building blocks, two promising routes towards 31 have been identified and explored. It is now the time to perform these reactions on larger scales, to obtain larger quantities of 31 and to study its potential in light-driven ET processes and ultimately the light-driven reduction of protons. Efforts in these directions are subject of on-going works.

63

6 Isotope-labelled, Mixed-Valent Fe(I)-Fe(II), Model Complexes

Most known model complexes are prepared in the Fe(I)-Fe(I) state while higher oxidation states have been identified in the active oxidized state of the enzymatic catalytic cycle. This chapter focuses on model complexes from which the Fe(I)-Fe(II) state can be generated by chemical or electrochemical oxidation. The oxidation states of these complexes are studied by electrochemistry, FTIR and EPR spectroscopy. Experimental details are found in Appendix III.

6.1 Introduction As described in Section 1.4.2, Pickett and co-workers have explored a complex (i) which can be oxidized to a semi-stable Fe(I)-Fe(II) state (ii) (Scheme 18).60 The greater stability of the oxidized state compared to those of other model complexes such as [Fe2(�-pdt)(CO)6] is due to the pendant thioether ligand which dynamically coordinates to one of the iron centres and compensates for the electron loss after oxidation of the diiron centre.

The structure of ii has been elucidated from FTIR spectroscopy and, with the cyanide ligands, the {Fe2S3} core and a bridging carbonyl ligand, it has been found to be one of the closest mimics of the CO-inhibited state of the [2Fe]H subsite, Hox(CO). The Fe(I)-Fe(II) state, ii, is paramagnetic and has been investigated by EPR spectroscopy. The observed g values are fairly similar to the ones found for Hox(CO).125,126 A complex (39 in Scheme 20) that contains a similar thioether moiety as the one reported by Pickett, but

Scheme 18. Oxidation of an diiron complex with a pendant thioether ligand

64

that includes a nitrogen heteroatom in the azadithiolate bridging ligand has been reported by Rauchfuss and co-workers.47 This complex however lacks electron donating ligands and was prepared for a different purpose than that discussed within this chapter.

As outlined in Section 1.3., the nature of the central atom of the bridging dithiolate ligand is still an unanswered question. ENDOR spectroscopy is an advanced EPR method that may provide the answer to this problem as it can identify nuclei that show weak interactions with the electron spin. During ENDOR studies of the natural system, our collaborators around Prof. Wolfgang Lubitz at the Max Planck Institute for Bioinorganic Chemistry have recently discovered a coupling of the Fe(I)-Fe(II) spin with an unidentified nitrogen heteroatom127 and suggested that this nitrogen is the one in the dithiolate bridge. In order to validate this hypothesis, we have initiate a project with the aim to prepare defined model complexes in the Fe(I)-Fe(II) state that contain the adt nitrogen.

Since we strive to discover a weak coupling of the unpaired spin with the bridge “N”, we decided to mimic the electron-donating cyanide ligands by electronically similar trimethylphosphine ligands. Furthermore, in order to distinguish the different couplings, it is very helpful to prepare and to study a set of isotope labelled complexes. A 15N-labeled analogue of 40, namely 41, is therefore highly desirable (Scheme 19). The identity of the coupling to the

-S-CH3 protons in 40 can unambiguously be identified by deuterium labelling and the -S-CD3 analogue 42 is thus also a valuable target. Moreover, the cyanide analogue of 43 is also a possible target for comparison and later studies.

6.2 Synthesis and Characterization Complexes 39 and 40 (Scheme 20) were prepared in a procedure that is similar to that used for the syntheses of complexes 3 and 1 in Section 2.2 (See Appendix III for experimental details). Complex 40 was fully

Scheme 19. Target complexes 40, 41, 42 and 43.

65

characterized by NMR and FTIR spectroscopy, LC-MS, elemental analysis and X-ray diffraction analysis. The X-ray structure of 40 bears resemblance

to the structure of 1, as both complexes show the apical-basal arrangement of the trimethylphosphine ligands (Figure 28). The Fe-Fe bond distance of 40 (2.58 Å) is only slightly longer than that of complex 1 (2.55 Å).

For the syntheses of the isotope-labelled complexes 41 and 42, the respective 2-(methylthio)ethylamine was prepared. Methylation of cysteamine by CD3I

O2

C5

C8

C2

C7 C10

S2P1

C12

P2Fe1

C9

C13

N1

C6

C1

C14

Fe2

S3

O1

C4

C11

S1

C3

O4

C15

O3

Figure 28. OTEP view (ellipsoids at 50% probability level) of 40. Selected bond lengths [Å]: Fe(1)–Fe(2) 2.578(3), Fe(1)–S(1) 2.263(7), Fe(1)–S(2) 2.260(7), Fe(2)–S(1) 2.254(7), Fe(2)–S(2) 2.254(7).



66

affords 2-(methyl-d3-thio)ethylamine (44) in 25% yield after extraction and Kugelrohr distillation (Scheme 21).

2-(methylthio)ethyl[15N]amine (45) was synthesized from [15N]-potassium phthalimide and 2-chloroethyl methyl sulphide. The phthalimide

was cleaved by treating 2-(methylthio)ethyl[15N]phthalimide with hydrazine in ethanol and then HCl/H2O (Scheme 22). Complexes 41 and 42 were prepared from the respective amines in the same manner as 40. To our knowledge, complex 41 is the first [2Fe]H model complex with a 15N-azadithiolate ligand.

Moreover, a cyanide analogue of 40 was prepared following the established procedure46,52 in which 39 is reacted with Et4NCN to give 43 in 46% yield.

6.3 Generation and Study of the Fe(I)-Fe(II) state The electrochemical oxidation of complex 40 was studied by cyclic voltammetry at 22 °C and at -40 °C (Figure 29). Whereas the voltammogram at 22 °C shows only one irreversible oxidation, the corresponding experiment at -40 °C shows two oxidations, the second of which is


Figure 29. Cyclic voltammograms of 40. The cyan trace is a second scan, others are first scans.

67

reversible. This electrochemical behaviour of 40 is similar to that of i,60 despite of the change form cyanide to phosphine ligands and from an all-carbon based dithiolate bridge to an adt type ligand. It can thus be safely assumed that the oxidation of 40 leads to structure 40+ where the pendant thioether coordinates to one of the Fe atoms through intermolecular nucleophilic attack (Scheme 23).

Further evidence for the structure of 40+ was obtained when the chemical oxidation of 40 which was monitored by in situ FTIR (Figure 30). The IR spectra show similar features as the one of ii (Scheme 18) with the band at 1770 cm-1 being the characteristic absorption of a bridging carbonyl ligand.

For the preparation of the EPR samples, a solution of 40 in a 1:1 mixture of CH2Cl2 and 2-methyl-THF was oxidized with one equivalent of ferrocenium hexafluorophosphate at -60 °C. The resulting solution was frozen in liquid nitrogen ca 70 s after mixing (see Appendix III for details). Oxidation of 43 was done in the same fashion but was conducted in acetonitrile solution at -40 °C instead.

Figure 30. In situ IR spectra (carbonyl region) of the chemical oxidation of 40 (6 mM) with 1 eq. of FcPF6 at -27°C. Grey thick trace: before addition of FcPF6; thin grey trace: 5 s after addition; thin black trace: 10 s after addition and thick black trace: 15 s after addition.

Scheme 23. Dynamic ligation upon oxidation of 40.

68

The EPR spectra of the oxidation products of 40 (left panel) and 43 (right panel) recorded at 45 K are shown in Figure 31. The spectrum of 43+ shows a rhombic EPR signal with g values of g1 = 2.028, g2 = 2.018 and g3 = 2.006. A similar signal with g values of g1 = 2.017, g2 = 2.006 and g3 = 1.988 was observed by Pickett and co-workers assigned to the Fe(I)-Fe(II) analogous complex.60 The yield for the oxidation of 43 by ferrocenium

hexafluorophosphate was judged to be ca. 20% on the basis of spin quantification.

The EPR spectrum on the left of Figure 31 shows the EPR signal of 40+ with fairly well-resolved hyperfine lines originating from the 31P (I = 1/2) nuclear interaction. The g values (g1 = 2.028, g2 = 2.018 and g3 = 2.008) in the most central part (as indicated in Figure 31) correlate very well with those in the spectrum of 43+. Spin counting gave similar oxidation yield of ~ 20% as for the oxidation of complex 43. It is noteworthy that although the oxidation yield seems low, no Fe(III) EPR signal was observed. EPR samples of the oxidation products of 41 and 42 have also been prepared and are currently investigated using ENDOR spectroscopy.

6.4 Conclusions Complex 40, together with the 15N-labelled analogue 41 and the CD3-substituted 42 have successfully been synthesized. In addition, a cyanide analogue of 40 has been prepared. Chemical and electrochemical oxidation of 40 has been studied by cyclic voltammetry and in situ FTIR and EPR spectroscopy. Oxidation products of 40, 41 and 42 are currently investigated by ENDOR spectroscopy.

Figure 31. EPR spectra of the oxidation products of 40 (left) and 43 (right) recorded at microwave frequency 9.27 GHz; modulation frequency of 100 kHz and amplitude of 5 G; microwave power 6 μW, and T = 45K.

69

7 Concluding Remarks

The present work has contributed to the field of synthetic [FeFe] hydrogenase active site model complexes. A wide scope of subjects, ranging from an investigation of functional and structural details of the active site to the development of bio-inspired proton reduction catalysts has been explored.

The specific conclusions are:

• A dibasic model complex was synthesized and its protonation

states were studied by NMR and IR spectroscopy. Kinetic factures give rise to four discrete protonation states with the twofold protonated state [1HHy]2+ being the first model complex that simultaneously carries a proton at the azadithiolate nitrogen and a bridging hydride at the Fe-Fe bond. Although this species is reduced at very mild potential, no catalysis could be demonstrated that involves the double protonated species. This lack of reactivity may be explained by the slow formation of the hydride or by the distance between the bridging hydride and the azadithiolate proton that may be too far to allow for intramolecular H-H bond formation.

• The first [2Fe]H model complex with an unprecedented amine

ligand was synthesized and studied. The ability of the amine ligand to operate as a labile ligand was shown by IR spectroscopy and cyclic voltammetry. This feature together with the formation of a bridging carbonyl upon reduction have resemblance to the enzyme active site. The complex can be utilized as a precursor in the synthesis of future asymmetric model complexes.

• It was shown that the introduction of electron-withdrawing

substituents at aromatic bridging dithiolate ligands is communicated to the diiron site and results in higher energy IR carbonyl stretching frequencies, anodically shifted reduction potentials, shorter CO bonds and longer Fe–CCO distances. This tuning of the redox properties resulted in an improved diiron

70

dithiolate complex which catalyzes proton reduction at milder potentials than its parent non-substituted complex.

• Two possible synthetic pathways towards a new ruthenium-diiron

dyad were identified and explored. Preliminary experimental data indicate that viable synthetic pathways were established and that the synthesis of the dyad can be accomplished in the near future.

• Mixed valent Fe(I)-Fe(II) model complexes were synthesized that

contain an adt ligand and that are stabilized by an intramolecular thioether coordination. Differently isotope-labelled complexes were synthesized, in particular the unprecedented 15N labelled analogue, with the aim to provide EPR-spectroscopic references that will allow the elucidation of the nature of the central atom in the dithiolate bridge of the [FeFe] hydrogenase active site.

71

Acknowledgements

Ok, I did not do everything myself.... Therefore I would like to express my deepest gratitude to the following people: My supervisor Dr. Sascha Ott for giving me a second chance to become his student, for always having the time for questions and for having patience with me… Prof. Leif Hammarström and Prof. Stenbjörn Styring for rescuing me when things got troublesome and for showing a lot of interest in my work… Dr. Reiner Lomoth for his guidance through the world of electrochemistry… Dr. Gerriet Eilers for finding out a lot about one of my complexes… Prof. Leif Hammarström, Prof. Stenbjörn Styring and Dr. Ann Magnuson for keeping the Consortium and the Department to what it is… Dr. Olof Johansson and Dr. Magnus Anderlund for always having the time to answer questions and for trying to keep the lab in shape… Dr. Ping Huang for all the help with the EPR experiments… The people at the Department of Photochemistry and Molecular Science… The people in the Consortium for making the workshops and meetings to what it is… Michael Jäger for never giving up on the dyad story, for his companionship in Wienna and in New York/Boston and for many laughs… Gustav (Mr endurance) Berggren for his light mood and attitude and for his metal Fridays… The past and present people in our synthesis group… The people at the Organic Chemistry department at Stockholm University and the people at the former Organic Chemistry department at BMC…

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Dr. Jesper (La frog) Ekström who always had time to discuss projects and for the collaborations… Dr. Lars Eriksson for trying hard to keep up and running the diffractometer on the single crystals that I handed over and for his cheerful mood… Dr. Michael Haumann, Dr. Simone Löscher, Dr. Matthias Stein, Dr. Giuseppe Zampella and Prof. Luca de Gioia for nice collaborations… Prof. Wolfgang Lubitz and Dr. Edward Reijerse together with Dr. Erdem Özlen, Dr. Alex Silakov and Dr. Jennifer Shaw for the collaboration in the Fe(I)Fe(II)-project… Prof. Francesc Teixidor and Prof. Clara Viñas for providing the carborane… The administrative staff: Gunilla Hjort, Sven Johansson, Åsa Furberg and Susanne Söderberg… CF Liljewalchs resestipendier who gave me money (three times) for conferences, but not Svenska Kemistsamfundet who never gave me stipends despite faithful membership… My friends (if I have any left after this) for trying to keep me away from the lab time to time… Tack mamma och pappa, ni skämmer alltid bort mig. Jag skulle aldrig klarat det här utan er... Tack syster för att du är en snäll syster mot en jobbig lillebror... Tack familjen Irebo som ställer upp och avlastar lite... Ok, baby...lovade ju att inte skriva något men...tack för att du har haft tålamod med mig under de senaste månaderna. Nu är det din tur, pappa skall bygga koja med Laban! Tack å bock /Lennart

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78

Appendix I

[Fe2(�-SCH2N(CH2Ph)CH2S)(CO)5(H2NCH2CH2CH3)] (9) A 25 mL schlenk tube was charged with [Fe2(�-SCH2N(CH2Ph)CH2S)(CO)6] (3) (0.27 g, 0.56 mmol) and 15 mL of well degassed DCM. Me3NO (0.07 g, 0.6 mmol) was added and the reaction mixture was stirred for 1.5 h under argon atmosphere. n-propylamine (0.35 mL) was added and the reaction mixture was stirred for another hour. The solvents were removed in vacuo and the remaining residue was purified by column chromatography under nitrogen, using degassed toluene/hexane (50/50) as eluent. Starting mtrl. [Fe2(�-SCH2N(CH2Ph)CH2S)(CO)6 ] could be recovered (0.15 g, 55 %). The yielded brown product was recrystallized in degassed pentane which gave brown single crystals of the product (3 mg, 1%). The product was characterized by X-ray diffraction analysis. Initial IR (CH3CN, cm-1): �CO = 2044 (m), 1977 (s), 1954 (sh), 1916 (s).

79

Appendix II

Experimental Section NMR spectra were recorded on a JEOL 400 MHz spectrometer at 293 K. Chemical shifts are given in ppm and referenced internally to the residual solvent signal. Microwave heating was performed in an InitiatorTM single mode microwave cavity at 2450 MHz (Biotage). HPLC-MS data were obtained on a Dionex Ultimate 3000 system on a Phenomenex Gemini C18 column (150 x 3.0 mm, 5μ) coupled to Thermo LCQ Deca XP with electrospray ionization (ESI). Solvents used for HPLC: 0.05 % HCO2H in H2O and 0.05 % HCO2H in MeCN. Materials. All commercially available reagents were used as received unless otherwise noted. The ligands dqpOH and dqpOMe were prepared as described previously.117 Tetrahydrofuran was distilled from sodium/benzophenone ketyl. Cyclohexane was dried over sodium. TMEDA was distilled from CaH2 and stored over activated 4Å molecular sieves. dqp-OCH2-C6F5 To a solution of dqp-OH (0.058 g, 0.166 mmol) in dry THF (3 mL) was added K2CO3 (0.027 g, 0.196 mmol) and pentafluorobenzyl bromide (0.128 g, 0.490 mmol). After stirring for 2d at room temperature, the crude product was purified by column chromatgraphy on silica (Flashmaster EtOAc in hexanes 10 to 90%) to yield dqp-OCH2-C6F5 (0.061 g, 0.115 mmol, 69%). 1H-NMR (400 MHz, CDCl3): δ 8.98 (2H, dd, J = 4.2, 1.8 Hz), 8.29 (2H, dm, J = 7.2 Hz), 8.22 (2H, dd, J = 8.3, 1.8 Hz), 7.87 (2H, dd, J = 8.2, 1.5 Hz), 7.81 (2H, s), 7.64 (2H, dd, J = 8.2, 7.2 Hz), 7.43 (2H, dd, J = 8.3, 4.2 Hz), 5.33 (2H, s). ESI-MS: calc. C30H16F5N3O: 529; found [M+H]+ 530. [Ru(dqpOMe)Cl3] A microwave vial was charged with dqpOMe (0.252 g, 0.694 mmol), RuCl3�xH2O (0.200 g, 0.693 mmol) and EtOH (10 mL), sealed and heated to 120 °C overnight. The solids were filtered from the solution, washed with EtOH and Et2O, and dried in vacuo. Yield: 0.360 g, 91%. [Ru(dqpOMe)(MeCN)3][PF6]2 A suspension of [Ru(dqpOMe)Cl3] (0.31 g, 0.55 mmol) and AgNO3 (0.30 g, 1.8 mmol) in EtOH (10 mL), H2O (2 mL) and MeCN (2 mL) was heated to 80 °C overnight. The mixture was allowed to cool to room temperature, filtered and excess

80

solvent was removed in vacuo. The crude product was purified by column chromatography on silica using MeCN/H2O/sat. aq. KNO3 (40:4:1) as the eluent. After counterion exchange with NH4PF6 and drying in vacuo, a yellow powder was obtained. Yield: 0.350 g, 66 %. 1H NMR (400 MHz, d6-acetone): δ 9.39 (2H, dd, J = 5.1, 1.5 Hz), 8.80 (2H, dd, J= 7.5, 1.3 Hz), 8.77 (2H, dd, J = 8.2, 1.5 Hz), 8.40 (2H, dd, J = 8.2, 1.3 Hz), 8.40 (1H, dd, J= 8.2, 1.3 Hz), 8.00 (2H, dd, J = 8.2, 7.5 Hz), 7.77 (2H, s), 7.76 (2H, dd, J = 8.2, 5.1 Hz), 4.17 (3H, s), 2.59 (3H, s), 2.18 (6H, s). MS (ESI): m/z 253 ([M-2MeCN-2PF6]

2+), 294 ([M-2PF6]2+).

[Ru(dqpOMe)(dqp-OH)][PF6]2 A flask was charged with [Ru(dqpOMe)(MeCN)3][PF6]2 (0.200 g, 0.208 mmol), dqpOH (0.078 g, 0.223 mmol) and n-BuOH (5 mL). The mixture was heated to reflux for 4 hours under a gentle argon flow. The mixture was cooled to room temperature, excess solvent was removed in vacuo. The crude product purified twice by column chromatography on silica using MeCN/H2O/sat. aq. KNO3 (40:4:1) as the eluent. The counterion was exchanged with NH4PF6 and dried in vacuo to give [Ru(dqpOMe)(dqp-OH)][PF6]2 as a red powder. Yield: 0.025 g, 11 %. 1H-NMR (400 MHz, CD3CN): δ 8.13 (2H, dd, J = 5.2, 1.4 Hz), 8.12 (2H, dd, J = 5.2, 1.5 Hz), 8.05 (2H, dm, J = 8.2 Hz), 8.04 (2H, dm, J = 8.2 Hz), 7.74 (2H, dd, J = 7.4, 1.3 Hz), 7.68 (2H, dd, J = 7.4, 1.3 Hz), 7.66 (2H, dm, J = 8.3 Hz), 7.65 (2H, dm, J = 8.3 Hz), 7.42 (2H, s), 7.42 (2H, dd, w = 15.6 Hz), 7.33 (2H, s), 7.06 (2H, dd, J = 8.2, 5.2 Hz), 7.05 (2H, dd, J = 8.2, 5.2 Hz), 4.02 (3H, s). The OH-resonances might be split at 9.15 (0.5H, s br) and 5.97 (0.5H, s br). ESI-MS: found: (calc. C47H32N6O2Ru 813); found: 813 [M-2PF6-H]+; (calc. C47H33N6O2Ru 407); found: 407 [M-2PF6]

2+. [Ru(dqpOMe)(dqp-OCH2-C6F5)][PF6]2 (33) To a solution of [Ru(dqpOMe)(dqp-OH)][PF6]2 (0.045 g, 0.040 mmol) in MeCN (4 mL) was added a solution (0.6 mL) of pentafluorobenzyl bromide (0.107 g in 4 mL MeCN). After the addition of K2CO3 (0.037 g, 0.263 mmol) the mixture was stirred for 1 hour at room temperature. The crude product was poured into aqueous NH4PF6 and CH2Cl2, the organic layer removed and concentrated in vacuo. After purification by column chromatography on silica gel, using a mixture of MeCN/H2O/sat. KNO3 (50:5:0.5) as the eluent, the counterion was exchanged with NH4PF6 to yield pure [Ru(dqpOMe)(dqp-OCH2-C6F5)][PF6]2 (0.047 g, 0.037 mmol, 92 %). 1H-NMR (400 MHz, CD3CN): δ 8.12 (2H, dd, J = 5.2, 1.5 Hz), 8.11 (2H, dd, J = 5.2, 1.5 Hz), 8.06 (2H, dd, J = 8.2, 1.5 Hz), 8.05 (2H, dd, J = 8.2, 1.5 Hz), 7.75 (2H, dm, J = 7.4 Hz), 7.74 (2H, dm, J = 7.4 Hz), 7.67 (2H, dm, J = 8.1 Hz), 7.66 (2H, dm, J = 8.2 Hz), 7.49 (2H, s), 7.78 (2H, dd, J = 8.1, 1.5 Hz), 7.43 (2H, s), 7.43 (4H, m, w = 15.6 Hz), 7.07 (2H, dd, J = 8.2, 5.2 Hz), 7.06 (2H, dd, J = 8.2, 5.2 Hz), 5.48 (1H, d, J = 11.2 Hz), 5.37 (1H, d, J = 11.2 Hz), 4.02 (3H, s). ESI-MS: (calc. C54H33F5N6O2Ru 994); found: 497 [M-2PF6]

2+.

81

3-(trimethylsilyl)benzene-1,2-dithiol (37) Prepared according to modified procedure of Block et al.123,128 Degassed cyclohexane (17 mL), TMEDA (0.174 mL, 17.6 mmol) and 2.5 M n-BuLi (7.0 mL, 17.6 mmol) were added to an argon-filled 100 mL schlenk tube at ambient temperature. After cooling to 0 °C, 1,2-benzenedithiol (0.50 g, 3.5 mmol) was slowly added (as a solution in 10 mL of degassed cyclohexane). The reaction mixture was allowed to warm to ambient temperature and was then stirred for 24 h. Trimethylsilyl chloride (0.156 mL, 12.3 mmol) was added slowly and the reaction was stirred for an additional 12 h. H2O (2 mL) was added and the mixture was concentrated in vacuo. The remaining solid was dissolved in 100 mL of Et2O and the organic phase was extracted with 5% HCl (3 × 100 mL) and washed with brine (2 × 100 mL). The ether solution was dried with Na2SO4 and concentrated in vacuo. The residue was dissolved in absolute MeOH (12mL) and refluxed for 5 h. Solvents were removed in vacuo and the off-white oil was used without further purification. [Fe2(�-3-trimethylsilyl-1,2-benzenedithiolate)(CO)6] (32) Distilled THF (10 mL) and Fe3(CO)12 (0.30 g, 0.60 mmol) were added to the crude product of 37. The reaction mixture was reflux for 25 min, cooled and the solvent was removed in vacuo. Column chromatography (using hexane as eluent) yielded the pure product (204 mg, 0.410 mmol, 12% yield over 3 steps). 1H-NMR (400 MHz, CDCl3): δ = 7.14 (1H, dd, J = 7.3, 1.1 Hz), 6.74 (1H, dd, J = 7.7, 1.1 Hz), 6.60 (1H, dd, J = 7.3, 7.7 Hz), 0.31 (9H, s) ppm; 13C-NMR (100 MHz, CDCl3): δ = 207.7, 153.9, 147.1, 141.5, 132.0, 128.7, 125.9, -0.5 ppm. IR (CH3CN, cm-1): �CO = 2080 (m), 2043 (s), 2003 (s). 4-bromo-1,2-diiodobenzene (34) Sodium nitrate (1.59 g, 23 mmol) was added as a fine grained powder to 11 mL of H2SO4 at 0 °C. After 10 min of stirring, the mixture was heated gradually to 70 °C and then cooled to r.t. 4-bromobenzene-1,2-diamine (1.87 g, 10 mmol) was added to slowly to 15 mL of acetic acid and this mixture was slowly poured to the NaNO2/H2SO4 mixture at 0 °C. After stirring for 20 min at 2 °C, the slurry was poured into a solution of KI in 60 mL of H20 at 60 °C. After 15 min at this temperature NaOH(aq) (26 g in 50 mL of H20) was added. CH2Cl2 (200 mL) was added after cooling and the organic phase was washed with H2O and then with saturated NaHSO3(aq) (3 × 50 mL) and dried with Na2SO4.

1H-NMR (400 MHz, CDCl3): δ = 8.00 (1H, d, J = 2.4 Hz), 7.70 (1H, d, J = 8.4 Hz), 7.16 (1H, dd, J = 8.4, 2.4 Hz) ppm. [Fe2(�-4-bromo-1,2-benzenedithiolate)(CO)6] (36) A 20 mL microwave vial was charged with 4-bromo-1,2-diiodobenzene (0.45 g, 1.1 mmol), Pd(PPh3)4 (0.13 g, 0.11 mmol) and CsCO3 (0.93 g, 2.9 mmol). The vial was sealed and then evacuated and filled with argon. 10 mL of dry toluene (dried over sodium) was added via syringe. The solution was degassed and triisopropylsilanethiol was added via syringe. The mixture was heated stirred at 100

82

°C for 26 h. After cooling, 10 mL of saturated NH4Cl(aq) was added and the reaction contents were extracted with Et2O (2 × 100 mL). The combined organic phases were dried with Na2SO4, filtered and dried in vacuo. The remaining residue was redissolved in distilled THF (12 mL) and TBAF (1.0 M in THF, 2.3 mL) was added via syringe. The mixture was refluxed under argon for 1 h and 15 min, cooled and 10 mL of H2O and 20 mL of CH2Cl2 were added. The organic phase was washed with brine once, dried with Na2SO4, filtrated and concentrated in vacuo. The remaining residue was redissolved in 20 mL of distilled THF and Fe3(CO)12 (0.90 g, 1.8 mmol) was added. The mixture was reflux under argon for 30 min and the solvents were removed in vacuo. ). Purification by column chromatography gave pure product (75 mg, 1H-NMR (400 MHz, CDCl3): δ = 7.25 (1H, d, J = 1.8 Hz), 6.97 (1H, d, J = 8.0 Hz), 6.76 (1H, dd, J = 8.0, 1.8 Hz), 0.31 (9H, s) ppm; 13C-NMR (100 MHz, CDCl3): δ = 207.7, 153.9, 147.1, 141.5, 132.0, 128.7, 125.9, -0.5 ppm. IR (CH3CN, cm-1): �CO = 2080 (m), 2043 (s), 2003 (s). [1] Jäger, M., L. Eriksson, J. Bergquist, O. Johansson, J. Org. Chem. 2007, 72,

10227 [2] Block, E., V. Eswarakrishnan, M. Gernon, G. Oforiokai, C. Saha, K. Tang,

J. Zubieta, J. Am. Chem. Soc. 1989, 111, 658 [3] Ogawa, S., N. Yomoji, S. Chida, R. Sato, Chem. Lett. 1994, 507

83

Appendix III

Experimental Section Thionyl chloride, p-formaldehyde, [15N]-potassium phthalimide (98 atom%), trimethylphosphine, Et4NCN and ferrocenium hexafluorophosphate were purchased from commercial suppliers and were used as received. Tetrahydrofuran was distilled from sodium/benzophenone ketyl under nitrogen atmosphere. Dichloromethane was distilled from calcium hydride under a nitrogen atmosphere. Dimethylformamide was dried over activated 4Å molecular sieves. 1H NMR spectra were recorded on a JEOL Eclipse+ 400 MHz spectrometer (operating at 399.8 MHz) together with the JEOL Delta NMR Processing Software version 4.3. in acetonitrile or chloroform. Residual protic solvent peaks CHCl3 (�H = 7.26 ppm) were used as internal reference. 13C NMR spectra were recorded on the same instrument operating at a frequency of 100.5 MHz using the central signals of CDCl3 (� = 77.16 ppm) as reference signal. 31P NMR spectra were also measured on a JEOL Eclipse+ 400 MHz instrument at 161.9 MHz, with chemical shifts referenced to 85% H3PO4 as an external standard. 2-(methyl-d3-thio)ethylamine (44) A 250 schlenk tube was charged with cysteamine (7.00 g, 91 mmol). After dried in vacuo, the schlenk tube was argon filled and distilled THF (110 mL) was added. The solution was cooled to 0 °C and became a yellow slurry upon slow addition of n-BuLi (2.5 M, 36 mL, 91 mmol). The reaction mixture was stirred at 0 °C for 15 min and CD3I (5.7 mL, 91 mmol) was added. The now clear solution was stirred at room temperature for 10 min and 50 mL of H2O was added. Two spoons of NaCl were added and the solution was reduced by rotary evaporation. The remaining water phase was extracted with 3 × 100 mL of DCM and the combined organic phases were dried with Na2SO4. After filtration and removal of solvent, kugelrohr distillation was performed (60 °C, 15 mbar) to give the pure product 44 (2.15 g, 25%). 1H NMR (400 MHz, CDCl3): δ = 2.87 (2H, t, J = 6.4 Hz), 2.58 (2H, t, J = 6.4 Hz), 1.48 (2H, br s) ppm. 2-(methylthio)ethyl[15N]amine (45) [15N]-potassium phthalimide (7.57 g, 40.7 mmol), 2-chloroethyl methyl sulfide (4.50 g, 40.7 mmol) and KI (500 mg, 3.0 mmol) were added to a 100 mL r.b. flask together with 100 mL of dry DMF. The reaction mixture was stirred at 115 °C for 22

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h under nitrogen atmosphere. The solvent was removed by rotary evaporation and the remaining residue was transferred to a 1 L r.b. and redissolved in 500 mL of absolute EtOH. H2NNH2·H2O (8 mL, 0.15 mol) was added and the reaction mixture was refluxed for 1.5 h. After cooling, 100 mL of H2O was added to the now white slurry. The ethanol solvent was removed by rotary evaporation and 150 mL of 4M HCl was added to the residue. 50 mL of conc. HCl was added and the reaction was refluxed for 30 min, then cooled to 0 °C and filtrated. The filtrate was treated with NaOH(aq) (80 g in 200 mL), extracted with Et2O (4 × 250 mL) and dried with Na2SO4 to yield 0.42 g (~90% pure) of 45. 1H NMR (400 MHz, CDCl3): δ = 2.89 (2H, t, J = 6.4 Hz), 2.59 (2H, dt, J = 6.4, 2.0 Hz), 2.09 (3H, s), 1.54 (2H, br s) ppm. N,N-bis(chloromethyl)-2-(methylthio)ethanamine (38) Adapted procedure from Lawrence et al.47 2-(methylthio)ethylamine (2.52 g, 27.6 mmol) was dissolved in dry DCM (30 mL). p-Formaldehyde (2.07 g, 69 mmol) was added and the slurry was stirred at room temperature for 3 h. The slurry was cooled to 0 °C and thionyl chloride (8.05 mL, 110 mmol) was added slowly. The reaction was allowed to warm to room temperature and was stirred for 1 h. The solvents were removed in vacuo and the crude product was used without any further purification. N,N-bis(chloromethyl)-2-(methyl-d3-thio)ethanamine This compound was synthesized in analogy to the preparation of N,N-bis(chloromethyl)-2-(methylthio)ethanamine (38), starting from 2-(methyl-d3-thio)ethylamine (44) (1.77 g, 18.8 mmol), p-CHO (1.41 g, 47 mmol) and SOCl2 (5.50 mL, 75 mmol). N,N-bis(chloromethyl)-2-(methylthio)ethan[15N]amine This compound was synthesized in analogy to the preparation of N,N-bis(chloromethyl)-2-(methylthio)ethanamine (38), starting from 2-(methylthio)ethyl[15N]amine (45) (115 mg, 1.25 mmol), p-CHO (95 mg, 3.15 mmol) and SOCl2 (0.37 mL, 5.0 mmol). [Fe2(�-SCH2N(CH2CH2SCH3)CH2S)(CO)6] (39) Adapted procedure from Lawrence et al.46 To a 40 mL THF solution of [Fe2S2(CO)6]

129 (0.70 g, 2.00 mmol), super hydride (LiEt3BH, 1M solution in THF, 2.28 mL, 4.3 mmol) was added at -78 °C. After 10 min stirring, N,N-bis(chloromethyl)-2-(methylthio)ethanamine (38) was added slowly as a solution in THF (10 mL). The reaction was stirred at -78 °C for 30 min and was then allowed to warm to room temperature. Solvents were removed in vacuo and the resulting red solid was purified by column chromatography (silica, 20% toluene in hexane). Red solid (0.33 g, 35%). 1H NMR (400 MHz, CDCl3): δ = 3.62 (4H, s), 2.94 (2H, t, J = 7.0 Hz), 2.40 (2H, dt, J = 7.0 Hz), 2.07 (3H, s) ppm.

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[Fe2(�-SCH2N(CH2CH2SCD3)CH2S)(CO)6] Adapted procedure from Lawrence et al.47 To a 40 mL THF solution of [Fe2S2(CO)6]

129 (0.69 g, 2.0 mmol), super hydride (LiEt3BH, 1M solution in THF, 4.30 mL, 4.30 mmol) was added at -78 °C. After 10 min stirring, N,N-bis(chloromethyl)-2-(methyl-d3-thio)ethanamine was added as a solid. The reaction was stirred at -78 °C for 30 min and was then allowed to warm to room temperature. Solvents were removed in vacuo and the resulting red solid was purified by column chromatography (silica, 20% toluene in hexane). Red solid (99 mg, 11%). 1H NMR (400 MHz, CDCl3): δ = 3.62 (4H, s), 2.94 (2H, t, J = 7.0 Hz), 2.40 (2H, dt, J = 7.0 Hz) ppm. [Fe2(�-SCH2[15N](CH2CH2SCH3)CH2S)(CO)6] Adapted procedure from Lawrence et al.47 To a 28 mL THF solution of [Fe2S2(CO)6]

129 (0.42 g, 1.20 mmol), super hydride (LiEt3BH, 1M solution in THF, 0.250 mL, 2.5 mmol) was added at -78 °C. After 10 min stirring, N,N-bis(chloromethyl)-2-(methylthio)ethan[15N]amine was added slowly as a solution in THF (8 mL). The reaction was stirred at -78 °C for 30 min and was then allowed to warm to room temperature. Solvents were removed in vacuo and the resulting red solid was purified by column chromatography (silica, 20% toluene in hexane). Red solid (130 mg, 23%). 1H NMR (400 MHz, CDCl3): δ = 3.62 (4H, s), 2.94 (2H, t, J = 7.2 Hz), 2.40 (2H, dt, J = 7.2, 2.0 Hz), 2.07 (2H, s) ppm. [Fe2(�-SCH2N(CH2CH2SCH3)CH2S)(CO)4(PMe3)2] (40) Fe2(�-SCH2N(CH2CH2SCH3)CH2S)(CO)6] (39) (154 mg, 0.334 mmol) was added to a 10 mL argon filled schlenk tube. Well degassed hexane (5 mL) and trimethylphosphine (400 �L, 3.90 mmol) were added and the reaction mixture was stirred for 3.5 h. The solvent was removed in vacuo and the remaining solid was re-dissolved in degassed hexane, filtrated through a syringe filter and then dried in vacuo. Red solid (176 mg, 95%). 1H NMR (400 MHz, CDCl3): δ = 3.38 (4H, s), 2.84 (2H, t, J = 7.2 Hz), 2.40 (2H, t, J = 7.2 Hz), 2.06 (3H, s), 1.49 (18H, d, JH–P = 8.8 Hz) ppm; 13C NMR (100 MHz, CDCl3): δ = 216.0, 216.2, 57.4, 53.5, 31.6, 20.4, 20.2 (d, JC-P = 28 Hz), 15.6 ppm; 31P NMR (161.9 MHz): δ = 27.2 ppm. Elemental analysis calcd. (%) for C15H29Fe2NO4P2S3: C 32.33, H 5.25; found C 32.08; H, 5.26. IR (CH3CN, cm-1): �CO = 1981 (m), 1943 (s), 1908 (s), 1894 (sh). Direct inlet-ESI-MS: m/z = [Fe2(�-SCH2N(CH2CH2SCD3)CH2S)(CO)4(PMe3)2] (41) This compound was synthesized in analogy to the preparation of Fe2(�-SCH2N(CH2CH2SCH3)CH2S)(CO)4(PMe3)2] (40), starting from Fe2(�-SCH2N(CH2CH2SCD3)CH2S)(CO)6] (66 mg, 0.14 mmol) and trimethylphosphine (150 �L, 1.5 mmol). Red solid (70 mg, 89%). IR (CH3CN, cm-1): �CO = 1981 (m), 1943 (s), 1908 (s), 1894 (sh).

86

[Fe2(�-SCH2[15N](CH2CH2SCH3)CH2S)(CO)4(PMe3)2] (42) This compound was synthesized in analogy to the preparation of Fe2(�-SCH2N(CH2CH2SCH3)CH2S)(CO)4(PMe3)2] (40), starting from Fe2(�-SCH2[

15N](CH2CH2SCH3)CH2S)(CO)6] (70 mg, 0.15 mmol) and trimethylphosphine (150 �L, 1.5 mmol). Red solid (75 mg, 90%). IR (CH3CN, cm-1): �CO = 1981 (m), 1943 (s), 1908 (s), 1894 (sh). [Fe2(�-SCH2N(CH2CH2SCH3)CH2S)(CO)4(CN)2] (Et4N)2 (43) 39 (128 mg, 0.280 mmol) was added to an argon filled 25 mL schlenk tube, containing 10 mL of degassed acetonitrile. Et4NCN (110 mg, 0.70 mmol) was added and the reaction mixture was stirred for 2.5 h. The volume was reduced in vacuo and 10 mL of degassed Et2O was added. The solution was decanted using a pipette and the procedure was repeated once and dried in vacuo. Red solid (58 mg, 46%). 1H NMR (400 MHz, CDCl3): δ = 3.63 (4H, s), 3.16 (16H, br) 2.46 (2H, br m), 2.29 (2H, t, J = 7.2 Hz), 2.04 (3H, s), 1.20 (24H, br) ppm. IR (CH3CN, cm-1): �CO = 2077 (m), 1967 (s), 1924 (s), 1884 (s), 1875 (sh).

Preparation of EPR samples 40+: 40 (1.67 mg, 3·10-6 mol) was added to a degassed solution of DCM and 2-methyl-THF (1:1 mixture, total volume 2.75 mL) under argon atmosphere. The solution was cooled to -60 °C and ferrocenium hexafluorophosphate (1.00 mg, 3·10-6 mol) was added as a solution in degassed DCM (250 �L). Two samples were withdrawn (at t = 20 s and 55 s) using a gastight syringe. During the course of 15 s, each sample was transferred to an EPR tube (cooled to -60 °C) which was then after frozen in liquid nitrogen. 41+ and 42+: Prepared in analogy to 40+. 43+: Prepared in analogy to 40+ but was conducted in acetonitrile solution at -40 °C.

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Swedish Summary

För att kunna minska på utläppen av koldioxid och för att kunna behålla vår livstil är behovet av förnyelsebara energikällor uppenbart. Det finns många tänkbara alternativ och förmodligen kommer, som nu, det framtida energibehovet att täckas av många olika energikällor. Solenergi är, i förhållande till dess stora potential, fortfarande ganska outnyttjad. Ett sätt att fånga solenergi på är att använda sig av solceller, men svårigheten ligger i själva lagringen av energin. Eftersom soljuset fluktuerar måste man hitta ett effektivt sätt att kunna lagra energin på, för att sedan kunna användas t.ex. under vintertid i Sverige. Elektricitet kan lagras i batterier eller omvandlas till mekanisk energi, t.ex. där elektricitet används för att pumpa vatten till en högre nivå. Men dessa lagringssätt är dock inte tillämpbara i ett globalt perspektiv då energin måste kunna distribueras på ett smidigt sätt. En ny energibärare som ersätter olja och el behövs. Framtidens energibärare bör kunna skapas från ett billigt och lättillgängligt ämne och det absolut bästa vore om det kan återanvändas. Vätgas är en ideal energibärare eftersom det

Figur 1. Schematisk bild av ett artificiellt fotosystem.

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enda som skapas under förbränning är vatten. Uttryck som ”vätgasekonomi” (hydrogen economy) och ”vätgassamhälle” talar sitt tydliga språk om

förväntningarna på en ny global energibärare. För att detta skall bli verklighet behövs inte bara stora infrastrukturella förändringar utan en lösning på de två problemen; hur skall vätgasen kunna lagras på ett säkert sätt och hur skall den produceras. Vätgas kan produceras från elektrolys av vatten. Detta är dock inte speciellt effektivt. Ett bättre sätt är att producera vätgasen direkt från solenergin. Att härma nyckelfunktionerna i fotosyntesen kan vara en lösning. Växter sparar solens energi genom att bilda kolhydrater av vatten och koldioxid. Istället för kolhydrater vill vi använda fotosyntesens kemi för att producera vätgas från vatten men hjälp av solljus. Detta kallas för artificiell fotosyntes. För att kunna åstadkomma detta behövs ett system med flera komponenter: en katalysator som kan spjälka vatten, en fotosensiterare som kan fånga solljuset och driva reaktionen samt en del, där protoner kan reduceras till vätgas (Figur 1). Medan de två första komponenterna har sin motpart i den naturliga fotosyntesen, kan funktionen för reduktion av protoner återfinnas hos vissa mikroorganismer. Gemensamt för dessa är att de använder sig av ett enzym som kallas hydrogenas. Genom att härma det aktiva centrumet i detta enzym, som består av ett järn-svavelkomplex (Figur 2), hoppas vi att på syntetisk väg kunna skapa något liknande men med samma funktion. Denna avhandling handlar om just detta. Flertalet biomimetiska järn-svavel komplex har syntetiserats för olika ändamål. Vissa av dessa molekyler är designade för att lösa vissa gåtor hos det naturliga enzymet, medan andra är tillverkade för att kunna reducera protoner till vätgas. Genom syntes av ett speciellt komplex har vi kunnat härma det aktiva centrumets sätt att aktivera sig. Ett annat komplex har visat sig att kunna bära på både en proton samt en metall-hydrid. I detta diprotonerade tillstånd kan komplexet ses som en ögonblicksbild över det aktiva centrumet innan en vätgasmolekyl avgår. I ett försök i att förbättra de katalytiska egenskaparna har flera komplex finjusterats för att kunna generera vätgas vid mildare elektrokemiska potentialer.

Figur 2. Det aktiva centrumet i [FeFe] hydrogenas.

Acta Universitatis UpsaliensisDigital Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Science and Technology 599

Editor: The Dean of the Faculty of Science and Technology

A doctoral dissertation from the Faculty of Science andTechnology, Uppsala University, is usually a summary of anumber of papers. A few copies of the complete dissertationare kept at major Swedish research libraries, while thesummary alone is distributed internationally through theseries Digital Comprehensive Summaries of UppsalaDissertations from the Faculty of Science and Technology.(Prior to January, 2005, the series was published under thetitle “Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Science and Technology”.)

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