The Development of a Diiron Hydrogenase Mimic Catalyst for Efficient Dihydrogen Production

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Master's Theses and Capstones Student Scholarship

Spring 2017

THE DEVELOPMENT OF A DIIRON HYDROGENASE MIMIC CATALYST FOR EFFICIENT DIHYDROGEN PRODUCTION

David S. Danico University of New Hampshire, Durham

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THE DEVELOPMENT OF A DIIRON HYDROGENASE MIMIC CATALYST

FOR EFFICIENT DIHYDROGEN PRODUCTION

David Scott Danico

B.S., Worcester Polytechnic Institute, 2012

Thesis

Submitted to the University of New Hampshire

In Partial Fulfillment of

the Requirement for the Degree of

Master of Science

Chemistry

May, 2017

This thesis has been examined and approved in partial fulfillment of the requirements for the degree of Master of Science in Chemistry by:

Thesis Director, Samuel Pazicni, Associate Professor of Chemistry

Christine Caputo, Assistant Professor of Chemistry

Sterling Tomellini, Professor of Chemistry

On April 14, 2017

Original approval signatures are on file with the University of New Hampshire Graduate

School.

Dedication

To my parents, Scott and Susan, who have given me all their love, support, and encouragement throughout my academic career. Without this, I would never have been able to accomplish all of my goals.

Table of Contents

Dedication ...... iv Table of Figures ...... vii Table of Synthetic Schemes...... viii Abstract ...... ix

Introduction ...... 1 The Threat of Global Warming ...... 1 Alternative Fuels ...... 3 Hydrogenase ...... 8 [FeFe]-Hydrogenase Mimic Catalyst Literature ...... 11 Design of the [FeFe]-Hydrogenase Mimic Catalyst ...... 15

Results and Discussion ...... 20 Objective ...... 20 N-Azadithiolate Diiron Cluster Mimic ...... 20 4-Penten-1-Amine ...... 23 Hydroboration of Terminal Alkyne ...... 23 Hydroboration of Boc Protected 4-Pentyn-1-Amine ...... 24 Alkylation of Ammonia with 4-Penten-1-ol ...... 25 Synthesis of Diiron Cluster with decreased Amine Steric Hindrance ...... 26 Dimethyl Azadithiolate FeFe Cluster ...... 27 Methyl Azadithiolate Diiron Cluster Mimic ...... 27 Swern Oxidation of Terminal Alkene Primary Alcohols ...... 30 Bisbuten Azadithiolate Diiron Cluster ...... 33 Buten Azadithiolate Diiron Cluster ...... 35 Conclusion ...... 36

Experimental Section ...... 37 General Experimental Section ...... 37

Reagents ...... 37 Reactions ...... 37 Chromatography ...... 37 Detailed Experimental Section ...... 38 FeFe cluster mimic ...... 38

a) Fe2S2(CO)6 (1) ...... 38

b) Attachment of N-Allyl Azadithiolate bridgehead to Fe2S2(CO)6 (2) ...... 39

C) Attachment of N-Buten-Azadithiolate bridgehead to Fe2S2(CO)6 (3) ...... 40

D) Attachment of N-Penten-Azadithiolate bridgehead to Fe2S2(CO)6 (4) ...... 40

E) Attachment of N-Hexen-Azadithiolate bridgehead to Fe2S2(CO)6 (5) ...... 41 4-Penten-1-Amine (8) ...... 41 a) Hydroboration of terminal alkyne amine ...... 41 b) Hydroboration of boc protected terminal alkyne amine ...... 42 c) Alkylation of ammonia with 4-penten-1-ol ...... 42 Dimethyl Azadithiolate FeFe Cluster ...... 44 Methyl Azadithiolate FeFe Cluster ...... 44 3-Butenal ...... 45 Allyl Azadithiolate FeFe Cluster ...... 46 4-Pentenal ...... 47 Bisbuten Azadithiolate FeFe cluster ...... 48 Buten Azadithiolate FeFe Cluster ...... 49

List of References ...... 51

Appendices ...... 58 Appendix A: Characterization of Compounds ...... 59

Table of Figures

Figure 1: Global Surface temperature average in relation to the 1951-1980 Average temperatures...... ………………………………….……………….1 Figure 2: 2014 US greenhouse gas emissions…………..………………………………….2 Figure 3: Areas of the US Production of Carbon Dioxide…………………………………..2 Figure 4: Hydrogen Fuel Cell Reaction………………………….…………...……………….4 Figure 5: Steam Reforming Reactions………………………………………………………..5 Figure 6: Electrolysis of Water…………..…………………………………………………….6 Figure 7: Reversible reaction of protons to form dihydrogen……………………….………8 Figure 8: Active sites of Hydrogenase………………………………………………….……..8 Figure 9: Hydrogen production reaction data for immobilized cluster (Ps-Hy@MCM-41) and free cluster (PsHy)…………..….....……………………….11 Figure 10: Diiron Cluster mimic with ferrocenium ligand………………………...…………12 Figure 11: Dendritic diiron cluster mimic developed by Li and coworkers………….....….13 Figure 12: A) Active Site of [FeFe]-Hydrogenase. B) Ally functionalized diiron cluster mimic…………………………………………………………………….15 Figure 13: Attachment of diiron cluster to amorphous carbon surface and electron tunneling………………………………………………………………………………..17 Figure 14: Azadithiolate diiron cluster with decrease steric hindrance on the amine…..17 Figure 15: The target diiron cluster mimics…………………………………………………19 Figure 16: COSY spectrum of n-hexen-azadithiolate diiron cluster………..………...…...22 Figure 17: 1H NMR peaks representing the bridgehead protons……………..…….……..29 Figure 18: 1H NMR of 3-butenal………………………………….…………………………..31

Figure 19: 1H peaks of the Buten and Bisbuten diiron cluster bridgehead……….……….36

vii

Table of Synthetic Schemes

Scheme 1: N-Azadithiolate Diiron Cluster Mimic Synthesis………………………….…...20 Scheme 2: Hydroboration of 4-Pentyn-1-Amine……………………………………...…….23 Scheme 3: Boc protection and hydroboration of 4-pentyn-1-amine……………...……….24 Scheme 4: Alkylation of Ammonia with 4-Penten-1-ol…………...….……………………..25 Scheme 5: Synthesis of Dimethyl Azadithiolate Diiron Cluster…………………….…..….27 Scheme 6: Synthesis of Methyl Azadithiolate Diiron cluster………………..……………..28 Scheme 7: Swern oxidation of 3-buten-1-ol…………………………………………………30 Scheme 8: Synthesis of Bisallyl Azadithiolate Diiron Cluster………..………….….……..32 Scheme 9: Swern Oxidation of 4-Pentenol…………………...……………………………..32 Scheme 10: Synthesis of Bisbuten Azadithiolate Diiron Cluster……………….……..…..34 Scheme 11: Synthesis of Buten Azadithiolate Diiron Cluster……….……………………..35

viii

Abstract

THE DEVELOPMENT OF A DIIRON HYDROGENASE MIMIC CATALYST

FOR EFFICIENT DIHYDROGEN PRODUCTION

David Scott Danico

University of New Hampshire, May, 2017

Carbon dioxide has become an ever growing problem facing life on Earth due to the theory that the increase in CO2 levels has been the leading cause of global warming and could initiate significant climate change. Most of the CO2 produced by humans comes from the burning of fossil fuels for energy. Because of this, the development of a clean alternative fuel is a primary concern. Dihydrogen is looked at as a possible alternative because it has already demonstrated the ability to produce energy in fuel cells and could conceivably replace fossil fuels in every aspect of its use. The main problem facing dihydrogen as an alternative fuel is hydrogen production. The purpose of this research is to design a novel dihydrogen catalyst modeled after the active site of [FeFe]-Hydrogenase. Past research has shown that this enzyme can very efficiently catalyze the forward reaction of protons and electrons to form dihydrogen.

Diiron cluster mimics were synthesized with a spectrum of clickable terminal alkene bridgeheads with chain lengths ranging from 3 to 6 carbons for the purpose of attaching

them to amorphous carbon surfaces. In addition, the effect of steric hindrance on the diiron cluster bridgehead is being investigated. This was done by creating diiron cluster mimics with the alkene chain attached to the carbon atom of the bridgehead as opposed to the nitrogen. It is thought that reducing the steric hindrance around the nitrogen will increase the rate of proton shuttling to the iron metal center thereby increasing the turn over frequency. The synthetic routes to create these mimics were explored and the products were characterized using 1H NMR, 13C NMR, and IR spectroscopies. This research provides the initial steps in designing a dihydrogen catalyst that can efficiently generate hydrogen fuel.

Introduction

The Threat of Global Warming

Global warming is the observable, gradual change in climate that has occurred since the mid-19th century.1 It is theorized that the increase in global temperatures (Figure 1) will have severe consequences that will affect our daily life. In addition to increases in temperature, these consequences include rising sea levels, widening of deserts, and the changing of precipitation patterns.2 Also, it is expected to cause increases in the frequency of extreme weather such as hurricanes, droughts, and heavy snowfall.3,4 If these predictions do come to fruition, the negative consequences would include the disappearance of coastal land masses,6 decreases in crop yield,3 and changes in animal migration.2 Because of this, a significant amount of effort from the scientific community is being put into preventing global warming from progressing and curbing its negative effects.

Figure 1: Global Surface temperature average in relation to the 1951-1980 average temperatures. (Gray line = Annual Mean, Black Line = Five Year Mean) 5

There is a general consensus that the world is becoming warmer, but the cause of this is still being studied. It is widely theorized that the main cause of global warming is from humans increasing the amount of greenhouse gasses in the air which include carbon dioxide, methane, and

7 nitrous oxide. In the United States, CO2 has Figure 2: 2014 US greenhouse gas emissions.8 accounted for 81% of all greenhouse gasses produced by human activities, most of which is from the burning of fossil fuels for energy

(Figure 2-3).8 Carbon dioxide is a gas that naturally occurs in the earth’s atmosphere and is part of the carbon cycle, but with the addition of CO2 from human activities, it has become increasingly difficult for the Figure 3: Areas of the US Production of environment to compensate for this increase. Carbon Dioxide.8 The carbon cycle relies on natural sinks, such as plants, oceans, and bacteria that use photosynthesis, to absorb carbon dioxide from

9 the air but these sinks cannot compensate for the excess CO2. This causes the excess

CO2 to stay in the atmosphere and contribute to global warming.

The main source of carbon dioxide emissions comes from the burning of fossil fuels and, therefore, it is necessary to reduce the consumption of fossil fuels to

mitigate climate change. This can be done in a few ways. The first is increasing energy efficiency. The United States has undertaken many energy efficiency policies over the past few decades that has greatly decreased the amount of energy consumed by the public. The most notable being the Corporate Average Fuel Economy (CAFE) standards in 1975 which resulted in a large increase in the fuel economy of cars and light trucks.10 Next is simply reducing energy consumption. This can be accomplished by turning off lights and electronics when not in use, reducing distance traveled in personal vehicles, or switching to LED lightbulbs. Both of these steps will reduce the consumption of fossil fuels, but will not remove the need for it. In order to greatly reduce the amount of carbon dioxide produced by humans, a replacement for fossil fuels is necessary.

Alternative Fuels

The rise in concern over climate change has caused an immediate need for an alternative fuel. Common sources of alternative energy are wind, hydroelectric, geothermal, and solar. These energy sources have been implemented because they’re renewable and produce no harmful byproducts. Although these have all proven to produce energy effectively, they all have inherent problems. Wind power is dependent on the weather of the location and isn’t able to be used everywhere especially large cities.11 Hydroelectric power plants change the surrounding habitat of its location and has large initial cost that make it an unattractive alternative.12 Geothermal energy is usually produced in remote areas far from where energy is needed and has a large

initial plant cost. In addition, there is also a chance of releasing harmful gasses when harnessing this energy.13 Lastly, solar energy is dependent on the weather and solar panels have a low efficiency.14 The disadvantages for these alternative energy sources have prevented them from becoming more widely used.

Dihydrogen is looked at as a possible replacement for fossil fuels in every aspect of its use. Dihydrogen is a zero emission fuel with the only byproduct being water which makes it a very attractive alternative energy source. Figure 4 depicts the reaction of turning dihydrogen into energy. Fuels cells have the ability to combine fuel through electrotrochemical energy converters, in this case hydrogen and oxygen gasses, with no immidiate steps inbetween.15 There are two main components of a fuel

Figure 4: Hydrogen Fuel Cell Reaction15

cell that make it work, the catalyst and the proton exchange membrane. The role of the catalyst is to break the dihydrogen in to its electron and proton component parts. The protons are able to pass through the membrane while the electrons are sent though a circuit to provide energy. On the other side of the membrane, the electrons, after being used for enegy, react with the protons and oxygen supplied from the air to create water.16 The US department of Energy estimates the efficiency of fuel cells to be between 40-60%.17 In comparison, an internal combustion engine of a car has an efficiency of about 25%.18 Because of this high eficienc, fuels cells are an appealing way to produce energy and have the ability to provide industrial, commercial, and residential power, in addition to motor vehicles.

One of the main challenges of dihydrogen becoming a more widely used alternative fuel is dihydrogen production. Dihydrogen does not occur naturally in large amounts due to its low molecular weight but is stored in hydrocarbons and water.19 The goal is to be able to produce dihydrogen from these sources. The most common ways of doing this are from steam reforming of hydrocarbons and electrolysis. Steam refroming makes up over 90% of the dihydrogen produced today.20 Generally, dihydrogen is produced this way by heating methane (~1000°C) in the presence of H2O.

This produces carbon monoxide and dihydrogen. In addition, the CO can be further reacted with H2O in the Figure 5: Steam Reforming Reactions. A) Steam- methane reforming reaction. B) Water-gas shift presence of a catalyst to reaction produce carbon dioxide and

more dihdrogen (Figure 5).21 In addition to natural gas, steam reforming can be done with multiple hydrocarbons such as oil,22 coal,23 ethanol,24 and methanol.25 Even though this proccess does produce dihydrogen in large quantities, it also produces carbon dioxide, the leading factor for global warming. Therefore, the use of this method makes the dihydrogen produced not a clean alternative fuel.

Figure 6: Electrolysis of Water26

Electrolysis is the other major source of dihydrogen. It accounts for 4% of the total dihydrogen production in the United States.27 This process involves applying a voltage to water where the two electrodes are separated by a semipermeable membrane (Figure 6). As the water separates, the oxygen ions are drawn to the anode while the hydrogen ions are drawn to the cathode. Oxygen gas and hydrogen gas are formed at these electrodes and bubble out of solution where they can be collected. The

most attractive aspect of electrolysis is that the energy needed for this process could be collected from one of the previously mentioned alternative energies; solar, wind, and hydroelectric. This would mean the energy generated could be stored in the way of dihydrogen which could then be used for future energy.28 Unfortunately, there are some drawbacks to water electrolysis. High production costs and low efficiency have prevented it from being used on a larger scale. This process requires an energy input of

34 kWh/kg of hydrogen generation at full conversion efficiency but a normal electrolysis apparatus needs 50 kWh to produce 1 kg of Hydrogen gas.29 This large energy input makes electrolysis unappealing for industrial use.

There is a significant amount of research being done on the alternative energy sources described in this section but they all have inherent problems.30,31,32,33 In addition, it is thought that a combination of these is required to meet the planet’s energy needs. Dihydrogen is looked at as a possible all-encompassing solution to this problem. It has already proven the ability to produce energy in fuel cells and is already in the beginning stages of being implemented in vehicles.34 Hydrogen production is the largest obstacle facing dihydrogen fuel and more research needs to be done in this area. Steam reforming and electrolysis have been the major sources of dihydrogen but there needs to be a new hydrogen source that is both energy efficient, and doesn’t produce greenhouse gasses nor uses fossil fuels. Hydrogen catalysis is a relatively new area of research that could solve this problem.

Hydrogenase

Hydrogenase is a naturally occurring enzyme that catalyzes the reversible reduction of protons to dihydrogen at neutral pH and with mild reduction potentials (-0.4

V vs NHE) (Figure 7).35 This enzyme occurs in micro-organisms for the purpose of either regulating Figure 7: Reversible reaction the number of protons present or producing needed of protons to form dihydrogen

36 H2 molecules. There are four types of hydrogenase enzymes which are denoted by the metal center of their active sites. They are [NiFe]-H2ase, [FeFe]-H2ase, [Fe-only]-

37 H2ase, and [NiFeSe]-H2ase (figure 8).

A) B)

C) D)

Figure 8: Active sites of Hydrogenase. A) [FeFe]-H2ase, B) [NiFe]-H2ase, C) [NiFeSe]-H2ase, D) [Fe-only]-H2ase.

The [NiFe]-hydrogenases generally react to form protons from dihydrogen,

38 but has the added benefit of being more resistant to decomposition from O2. The structure of [NiFe] hydrogenase consists of the metal centers nickel and Iron that are ligated by the high field ligands CO and CN and bridged by sulfur atoms. It is thought that catalysis takes place at the nickel site but some theorize that it’s the iron that takes part due to DFT calculations and dihydrogen’s affinity for low spin d6 metals.39,40

The [FeFe]-hydrogenase active site contains two iron metal centers and, similar to the [NiFe]-hydrogenase, is ligated by the high field ligands CO and CN, in addition to a disulfur bridge. Unlike the [NiFe], the bridgehead of the diiron active site bridgehead contains an aza chain. This chain is theorized to be part of the catalytic process by shuttling protons to the distal iron.41 Also unlike the [NiFe], [FeFe]- hydrogenase more readily catalyzes the forward reaction to produce H2. The turn over frequency of [FeFe]-hydrogenase from Clostridium acetobutylicum has been reported as 10,000 s-1.42

The [NiFeSe]-hydrogenase is very similar to the [NiFe] hydrogenase except for one of the ligands on the nitrogen atom is seleno-cysteine instead of a thio- cysteine. This hydrogenase enzyme of Desulfomicrobium baculatum has shown a greater ability to produce H2 compared to any [NiFe]-hydrogenase. Unfortunately, this

43 enzyme will become inactive in the presence of O2 but can also be reactivated. In addition, it has shown less reaction inhibition from the H2 product which is another area

44 the [NiFe]-hydrogenase struggles. In terms of H2 production, the selenium derivative significantly outperforms the [NiFe]-hydrogenase.

The [Fe]-Hydrogenase is considerably different from the previously mentioned active sites. The structure contains only one Fe metal center that is ligated by carbonyl ligands, a sulfur-cysteine, a sp2-pyridinol nitrogen, and an acyl-carbon.45

Unlike the other enzymes, [Fe]-hydrogenase does not oxidize H2. Instead it functions to reversibly reduce methenyltetrahydromethanopterin to methylenetetrahydromethanopterin (methylene-H4MPT). This enzyme also has the

46 ability to catalyze the removal of H2 from methylene-H4MPT.

All together there are about 450 different hydrogenases that differ in size, quaternary structure, electron donors, acceptors, etc., but can all be put into the subgroups described.47 The majority of the research done today is on the [FeFe] and

[NiFe] hydrogenases where the [FeFe]-hydrogenase is used for the catalytic production

48 of H2 research and [NiFe]-hydrogenase is used for H2 activation research. Platinum, an extremely expensive and rare metal, is used in fuel cells as the catalyst to separate dihydrogen.49 The [NiFe]-hydrogenase research could lead to a cheap replacement for platinum that would make fuel cells significantly more attractive for energy generation.

[FeFe]-hydrogenase research could lead to the development of a proton reduction catalyst which would replace steam reforming and electrolysis as the primary ways of generating hydrogen fuel.50 Advances in this field would make hydrogen fuel more appealing and a hydrogen economy more feasible.

[FeFe]-Hydrogenase Mimic Catalyst Literature

Often times scientist look towards nature to find inspiration when attempting to develop a new technology. In this case, the active site of [FeFe]- hydrogenase is being investigated in order to create a new dihydrogen catalyst. As previously stated, the active site of this enzyme has a diiron cluster ligated by high field

CO and CN ligands and an azadithiolate bridgehead. By mimicking this active site, it is possible to create a catalyst that can efficiently produce dihydrogen. Presently, the diiron cluster mimics that have been produced fall short of the dihydrogen output of the native enzyme.51,52,53 Despite the low turnover numbers (TON), the previous research done on [FeFe] mimics gives insight into the characteristics that could benefit diiron cluster mimics in the future.

One of the most important aspects of creating a diiron mimic catalyst is stability. Research has shown that immobilizing the diiron cluster has resulted in higher

TON with the rational that it stabilizes the cluster. Li, et al. has designed a diiron cluster mimic that was attached to an MCM-41 sieve and, through hydrogen production studies, discovered that immobilizing their cluster on this sieve produced more favorable Figure 9: Hydrogen production reaction data for TON (Figure 9).54 This data shows immobilized cluster (Ps-Hy@MCM-41) and free cluster (Ps-Hy).54 that not only does the cluster

produce a higher TON, but lasts twice as long as the diiron cluster free in solution. In addition to the MCM-41 sieve, researchers have seen positive results immobilizing their diiron cluster using peptides,55 carbon nanotubes,56 and metal surfaces.57

An important part of the catalytic process of the diiron cluster is the need for an electron source. During the catalytic cycle, the active site needs two equivalents

- 58 of e in order to create 1 equivalent of H2. These electrons are provided by the [Fe4S4] cubane subunit. Rauchfuss and coworkers were able to substitute this subunit for a ferrocenium ligand which was able to provide the necessary electrons (Figure 10).59

Even though this catalyst only produced 3.3 eq of H2, it does indicate that the [Fe4S4] cubane structure can be replaced by another electron donor.

The use of light to provide the catalyst with the energy it needs is desirable due to light Figure 10: Diiron Cluster mimic with essentially being free energy. This is ferrocenium ligand developed by Rauchfuss and coworkers. X=H and Y= CO.59 done by incorporating a photosensitizer on the catalyst. Li and coworkers were able to accomplish this by creating a dendritic diiron cluster with ruthenium photesensitizers branching out (Figure

11).60 A TON of 229 was produced for this catalyst. Along with the diiron cluster and photosensitizers, a sacrificial electron donor and a light source were used to produce

H2. In addition to demonstrating the possibility of incorporating photosensitizers onto diiron cluster mimics, their data indicated that excluding one part of the catalytic system

would yield no product, which highlights the importance of incorporating each aspect of the system to generate catalytic activity.

Figure 11: Dendritic diiron cluster mimic developed by Li and coworkers.60

Another important aspect of the [FeFe]-hydrogenase active site is the bridgehead. It is thought that the bridgehead takes part in the catalytic cycle by shuttling protons to the distal iron where dihydrogen production takes place.41 To work out the most beneficial pendent bridgehead for diiron cluster mimics, Berggren and

Esmieu compared the catalytic activity of dihydrogen clusters with azadithiolate (adt)

bridgeheads with that of diiron clusters with propylenedithiolate (pdt) bridgeheads.61

They were able to obtain a TON of 41 for the adt bridgehead whereas the pdt bridgehead diiron cluster produced no catalytic activity. In addition, a comparison was made between the adt bridgehead and an oxadithiolate (odt) bridgehead by Rauchfuss and coworkers.62 This research looked into the ability of the bridgeheads to create a terminal hydride ligand on the iron metal center using different strengths of acids. It was found that, although both bridgeheads were able to accomplish this, only the adt

CD Cl bridgehead was able to create the terminal hydride ligand with weaker acids (pK 2 2 =

5.7). This is important because weaker acids need lower overpotentials which is beneficial for hydrogen production.63 The research done on the different bridgeheads on diiron cluster mimics shows the importance of incorporating an azadithiolate bridgehead on future diiron cluster mimic catalysts.

The research presented in this section has identified some of the important characteristics that could benefit diiron cluster mimic catalysts in the future.

These characteristics include attaching an electron donor to the cluster to provide the necessary electrons for catalysis. Moreover, this electron donor could be a photosensitizer that uses light energy to provide electrons. Immobilization of the diiron cluster data has shown increased TON and reaction time compared to diiron clusters free in solution. Lastly, research has been done showing the importance of the azadithiolate bridgeheads to help catalysis compared to the propylenedithiolate and oxadithiolate bridgeheads. With these in mind, a [FeFe]-hydrogenase mimic catalyst can be created that can more efficiently produce dihydrogen.

Design of the [FeFe]-Hydrogenase Mimic Catalyst

The purpose of this research is to develop a dihydrogen catalyst modeled after the active site of [FeFe]-hydrogenase. The first step in this process is designing the diiron cluster. The most simple and well researched diiron cluster to date is the azadithiolate diiron cluster with a variety of pendent amine bridgeheads.64,65,66 The allyl azadithiolate diiron cluster synthesis was first elucidated by Rauchfuss and coworkers in

2001 and is the basis of much of this research.67 The synthesis of this mimic is relatively simple and the structure is very comparable to that of the native enzyme, both having two iron metal centers ligated by high field ligands and an azadithiolate bridgehead (Figure 12). This makes it an obvious starting point for designing this new catalyst.

This cluster was synthesized with a spectrum of terminal alkene chain lengths. The purpose of these alkene chains is to take part in click chemistry to attach the diiron cluster mimic to an amorphous carbon surface (sp2/sp3).68 This is done by irradiating light on the carbon surface which causes an electron to be ejected. This

A) B)

Figure 12: A) Active Site of [FeFe]-Hydrogenase. B) Ally functionalized diiron cluster mimic

initiates a radical reaction with the terminal alkene depositing electron density into the electron sink to form a new bond. Pazicni et al. showed that the diiron cluster is able to take part in radical reactions without decomposing by using thiol-ene click chemistry to attach a diiron cluster mimic to a single chain polymer.69 There are multiple benefits to attaching the diiron cluster to this surface. The first is that it immobilizes the diiron cluster and this, as previously stated, could help the diiron cluster’s stability and produce higher dihydrogen yields. The second is that, because the amorphous carbon surface has shown the ability to eject electrons upon the irradiation of light, it could have the ability to donate the necessary electrons to the diiron cluster which eliminates the need for incorporating a photosensitizer.70 This helps simplify the system and the synthesis of the diiron cluster. In addition, the use of light to promote hydrogen production makes this catalytic system that much more attractive because light is essentially free energy which would be stored in the way of hydrogen fuel.

Furthermore, the amorphous carbon surface can be used as an electrode in electrochemical catalysis providing another avenue for dihydrogen production.71 Lastly, the amorphous surface can easily be functionalized.72 [FeFe]-hydrogenase encases the active site in a hydrophobic pocket inside the enzyme. By functionalizing the surface with hydrophobic chains surrounding the diiron cluster mimic, an environment can be created similar to that of the native enzyme.73

After the attachment of the diiron cluster to the amorphous carbon surface, it is important to ascertain if the catalyst is working properly. This is the purpose of synthesizing clusters with a range of terminal alkene lengths. Once attached, kinetic

experiments on the electron tunneling (the electron being ejected from the carbon surface and traveling though the antibonding sigma orbitals of the chain to the diiron

hv - e hv

Figure 13: Attachment of diiron cluster to amorphous carbon surface and electron tunneling. (n = 1-4)

cluster) can be conducted (Figure 13). The alkane chain acts as a spacer between the surface and the diiron cluster and the rate of electron tunneling can be measured over this distance. This data can now be compared to that predicted by the

Simmons equation.74 The Simmons equations is a quantum mechanical tool used to predict the behavior of electron tunneling and, if the kinetic experiments match up with what is predicted, the system can be considered working properly. Figure 14: Azadithiolate diiron cluster with decreased steric hindrance on the amine

In addition to creating this diiron cluster catalyst, this research is also looking into the effects of the pendent amine bridge. As previously stated, this bridgehead is thought to act as a proton shuttle which greatly increases catalytic activity. Currently, the effect of bridgehead steric hindrance has not been investigated.

It is theorized that decreasing the steric bulk on the amine will increase the rate of proton shuttling thereby increasing turn over frequency. To test this theory, diiron clusters can be synthesized with terminal alkene azadithiolate bridgeheads with the alkene chain not bound to the nitrogen atom but to the adjacent carbon (Figure 14).

Once synthesized, this cluster can undergo hydrogen production reactions and that data can be compared to the data collected for its N-diiron cluster counterpart. This will bring to light the effects of steric hindrance on the diiron cluster bridgehead.

This thesis will discuss the target diiron cluster mimics (Figure 15) and the synthetic approaches to create them. In addition, the characterization of these mimics will also be examined.

Figure 15: The target diiron cluster mimics. (top row, from left to right) N-allyl azadithiolate diiron cluster, N-buten azadithiolate diiron cluster, N-penten azadithiolate diiron cluster. (second row, from left to right) N-hexen azadithiolate diiron cluster, dimethyl azadithiolate diiron cluster, methyl azadithiolate diiron cluster. (third row, from left to right) diallyl azadithiolate diiron cluster, allyl azadithiolate diiton cluster, dibuten azadithiolate diiron cluster. (fourth row) buten azadithiolate diiron cluster

Results and Discussion

Objective

This thesis is dedicated to the synthetic aspect of creating a dihydrogen catalyst modeled after the active site of [FeFe]-hydrogenase. In addition, the synthetic routes for the starting materials needed to create these diiron cluster mimics were investigated. Each of the reactions attempted will be gone over in detail and the results of which will be discussed. The ultimate goal of this project is to develop an efficient dihydrogen catalyst and this research provides the initial steps required to accomplish this goal.

N-Azadithiolate Diiron Cluster Mimic

(1)

R= -CH2-CH=CH2 (2) -CH2-CH2-CH=CH2 (3) -CH2-CH2- CH2-CH=CH2 (4) -CH2-CH2- CH2-CH2-CH=CH2 (5)

Scheme 1: N-Azadithiolate Diiron cluster mimic synthesis

The diiron cluster mimic has been successfully synthesized with terminal alkene chain lengths of 3 to 6 carbon atoms long using Scheme 1.67 This is a two-step process with iron pentacarbonyl and elemental sodium as the starting materials. First a carbonyl ligand dissociates from two iron pentacarbonyl compounds and the iron atoms dimerize. Upon the addition of elemental sulfur, the disulfur bridge forms (1). This is reacted for 6 minutes before hexanes, water and ammonium carbonate are added.

After 6 minutes the visible carbon monoxide gas bubbles begin to slow and ammonium carbonate is added to quench the reaction to try to limit the formation of the trimer and maximize the product. Lithium triethylborohydride and triflouroacetic acid are then used to protonate the sulfur atoms. In a separate reaction, the terminal alkene amine is reacted with 2 equivalents of formaldehyde to create the bishemiaminal precursor compound. Lastly, the addition of the dithiolato diiron precursor cluster affords the N- azadithiolate diiron cluster with the desired alkene chain length (2-5). To increase the reaction yield, dry THF solvent was used because water is a byproduct of this reaction and dry solvent helps limit the amount of water in solution and pushes the equilibrium to the product.

These compounds were characterized through 1H and 13C NMR spectroscopy all of which resulted in the expected peaks and shifts. These included a doublet of doublet of triplets at ~5.7 ppm which was integrated to 1H and a multiplet at

~5.0 ppm which was integrated to 2H which are characteristic of a terminal alkene and a singlet at ~3.4 ppm that was integrated to 4H representing the protons on the azadithiolate bridge. Aliphatic peaks can be seen ranging from 2.0-3.2 ppm with the expected splitting and integration depending on the alkene chain length. The 13C NMR

spectrum also had the characteristic peaks for the clusters. In addition, these compounds where characterized by Infrared (IR) spectroscopy resulting in similar carbonyl stretches of ~1950, ~2025, and ~2070 cm-1.

Unfortunately, The NMR spectra for the diiron clusters synthesized contained large hexanes impurity peaks at 1-2 ppm which, in the case of N-hexen azadithiolate diiron cluster, actually obscured some of the aliphatic proton peaks. To determine if these aliphatic peaks where under the hexanes impurities, a COSY NMR spectrum was obtained (Figure 16). The peaks in this spectrum representing protons B and E are observed to be coupling with peaks under the hexanes impurity peaks at about 1.2 ppm. This is direct evidence that the missing aliphatic peaks are being obscured in this region. The 13C NMR spectrum also showed peaks representing all the

Figure 16: COSY spectrum of n-hexen-azadithiolate diiron cluster

carbon atoms of this compound. The yield of these reactions were from 50-70% yield.

One way that this could be increased is by adding a drying agent to the reaction flask to further remove the water byproduct.

After characterizing the synthesized compounds it was determined that the reactions were successful and these diiron clusters can now be attached to the amorphous carbon surface and hydrogen production reactions can be completed.

4-Penten-1-Amine

Hydroboration of Terminal Alkyne

Scheme 2: Hydroboration of 4-pentyn-1-amine

The lack of a good commercial source for the 4-penten-1-amine starting material required it to be synthesized to be used in the n-azadithiolate diiron cluster reactions. The hydroboration of alkynes using catechol borane is well established in the literature as being able reduce alkynes to alkenes without the further reduction to an

alkane.75,76,77 This seemed advantageous due to these reactions reporting high yields.

Catechol borane was reacted with 4-pentyn-1-amine at 70°C which produced a milky white solution, then glacial acetic acid was added at 100°C which produced a pale yellow solution (Scheme 2). These color changes are characteristic of the reactions found in the literature. Right after cooling the solution to RT, it began to turn black. After attempts to purify this with TLC, silica gel flash column chromatography, and distillation, no product was produced. After distillation, the solution turned into a hard, insoluble black solid. It is believed that these reagents further reacted to produce an amine/catechol borane adduct. This is because nitrogen and boron compounds tend to form strong Lewis acid/base pairs when not sterically hindered.78 Unfortunately, this black solid was not able to dissolve in NMR solvents and this theory could not be tested spectroscopically.

Hydroboration of Boc Protected 4-Pentyn-1-Amine

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Scheme 3: Boc protection and hydroboration of 4-pentyn-1-amine

In an effort to investigate any interactions between the nitrogen and boron atoms and to try and prevent these interactions, a Boc protecting group was added to the amine before hydroboration (Scheme 3). The Boc anhydride protecting group was succesfully added to the amine (6) and a 1H NMR spectrum was taken showing the expected peaks.79 After, the hydroboration reaction was repeated using catechol borane. This reaction yielded similar results with the production of the hard, insoluble black solid. Interestingly, after the glacial acetic acid reaction and cooling down of the reaction flask, the black product took about 15 mins to be produced as opposed to the unprotected amine that produced the black product almost immediately. This reaction is evidence that the nitrogen and boron atoms are interacting to form an adduct byproduct which inhibited the desired 4-penten-1-amine product from being synthesized.

Alkylation of Ammonia with 4-Penten-1-ol

(7) (8)

Scheme 4: Alkylation of ammonia with 4-penten-1-ol

Due to difficulties synthesizing 4-penten-1-amine through the hydroboration route, a new course was taken. It was discovered that alcohols can be transformed into amines using mesyl chloride (scheme 4).80 The first step of this reaction involved the addition of mesyl chloride onto the alcohol group then the trimethylamine deprotonates the alcohol resulting in (7). Triethylamine is used in this case to help speed up the reaction by removing the HCl byproduct. Once the

mesylated alcohol is formed, 30% ammonia solution was introduced to act as the nucleophile and replace the mesyl alcohol group on the alkene to produce the desired product (8).

After the synthesis of the mesylated complex (7), a 1H NMR spectrum was taken showing a singlet at 3.01ppm that was integrated to 3H, representative of the mesyl group protons. In addition, the peaks representing the terminal pentene chain were observed. Upon the addition of ammonia, the 1H NMR spectrum showed a disappearance of the mesyl peak and the appearance of a singlet at 2.18 ppm that was integrated to 2H, representing the amine protons. Additionally, the 13C NMR spectrum for each of the products displayed their characteristic peaks and are in good agreement with the literature. This reaction resulted in a 55% yield and the product was able to be used in the N-penten-azadithiolate diiron cluster reaction.

Synthesis of Diiron Clusters with decreased Amine Steric Hindrance

This section goes over the steps taken to synthesize diiron clusters with reduced steric hindrance on the pendent amine. The strategy taken to accomplish this is to use the previously mentioned N-azadithiolate diiron cluster reaction but perform it using ammonium carbonate and an aldehyde with the desired alkane/alkene chain length instead of an alkene amine to create the necessary bishemiaminal bridgehead.

The following reactions were completed in chronological order starting with the simplest aldehyde, acetaldehyde, then moving to the creation of clickable alkene diiron clusters

Bismethyl Azadithiolate FeFe Cluster

(9) Scheme 5: Synthesis of Bismethyl Azadithiolate Diiron Cluster

In order to test the concept of using a more sterically hindered aldehyde than formaldehyde for the diiron cluster reaction previously mentioned, acetaldehyde was used. This was performed in the same fashion as scheme 1, except ammonium carbonate was reacted with 2 equivalents of acetaldehyde for one hour to get the dimethyl bishemiaminal. To this, the diiron cluster precursor (1) was added to form bismethyl azadithiolate diiron cluster (9) (Scheme 5).81

The 1H NMR spectrum of this molecule displayed a doublet at 1.36 ppm that was integrated to 3H representing the methyl protons and a six peak multiplet at

3.52 ppm which was integrated to 1H representing the bridge protons. This six peak multiplet is the result of overlapping quartets which is evidence that both enantiomers where synthesized during this reaction.82 In addition, two peaks 57.27 ppm and 26.76 ppm were observed in the 13C NMR spectrum which are characteristic of this compound. Even though the yield was only 28%, this reaction is evidence the diiron cluster synthesis is able to function with aldehydes that are more sterically hindered than formaldehyde.

Methyl Azadithiolate Diiron Cluster Mimic

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Scheme 6: Synthesis of Methyl Azadithiolate Diiron Cluster

The synthesis to produce the asymmetric methyl azadithiolate diiron cluster was accomplished by reacting ammonium carbonate with 1 equivalent of acetaldehyde and 1 equivalent of formaldehyde to get the asymmetric methyl bishemiaminal. Then, upon the addition of the diiron cluster precursor (1), the desired product was obtained (Scheme 6). The acetaldehyde was reacted with the ammonium carbonate for 1 hour before formaldehyde was added and reacted for an additional hour. The reasoning for this is that, when the acetaldehyde is added to the ammonia, it provides slightly more steric hindrance so that a second acetaldehyde would be less likely to be added to the same nitrogen. This was done in an effort to maximize the formation of the asymmetric bishemiaminal. As expected there where three products that formed from this reaction; the azadithiolate diiron cluster, the bismethyl azadithiolate diiron cluster, and the methyl azadithiolate diiron cluster (10) (Scheme 6).

These three clusters can be differentiated by the splitting patters of the peaks between

3 and 4.5 ppm of the 1H NMR spectrum that represent the protons on the bridgehead of the diiron cluster (Figure 17). The azadithiolate diiron cluster has a very broad peak at

~3.6 ppm that was integrated to 4H. The dimethyl azadithiolate diiron cluster has a six peak multiplet at ~3.5 ppm that was integrated to 2H. Lastly the methyl azadithiolatediiron cluster has two peaks; a triplet at ~3.5 ppm which was integrated to

2H and a doublet of doublets at 3.9 ppm that was integrated to to 1H. Therefore, when working out which diiron cluster was synthesized, these are the peaks that need to be examined.

A) B)

Figure 17: 1H NMR peaks representing the bridgehead protons.

A) Azadithiolate Diiron Cluster; B) Dimethyl Azadithiolate Diiron Cluster; C) Methyl Azadithiolate Diiron Cluster

Another important thing about this reaction is the ratio of the products obtained. The desired product, methyl azadithiolate diiron cluster, had a yield of 46% with a ratio of 1.75: 1.0: 0.1 (Methyl azadithiolate: bismethyl azadithiolate:

Azadithiolate). This result was encouraging for reactions going forward where the desired product was a mono substituted bridgehead diiron cluster.

Swern Oxidation of Terminal Alkene Primary Alcohols

The next step in this process was to synthesize a clickable diiron cluster with decreased amine bridgehead steric hindrance. The bisallyl azadithiolate diiron cluster was attempted first. Unfortunately, the aldehyde starting materials needed for this type of reaction were not commercially available and needed to be synthesized. A common way of creating an aldehyde is using a Swern oxidation to oxidize an alcohol.83

This was used in an attempt to create the 3-butenal needed for the reaction (Scheme

7).

(11) Scheme 7: Swern oxidation of 3-buten-1-ol

The first step of this reaction is the combination of the DMSO and oxalyl chloride at -78°C to give an alkoxysulphonium ion. This then reacts with the alcohol to give a sulfur ylide and, upon the addition of trimethylamine, this structure undertakes an

intramolecular deprotonation via a five-membered ring transition state which produces the desired product (11) and dimethyl sulfide.

Figure 18: 1H NMR of 3-butenal

With the reaction completed, a 1H NMR (Figure 18) was taken of the product. At first glance, this NMR spectrum indicated that the desired product was synthesized showing the correct number of peaks in the general location that one would expect. But under further investigation, this peak splitting does not match with the literature. The peak at 9.5 ppm should be a triplet and the peaks between 6 and 5 ppm do not match with what would be expected with a terminal alkene. These peaks are more indicative of an internal alkene. It is thought that during the Swern oxidation, the product isomerized to 2-butanal. At the time, it wasn’t certain that this was the case so the bisallyl azadithiolate diiron cluster reaction was attempted (Scheme 8). This was

done in the same fashion as the dimethyl azadithiolate diiron cluster reaction.

Unfortunately, no product was obtained from this synthesis.

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Scheme 8: Synthesis of Bisallyl Azadithiolate Diiron Cluster

Even though 4-pentenal is available commercially, the Swern oxidation was attempted on 4-pentenol. Doing this was an attempt to figure out if the Swern oxidation is inherently problematic for 3-butenol or if there was a problem with the execution of this method. A new reference for the Swern oxidation was discovered with slight changes to the procedure. First the reaction time was increased and second, instead of quickly increasing the temperature to 0°C, the temperature was slowly increased over a 3 hour period.84 These changes were made to the original procedure and attempted on 4-pentenol.

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Scheme 9: Swern Oxidation of 4-Pentenol

This reaction was completed in the same fashion as the Swern oxidation of 3-butenol except with the previously described changes. DMSO and oxalyl chloride are combined at -78°C to give an alkoxysulphonium ion. This then reacts with the alcohol to give a sulfur ylide and, upon the addition of trimethylamine, the temperature was slowly increased to 0°C over a three hour period which causes this structure to undertake an intramolecular deprotonation via a five-membered ring transition state.

This produced the desired product (13) and dimethyl sulfide (Scheme 9).

Once this reaction was complete, a 1H NMR spectrum was taken. This showed a triplet at 9.75 ppm which was integrated to 1H representing the aldehyde proton, and peaks representing the terminal alkene which were a doublet of doublet of triplets that was integrated to 1H at 5.80 ppm and a multiplet that was integrated to 2H at 5.01 ppm. These peaks were in good agreement with the literature values. In addition, a 13C NMR spectrum was taken displaying the peaks expected for this compound.

With the changes made to the Swern oxidation giving the desired product with 4-pentenol, the Swern oxidation was reattempted for 3-butenal. This reaction provided identical results. This leads to the conclusion that there are inherent problems using the Swern oxidation reaction for 3-butenol. More research needs to be done on the synthesis to create 3-butenal.

Bisbuten Azadithiolate Diiron Cluster

Once 4-pentenal was synthesized, it was used as the starting material for the diiron cluster reaction. This was done in the same fashion as the methyl

azadithiolate diiron cluster, with first synthesizing the disubstituted bridgehead in order to investigate if this reaction would work for a much more sterically hindered aldehyde then synthesizing the asymmetric monosubstituted bridgehead diiron cluster.

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Scheme 10: Synthesis of Bisbuten Azadithiolate Diiron Cluster

To start, ammonium carbonate was reacted with 2 equivalents 4-pentenal.

This resulted in the bisbuten bishemiaminal precursor which, upon the addition of the diiron precursor (1), resulted in the desired product of bisbuten azadithiolate diiron cluster (14) with a 69% yield (Scheme 10). After completion, a 1H NMR spectrum was taken showing the expected peaks which include a doublet of doublets of triplets at 5.74 ppm which was integrated to 1H and a multiplet at 5.02 ppm which was integrated to 2H representing the alkene protons. One of the aliphatic peaks was obscured by hexanes impurities but the carbon these protons were bonded to was identified through 13C

NMR. In addition, the protons on the bridgehead where identified as a multiplet at 3.39 ppm which was integrated to 1H. This is evidence that this type of reaction is able to work with much more sterically hindered aldehydes.

Buten Azadithiolate Diiron Cluster

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Scheme 11: Synthesis of Buten Azadithiolate Diiron Cluster

The synthesis of the asymmetric buten azadithiolate diiron cluster was completed in the same fashion as the methyl azadithiolate diiron cluster where ammonium carbonate was combined with one equivalent of 4-pentenal and stirred for one hour then 1 equivalent of formaldehyde was added and left to stir for an additional hour. This created the asymmetric buten bishemiaminal that, when introduced to the diiron cluster precursor (1), formed the desired product, buten azadithiolate diiron cluster (15) with a 50% yield (Scheme 11). Once synthesized, a 1H NMR spectrum was collected showing the characteristic peak splitting and shifts for this compound. Like the bisbuten azadithiolate diiron cluster, one of the aliphatic peaks was obscured by hexanes impurities. The carbon those protons are bound to was also identified through

13C NMR.

Similar to the methyl and dimethyl azadithiolate diiron clusters, the buten azadithiolate can be differentiated from the bisbuten bridgehead by comparing the peaks between 4.5 and 3.0 ppm (figure 19). The bisbuten azadithiolate diiron cluster has one multiplet at about 3.40 ppm that was integrated to 1H. The buten azadithiolate diiron cluster has two peaks in this region; one being a triplet that was integrated to 2H

and a multiplet that was integrated to 1H. By looking at these peaks, one can differentiate the mixture of products that are created during this reaction.

A) B)

Figure 19: 1H peaks of the buten and bisbuten diiron cluster bridgehead. A) Bisbuten Azadithiolate Diiron Cluster. B) Buten Azadithiolate Diiron Cluster

Conclusion

In conclusion, the synthetic routes to make clickable N-azadithiolate diiron clusters with a spectrum of terminal alkenes was completed. Additionally, the synthetic route for the amine starting materials for these reactions was elucidated. These clusters can now be attached to amorphous carbon surfaces and hydrogen production reactions can be completed. Lastly, diiron clusters were synthesized with terminal alkene chains attached to the carbon atom of the pendent amine bridgehead and the effect of steric hindrance on the amine can now be studied. This research provides the first steps in creating a dihydrogen catalyst modeled after the active site of [FeFe]- hydrogenase that can efficiently produce hydrogen fuel.

Experimental Section

General Experimental Section

Reagents

All reagents were received from commercial sources and were used as received. Reagents were obtained from Alfa Aesar, Sigma-Aldrich, GFS Chemicals,

EMD, Cambridge Isotope Laboratories, and Fisher Scientific (Acros).

Reactions

Nitrogen was obtained from the in-house liquid nitrogen boil-off system and was not further dried before use. Reactions were sparged using a syringe needle connected to rubber vacuum tubing where indicated. Standard Schlenk techniques were used and the volumetric addition of reagents and solvents were carried out using either plastic or glass syringes unless otherwise noted. Reactions were heated in an oil bath, cooled in an ice bath (0°C), or cooled in an acetone/dry ice bath (-78°C) where indicated.

Chromatography

Flash column chromatography was performed using Silicycle SiliaFlash

P60 40-63 μm particles. Silica gel was freshly prepared using the solvents described in the detailed experimental section. Thin layer chromatography (TLC), using Sigma-

Aldrich Silica Gel with 60 Å medium pore diameter with fluorescent indicator, was performed in order to ascertain silica gel mobile phases.

Instrumentation

Nuclear Magnetic Resonance (NMR) analysis was recorded on a Varian

Mercury 400 MHz NMR for both 1H and 13C spectroscopy. All of the NMR spectra were measured using deuterated chloroform, purchased from Cambridge Isotope

Laboratories, as the NMR solvent. NMR solvent was stored in a desiccator over 8 mesh anhydrous calcium sulfate. All 1H NMR shifts are reported relative to the internal standard of tetramethylsilane (TMS) (δ 0 ppm). Abbreviations were used to describe peak multiplicity and they are as follows: s = singlet, d = doublet, t = triplet, q = quartet, dd =doublet of doublets, ddt = doublet of doublet of triplets, m = multiplet. Infrared spectra were acquired using Thermo Nicolet iS10 FTIR with a diamond ATR probe.

Products were measured as is (neat) with 64 scans and a resolution of 1 cm-1.

Detailed Experimental Section

FeFe cluster mimic

a) Fe2S2(CO)6 (1)

Into a 500mL Schlenk flask, methanol (35mL), 30% KOHaq (20mL) and a

stir bar were added and the solution was cooled to 0°C and sparged with

N2 for 15 minutes. Iron pentacarbonyl (7.5mL, 56mmol) was added

dropwise via syringe and the contents were stirred until they became

homogenous. Elemental sulfur (10g) was added to the flask and stirred

for 6 minutes. To this mixture, DI water (80mL), hexanes (200mL), and

ammonium chloride (25g) were added and the solution was stirred for 2

hours under a N2 atmosphere. The product was extracted with hexanes (3

x 150mL) by decanting off the top layer of the solution. The extracts were

filtered through celite, washed with DI water (3 x 100mL), dried over

magnesium sulfate, and then filtered. The organic phase was removed

under reduced pressure and the product was purified through silica gel

with hexanes affording a red oil. (18%); IR (neat, cm-1): 1943 (C=O), 2020

13 (C=O), 2066 (C=O). C NMR (CDCl3): δ 208.29.

b) Attachment of N-Allyl Azadithiolate bridgehead to Fe2S2(CO)6 (2)

Dried THF (30mL) was added to a 100mL Schlenk flask and was heated

to 60°C. The flask was sparged with N2 then allyl amine (0.133mL,

1.769mmol) and formaldehyde (1.32mL, 10 eq) were added. The solution

was magnetically stirred for 15 minutes at 60°C then an addition 45

minutes at room temperature.

In a separate 100mL Schlenk flask, (1) (0.6082g, 1.769mmol) and dried

THF (20mL) were added. The solution was cooled to -73°C and sparged

with N2 for 15 mins. Lithium triethyl borohydride (4.0mL, 2.25 eq) was

added and stirred for 15 minutes producing a green solution.

Triflouroacetic acid (0.56mL, 4.15 eq) was added and the solution was

stirred for an additional 15 minutes producing a red liquid. The flask was

allowed to return to room temperature and the two Schlenk flasks were

combined. The resulting mixture was stirred for ~20 hours under a N2

atmosphere. The mixture was condensed under reduced pressure and

hexanes (200mL) was added. The product was extracted via sonication

for 2 hours. The solution was then washed with DI water (2x 150mL) and

aqueous sodium bicarbonate (150mL) and the organic phase was dried

over magnesium sulfate. The product filtered then was condensed under

reduced pressure and purified through silica gel (19:1, hexanes: ethyl

1 acetate) yielding a red oil. (0.489g, 64.8%) H NMR (CDCl3): δ 3.18 (d,

2H), 3.33 (s, 4H), 5.14 (m, 2H), 5.64 (ddt, 1H). IR (neat, cm-1): 1642

(C=C), 1949 (C=O), 2028 (C=O), 2071 (C=O), 2925 (C-H), 3072 (C=C-H).

C) Attachment of N-Buten-Azadithiolate bridgehead to Fe2S2(CO)6 (3)

Prepared in the same fashion as (2) using 3-buten-1-amine (0.39mL,

4.075mmol) and (1) (1.4012g, 4.075mmol). (0.6846g, 38%) 1H NMR

(CDCl3): δ 2.06 (m, 2H), 2.75 (t, 2H), 3.53 (s, 4H), 5.02 (m, 2H), 5.65 (ddt,

13 -1 1H). C NMR (CDCl3): δ 138.10, 125.53, 34.39, 22.60; IR (neat, cm ):

1641 (C=C), 1959 (C=O), 2025 (C=O), 2070 (C=O), 2925 (C-H), 3081

(C=C-H).

D) Attachment of N-Penten-Azadithiolate bridgehead to Fe2S2(CO)6 (4)

Prepared in the same fashion as (2) using 4-penten-1-amine (0.38mL,

3.56mmol) and (1) (1.2236g, 3.56mmol). (0.5509g, 34%) 1H NMR

(CDCl3): δ 1.39 (p, 2H), 1.96 (q, 2H), 2.66 (t, 2H), 3.52 (s, 4H), 4.99 (m,

13 2H), 5.73 (m, 1H). C NMR (CDCl3): δ 208.01, 137.83, 115.53, 60.62,

56.75, 53.25, 26.94; IR (neat, cm-1): 1641 (C=C), 1959 (C=O), 2025

(C=O), 2070 (C=O), 2930 (C-H), 3079 (C=C-H).

E) Attachment of N-Hexen-Azadithiolate bridgehead to Fe2S2(CO)6 (5)

Prepared in the same fashion as (2) using 5-hexen-1-amine (0.527mL,

4.165mmol) and (1) (1.4322g, 4.165mmol). (1.1783g, 60%) 1H NMR

(CDCl3): δ 2.05 (q, 2H), 2.64 (t, 2H), 3.49 (s, 4H), 4.96 (m, 2H), 5.75 (ddt,

1H). (Aliphatic peaks obscured by hexanes impurities at ~1.2ppm,

13 identified with COSY spectrum); C NMR (CDCl3): δ 208.03, 138.50,

115.05, 57.42, 53.25, 33.59, 27.29, 26.25; IR (neat, cm-1): 1641 (C=C),

1972 (C=O), 2027 (C=O), 2071 (C=O), 2924 (C-H), 3078 (C=C-H).

4-Penten-1-Amine (8)

a) Hydroboration of terminal alkyne amine

4-pentyl-1-amine (0.87mL, 9.022mmol) was added to a 50mL Schlenk

flask and sparged with N2 for fifteen minutes. The flask was heated to

70°C and 50% Catechol Borane in toluene was added. The solution was

stirred for 2 hours producing a milky white color. The temperature was

increased to 100°C and Glacial acetic acid (4.6mL) was added. This

solution was stirred for 2 hours producing a transparent yellow color. The

Product was extracted with dichloromethane (3 x 15mL) and washed with

water (2 x 15mL) and brine (15mL). The organic layer was condensed

under reduced pressure producing a black solid. This reaction did not yield

the desired product.

b) Hydroboration of Boc protected terminal alkyne amine

To a 50mL one necked round bottom flask, 4-pentyn-1-amine (1.16mL,

12.0mmol), dried THF (10mL), and triethylamine (2.51mL) were added

and the flask was sparged with N2 for 10mins. Boc anhydride (3.94g) was

dissolved in THF (10mL) and slowly added. The solution was stirred at

room temperature for 3 hours under N2 atmosphere. The product was

extracted with diethyl ether, and then washed with DI water (2 x 20mL),

dried over magnesium sulfate, and filtered. The organic phase was

condensed under reduced pressure producing a pale yellow, oily solution.

The product was purified though a silica gel column (2:1, ethyl acetate:

1 Hexanes). (6) H NMR (CDCl3): δ 1.44 (s, 9H), 1.72 (p, 2H), 1.97 (t, 2H),

2.24 (td, 2H), 3.24 (q, 2H), 4.71 (br. S, 1H).

The boc protected 4-pentynamine was added to a 100mL Schlenk flask

and sparged with N2 for 15 minutes. The flask was heated to 60°C and

50% catechol borane in toluene (3.9mL) was added. The solution was

stirred for 2 hours then the temperature was increased to 100°C. Glacial

acetic acid (6.2mL) was added and the solution was stirred for an

additional 2 hours. The solution was condensed under reduced pressure

yielding a black solid. This reaction did not yield the desired product.

c) Alkylation of Ammonia with 4-Penten-1-ol

To a 100mL Schlenk flask, 4-penten-1-ol (1g, 11.6mmols), triethylamine

(1.94mL), and dry dichloromethane (25mL) were added and sparged with

N2 for 15 minutes. The solution was cooled to 0°C and MsCl (1.08mL) was added dropwise. The solution was allowed to return to room temperature and was stirred for 2 hours. Sodium bicarbonate (50mL) was added and the product was extracted with dichloromethane (3 x 50mL).

The organic phase was dried over magnesium sulfate, filtered, and condensed under reduced pressure. The product was purified through silica gel (1:1, ethyl acetate: Hexanes) yielding the mesylated product (7).

1 H NMR (CDCl3): δ 1.86 (p, 2H), 2.19 (m, 2H), 3.01 (s, 3H), 4.24 (t, 2H),

13 5.06 (m, 2H), 5.79 (ddt, 1H); C NMR (CDCl3): δ 136.80, 116.27, 69.52,

37.55, 29.64, 28.41.

The product was diluted with methanol (25mL) and treated with 30% ammonia solution (30mL) in a 100mL Schlenk flask and the mixture was stirred at room temperature for ~18 hours under N2 atmosphere. The solution was diluted with sodium bicarbonate (20mL) and dry dichloromethane (20mL) and was extracted with dichloromethane (3 x

20mL). The organic phase was dried over magnesium sulfate and filtered.

The solution was condensed under reduced pressure and purified through alumina gel (1:1, ethyl acetate: hexanes) yielding a pale yellow oil (8).

1 (0.5502g, 55%): H NMR (CDCl3): δ 1.83 (t, 2H), 2.01 (t, 2H), 2.11 (m,

13 2H), 2.18 (s, 2H), 5.01 (m, 2H), 5.84 (m, 1H); C NMR (CDCl3): δ 138.32,

115.14, 41.39, 31.20, 28.64.

Dimethyl Azadithiolate FeFe Cluster (9)

Into a 100mL Schlenk flask, THF (30mL) was added and was sparged

with N2 for 5 mins. The flask was heated to 60°C and Acetaldehyde

(6.4mL) and Ammonium Carbonate (2.75g) were added. The solution was

magnetically stirred for 1 hr.

In another 100mL Schlenk flask, THF (20mL) and (1) (1.9693g) were

added and the flask was cooled to -78°C and sparged with N2 for 5mins.

Lithium triethylborohydride (1M in THF, 12.9mL) was added and stirred for

15mins. Triflouroacetic acid (1.8mL) was then added and stirred for an

additional 15mins. The Schlenk flasks were then combined and the

solution was stirred for ~20hrs at RT and under a N2 atmosphere. The

solution was concentrated under reduced pressure then diluted with

hexanes (200mL). The product was extracted through sonication (2hrs).

The solution was then washed with water (2x 150mL) and sodium

bicarbonate (150mL). The organic layer was dried over magnesium

sulfate, vacuum filtered, concentrated under reduced pressure, then

purified through silica gel (95:5, Hexanes: Ethyl Acetate) yielding a red oil

1 (0.6717g, 28.3%). H NMR (CDCl3): δ 1.36 (d, 3H), 1.46 (t, 1H), 3.52 (m,

13 1H); C NMR (CDCl3): δ 208.61, 57.27, 26.76.

Methyl Azadithiolate FeFe Cluster (10)

THF (30mL) was added to a 100mL Schlenk flask then was heated to

60°C and sparged with N2 for 5 mins. Acetaldehyde (1.37mL) and

ammonium carbonate (2.1230g) were added to the flask and were stirred

for 1 hour. Formaldehyde (37% in H2O, 1.81mL) was then added and the

solution was stirred for an additional hour. In another 100mL Schlenk

flask, THF (30mL) and (1) (1.5217g) were added. The flask was cooled to

-78°C and sparged with N2 for 5mins, then lithium triethylborohydride (1M

in THF, 10.0mL) was added and the solution was stirred for 15mins. Next

triflouroacetic acid (1.41mL) was added and the solution was stirred for an

additional 15mins. The Schlenk flasks were then combined and the

resulting solution was mixed at RT for ~20hr. The solution was then

condensed under reduced pressure and diluted with hexanes (200mL).

The product was then extracted through sonication (2hr). Next the

solution was washed with water (2x150mL) and saturated sodium

bicarbonate (150mL), dried over magnesium sulfate, vacuum filtered,

concentrated under reduced pressure, and purified through silica gel

(95:5, Hexanes: Ethyl Acetate) resulting in a red oil (1.2646g, 71.3%). 1H

13 NMR (CDCl3): δ 1.36 (d, 2H), 1.51 (s, 1H), 3.46 (t, 2H), 3.92 (dd, 1H); C

-1 NMR (CDCl3): δ 207.36, 54.90, 47.54, 20.92; IR (neat, cm ): 1286 (C-N),

1963 (C=O), 1986 (C=O), 2063 (C=O), 3403 (N-H).

3-Butenal (11)

Into a 250mL Schlenk flask, DMSO (3.75mL) and DCM (80mL) were

added and the flask was cooled to -78°C. Oxalyl Chloride (2.40mL) was

then added and the solution was stirred for 30 mins. A mixture of 3-buten-

1-ol (2.0mL) and DCM (20mL) was then added to the flask dropwise and

stirred for 25mins. Triethylamine (16.3mL) was then added and the

solution was stirred for an additional 30mins at 0°C. The reaction was

quenched with water (50mL) and stirred for 20mins with the temperature

gradually increasing to RT over that time. The solution was washed with

HCl (1M, 50mL), aqueous sodium bicarbonate (50mL), and brine (50mL).

The organic layer was dried over magnesium sulfate and filtered. The

product was concentrated under reduced pressure in an ice bath then was

purified through distillation. The product was collected from 69-75°C

(crude yield: 1.63g). This product was used in further reactions without

further purification. IR (neat, cm-1): 1642 (C=C), 1725 (C=O), 2719 (O=C-

H), 2858 (O=C-H).

Allyl Azadithiolate FeFe Cluster

In a 100mL Schlenk flask, THF (30mL) and ammonium carbonate

(2.243g) were added and the flask was heated to 60°C and sparged with

N2 for 5mins. Formaldehyde (0.7mL) was added and the solution was

stirred for 1hr. Next, crude 3-butenal (1.63g) was added and the solution

was stirred for an additional hour. In another Schlenk flask, THF (20mL)

and (1) (1.61g) were added and the flask was cooled to -78°C and

sparged with N2 for 5mins. Lithium triethylborohydride (11.68mL) was

added and the solution was stirred for 15mins. Next, triflouroacetic acid

(1.48mL) was added and the mixture was stirred for an additional 15mins.

After this, the flask was allowed to return to RT. The two Schlenk flasks

were then combined and allowed to stir at RT for ~20hrs. The solution

was then condensed under reduced pressure then diluted with hexanes

(200mL). The product was extracted through sonication (2hrs) and was

washed with water (2x 150mL) and aqueous sodium bicarbonate (150mL).

The organic layer was dried over magnesium sulfate, filtered, and then

concentrated under reduced pressure. This reaction did not yield the

desired result.

4-Pentenal (13)

Into a 250mL round bottom flask, DMSO (3.1mL) and DCM (80mL) were

added and the flask was cooled to -78°C. Oxalyl Chloride (2.0mL) was

added dropwise and the solution was stirred for 15mins. Next, 4-penten-

1-ol (2.0mL) was added to the flask and the solution was stirred an

additional 25mins. Triethylamine (13.5mL) was then added. The solution

was stirred and the temperature was allowed to gradually increase to 0°C

over a 3hr period. The reaction was quenched with water (50mL) then the

flask was stirred and the temperature was allowed to increase to RT over

20mins. The solution was washed with HCL (1M, 50mL), aqueous sodium

bicarbonate (50mL), and brine (50mL). The organic layer was dried over

magnesium sulfate, filtered, and concentrated under reduced pressure in

an ice bath yielding a clear liquid (crude yield: 1.1061g, 67.8%). The

product was used in further reactions without further purification. 1H NMR

(CDCl3): δ 2.37 (q, 2H), 2.52 (t, 2H), 5.01 (m, 2H), 5.80 (ddt, 1H), 9.75 (t,

13 1H); C NMR (CDCl3): δ 201.92, 136.37, 115.63, 42.69, 26.06; IR (neat,

cm-1): 1642 (C=C), 1723 (C=O), 2724 (O=C-H), 2840 (O=C-H), 2923 (C-

H), 3079 (C=C-H).

Bisbuten Azadithiolate FeFe cluster (14)

In a 100mL Schlenk flask, THF (30mL) and ammonium carbonate

(0.2831g) were added and the flask was heated to 60°C and sparged with

N2 for 5mins. Next, 4-pentenal was added to the flask and the solution

was stirred for 1hr. In another 100mL Schlenk flask, THF (20mL) and (1)

(0.4118g) were added. The flask was cooled to -78°C and sparged with

N2 for 5mins. Lithium triethylborohydride (2.7 mL) was added and the

solution was stirred for 15mins. Next triflouroacetic acid (0.38mL) was

added and the solution was stirred for an additional 15mins. The two

flasks were combined and the resulting mixture was stirred for ~20 hours

at RT. The solution was condensed under reduced pressure then diluted

with hexanes (200mL). The product was extract through sonication (2hrs).

The solution was washed with water (2x 100mL) and brine (100mL). The

organic layer dried over magnesium sulfate, filtered, and concentrated

under reduced pressure. The product was purified through silica gel

(95:5, Hexanes: Ethyl Acetate) yielding a red oil (0.4081g, 69.4%). 1H

NMR (CDCl3): δ 1.78 (m), 2.17 (m, 2H), 3.39 (m, 1H), 5.02 (m, 2H), 5.74

13 (ddt, 1H); C NMR (CDCl3): δ 208.34, 136.74, 115.84, 61.54, 39.28,

29.78.

Buten Azadithiolate FeFe Cluster (15)

In a 100mL Schlenk flask, THF (30mL) and 4-pentenal (0.6872g) were

added and the flask was sparged with N2 for 5mins and heated to 60°C.

Ammonium carbonate (0.6594g) was then added and the solution was

stirred for 1hr. Next, formaldehyde (0.55mL) was added and the solution

was stirred for an additional hour. In another 100 mL Schlenk flask, THF

(20mL) and (1) (0.4720g) were added and the flask was cooled to -78°C

and sparged with N2 for 5mins. Lithium triethylborohydride (3.4mL) was

then added to the flask and the solution was stirred for 15mins. Next,

trichloroacetic acid (0.44mL) was added and the solution was stirred for an

additional 15mins. The Schlenk flasks were then combined and the

mixture was stirred for ~20 hours at RT. The solution was then

condensed under reduced pressure and diluted with hexanes (200mL).

The product was then extracted through sonication (2hrs). The solution

was then washed with water (2x150mL) and aqueous sodium bicarbonate

(150mL). The organic layer was dried over magnesium sulfate, filtered,

and concentrated under reduced pressure. The product was purified

through silica gel (95:5, Hexanes: Ethyl Acetate) to produce a red oil

1 (0.2993g, 49.5%). H NMR (CDCl3): δ 1.78 (m), 2.18 (m, 2H), 3.34 (s, 1H),

13 3.46 (t, 2H), 2.93 (m, 1H), 5.02 (m, 2H), 5.73 (ddt, 1H); C NMR (CDCl3):

δ 208.33, 136.75, 115.84, 67.47, 61.53, 39.27, 29.78; IR (neat, cm-1):

1269 (C-N), 1642 (C=C), 1962 (C=O), 2025 (C=O), 2071 (C=O), 2922 (C-

H), 3081 (C=C-H), 3358 (N-H).

List of References

(1) “Global Warming”. Oxford English Dictionary 2017. (accessed Mar 25, 2017). (2) Global Warming Effects. www.nationalgeographic.com/environment/global- warming/global-warming-effects/ (accessed Mar 25, 2017). (3) Battisti, D. S.; Naylor, R. L., Historical Warnings of Future Food Insecurity with Unprecedented Seasonal Heat. Science 2009, 323, 240–244 (4) Joyce, C. Get This: Warming Planet Can Mean More Snow. www.npr.org/templates/story/story.php?storyId=123671588 (accessed Mar 25, 2017) (5) Global surface temperature | NASA Global Climate Change. Climate.nasa.gov/vital-signs/global-temperature/ (accessed Mar 25, 2017) (6) Michener, W. K.; Blood, E. R.; Bildstein, K. L.; Brinson, M. M.; Gardner, L. R., Climate Change, Hurricanes and Tropical Storms, and Rising Sea Level in Coastal Wetlands. Ecol. Appl. 1997, 7, 770–801

(7) Solomon, S.; Plattner, G.-K.; Knutti, R.; Friedlingstein, P., Irreversible Climate Change Due to Carbon Dioxide Emissions. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 1704–1709 (8) EPA. Carbon Dioxide Emissions. www3.epa.gov/climatechange/ghgemissions/gases/co2.html. (accessed Mar 25, 2017). (9) Melillo, J. M.; Lu, X.; Kicklighter, D. W.; Reilly, J. M.; Cai, Y.; Sokolov, A. P., Protected Areas’ Role in Climate-Change Mitigation. Ambio 2015, 45, 133– 145 (10) Geller, H.; Harrington, P.; Rosenfeld, A. H.; Tanishima, S.; Unander, F., Polices for increasing energy efficiency: Thirty years of experience in OECD countries. Energy Pol. 2006, 34, 556–573 (11) Advantages and Challenges of Wind Energy. Energy.gov/eere/wind/advantages-and-challenges-wind-energy (accessed Mar 25, 2017 (12) Disadvantages of Hydro Power. www.conserve-energy- future.com/disadvantages_hydropower.php (accessed Mar 25, 2017) (13) Bagher, A. M.; Vahid, M.; Mohsen, M., Geothermal Energy. J. Eng. Technol. Res. 2014, 6, 146–150

(14) Lakatos, L.; Hevessy, G.; Kovács, J., Advantages and Disadvantages of Solar Energy and Wind-Power Utilization. World Futures 2011, 67, 395–408 (15) Puiu, T., Graphene membrane allows mobile Fuel Cells to harvest Hydrogen straight from Air. www.zmescience.com/science/physics/graphene-membrane- fuel-cell-hydrogen-95421/ (accessed Mar 26, 2017) (16) Hydrogen Fuel Cells www.hydrogen.energy.gov/pdfs/doe_fuelcell_factsheet.pdf (accessed Mar 26, 2017). (17) Comparison of Fuel Cell Technologies. www1.eere.energy.gov/hydrogenandfuelcells/fuelcells/pdfs/fc_comparison _chart.pdf (accessed Mar 26, 2017). (18) Where the Energy Goes: Gasoline Vehicles. www.fueleconomy.gov/feg/atv.shtml (accessed Mar 26, 2017) (19) Miessler, G. L.; Tarr, D. A. Inorganic chemistry, 4th ed.; Prentice Hall: Boston, MA, 2011 (20) Ogden, J. M., Prospects for Building a Hydrogen Energy Infrastructure. Annu. Rev. Energy. Environ. 1999, 24, 227–279 (21) Hydrogen Production: Natural Gas Reforming. energy.gov/eere/fuelcells/hydrogen-production-natural-gas-reforming (accessed Mar 26, 2017). (22) Czernik, S.; Evans, R.; French, R., Hydrogen from Biomass-Broduction by Steam Reforming of Biomass Pyrolysis Oil. Catal. Today 2007, 129, 265–268

(23) Barelli, L.; Bidini, G.; Gallorini, F.; Servili, S., Hydrogen Production Through Sorption-Enhanced Steam Methane Reforming and Membrane technology: A Review. Energy 2008, 33, 554–570 (24) Llorca, J.; Homs Narcıś ; Sales, J.; Piscina Pilar Ramıŕ ez De La., Efficient Production of Hydrogen over Supported Cobalt Catalysts from Ethanol Steam Reforming. J. Catal. 2002, 209, 306–317 (25) Chen, W.-H.; Syu, Y.-J., Methanol Steam Reforming for Hydrogen Production. Int. J. Hydrogen Energy 2011, 36, 3397–3408 (26) Hydrogen Production: Electrolysis. https://energy.gov/eere/fuelcells/hydrogen- production-electrolysis (accessed Mar 26, 2017). (27) Zeng, K.; Zhang, D., Recent progress in alkaline water electrolysis for hydrogen production and applications. Prog. Energy Combust. Sci. 2010, 36, 307–326 (28) Turner, J. A., Sustainable Hydrogen Production. Science 2004, 305, 972– 974 (29) Mazloomi, K.; Gomes, C., Hydrogen as an energy carrier: Prospects and challenges. Renew. Sustainable Energy Rev. 2012, 16, 3024–3033

(30) You, J.; Chen, C.-C.; Hong, Z.; Yoshimura, K.; Ohya, K.; Xu, R.; Ye, S.; Gao, J.; Li, G.; Yang, Y., 10.2% Power Conversion Efficiency Polymer Tandem Solar Cells Consisting of Two Identical Sub-Cells. Adv. Mater. 2013, 25, 3973–3978 (31) Chinchilla, M.; Arnaltes, S.; Burgos, J., Control of permanent-magnet generators applied to variable-speed wind-energy systems connected to the grid. IEEE Trans. Energy Convers. 2006, 21, 130–135 (32) Chuanwena, J.; Bompard, E., A Self-Adaptive Chaotic Particle Swarm Algorithm for Short Term Hydroelectric System Scheduling in Deregulated Environment. Energ. Convers. Manage 2005, 46, 2689–2696 (33) Hettiarachchi, H. M.; Golubovic, M.; Worek, W. M.; Ikegami, Y., Optimum design criteria for an Organic Rankine cycle using low-temperature geothermal heat sources. Energy 2007, 32, 1698–1706 (34) Bakker, S., The Car Industry and the Blow-Out of the Hydrogen Hype. Energy Pol. 2010, 38, 6540–6544 (35) Lubitz, W.; Ogata, H.; Rüdiger, O.; Reijerse, E., Hydrogenases. Chem. Rev. 2014, 114, 4081–4148 (36) Kubas, G. J., Fundamentals of H2 Binding and Reactivity on Transition Metals Underlying Hydrogenase Function and H2 Production and Storage. Chem. Rev. 2007, 107, 4152–4205 (37) Buhrke, T.; Lenz, O.; Krauss, N.; Friedrich, B., Oxygen Tolerance of the H2- sensing [NiFe] Hydrogenase from Ralstonia eutropha H16 Is Based on Limited Access of Oxygen to the Active Site. J. Biol. Chem. 2005, 280, 23791–23796

(38) Tard, C., Structural and Functional Analogues of the Active Sites of the [Fe]-, [NiFe]-, and [FeFe]-Hydrogenases. Chemical Reviews 2009, 109, 2245–2274 (39) Lacey, A. L. D.; Fernández, V. M.; Rousset, M.; Cammack, R., Activation and inactivation of hydrogenase function and the catalytic cycle: spectroelectrochemical studies. Chem. Rev. 2007, 107, 4304–4330 (40) Capon, J.-F. C. A.; Ezzaher, S.; Gloaguen, F.; Pétillon, F. Y.; Schollhammer, P.; Talarmin, J., Electrochemical Insights into the Mechanisms of Proton Reduction by [Fe2(CO)6{μ-SCH2NICH2S}] Complexes Related to the [2Fe]H Subsite of [FeFe]Hydrogenase. Chem. Eur. J. 2008, 14, 1954–1964 (41) Wang, N.; Wang, M.; Chen, L.; Sun, L., Reactions Of [FeFe]-Hydrogenase Models Involving the Formation of Hydrides Related to Proton Reduction and Hydrogen Oxidation. Dalton Trans. 2013, 42, 12059–12071 (42) Madden, C.; Vaughn, M. D.; Díez-Pérez, I.; Brown, K. A.; King, P. W.; Gust, D.; Moore, A. L.; Moore, T. A., Catalytic Turnover of [FeFe]-Hydrogenase Based on Single-Molecule Imaging. J. Am. Chem. Soc. 2012, 134, 1577–1582

(43) Parkin, A.; Goldet, G.; Cavazza, C.; Fontecilla-Camps, J. C.; Armstrong, F. A., The Difference a Se Makes? Oxygen-Tolerant Hydrogen Production by the [NiFeSe]-Hydrogenase from Desulfomicrobium baculatum. J. Am. Chem. Soc. 2008, 130, 13410–13416 (44) Wombwell, C.; Caputo, C. A.; Reisner , E., [NiFeSe]-Hydrogenase Chemistry. Acc. Chem. Res. 2015, 2858–2885 (45) Shima, S.; Pilak, O.; Vogt, S.; Schick, M.; Stagni, M.; Meyer-Klaucke, W.; Warkentin, E.; Thauer, R. K.; Ermler, U., The Crystal Structure of [Fe]- Hydrogenase Reveals the Geometry of the Active Site. Science 2008, 321, 572– 575 (46) Salomone-Stagni, M.; Stellato, F.; Whaley, C. M.; Vogt, S.; Morante, S.; Shima, S.; Rauchfuss, T. B.; Meyer-Klaucke, W., The iron-site structure of [Fe]- hydrogenase and model systems: an X-ray absorption near edge spectroscopy study. Dalton Trans. 2010, 39, 3057 (47) Vignais, P. M.; Billoud, B., Occurrence, Classification, and Biological Function of Hydrogenases: An Overview. Chem. Rev. 2007, 107, 4206–4272 (48) Posewitz, M.; Mulder, D.; Peters, J., New Frontiers in Hydrogenase Structure and Biosynthesis. Curr. Chem. Biol. 2008, 2, 178–199 (49) Tye, J. W.; Hall, M. B.; Darensbourg, M. Y., Better than platinum? Fuel cells energized by enzymes. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 16911–16912 (50) Hambourger, M.; Gervaldo, M.; Svedruzic, D.; King, P. W.; Gust, D.; Ghirardi, M.; Moore, A. L.; Moore, T. A., [FeFe]-Hydrogenase-Catalyzed H2 Production in a Photoelectrochemical Biofuel Cell. J. Am. Chem. Soc. 2008, 130, 2015–2022

(51) Na, Y.; Wei, P.; Zhou, L., Photochemical Hydrogen Generation Initiated by Oxidative Quenching of the Excited Ru(bpy)32+* by a Bio-Inspired [2Fe2S] Complex. Chem. Eur. J. 2016, 22, 10365–10368 (52) Goy, R.; Bertini, L.; Rudolph, T.; Lin, S.; Schulz, M.; Zampella, G.; Dietzek, B.; Schacher, F. H.; De Gioia, L.; Sakai, K.; Weigand, W., Photocatalytic Hydrogen Evolution Driven by [FeFe] Hydrogenase Models Tethered to Fluorene and Silafluorene Sensitizers. Chem. Eur. J. 2016, 23, 334–345 (53) Song, L.-C.; Wang, Y.-X.; Xing, X.-K.; Ding, S.-D.; Zhang, L.-D.; Wang, X.-Y.; Zhang, H.-T., Hydrophilic Quaternary Ammonium-Group-Containing [FeFe]- Hydrogenase Models: Synthesis, Structures, and Electrocatalytic Hydrogen Production. Chem. Eur. J. 2016, 22, 16304–16314 (54) Wang, W.; Yu, T.; Zeng, Y.; Chen, J.; Yang, G.; Li, Y., Enhanced photocatalytic hydrogen production from an MCM-41-immobilized photosensitizer–[Fe–Fe] hydrogenase mimic dyad Photochem. Photobiol. Sci. 2014, 13, 1590–1597

(55) Roy, A.; Madden, C.; Ghirlanda, G., Photo-induced hydrogen production in a helical peptide incorporating a [FeFe] hydrogenase active site mimic. Chem. Commun. 2012, 48, 9816–9818

(56) Svedruž ić, D. C. C. C.; Blackburn, J. L.; Tenent, R. C.; Rocha, J.-D. R.; Vinzant, T. B.; Heben, M. J.; King, P. W., High-Performance Hydrogen Production and Hydrogenase Oxidation Electrodes with Supported on Metallic Single-Wall Carbon Nanotube Networks. J. Am. Chem. Soc. 2011, 133, 4299–4306 (57) Garrett, B. R.; Awad, A.; He, M.; Click, K. A.; Durr, C. B.; Gallucci, J. C.; Hadad, C. M.; Wu, Y., Garrett, B. R.; Awad, A.; He, M.; Click, K. A.; Durr, C. B.; Gallucci, J. C.; Hadad, C. M.; Wu, Y., Dimeric FeFe-hydrogenase mimics bearing carboxylic acids: Synthesis and electrochemical investigation. Polyhedron 2016, 103, 21–27 (58) Sommer, C.; Adamska-Venkatesh, A.; Pawlak, K.; Birrell, J. A.; Rüdiger, O.; Reijerse, E. J.; Lubitz, W., Proton Coupled Electronic Rearrangement within the H-Cluster as an Essential Step in the Catalytic Cycle of [FeFe] Hydrogenases. J. Am. Chem. Soc 2017, 139, 1440–1443 (59) Lansing, J. C.; Camara, J. M.; Gray, D. E.; Rauchfuss, T. B., Hydrogen Production Catalyzed by Bidirectional, Biomimetic Models of the [FeFe]- Hydrogenase Active Site. Organometallics 2014, 33, 5897–5906 (60) Xun, Z.; Yu, T.; Zeng, Y.; Chen, J.; Zhang, X.; Yang, G.; Li, Y., Artificial photosynthesis dendrimers integrating light-harvesting, electron delivery and hydrogen production. J. Mater. Chem. A 2015, 3, 12965-12971 (61) Esmieu, C.; Berggren, G., Characterization of a monocyanide model of FeFe hydrogenases – highlighting the importance of the bridgehead nitrogen for catalysis. Dalton Trans. 2006, 45, 19242–19248 (62) Barton, B.; Olsen, M.; Rauchfuss, T., Aza- and Oxadithiolates Are Probable Proton Relays in Functional Models for the [FeFe]-Hydrogenases. J. Am. Chem. Soc. 2008, 103, 16834–16835 (63) Hu, X.; Brunschwig, B. S.; Peters, J. C., Electrocatalytic Hydrogen Evolution at Low Overpotentials by Cobalt Macrocyclic Glyoxime and Tetraimine Complexes. J. Am. Chem. Soc. 2007, 129, 8988–8998 (64) Li, X.; Liu, Y.; Zhao, P., Synthesis and structural characterization of a novel carboxy-functionalized diiron dithiolate complex. Asian J. Chem.2013, 25, 5428- 5430 (65) Gao, W.; Zhang, J.; Yang, J. Synthesis And Structural Characterization Of Diiron Dithiolate Complex [(Μsch2)2Nch2phfe2(CO)5][(Η5-Ph2pc5h4)2Fe] Containing Diphosphine Ligand. Asian J. Chem. 2014, 26, 2089-2091 (66) Song, L.; Wang, L.; Yin, B.; Li, Y.; Zhang, X.; Zhang, Y.; Luo, X.; Hu, Q. Then- Acylated Derivatives Of Parent Complex [{(Μ-SCH2)2NH}Fe2(CO)6] As Active Site Models Of Fe-Only Hydrogenases: Synthesis, Characterization, And Related Properties. Eur. J. Inorg. Chem. 2008, 2008, 291-297

(67) Lawrence, J.; Li, H.; Rauchfuss, T. Beyond Fe-Only Hydrogenases: N- Functionalized 2-Aza-1,3-Dithiolates Fe2[(SCH2)2NR](CO)X (X = 5, 6). Chem. Commun. 2001, 1482-1483. (68) Colavita, P.E.; Sun, B.; Wang, X.Y.; Hamers, R.J., Influence of surface termination and electronicstructure on the photochemical grafting of alkenes to carbon surfaces. J. Phys. Chem. B. 2009, 113, 1526-1535 (69) Tooley, C. A.; Pazicni, S.; Berda, E. B., Toward a tunable synthetic [FeFe] hydrogenase mimic: single-chain nanoparticles functionalized with a single diiron cluster Polym. Chem. 2015, 6, 7646–7651 (70) Colavita, P.; Sun, B.; Tse, K.; Hamers, R., Photochemical Grafting Of N –Alkenes Onto Carbon Surfaces: The Role Of Photoelectron Ejection. J. Am. Chem. Soc. 2007, 129, 13554-13565 (71) Chang, K.; Chen, W., Single-Layer Mos2/Graphene Dispersed In Amorphous Carbon: Towards High Electrochemical Performances In Rechargeable Lithium Ion Batteries. J. Mater. Chem. 2011, 21, 17175-17185 (72) Lockett, M. R.; Carlisle, J. C.; Le, D. V.; Smith, L. M., Acyl Chloride-Modified Amorphous Carbon Substrates For the Attachment of Alcohol-, Thiol-, and Amine-Containing Molecules. Langmuir 2009, 25, 5120–5126 (73) Mulder, D. W.; Shepard, E. M.; Meuser, J. E.; Joshi, N.; King, P. W.; Posewitz, M. C.; Broderick, J. B.; Peters, J. W., Insights Into [FeFe]-Hydrogenase Structure, Mechanism, and Maturation. Structure 2011, 19, 1038–1052 (74) Baghbanzadeh, M.; Simeone, F.; Bowers, C.; Liao, K.; Thuo, M.; Baghbanzadeh, M.; Miller, M.; Carmichael, T.; Whitesides, G., Odd–Even Effects in Charge Transport across n-Alkanethiolate-Based SAMs. J. Am. Chem. Soc. 2014, 136, 16919-16925 (75) Brown, H. C.; Gupta, S. K., Catecholborane (1,3,2-benzodioxaorole) as a new, general monohydroboration reagent for alkynes. Convenient synthesis of alkeneboronic esters and acids from alkynes via hydroboration J. Am. Chem. Soc. 1972, 94, 4370–4371 (76) Lennox, A. J. J.; Lloyd-Jones, G. C., Selection of Boron Reagents for Suzuki– Miyaura Coupling. Chem. Soc. Rev. 2014, 43, 412–443 (77) Sundararaju, B.; Fürstner, A., A Trans –Selective Hydroboration of Internal Alkynes. Angew. Chem. Int. Ed. 2013, 52, 14050–14054 (78) Höpfl, H., The Tetrahedral Character of the Boron Atom Newly Defined—a Useful Tool to Evaluate the N→B Bond. J. Organomet. Chem. 1999, 581, 129–149 (79) Spingler, B.; Pieve, C. D.; Medina-Molner, A., Efficient Routes For the Synthesis of 1,4,7,10,13-Pentaazacyclohexadecane-14,16-Dione. Synthesis. 2007, 5, 679–682

(80) Yazici, A.; Pyne, S. G., Sequential 1,4- And 1,2-Addition Reactions to α,β- Unsaturated N –Acyliminium Ions: A New Strategy for the Synthesis of Spiro and Bridged Heterocycles. Org. Lett. 2013, 15, 5878–5881 (81) Stanley, J.; Rauchfuss, T.; Wilson, S. Studies On The Condensation Pathway To And Properties Of Diiron Azadithiolate Carbonyls. Organometallics 2007, 26, 1907-1911 (82) Stanley, J. L.; Heiden, Z. M.; Rauchfuss, T. B.; Wilson, S. R.; Gioia, L. D.; Zampella, G., Desymmetrized Diiron Azadithiolato Carbonyls: A Step Toward Modeling the Iron-Only Hydrogenases. Organometallics 2008, 27, 119–125 (83) Shen, G.; Hong, J., Synthesis And Antiviral Evaluation Of Novel 2′,2′-Difluoro 5′- Norcarbocyclic Phosphonic Acid Nucleosides As Antiviral Agents. Nucleosides, Nucleotides and Nucleic Acids 2014, 33, 1-17 (84) Ogura, Y.; Sato, H.; Kuwahara, S., Total Synthesis Of Amphirionin-4. Org. Lett. 2016, 18, 2399-2402

Appendices

Appendix A: Characterization of Compounds

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