ACTAUNIVERSITATIS
UPSALIENSISUPPSALA
2015
Digital Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Science and Technology 1258
Synthesis of Biomimetic Systemsfor Proton and Electron TransferReactions in the Ground andExcited State
GIOVANNY A. PARADA
ISSN 1651-6214ISBN 978-91-554-9253-3urn:nbn:se:uu:diva-251471
Dissertation presented at Uppsala University to be publicly examined in Häggsalen,Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, Friday, 12 June 2015 at 10:00 for thedegree of Doctor of Philosophy. The examination will be conducted in English. Facultyexaminer: Professor Ana Moore (Arizona State University, Department of Chemistry &Biochemistry).
AbstractParada, G. A. 2015. Synthesis of Biomimetic Systems for Proton and Electron TransferReactions in the Ground and Excited State. Digital Comprehensive Summaries of UppsalaDissertations from the Faculty of Science and Technology 1258. 104 pp. Uppsala: ActaUniversitatis Upsaliensis. ISBN 978-91-554-9253-3.
A detailed understanding of natural photosynthesis provides inspiration for the development ofsustainable and renewable energy sources, i.e. a technology that is capable of converting solarenergy directly into chemical fuels. This concept is called artificial photosynthesis. The workdescribed in this thesis contains contributions to the development of artificial photosynthesisin two separate areas.
The first one relates to light harvesting with a focus on the question of how electronicproperties of photosensitizers can be tuned to allow for efficient photo-induced electron transferprocesses. The study is based on a series of bis(tridentate)ruthenium(II) polypyridyl complexes,the geometric properties of which make them highly appealing for the construction of lineardonor-photosensitizer-acceptor arrangements for efficient vectorial photo-induced electrontransfer reactions. The chromophores possess remarkably long lived 3MLCT excited states andit is shown that their excited-state oxidation strength can be altered by variations of the ligandscaffold over a remarkably large range of 900 mV.
The second area of relevance to natural and artificial photosynthesis that is discussed inthis thesis relates to the coupled movement of protons and electrons. The delicate interplaybetween these two charged particles regulates thermodynamic and kinetic aspects in many keyelementary steps of natural photosynthesis, and further studies are needed to fully understandthis concept. The studies are based on redox active phenols with intramolecular hydrogenbonds to quinolines. The compounds thus bear a strong resemblance to the tyrosine/histidinecouple in photosystem II, i.e. the water-plastoquinone oxidoreductase enzyme in photosynthesis.The design of the biomimetic models is such that the distance between the proton donor andacceptor is varied, enabling studies on the effect the proton transfer distance has on the rate ofproton-coupled electron transfer reactions. The results of the studies have implications for thedevelopment of artificial photosynthesis, in particular in connection with redox leveling, chargeaccumulation, as well as electron and proton transfer.
In addition to these two contributions, the excited-state dynamics of the intramolecularhydrogen-bonded phenols was investigated, thereby revealing design principles fortechnological applications based on excited-state intramolecular proton transfer andphotoinduced tautomerization.
Keywords: Solar energy conversion, artificial photosynthesis, hydrogen bonds, excitedstate intramolecular proton transfer, tautomerization, proton-coupled electron transfer,photosensitizer, ruthenium complex.
Giovanny A. Parada, Department of Chemistry - Ångström, Box 523, Uppsala University,SE-75120 Uppsala, Sweden.
© Giovanny A. Parada 2015
ISSN 1651-6214ISBN 978-91-554-9253-3urn:nbn:se:uu:diva-251471 (http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-251471)
... para mi Piojito, mi Pelidoja, Pito, mi Camensita, Dudu y Pacelita
con todo mi amor y agradecimiento por tanta ternura
List of Papers
This thesis is based on the following papers, which are referred to in the text by their Roman numerals.
I Tuning the Electronics of Bis(tridentate)ruthenium(II)
Complexes with Long-Lived Excited States: Modifications to the Ligand Skeleton beyond Classical Electron Donor or Electron Withdrawing Group Decorations Giovanny A. Parada, Lisa A. Fredin, Marie-Pierre Santoni, Mi-chael Jäger, Reiner Lomoth, Leif Hammarström, Olof Johans-son, Petter Persson, and Sascha Ott Inorganic Chemistry 2013, 52, 5128-5137
II Synthesis of Phenol-Quinolines with Hydrogen-Bonds of Different Strength Giovanny A. Parada, Starla D. Glover, Andreas Orthaber, Leif Hammarström, Sascha Ott. Manuscript in preparation
III Control over Excited state Intramolecular Proton Transfer and Photo-induced Tautomerization: Influence of the Hy-drogen-Bond Geometry Giovanny A. Parada, Todd F. Markle, Starla D. Glover, Leif Hammarström, Sascha Ott, Burkhard Zietz Chemistry-A European Journal 2015, 21, 6362-6366
IV A Study of Concerted Proton-Coupled Electron Transfer as a Function of Intramolecular Proton Tunneling Distance Starla D. Glover,* Giovanny A. Parada,* Todd F. Markle, And-reas Orthaber, Sascha Ott, Leif Hammarström. Manuscript in preparation
* Contributed to work equally
Reprints were made with permission from the respective publishers.
Contribution report
I am responsible for synthesis design, its implementation and characteriza-tion of the studied molecules in papers I-IV, except for the X-ray crystallog-raphy. In paper I, I performed all the experiments except for quantum chem-ical computations, with major contribution to interpret the results and writing the manuscript. In paper II, I interpreted the results and had major contribu-tion writing manuscript. In paper III, I designed the project, performed the steady state fluorescence measurements and had a major contribution to in-terpret the results and writing of the manuscript. In paper IV, I contributed to discussion of experimental planning and results interpretation, with minor contribution to writing the manuscript.
Contents
Introduction ................................................................................................... 13 1.1 Energy Problem - Photosynthesis and Humans.................................. 13 1.2 Fundamental Aspects of Photosynthesis ............................................ 14 1.3 General Objectives and Approach ...................................................... 15 1.4 Outline ................................................................................................ 16
2. Fundamentals ............................................................................................ 17 2.1 Photosystem II – An overview ........................................................... 17 2.2 Hydrogen Bonds ................................................................................. 20 2.3 Proton-Coupled Electron Transfer ..................................................... 23
3. Tunability of the Redox Properties of [Ru(dqp)2]2+ Analog Complexes .. 26 3.1 Background ........................................................................................ 26 3.2 Substitution of the Lateral Heterocycle Units of [Ru(dqp)2]2+
Analogues. ................................................................................................ 29 3.2.1 Synthesis ..................................................................................... 29
3.3 Structural Characterization of the Complexes. ................................... 31 3.4 Ground State Redox Properties of the Complexes. ............................ 32 3.5 Photophysics and Excited State Redox Properties of the Complexes 34 3.6 Conclusions ........................................................................................ 36
4. Synthesis and Characterization of IMHB Phenols. ................................... 37 4.1 Background ........................................................................................ 37 4.2 Retrosynthetic Considerations ............................................................ 38
4.2.2 Approach 1: Carbocycle Ring Formation. .................................. 39 4.2.3 Approach 2: Heterocycle Ring Formation. ................................. 40
4.3 Synthesis............................................................................................. 42 4.3.1 Synthesis of P5Q......................................................................... 43 4.3.2 Synthesis of P6Q......................................................................... 43 4.3.3 Synthesis of P7Q......................................................................... 44
4.4 Structural Characterization of the PnQ Phenols. ................................. 45 4.4.1 1H-NMR of the IMHB PnQ phenols. .......................................... 45 4.4.2 H-bond Geometry of the IMHB PnQ Phenols. ............................ 47
4.5 Conclusions ........................................................................................ 49
5. Excited State Proton Transfer and Tautomerization of IMHB PnQ Phenols. ......................................................................................................... 50
5.1 Background ........................................................................................ 50 5.2 Electronic Excited State Dynamics of IMHB Phenols ....................... 53
5.2.1 Influence of Equilibrium Proton Donor-Acceptor Distance ....... 54 5.2.2 Influence of the Dihedral Angle Between Proton Donor-
.......................................................................... 57 5.3 Conclusions ........................................................................................ 60
6. Bimolecular Proton-Coupled Electron Transfer of IMHB PnQ Phenols. .. 61 6.1 Background ........................................................................................ 61 6.2 Kinetic PCET Studies ......................................................................... 64
6.2.1 PCET Rates ................................................................................. 64 6.2.2 PCET Driving Force ................................................................... 66 6.2.3 Dependence of the PCET Rate on the Proton Transfer Distance ............................................................................................... 68
6.3 Conclusions ........................................................................................ 70
7. Synthesis of Ruthenium(II) Polypyridyl Dyads Bearing IMHB PnQ Phenols .......................................................................................................... 71
7.1 Background ........................................................................................ 71 7.2 Retrosynthetic Considerations ............................................................ 72 7.3 Synthesis............................................................................................. 74 7.4 Conclusions and Outlook ................................................................... 80
8. Summary and Outlook .............................................................................. 81
Populärvetenskaplig sammanfattning på svenska ......................................... 83
Resumen en Español ..................................................................................... 87
Acknowledgements ....................................................................................... 91
References ..................................................................................................... 93
Abbreviations
:A proton acceptor A proton or electron acceptor A5Q 4-methoxy-11H-indeno[1,2-b]quinoline A6Q 1-methoxy-5,6-dihydrobenzo[c]acridine A7Q 1-methoxy-6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]quinoline ATP Adenosine triphosphate B3LYP Becke, 3-parameter, Lee-Yang-Parr hybrid functional Boc tert-butyloxycarbonyl bpy 2,2’-bipyridine CAHB charge-assisted hydrogen-bond CPET concerted proton electron transfer CI conical intersection COSY correlation spectroscopy CuAAC copper(I) catalyzed azide-alkyne cycloaddition D proton or electron donor DCM dichloromethane dDA proton or electron donor-acceptor distance deeb diethyl-(2,2'-bipyridine)-4,4'-dicarboxylate DFT density functional theory dmb 4,4'-methyl-2,2'-bipyridine dmb-Br 4-(bromomethyl)-4'-methyl-2,2'-bipyridine DMSO dimethyl sulfoxide dNH nitrogen to hydrogen distance dNinp 2,6-di(N-7-azaindol-1-yl)pyridine dOH oxygen to hydrogen distance dON oxygen to nitrogen distance dqp 2,6-di(quinolin-8-yl)pyridine dqxp 2,6-di-(quinoxalin-5-yl)pyridine e- electron EDG electron donating groups Eº standard redox potential Eº’ formal redox potential ESA excited state absorption ESIPT excited state intramolecular proton transfer ET electron transfer
EWG electron withdrawing groups G° standard Gibbs free energy H-bond hydrogen bond HOMO highest occupied molecular orbital
light frequency ICT intramolecular charge-transfer IMHB intramolecular hydrogen bond ISC intersystem crossing IVR intramolecular vibrational redistribution K equilibrium constant k rate constant KIE kinetic isotope effect L ligand LHCs light harvesting complexes LUMO lowest unoccupied molecular orbital MC metal centered excited state MeCN acetonitrile MLCT metal to ligand charge transfer state MV2+ methyl viologen N normal state or enol isomer form NAHPH reduced nicotinamide adenine dinucleotide phosphate NBS N-bromosuccinimide NHE normal hydrogen electrode NIS N-iodosuccinimide NMR nuclear magnetic resonance OEC oxygen evolving complex in Photosystem II OLEDs organic light-emitting diodes P5Q 8-hydroxy-3,4-dihydronaphthalen-1(2H)-one P5Q-2I 1,3-diiodo-11H-indeno[1,2-b]quinolin-4-ol P680 chlorophyll dimer (P680) in Photosystem II P6Q 5,6-dihydrobenzo[c]acridin-1-ol P7Q 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]quinolin-1-ol PA proton affinity PAHB -bond cooperative or polarization-assisted hydrogen-bond PCET proton-coupled electron transfer PCM polarizable continuum model PES potential energy surface PET photo-induced electron transfer Pheo pheophytin pKa -log10(Ka), Ka acid dissociation constant PnQ phenols P5Q, P6Q and P7Q PnQ phenoxyl radical of the PnQ phenols PSII Photosystem II PT proton transfer
py pyridine Qa plastoquinone A in Photosystem II QB plastoquinone B in Photosystem II r0 proton tunneling distance RAHB resonance-assisted hydrogen bond SE stimulated emission SEAR electrophilic aromatic substitution SNuAr nucleophilic aromatic substitution T tautomer state or keto isomer form TD-DFT time dependant density functional theory tpy 2,2’:6’,2’’-terpyridine TyrZ tyrosine 161 in Photosystem II TyrZ-O tyrosine 161 radical in Photosystem II
distance wavefunctions overlap attenuation factor dihedral angle formed between the phenol and quinoline reorganization energy
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Introduction
1.1 Energy Problem - Photosynthesis and Humans Our society is confronted by the daunting challenge of finding renewable energy sources that are abundant, sustainable, economically efficient and easy to integrate into our existing energy infrastructure. The solution to this problem will provide a secure solution to the increasing energetic demands of our society, while avoiding irreversible global environmental changes.1-3 This will inevitably require breakthroughs in many fields of natural sciences and engineering, as well as the utmost commitment of international and na-tional institutions to promote policies that give incentives to the diversifica-tion of our current global energy platform, towards more alternatives of clean renewable energy. This in its turn requires a social breakthrough in policy-making that guarantees environmental sustainability over economic growth, combined with general public awareness of the environmental im-pact of our lifestyle.1,4-8
Today, the vast majority of energy consumed globally is generated from fuels originating from photosynthetically produced biomass mostly acquired about 300 million years ago in the Carboniferous Period.9 This biomass was exposed to heat and pressure in the Earth’s crust forming today’s oil, coal and natural gas, i.e. Fossil Fuels. It is thereby clear that the energy supply for our current society relies primarily –though indirectly– on the conversion of solar energy into chemical energy in the form of chemically reduced mole-cules, that Nature had perfected since the appearance of the first photosyn-thetic bacteria more than 3 billion years ago.10 Humans have been harvesting this ‘archived’ chemical energy by combustion of fossil fuels since the be-ginning of the industrial era at a pace that has caused an increase of the at-mospheric CO2 concentration to the highest levels in the last 650.000 years, greatly disturbing the long-term carbon cycle that has operated in the planet over millions of years.9 The increase of atmospheric CO2 concentration of this and other greenhouse gases has caused global warming and the related environmental changes observed in recent decades.2
Indeed, humans depend on photosynthesis for food production and as a source of energy from ‘archived photosynthesis’ fuels, and the preservation of all the integrated self-regulating mechanisms of the biosphere. As a source of energy, nothing can match the sun. Solar energy is abundant, and in terms of power output, our nearest star has no equal since stellar nuclear
13
fusion out-powers any technology that human can produce. Only a small fraction of the sun’s power output reaches the Earth’s surface (ca. 255000TW),i but it is enough to provide more than 10,000 times more ener-gy than the total worldwide energy consumption (average during 2012: 18 TW).11 The challenge of solar energy technologies is then to harvest a small fraction of that energy in an efficient way, both energetically and economi-cally, and make it easy to integrate into our existing energy infrastructure.
Among the different solar energy technologies, artificial photosynthesis is a visionary strategy aimed to convert solar energy directly into usable chem-ically reduced molecules that can be used as a fuel (Solar fuels), e.g. molecu-lar hydrogen, with the potential of becoming a long term “off-grid”, zero-carbon energy solution.12-15 To this aim, multidisciplinary efforts (e.g. from chemistry, biology, physics, material science, nano-sciences) have been joined to understand fundamental principles of natural photosynthesis and to rationally develop a new technology that contributes to the solution of our contemporary problems in energy security and environmental change, espe-cially regarding pollutant emission and climate change.13
1.2 Fundamental Aspects of Photosynthesis Harvest a portion of the abundant solar energy that strikes the Earth’s sur-face, use part of it to drive the formation of new chemical bonds that can store the remaining energy, while taking electrons from an abundant source to form these chemical bonds. Finally use the stored energy for your needs and do not disturb the biosphere.
These oversimplified guidelines from photosynthesis underpin a clear path for energetic sustainability, yet it is very challenging to combine them in a technology that is efficient, both energetically and economically, and easy to integrate into our current energy infrastructure. This is simple to understand considering that in oxygenic photosynthetic organisms (cyano-bacteria, eukaryotic algae and green plants), photosynthesis requires a highly complex molecular machinery that has evolved over billions of years. There-fore, it is necessary to concentrate only on fundamental aspects to develop artificial photosynthesis.15 In oxygenic photosynthetic organisms, water oxi-dation provides an abundant source of electrons used to form energetic chemical bonds in ATP and NADPH, which are further used as the energy currency for metabolic function. To achieve this, many thermodynamic, kinetic, mechanistic and quantum mechanical aspects play critical roles in a plethora of elementary steps including –but not limited to– energy transfer,
i At the Earth’s surface, the solar energy density is approximately 1000 W/m2 for a surface perpendicular to the Sun’s rays at sea level on a clear day.
14
electron and proton transfer, charge separation, charge accumulation, redox leveling and catalysis. This broad range of aspects of photosynthesis have been the subject of extensive studies for academic purposes and also aiming to provide insight into fundamental aspects to develop artificial photosynthe-sis.
Natural photosynthesis involves many different electron and proton trans-fer reactions.16,17 These reactions are essential for photosynthesis allowing processes like charge separation, charge accumulation, redox leveling, pro-ton-coupled electron transfer and catalysis. The intercorrelation between these processes is such that they often are part of “electron cascades” or “electron chain” mechanisms such that they often need to be considered as a whole rather than isolated cases of electron transfer. These processes are carried out by enzymes, which consist of a complex system of redox active bioinorganic complexes and organic compounds supported by a protein scaf-fold. For example, the first enzyme in the photosynthetic apparatus of oxygenic photosynthetic organisms is Photosystem II (PSII). This enzyme contains a redox active chlorophyll dimer (P680) responsible for using solar energy for (photo-induced) electron transfer. This enzyme also features another very important –and rather unique– bioinorganic complex: a polynuclear manga-nese cluster known as the oxygen evolving complex (OEC) responsible for water oxidation. Electron transfer between P680 and OEC is efficiently medi-ated by a neighboring tyrosine residue, Tyrosine-161 (TyrZ). Extensive re-search has been devoted to obtaining a detailed understanding of the thermo-dynamic, kinetic and mechanistic behavior of this particular enzyme.17 In this context, the interplay of the redox centers P680, OEC and TyrZ has re-ceived much attention.18-22 Unlocking these details in PSII will provide valu-able information to construct a functional and efficient artificial photosyn-thetic systems.23-32
The number of chemical principles inspired by natural photosynthesis that are required for a particular type of technology for solar energy conversion based on artificial photosynthesis depends on specific technical characteris-tics of the embodiment of the invention. In any case, however, the need for a high degree of control of electron transfer processes is a crucial prerequisite. Two types of electron transfer reactions relevant for artificial photosynthesis are photo-induced electron transfer and proton-coupled electron transfer.
1.3 General Objectives and Approach The central topic of this thesis is the synthesis of bioinspired models systems of Chlorophyll dimer (P680) and Tyrosine-161 (TyrZ) in PSII. These model systems allow us to investigate important aspects of photo-induced electron transfer and proton-coupled electron transfer.
15
Biomimetic functional models of the chlorophyll dimer (P680) are homo-leptic and heteroleptic bis(tridentate)ruthenium(II) polypyridyl complexes that feature long-lived 3MLCT excited states and a topology suitable for the construction of rod-like donor-photosensitizer-acceptor arrangements for efficient vectorial photo-induced electron transfer reactions. These complex-es are designed to study their tunability of the ground and excited state redox properties. Biomimetic models of tyrosine-161 (TyrZ) are intramolecularly hydrogen-bonded (IMHB) phenols that feature similar conjugation patterns between the proton donor-acceptor fragments, but dissimilar hydrogen-bond geometries. These phenols are designed to study the proton transfer distance dependence of the proton-coupled electron transfer rate.
After the synthesis design to access the biomimetic systems and their syn-thetic realization and structural characterization, the compounds are investi-gated by physical methods including steady state and transient optical spec-troscopies, electrochemistry and DFT. These studies provide information of their ground and excited state reactivity in electron transfer and proton cou-pled electron transfer reactions.
1.4 Outline This thesis is based on the results presented in four papers (I-IV) that have been listed in the beginning and are included in the end, as well as an appen-dix. In chapter 2, the main fundamental concepts that are relevant for this work are presented. In chapter 3, the synthesis and structural characterization of bis(tridentate)ruthenium(II) polypyridyl complexes and their ground and excited state redox properties is presented. In chapter 4, the synthesis and structural characterization of intramolecularly hydrogen-bonded phenols is discussed. In chapters 5 and 6, studies of proton-coupled electron transfer of the phenols are presented. In chapter 5, the focus is on excited state intramo-lecular proton transfer, while chapter 6 concentrates on bimolecular proton-coupled electron transfer reactions. In chapter 7, the synthesis and structural characterization of molecular dyads based on tris(bidentate)ruthenium(II) polypyridyl complexes with covalently linked IMHB phenols is presented. Finally, chapter 8 closes this thesis with a general summary.
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2. Fundamentals
This chapter provides an introduction to the central concepts encountered in this thesis. This overview introduces the basic aspects of light, electron and proton management in Photosystem II, hydrogen bonds and proton-coupled electron transfer. The chapter aims to make the reader familiar with these concepts and to enable the understanding of the contributions of this thesis in a more general perspective.
2.1 Photosystem II – An overview Photosystem II (PSII) is the only enzyme in living organisms capable of converting solar energy (photons) into charge-separated electron-hole pairs (chemical energy) using water as primary source of electrons. It is a large multi-subunit enzyme imbedded in the thylakoid membrane of cyanobacte-ria, eukaryotic algae and green plants that initiates the photosynthetic cycle. This enzyme is responsible for water:plastoquinone oxidoreductase activity, in which electrons extracted from water are used to reduce a loosely bound plastoquinone (QB), according to the reaction: 2QB + 2H2 BH2 + O2. Once QBH2 is formed, it dissociates from PSII and carries reductive equivalents to the next enzyme in the photosynthetic apparatus, the cyto-chrome b6f complex (Cyt b6f). This enzyme uses QBH2 to reduce plastocya-nin (Pc) while pumping protons from the stroma into the thylakoid lumen to create a chemiosmotic pH gradient required for ATP synthesis.20,33,34
PSII interacts with membrane bound peripheral protein complexes with dozens or even hundreds of protein-bound pigments, termed light harvesting complexes, (LHC) or antenna complexes, that absorb light and funnel the excitation energy to the chlorophyll dimer (P680) in PS II.17 Although P680 can absorb light directly, the LHCs significantly increase the overall light ab-sorption efficiency. LHCs are also responsible for light management by reg-ulating the amount of excitation energy transferred to P680 by photo-protection mechanisms, and by initiating photo-repair mechanisms.35-37
17
Figure 2.1. Electron transfer events in PSII. Figure on the left adapted from ref 38. PET = photo-induced electron transfer, ET = electron transfer.
Photo-excited P680 (P680*) is a strong reductant and is responsible for the primary photochemical event in PSII, photo-induced electron transfer (PET). This reaction initiates a sequence of electron transfer (ET) events assisted by a vectorial arrangement of redox cofactors within the enzyme (Figure 2.1). First, P680* is oxidatively quenched by the primary acceptor pheophytin (Pheo) within a few ps resulting in the charge-separated state Pheo-
680+. In
the next ET event, Pheo- reduces the protein-bound quinone (Qa) within ca. 300 ps resulting in the charge-separated state QA
-680
+. ET from QA-
reduces QB, which after a two ET sequences takes two electrons and two protons (QBH2) and departs from PSII to enter the platoquinone (PQ) pool carrying reductive equivalents used in the metabolic function of Cyt b6f. This sequence of ET steps takes place in the side of PSII regarded as the “accep-tor side” of reducing equivalents.
Regeneration of P680+ occurs by ET from the side of PSII regarded as the
“donor side” of reductive equivalents. The driving force for regeneration of P680
+ arises from the formal redox potential of its redox couple, Eº’ (P680
+/P680) = +1.25 V versus NHE. This potential makes P680+ one of the
most powerful oxidants in nature, capable to provide enough driving force for water oxidation, Eº’(O2/H2O) = +0.91 at pH 5.5 versus NHE. This pro-cess takes place at the oxygen evolving complex (OEC), which is composed of a Mn4CaO5 cluster that accumulates oxidative equivalents for catalytic water oxidation and oxygen-oxygen bond formation. Four oxidative equiva-lents are required for this process, which are accumulated through four suc-cessive sequences of ET from the OEC to P680
+.
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Regeneration of P680+ occurs in the QA
-680
+ state by ET via tyro-sine-161 (TyrZ). This phenolic amino acid is strategically positioned be-tween P680
+ and the OEC: 12-14 Å to the nearest chlorophyll in P680 and 5-7 Å from the OEC. From this position TyrZ can mediate ET between the two.39 Oxidation and reduction of TryZ occurs on different time-scales de-pending on the redox state of the OEC. These redox stated are known as the Sn-states, n = 0-4, where S0 is the most reduced and S4 the most oxidized state (Figure 2.1 rigth). The ET event from TyrZ to P680
+ is coupled to proton transfer (PT). This is facilitated by the hydrogen-bond of the phenolic proton in TyrZ to a neighboring histidine residue, His190 (Figure 2.2). When an electron is transferred from TyrZ to P680
+, the phenolic proton is transferred to His190 to form a tyrosyl radical (TyrZ-O ···H-N+-His190). This particular reaction has been the subject of much research and has inspired work on proton-coupled electron transfer reactions that are studied in this thesis. 22,25,28,40 The TyrZ/ TyrZ-O redox couple operates at the upper limit of redox potentials occurring in Nature at about +1.0 V versus NHE, suitable for oxi-dation of the OEC.29,41-43 The high redox potential of this redox couple avoids energy losses while providing a sufficient driving force for water oxidation
Overall, PSII is capable of converting solar energy into chemical energy by successive charge transfer steps that stabilize reductive and oxidative equivalents across the enzyme over ca. 25 Å. All the ET reactions are initiat-ed by oxidative quenching of P680* and are thermodynamically downhill. This allows for the storage of about 60% of the energy derived from absorp-tion of 680 nm photons (1.84 eV) in the stabilized charge separated state QA
-
Pheo 680 OEC+ (Figure 2.1, right).17,44 Hydrogen bonding can play an important role in reactions involving PT.
There are some interesting features to mention concerning the hydrogen-bond between TyrZ and His190, (TyrZ-O-H···N-His190). From the most recent crystallographic structure of PSII at 1.9 Å resolution,45 it was discov-ered that the oxygen-nitrogen distance (dON) between TyrZ and His190 is 2.5 Å, which is very short and suggests an unusually strong hydrogen bond for a natural system.ii In a recent computational study,40,46 it has been found that the QM/MM geometry optimization of the neutral [TyrZ-O···H···N-His190-NH···O=Asn298] fragment reproduces the crystallographic dON coordinates only when two hydrogen-bonded waters, W4 and W7, were included in the calculation at their respective crystallographic positions at 1.9 Å resolution (Figure 2.2). This computational study also found that the proton free energy profile for this O–H -bond takes the form of a proton-centered, single-well profile. These results provide further insight into the role of this strong hydrogen-bond in the formation of the tyrosyl radical (TyrZ-O ) by
ii Long (weak) hydrogen-bonds out-number short (strong) hydrogen bonds in Nature.
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ET coupled with PT to His190, and regeneration of the TyrZ. This is a very active area of research due to its relevance for the understanding of the criti-cal elemental step in the function of PSII and the modeling of proton-coupled electron transfer reactions.21,22,25,47-49
Figure 2.2. A schematic of the hydrogen-bond network around TyrZ in PSII. Select-ed proton donor-acceptor distances are given in Ångströms. Dotted lines symbolize hydrogen bonds, W = water.
2.2 Hydrogen Bonds In the early 1900s, Alfred Werner was the first to suggest that the properties of ammonium salts (NH4X) can be better explained by assuming that the proton lies in between the ammonia molecule and the anion, (H3N H)X. He called this binding situation secondary valence (Nebenvalenz) –a concept also used to develop his model of coordination in metal complexes. The evolution of this concept throughout the 20th century resulted in a contem-porary interpretation that defines hydrogen bonds (H-bonds) as:
A three-center–four-electron (3c–4e-) shared-proton interaction having the a-
tive atom, such as F, O, N, C, S, Cl, Br and I) and :A the proton acceptor or lone-electron- -bond of a multiple bond). The H-bond can also be seen as a single proton sharing two electron-lone pairs from two adjacent electronegative atoms or groups:
:···H+
Additionally, it is important to note that H-bond donors and acceptors can be combined in multiple arrangements, with configurations that can include multiple H-bond donors and/or multiple acceptors.50
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The definition above emphasizes that the H-bond polarity (D ···:A ) is determined by the electronegativity of the donor and acceptor moieties, rather than by the electronegativity of the donor and ac-ceptor individual atoms. The criteria of a (3c–4e-) shared-proton interaction distinguishes true H-bonds from shared-proton interactions of the type (3c–2e-), presented for example in agostic interactions and boranes.50
H-bonds display a remarkable range of strengths and geometries, from strong, short, linear and proton-centered bonds (symmetric), to weak, long, bent and proton-out-centered bonds (asymmetric). The intercorrelation be-tween strength and geometry of the H-bond arises from the energy minimum that the D dipole experiences when it is collinear with the punctual charge A , as well as the increased orbital overlap provided by short, linear and symmetric (D ···:A ) arrangements. The terms strong, weak and moderate are inevitably arbitrary and must be used with caution. In an at-tempt to provide an energy borderline between them the energy ranges of 15 – 45, 4 – 15, and < 4 kcal mol have been assigned to strong, moderate, and weak H-bonds, respectively.50 Other structural and physicochemical de-scriptors have also been used to delineate these categories: H-bond lengths and angles, the decrease in the infrared frequency, the 1 –H) chemical shift, the proton free energy profile and proton transfer (PT) energy barrier, proton affinities (PA) and pKa equalization cri-teria, among many others. These descriptors are related to one another mak-ing it difficult to establish causality. That is, it becomes difficult to establish which descriptor is the independent variable that determines the H-bond strength and, in consequence, all the other dependant properties.50 At the same time, the intercorrelated character these descriptors allows one to for-mulate important empirical correlations among them.51,52
The strength of the H-bond can also be influenced by the presence of co-operative (also referred to as non-additive) effects. These correspond to a synergistic interplay in which a particular chemical structure operating in the arrangement R-D ···:A -R’ causes additional strengthening of the H-
-bond cooperative or reso-nance-assisted H-bond (RAHB), charge-assisted H- -bond cooperative or polarization-assisted H-bond (PAHB). RAHB was first used to explained the abnormally strong intramolecular H-bond (IMHB) formed by the ···O=C-C=C- -enolone fragmen -diketone enols,53 and later extended to ···O=C-C=C- -enaminones.54 However, it can also be found in inter-molecular H-bonded chains and dimers of car-boxylic acids, amides and amidines (Figure 2.3a and b). A phenomenologi-cal interpretation of the RAHB that occurs when the proton donor and accep-
-conjugated fragment is described by the synergistic reinforcement between H- -delocalization enhance-ment. In this interpretation b -delocalization) within the conjugated fragment establishes opposite partial charges in the proton
21
donor and acceptor. This causes the proton donor-acceptor distance dDA to be shortened while elongating acceptor) to cancel the charges. This leads to an increase in H-bond strength. This mechanism that compensates the partial charges on the heteroconjugat-
-delocalization, thereby establishing a positive self-feedback loop. This phenomenological description of the RAHB effect underlies the basis of the so-called RAHB ionic model. Other more elaborated semiempirical and quantum chemistry models have accounted for the same cooperative effect.50
Figure 2.3 RAHB in a) conjugated chains, b) conjugated dimers (Y and X = O or
-diketone enols. Left: Keto-enol tautomerization according to the RAHB ionic model. Right: Experimental evidence supports a proton-centered RAHB H-bond rather than a keto-enol equilibrium in symmetric very strong H-bonded systems.52
The strength of the H-bond has important implications for PT kinetics since it correlates with the proton free energy profile and the PT energy barrier. Very weak H-bonds are typically associated with asymmetric (different do-nor and acceptor moieties) single-well proton free energy profiles and high PT barriers. Progressive increase of the H-bond strength changes the proton free energy profiles towards asymmetric double-well, to symmetric double-wells with a concomitant decrease of the PT barrier. The unusual case of very strong H-bonds, typically associated with CAHB or RAHB symmetric H-bonds, features symmetric single-well proton free energy profiles. In this particular case the energy minimum corresponds to the proton centered in
22
the middle of the H-bond and therefore no PT transfer barrier exits (Figure 2.4).50
Figure 2.4. Schematic proton free energy profiles of H-bonds of various strengths.
2.3 Proton-Coupled Electron Transfer Changes in the redox potential or proton transfer equilibria of a chemical species can influence each other, thereby these two chemical reactions often occur in association. This fundamental concept of chemistry is best exempli-fied by the Nernst Equation which relates the variation of the aqueous oxida-tion/reduction potential of chemical reactions with the pH when protons are involved. In a more general sense, the thermodynamic correlation between electron an proton transfer establishes that the redox potential (oxidation state or electronic configuration) of a chemical species can affect its acid-base equilibria, that is, its pKa (or protonation state). This concept constitutes the thermodynamic basis of proton-coupled electron transfer (PCET) reac-tions, in which proton and electron movement are intercorrelated.55,56
Figure 2.5. a) Schematic PES for a bimolecular PCET reaction X = electron accep-tor, Y = proton donor and Z = proton donor. b) Schematic proton and electron ener-gy diagrams for a CEPT reaction (reactant (R) and product (P) states, Transition state (TS)).
Concerted proton electron transfer (CPET)57 involves the transfer of both a proton and an electron in a single chemical step. It implies that the reaction occurs without an intermediate, as opposed to the stepwise mechanism of a proton transfer followed by an electron transfer, PT-ET mechanism, or vice
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versa, in an ET-PT mechanism. Along a potential energy surface (PES) hav-ing collective ET and PT reaction coordinates, the CPET reactions occurs through the diagonal connecting reactants and products, while the stepwise mechanisms (ET-PT and PT-ET) occur along the edges of a square scheme (Figure 2.5a). Bidirectional PCET processes refer to the case in which the proton acceptor and the electron acceptors in the PCET reaction are different entities.
Kinetic formulations for ET and PT have been used to derive rate expres-sions for each of the charge transfer processes separately: Marcus formula-tion of ET,58 and Hynes formulations of PT.59-62 Only recently kinetic formu-lations have been derived for the coupled movement of protons and electrons (in a single chemical reaction step), incorporating the quantum mechanical behavior of the active transferring proton and electron, as a function of col-lective reaction coordinates for PT and ET.63,64 In the case of a CPET involv-ing H-bonding (Figure 2.5b), the ET component of the reaction is described by non-adiabatic parabolic functions according to the Marcus formulation in the reactants and product states. In this case, the PT component of the reac-tion is described by electronically adiabatic proton free energy profiles cal-culated along the ET coordinate. Two very important features of this formu-lation deserve to be highlighted in the context of this thesis. First, the pro-gress of the reaction in the ET coordinate determines the shape of the proton free energy profiles, specifically the relative energy of the proton in reactants and product states during the course of the reaction. Second, at the crossing point (transition state) the proton reactant and product states are degenerate. At this point, the specific shape of the proton free energy profiles (and PT energy barrier) becomes highly dependent on proton tunneling distance, determining the overlap of the proton reactant and product states wavefunc-tions, and thereby the proton tunneling probability. Regarding this feature, it is important to consider that since protons are much more localized than electrons, protons exhibit a much stronger distance dependence of the trans-fer rate.65 Additionally, the factors contributing to increase the strength of the H-bond also lead to more efficient PT rates (Figure 2.6).
Figure 2.6. Schematic proton free energy profiles at the transition state for a CPET reaction for various H-bond strengths.
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Stepwise PCET reactions are very important and can be treated using classi-cal thermodynamic and kinetic formulations. A particular case of stepwise PCET results when photo-induced electronic transitions change the pKa properties of proton donor and acceptors (photo-acidity). This case repre-sents the thermodynamic basis of excited state intramolecular proton transfer (ESIPT) of IMHB phenols studied in chapter 5.
The examples in which Nature uses the thermodynamic coupling of ET and PT to perform reactions that otherwise would be thermodynamically unfavorable and/or kinetically very slow are breathtaking,28,34,64,66-69 as well as the quantum chemical complexity of the new kinetic formulations that have been derived to describe them. Though PCET reactions may seem very complex, the current theoretical formulations of CPET reactions have pro-vided manageable criteria by which to study natural and biomimetic systems, whereby insights into the mechanistic and kinetic details of these processes can be elucidated. In addition to clarifying how enzymes perform catalysis efficiently, what we learn from PCET studies will better prepare researchers on how to predict and control PCET reactions that will inevitably be opera-tional within artificial synthetic schemes.
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3. Tunability of the Redox Properties of [Ru(dqp)2]2+ Analog Complexes
This chapter describes the synthesis and photoredox properties of homoleptic and heteroleptic bis(tridentate)ruthenium(II) polypyridyl complexes featur-ing six-membered chelate rings. Ground and excited state redox properties within this series of complexes can be tuned by inclusion of heterocycle rings with different electron-donating abilities in the lateral subunits of the tridentate dqp ligand.
3.1 Background Ruthenium(II) polypyridyl complexes meet most of the requirements for light harvesting units (photosensitizers) in a wide range of applications that rely on light-induced electron/energy transfer.70-72 Requirements for efficient photosensitizers include: 1) strong light absorption in the relevant spectral region, 2) suitable redox potentials in the ground and excited state to provide sufficient driving force to enable efficient photoredox reactions, 3) suffi-ciently long lifetimes of the redox active excited state, 4) chemical stability in the ground and excited state and, 5) facile synthesis that allows a high degree of tunability. Furthermore, photosensitizers suitable for the assembly of supramolecular structures (e.g. dyads and triads) need to meet an addi-tional topological requirement. Specifically, they need to provide geomet-rical control of the supramolecular ensemble affording rod-like arrays, ena-bling efficient vectorial electron transfer (Figure 3.1a).73
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Figure 3.1 a) Schematic rod-like supramolecular ensemble. Photo-induced electron transfer from a sensitizer (PS) is capable of reducing an acceptor (A) and oxidizing a donor (D). The moieties A and D are also capable of performing redox chemical transformations b) The 4,4’-di(substituted) [Ru(tpy)2]2+ sensitizer possess a C2 axis along the central pyridines suitable for rod-like assembles.
Photosensitizers based on bis(tridentate)ruthenium(II) polypyridyl complex-es provide a suitable scaffold for the construction of supramolecular rod-like molecular arrays due to their C2 symmetry axis along the central pyridine. Ruthenium(II) complexes based on the tridentate ligand 2,2’:6’,2’’-terpyridine (tpy) (e.g. [Ru(tpy)2]2+) are the most accessible (including several synthetic approaches to afford this class of ligands) and therefore, the most studied complexes (Figure 3.1b).74-76 However, this vast family of polypyridyl ruthenium(II) complexes in general displays poor photophysical performance at room temperature mainly attributed to a readily thermally accessible cross-point from the 3MLCT state to the 3MC state, from which efficient non-radiative deactivation to the ground state occurs.77,78
The focus of significant research efforts over the last three decades has been to enhance the photophysical properties of bis(tridentate)ruthenium(II) polypyridyl complexes.79,80 For this purpose, principles of ligand field theory have been applied with the aim to increase the 3MLCT - 3MC energy differ-ence in [Ru(tpy)2]2+ analogs. In general, this approach relies on a combina-tion of incorporating electron withdrawing groups (EWG) on the tpy scaf-
-acceptor ability and electron donating groups (EDG) that increase its -donating ability. The addition of EWG and EDG to the scaffold results in stabilization of the 3MLCT and destabilization of the 3MC.81
An alternative approach is to modify the ligand scaffold to encourage oc-tahedral geometry of the coordination polyhedron around the ruthenium(II) metal center.82-85 The idea behind this approach is based on the improving a somewhat distorted octahedral geometry of the coordination polyhedron of [Ru(tpy)2]2+ analogs, which is considered to be responsible for the small ligand field splitting that allows thermally accessible conversion from the 3MLCT to the 3MC. An increased octahedral geometry of the coordination polyhedron can be obtained by extending the bite angle of the tridentate polypyridyl ligand. In practice, larger bite angles can be formed upon mov-ing from five-membered chelate rings, as in tpy (~ 159º), towards six-membered chelate rings, such as dqp analog ligands dqp = 2,6-di(quinolin-8-
27
yl)pyridine, bite angle ~ 180º (Figure 3.2a). The success of this approach becomes clear considering that [Ru(dqp)2]2+ shows a remarkably long life-time of the 3 which is four orders of magnitude longer than its tpy analog [Ru(tpy)2]2+ (~ 250 ps).86 Quantum chemical calculations pro-vided insight into the underlying reasons of improved photophysical perfor-mance in [Ru(dqp)2]2+.87,88 The results can be summarized as follows: with similar calculated energies of the relaxed 3MLCT and
3MC states, the larger barrier for inter-conversion from the 3MLCT to the 3MC states is ascribed to an increased ligand field splitting in the Franck-Condon region together with a change in the energy and position of the relaxed 3MC minima (Figure 3.2b).
Figure 3.2a) Differences in the bite angle between tpy and dqp b) Schematic poten-tial energy surfaces of [Ru(tpy)2]2+ and [Ru(dqp)2]2+.
Since the introduction of this design principle, numerous bis(tridentate) polypyridyl ruthenium(II) complexes featuring six-member chelated rings have been studied.79,89-93 Among them, various [Ru(dqp)2]2+ analog com-plexes have demonstrated that introducing different EWG and EDG in the 4’-position of the dqp ligand provides a certain degree of redox tunability of excited and ground state of the complexes.85 Unfortunately, the 4’ position is also the position through which donor or acceptor groups would be linked for vectorial electron transfer processes in future assemblies, and redox tun-ing through substituents at this position is thus disadvantageous. This is even more so as different photo-driven redox processes require ground state oxi-dation potentials that are even higher than those achieved by simple 4’ sub-stitutions. This is the case, for example, in the use of currently available mo-lecular catalysts for photo-induced water oxidation.94,95 This limitation has motivated the investigation of new methodologies to increase the redox tunability of ruthenium(II) complexes based on the [Ru(dqp)2]2+ prototype. The underlying principle of the strategy herein investigated involves the replacement of the lateral quinolinyl heterocycle of dqp by isoelectronic heterocycle rings with different degrees of -accepting ability. This afforded
28
a series of [Ru(dqp)2]2+ analog complexes that show a high degree of ground and excited state redox tunability.
3.2 Substitution of the Lateral Heterocycle Units of [Ru(dqp)2]2+ Analogues. The fused ring heterocycle moieties quinoxalinyl and 7-N-azaindoyl were selected as suitable candidates to replace the lateral quinolinyl unit of dqp ligands. When attached to a central pyridine, these fragments afford the lig-ands 2,6-di-(quinoxalin-5-yl)pyridine (dqxp) and 2,6-di(N-7-azaindol-1-yl)pyridine (dNinp), which both fulfill the topological requirement of form-ing two six-membered chelate rings upon coordination to ruthenium(II). The quinoxalinyl fragment (a benzene-fused pyrazine) features a second imine nitrogen atom in place of the C-4 in quinoline. This results in a more elec-tron deficient heterocyclic moiety that renders the dqxp ligand a -acceptor compared to dqp. In contrast, the 7-N-azaindoyl fragment features a
-electron, five-membered aromatic ring; isolectronic with the cyclopentadienyl anion) in place of the benzene ring in quinoline. In consequence, this results in a more electron rich heterocycle that makes the dNinp ligand a -acceptor compared to dqp (Figure 3.3).
Figure 3.3. a) Quinoline and its isoelectronic 1,4-diazine analogue. b) Quinoline and its isoelectronic 5-membered aromatic carbocyclic and N-heterocyclic analogues.
3.2.1 Synthesis The synthesis of dqp analog ligands has been successfully optimized using
-coupling reaction of 2,6-dibromopyridines and quino-line-8-boronic acid. In this approach, the boronic coupling partner can be readily prepared by lithiation of the 5-bromoquinoline precursor, followed by borylation of the aryl-lithium intermediate.89 The adaptation of this meth-odology to afford dqxp via lithiation of the 5-bromoquinoxaline precursor proved to be not viable due to the enhanced nucleophylicity of C-2 and C-3 in the diazine heterocycle. An early approach to avoid this shortcoming was based on in-situ Suzuki borylation of the 5-bromoquinoxaline precursor to afford the intermediate quinoxaline-5-boronic acid pinacol ester, followed by
-coupling with 2,6-dibromopyridine. This method
29
afforded the desired dqxp ligand; however, in very low isolated yields (3%), despite extensive attempts to optimize different reaction parameters.
In order to overcome this limitation different alternative methods were explored. A particularly interesting strategy relies on switching the role of the substrates in the palladium catalyzed C-C cross-coupling. This was achieved by moving from a a Stille cross-coupling using 5-bromoquinoxaline and 2,6-di(trimethylstannyl)pyridine as coupling part-ners. In this case, the 5-bromoquinoxaline can readily enter the catalytic cycle as the halo-aryl substrate without further functionalization, whereas the 2,6-di(substituted)pyridine participates as the transmetalating agent in the form of a stannyl (Figure 3.4). This strategy afforded satisfying isolated yields of dqxp (59%). Finally, the dNinp ligand was obtained using het-eroaryl amination in analogy to an established procedure.96
Figure 3.4 Synthetic methods used to prepare the ligands dqxp, dNinp and dqp.
For the synthesis of homoleptic and heteroleptic ruthenium(II) complexes of the ligands dqxp, dNinp and dqp, numerous different ruthenium precursors and reaction conditions were screened. In the case of the homoleptic com-plexes [Ru(dqxp)2]2+ and [Ru(dNinp)2]2+ best yields were obtained using [RuCl2(DMSO)4] and RuCl3 precursors, respectively. Best yields for the synthesis of the heteroleptic complexes [Ru(dqxp)(dqp)]2+ and [Ru(dqxp)(dqp)]2+ were obtained using a [Ru(dqp)(MeCN)3]2+ precursor.
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Figure 3.5. Series of bis(tridentate)ruthenium(II) complexes studied.
3.3 Structural Characterization of the Complexes. Relevant structural information of the complexes [Ru(dqxp)2]2+
, [Ru(dNinp)2]2+, [Ru(dqxp)(dqp)]2+ and [Ru(dqxp)(dqp)]2+ was obtained by using both X-ray crystallography and DFT calculations. In general, the com-plexes have structural features similar to those of the [Ru(dqp)2]2+ prototype. All the complexes form an almost perfect octahedral coordination polyhe-dron around the ruthenium center, having ligand bite angles close to 180º and bond distances between the lateral heterocycle and the ruthenium(II) close to 2.07 Å. The most significant structural variations on this series are found in the bond distances between the central pyridine of the ligands and the ruthenium(II) center. Crystallographic information reveals that this dis-tance spans from 2.02 Å in dqxp (close to 2.03 Å in dqp) to 2.08 Å in dNinp. Importantly, a similar trend was also reproduced by DFT calculations of the homoleptic complexes of dqxp, dNinp and dqp. Additionally, the structural characterization of the complexes also shows that upon coordination to ru-thenium(II), dqxp and dNinp adopt non-planar helical conformations. This feature has also been described for dqp, and provides the complexes with conformational chirality.97
Figure 3.6. Ortep views of a) [Ru(dqxp)(dqp)]2+ and b) [Ru(dNinp)(dqp)]2+ (50% probability ellipsoids).
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3.4 Ground State Redox Properties of the Complexes. Cyclic voltammetry and differential pulse voltammetry were used to charac-terize the ground state redox properties of the complexes. Additionally, the observed trends were successfully reproduced by DFT calculations using adiabatic ionization potentials. All the complexes disclose a reversible Ru3+/2+ couple and a ligand based first reduction L0/1-, both assigned similarly to those of [Ru(dqp)2]2+ (E1/2(Ru3+/2+)/V= +0.71 and E1/2(L0/1-)/V= -1.73 vs Fc0/+). Using [Ru(dqp)2]2+ as reference, complexes [Ru(dqxp)(dqp)]2+ and [Ru(dqxp)2]2+ show sequential anodic shifts of the Ru3+/2+ couple of 240 mV and 470 mV, respectively. This anodic shift of the Ru3+/2+ couple originates from the stronger -acceptor ability of dqxp compared to dqp, and replace-ment of each individual dqp by a dqxp gives rise to a shift of 240 mV. Addi-
-bonding interaction between the ruthenium(II) d-orbitals and dqxp’s bonding orbitals, caus-ing the stabilization of the metal d-orbitals. The ligand based reductions of [Ru(dqxp)(dqp)]2+ and [Ru(dqxp)2]2+ are also anodically shifted compared to those of [Ru(dqp)2]2+, in line with the electron deficient character of dqxp compared to dqp. Small anodic shifts of the Ru3+/2+ couple of [Ru(dNinp)(dqp)]2+ and [Ru(dNinp)2]2+ were observed. This finding was reproduced by the calculated adiabatic ionization potentials. The L0/1- redox couple of [Ru(dNinp)2]2+ is cathodically shifted 330 mV compared to that of [Ru(dqp)2]2+. In the case of [Ru(dNinp)(dqp)]2+, the first ligand based reduc-tion occurs on the dqp. Comparison of the potentials of the Ru3+/2+ and L0/1- redox couples in [Ru(dNinp)2]2+ versus those of [Ru(dqp)2]2+ confirms the
-acceptor ability of dNinp compared to that of dqp (Figure 3.7).
Figure 3.7 a) Cyclic voltammograms of the series of complexes and b) tabulated redox potential of the first oxidation and reduction. All potentials are referenced to Fc0/+.
Analysis of the different contributions to the calculated frontier molecular orbitals of the homoleptic complexes of dqxp, dNinp and dqp reveals further insights. The HOMOs in [Ru(dqxp)2]2+ and [Ru(dNinp)2]2+ show contribu-tions from the ruthenium(II) 4d orbitals and the ligands, in particular from
32
the lateral fragments thereof. This situation is unlike the HOMO in [Ru(dqp)2]2+ which has dominant contributions of the ruthenium 4d orbitals.85 The stronger contribution of the dqxp and dNinp to the HOMO provides further stabilization, which in turn correlates with the observed anodic shifts of the Ru3+/2+ redox couples.
Important differences in the contributions to the LUMO of [Ru(dqxp)2]2+
and [Ru(dNinp)2]2+ were found. The LUMO of [Ru(dqxp)2]2+ shows signifi-cant distribution onto the quinoxalinyl fragments, with only small contribu-tions of central pyridines. Conversely, the LUMO of [Ru(dNinp)2]2+ is main-ly localized on the central pyridines, with only minor contributions from the lateral 7-N-azaindoyl fragments. This sharp difference in orbital contribu-tions to the LUMO of these complexes can be analyzed analogously to the particle in a box model learned in basic quantum mechanics. This model states that the energy of particle decreases as the length of the box increas-esiii. Thus, a one electron reduction in the case of [Ru(dNinp)2]2+ can be con-sidered to add an electron to a more localized, and therefore higher in energy LUMO orbital, 1.07 eV higher in energy to that of [Ru(dqxp)2]2+. Likewise, such differences account for ~900 mV difference in the potential of the L0/1- redox couple between [Ru(dqxp)2]2+ and [Ru(dNinp)2]2+(Figure 3.8).
Figure 3.8 Calculated frontier molecular orbitals of a) [Ru(dqxp)2]2+ and b) [Ru(dNinp)2]2+.
iii In the simplest form of the particle in a box model that considers a one-dimensional system the, the zero-point energy level (lowest possible energy of the particle) is given by =
2 where m is the mass of the particle and L is the length of the box.
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3.5 Photophysics and Excited State Redox Properties of the Complexes Complexes [Ru(dqxp)2]2+, [Ru(dqxp)(dqp)]2+ and [Ru(dNinp)(dqp)]2+ show absorptions in the visible range centered around 470 nm, assigned to broad 1MLCT transitions. Complex [Ru(dNinp)2]2+ exhibits a strongly blue-shifted 1MLCT transition center around 380 nm. This effect was reproduced by TD-DFT calculations, and was explained by the high energy of the LUMO or-bital in this complex, as described above. The [Ru(dqxp)2]2+, [Ru(dqxp)(dqp)]2+ and [Ru(dNinp)(dqp)]2+ complexes show a room tempera-ture emission from the 3MLCT state with emission excited state lifetime in deaerated solutions of 255, 120 and 1570 ns, respectively. These lifetimes are several orders of magnitude longer than that found in the [Ru(tpy)2]2+
parent complex. Complex [Ru(dNinp)2]2+ is not emissive at room temperature, suggesting
a readily accessible 3MLCT-3MC crossing point, at least in part due to a weak ligand field splitting in the complex. A weak ligand field splitting in [Ru(dNinp)2]2+ correlates with the long distance of the -central pyridine bond (2.10 Å, calculated in the ground state). Moreover, further
3MC are expected,87 which can cause the stabilization of the 3MC, as described for [Ru(dqp)2]2+. Thus, with a significantly stabilized 3MC in [Ru(dNinp)2]2+, a readily ther-mally accessible conversion from the 3MLCT to the 3MC can be anticipated. In addition, the observed broad band emission of [Ru(dNinp)2]2+ at 77 K supports the idea of a highly distorted (elongated) excited state.
The excited state reduction and oxidation potentials of the complexes ac-cording to the reactions in equations 3.1 and 3.2 respectively, can be esti-mated from the excited state energy and their respective ground state first oxidation and reduction potential according equations 3.3 and 3.4 respective-ly. Thus, the excited state reduction and oxidation redox potentials of the complexes are estimated with the excited state energies (E0-0) of about 1.8 eV and the redox potential of the different Ru3+/2+ and L0/1- couples (Figure 3.7b and 3.9, bottom). E0-0 values are in turn estimated from the peak with the highest energy in the vibrational progression from the emission maxima of the complexes measured at 77 K in n-BuCN glass.98-100
PS* + e- PS- E0(PS*/-) (eq 3.1) PS+ + e- PS* E0(PS+/*) (eq 3.2) E0(PS*/-) E0(PS+/0 (eq 3.3) E0(PS 0(PS ) + E (eq 3.4 )
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Figure 3.9. Diagram of the possible photoredox processes (top) and excited state redox potentials (bottom) for the investigated photosensitizers.
Significant differences in the excited state redox power of the studied com-plexes were observed on the basis of their calculated excited state reduction and oxidation potentials. Such differences reveal the high degree of redox tunability induced by variations on the lateral fragments of the ligand on [Ru(dqp)2]2+ analogs. Comparison of the excited state redox potential of the
-acceptor fragments stabilize the one electron reduced ground state of the photosensi-tizer, as in the case of [Ru(dqxp)2]2+ and [Ru(dqxp)(dqp)]2+. Such stabilizing effect accounts for the significant increase in the driving force for reductive quenching observed in complexes with dqxp compared to [Ru(dqp)2]2+. In-terestingly, compared to [Ru(dqp)2]2+, complexes [Ru(dqxp)2]2+ and [Ru(dqxp)(dqp)]2+ are stronger excited state oxidants by more than 500 mV and 300 mV, respectively (Figure 3.9).
Conversely, in the case of [Ru(dNinp)2]2+ the destabilizing effect of the electron rich lateral fragments of the ligand on the one electron reduced ground state of the photosensitizer accounts for the decrease in the driving force for reductive quenching compared to [Ru(dqp)2]2+. Complex [Ru(dNinp)(dqp)]2+ undergoing a first one electron reduction on the dqp ligand shows similar driving force for reductive quenching to [Ru(dqp)2]2+. In addition, the small influence of the dNinp ligand on the HOMO of the
35
complexes explains the limited ability of dNinp to influence the driving forces for oxidative quenching of [Ru(dNinp)2]2+ and [Ru(dNinp)(dqp)]2+.
3.6 Conclusions This study demonstrates that substitution of the quinolinyl fragments of dqp
-accepting fragments is a very effective way to alter the electronic properties of [Ru(dqp)2]2+ analog complexes. A combination of experimental and theoretical studies allowed us to delineate the electronic influence of the -accepting characters of ligands dqxp and dNinp the on bis(tridentate)ruthenium(II) polypyridyl complexes. While preserving an octahedral geometry of the coordination polyhedron around the rutheni-um(II) center, homoleptic and heteroleptic complexes of the ligands dqxp, dNinp and dqp show good photophysical properties that makes them suitable candidates for the development of rod-like supramolecular assemblies.
The -acceptor ability of dqxp on the one electron reduction of its ruthenium(II) complexes results in a large driving force for reduction of the ground and excited state. This feature makes ruthenium(II) complex of dqxp attractive candidates in photoredox applications that require high oxidation power, for example in the case of photo-induced water oxidation.
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4. Synthesis and Characterization of IMHB Phenols.
This chapter describes the synthesis and structural characterization of a se-ries of intramolecular H-bonded phenols featuring similar conjugation pat-terns between the proton donor-acceptor fragments and dissimilar H-bond geometries resulting in significant differences in the H-bond strength within the series.
4.1 Background The proton transfer distance dependence of the PCET rate has been previ-ously studied on intramolecularly H-bonded (IMHB) tyrosine analogs cova-lently attached to tris(bidentate)ruthenium(II) polypyridyl photosensitizers (Figure 4.1).101,102 These model systems have provided significant insight into the influence of the proton tunneling distance on the rate of PCET. A common feature of the IMHB tyrosines in these studies was that the proton donor-acceptor distance (dDA) had been varied by a methylene (-CH2-) frag-ment that acted as a spacer between the proton donor (an ortho-substituted phenol) and proton acceptor, (an (O)-carboxyl, (N)-pyridine or (N)-benzimidazol)). While this approach successfully modulates dDA, it also changes the conjugation pattern between the proton donor-acceptor frag-ments. As a consequence, the IMHB phenols with no methylene spacer are in -conjugation with the proton acceptor fragments which results in reso-nance assistance H-bond (RAHB). In contrast, such an effect is precluded in the respective IMHB phenols with the methylene spacer due to the broken conjugation pattern.
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Figure 4.1. Previously studied IMHB tyrosine analogs covalently attached to ruthe-nium(II) polypyridyl photosensitizers. a) Tyrosines featuring no methylene spacer (conjugated pattern highlighted by gray shadow) and, b) respective tyrosines with the methylene spacers.
This dichotomy has motivated the synthesis of a new series of IMHB tyro-sine analogs covalently attached to a tris(bidentate)ruthenium(II) polypyridyl photosensitizers in which the IMHB phenols maintain the same conjugation pattern along the series, while variations on dDA are introduced by virtue of a doubly fused cycloalkadiene ring of 5, 6 and 7 members (1,3-cyclopentadiene, 1,3-cyclohexadiene and 1,3-cycloheptadiene) between the phenol and a pyridine proton acceptor (Figure 4.2).
Figure 4.2. Proposed IMHB tyrosine analogs covalently attached to a ruthenium(II) polypyridyl photosensitizer. Gray shadows highlight the conjugated pattern between the proton donor-acceptor moieties.
4.2 Retrosynthetic Considerations Finding a synthetic route to the IMHB tyrosine analogs in Figure 4.2 de-manded a careful literature survey on different synthetic approaches in order to assess which one may be viable. This study finally determined whether or not the initially proposed IMHB tyrosine analogs were synthetically feasible.
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As a starting point, the synthesis of the previously studied IMHB tyrosine analogs was examined since, at first glance, the N-tert-butyloxylcarbonyl-3-(pyrid-2’-yl)-L-tyrosine ethyl ester (2-(2’-py)-Tyr, Figure 4.3) is the closest tyrosine analogue to the target structures. In all cases, the synthesis of the previously studied IMHB tyrosine analogs relies on the regioselective func-tionalization of the ortho position of the benzene ring of Boc-protected L-tyrosine (Figure 4.3). This common synthetic strategy is possible due to the strong activating effect on the ortho/para positions towards electrophilic aromatic substitution (SEAR), characteristic of classical phenol reactivity. Moreover, regioselective SEAR functionalization in the ortho position is guaranteed since the para in the Boc-protected L-tyrosine starting material is occupied by the alkyl amino acid fragment.
Figure 4.3. Retrosynthesis of the previously studied IMHB tyrosine analogs.
4.2.2 Approach 1: Carbocycle Ring Formation. Based on the easy accessibility of 2-(2’-py)-Tyr as a building block for the synthesis of the proposed IMHB tyrosine analogs, the feasibility of a syn-thetic strategy relying on a cycloalkadiene ring formation between the phe-nol and pyridine was evaluated (Figure 4.4).
Figure 4.4. Retrosynthesis analysis based on carbocycle ring formation.
In order to develop a synthetic strategy based on 2-(2’-py)-Tyr as a common precursor, suitable conditions to separately functionalize the phenol C-3 and the pyridine C-3’ would be required. Functionalization of the C-3 phenol in 2-(2’-pyridine)-tyrosine is synthetically challenging since such position is
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the least reactive towards SEAR. This limitation excludes the great majority of available synthetic methods. An alternative approach using nucleophilic aromatic substitution (SNuAr) on phenol C-3 is unfeasible since most syn-thetic methods require elimination of a good leaving group in such position, most often initially installed by SEAR. For the functionalization of the pyri-dine C-3’ in 2-(2’-py)-Tyr, a discrete number of SEAR methods can be used (e.g. nitration with N2O5,103 or bromination with Br2 66% in oleum.104 Unfor-tunately, vigorous conditions are required for these transformations due to the electron poor nature of pyridine. Such conditions may well compromise the chemoselectivity of the functionalization.
In addition to these limitations, and even if a multistep synthetic route for the functionalization of phenol C-3 and pyridine C-3’ would be developed, a subsequent synthetic method to insert alkyl chains of various lengths (meth-ylene, 1,2-ethylene and 1,3-propylene fragments), which could finally afford the proposed IMHB tyrosine analogs is still lacking. Considering this analy-sis, different synthetic routes were explored.
4.2.3 Approach 2: Heterocycle Ring Formation. Due to the limitations in using 2-(2’-py)-Tyr as the starting material, multi-ple retrosynthetic strategies were taken into consideration. In particular, a retrosynthetic strategy in which the pyridine ring is first disconnected from the carbocycles appeared suitable (Figure 4.5). This disconnectioniv yields the synthonsv -(allyl-imine)-cycloalkanes that are ring-fused to tyrosine that contain C- -nucleophilic carbocycle and a C- -electrophilic allyl. Suita-ble synthetic equivalentsvi for the latter type of synthons are oxime O-allyl ether cycloalkanones ring-fused to tyrosine. This is based on the thermal [2,3]-sigmatropic shift that oxime O-allyl ether clycloalkanones undergo in the presence of O2 to afford cycloalkenopyridines as reported by Koyama et al.105-107 In turn, the oxime O-allyl ether clycloalkanones can be readily pre-pared by condensation of clycloalkanones and oxime O-allyl ether.105
A synthetic route based on the above analysis is able to afford the target IMHB tyrosine analogs. Here the key synthetic step relies on the pyridine ring formation, which in consequence provides the advantage of transferring the majority of the synthetic load -keto cycloalkanones
iv Disconnections correspond to transformations conducted in the synthetic step, often called antisynthetic transforms, i.e., the reverse of synthetic steps. An open arrow symbol, , is used to indicate disconnections. v Synthons are retrosynthetic fragmentation structures of a target molecule resulting from disconnections. Although these do not exit per se, they have appropriate reactivity to allow bond formation. vi Accessible molecules that correspond to synthons. Their functional groups allow bond formation according to the retrosynthetic analysis.
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ring-fused tyrosines with 5, 6 and 7 member carboalkane rings. However, in order to afford the latter compounds a further disconnection of the alkyl amino acid fragment is necessary. The latter disconnection the -keto cycloalkanones ring-fused to phenol and oxime O-allyl ether as the simplest and most feasible synthetic equivalents (Figure 4.5).
Figure 4.5 Retrosynthetic analysis based on pyridine ring formation.
Mechanistic details of the thermal hydrolysis of oxime O-allyl ether clyclo-alkanones have not been fully understood. Although radical scavengers seem not to affect the yield of the reaction, substituent labelling of the O-allyl moiety leads to scrambling of the substituent in the 2,3- cycloalkenopyridine product, suggesting the presence of a radical intermediate.106,108 For this rea-son, an alternative method was explored since our synthetic intermediates (oxime O-allyl ether clycloalkanones ring-fused to phenol) could potentially undergo a very complex radical chemistry during the thermal hydrolysis.
Different alternative methods for pyridine ring formation exist. For ex-ample, ring closure of 1,5-dicarbonyl compounds, or condensation of 1,3-dicarbonyl compounds and a C2N unit have been reported.109 However, none of the classical methods allow the first disconnection described in the retro-synthetic analysis described above. This shortcoming in turn limits the versa-tility of the synthetic approach using classical methods for pyridine synthesis since further functionalization of the key intermediates -keto cycloalka-nones ring-fused to phenol) would be necessary.
A suitable option to overcome this obstacle required re-design of the tar-get molecules without compromising their main structural features. This was achieved by exchanging the [2,3]-ring-fused pyridine by a [2,3]-ring-fused quinoline heterocycle (Figure 4.6). Among the different methods for quino-line synthesis, the Friedländer annulation110 involves synthons that allow the same bond formation generated from disconnection of the pyridine ring out-
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lined in the above retrosynthetic analysis. In consequence, the same key -keto cycloalkanones ring-fused to phenol can be pre-
served in this adaptation. Moreover, quinoline ring formation through this method excludes radical intermediates since it relies on imine formation and aldol-type condensations. Similar structural functionally can also be pre-served since the involved synthons guarantee the correct regioselectivity in the annulation. In addition, the pKa of pyridine and quinoline are very similar (5.1 and 4.9, respectively), suggesting that only minor differences in the H-bond strength will be induced by the differences in pKa.
Figure 4.6 Retrosynthetic analysis based on quinoline ring formation.
4.3 Synthesis With the above considerations in mind, it was decided to follow the synthetic route based on quinoline ring formation for the synthesis of IMHB phenols. As previously mentioned, the retrosynthetic analysis implies that the alkyl amino acid fragment used for subsequent covalent linkage to a ruthenium(II) photosensitizer needs to be introduced at a later stage of the synthesis. A detailed description of the synthesis of ruthenium(II) dyads of the IMHB phenols is described in chapter 7.
In general, the synthetic approach demands the prep -keto cy-cloalkanones ring-fused to phenol, which then can be further used in Friedländer annulation with 2-aminobenzaldehyde. Importantly, the fused-ring phenols require hydroxyl protection in order to remain un-reacted dur-ing the annulation step. Therefore, anisoles of the respective phenols where prepared and deprotected subsequent to the annulation step. The general synthetic sequence is outlined in Figure 4.7, and the compounds are termed IMHB PnQ phenols (phenol–n-membered ring–quinoline, n = 5, 6, 7) hereafter.
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Figure 4.7 General scheme for the synthesis of IMHB PnQ phenols. a) Hydroxyl protection, c) quinoline annulation and c) Hydroxyl deprotection.
4.3.1 Synthesis of P5Q-keto cyclopentane ring-fused phenol was prepared via Fries rear-
rangement of 4-chromanone (60% yield, Figure 4.8). Hydroxyl protection was performed via etherification with KOH and MeI (81% yield). Subse-quently, Friedländer annulation with 2-aminobenzaldehyde in the presence of NH4OAc as base afforded the doubly ring-fused anisole intermediate A5Q (95% yield). Hydroxyl deprotection of A5Q proved difficult and proceeded in poor yields using classical deprotection methods. Suitable hydroxyl deprotection required somewhat harsh conditions using 4 equivalents of BBr3 at 65 ºC in CHCl3 to afford the IMHB phenol P5Q in excellent yield (93%).
Figure 4.8 Synthesis of IMHB phenol P5Q.
4.3.2 Synthesis of P6Q The preparation of the -keto cyclohexane ring-fused phenol starts with the palladium catalyzed hydrogenation of naphthalene-1,8-diol (95% yield, Fig-ure 4.9). Hydroxyl etherification was performed with KOH and MeI (66% yield). Subsequently, Friedländer annulation with 2-aminobenzaldehyde in the presence of NH4OAc as base afforded the doubly ring-fused anisole in-termediate A6Q (60% yield). Hydroxyl deprotection of A6Q was performed using the same conditions as for P5Q to afford the IMHB phenol P6Q in excellent yield (95%).
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Figure 4.9 Synthesis of IMHB phenol P6Q.
4.3.3 Synthesis of P7Q -keto cycloheptane ring-fused phenol was prepared in a multistep se-
quence starting with lithium-halogen exchange of 3-bromoanisole with n-BuLi, followed by alkylation with 4-equivalents of 1,4-dibromobutane to afford 1-(4-bromobutyl)-3-methoxybenzene (64% yield, Figure 4.10). The Grignard reagent of 1-(4-bromobutyl)-3-methoxybenzene was prepared and treated with gaseous CO2 to afford 5-(3-methoxyphenyl)pentanoic acid (78% yield). In order to guarantee the regioselective of the subsequent cyclization step, the para position of the anisole ring was blocked via bromination using Br2 in CHCl3, affording 5-(2-bromo-5-methoxyphenyl)pentanoic acid (96% yield). This intermediate was then cyclized using poly phosphoric acid (PPA) to yield -keto cycloheptane ring-fused anisole (99% yield). Subsequently, Friedländer annulation with 2-aminobenzaldehyde under the usual conditions gave access to the doubly ring-fused anisole in-termediate A7Q-Br (47% yield). Removal of the bromine in para position of A7Q-Br was performed by palladium catalyzed reductive hydro-dehalogenation to give A7Q (81 % yield). Finally, hydroxyl deprotection of A7Q under the usual conditions with BBr3 concluded the synthesis of the IMHB phenol P7Q (90% yield).
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Figure 4.10 Synthesis of IMHB phenol P7Q.
4.4 Structural Characterization of the PnQ Phenols. The IMBH phenols P5Q, P6Q and P7Q and their precursors were character-ized by NMR, a combination of mass spectroscopic methods and elemental analysis. 1H-NMR spectroscopy proved particularly valuable, not only for the characterization of the compounds, but also for qualitative information about the H-bond strength. This information was complemented by the oxy-gen to nitrogen distance (dON) obtained by single crystal X-ray crystallog-raphy. Moreover, X-ray crystallography provided important information of the differences in H-bond geometry in the series of phenols, specifically on the influence that the cycloalkadiene rings have on the H-bond geometry.
4.4.1 1H-NMR of the IMHB PnQ phenols. The IMBH phenols P5Q, P6Q and P7Q show a 1H-NMR pattern in the aro-matic region consistent with that expected for a [2,3]-fused ring phenol and a [2,3]-fused ring quinoline. The alkyl fragments of the cycloalkadiene ring in P5Q, P6Q and P7Q (i.e. methylene, 1,2-ethylene and 1,3-propylene, respec-tively) can be identified at low frequencies. In order to facilitate comparisons among the three phenols, a somewhat arbitrary numbering of the carbons has been adopted (Figure 4.11 - all spectra were measured in DCM-d2 and the residual protic solvent signal was used as reference). In general, aromatic protons in similar positions within the series show similar chemical shifts. Nonetheless, a trend is observed for the alkyl protons as successive addition
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of extra methylene units to the alkyl fragment shifts the 1H NMR signals to lower frequencies. This shift is visible for example for the 1c protons in P5Q and P7Q that differ by
Figure 4.11 1H-NMR of the IMHB PnQ phenols in DCM-d2 (*Et2O solvent residual in the spectrum of P7Q).
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The 1H-NMR signals of the phenolic protons in the series were observed at high frequencies above 9 ppm. This observation confirms the hydrogen bonded environment of the proton.vii The chemical shift of the IMHB phe-nolic proton spans over ca. 5 ppm and follows the trend P5Q (9.86 ppm) < P7Q (11.75 ppm) < P6Q (14.69 ppm). As discussed in chapter 2, the 1H-NMR chemical shift can be used as a qualitative probe for the H-bond strength. Thus, the H-bond strength follows the trend P5Q < P7Q < P6Q. Considering that this series of IMHB phenols features the same functionali-zation pattern around the proton donor-acceptor moieties (i.e. a [2,3]-ring-fused phenol and [2,3]-ring-fused quinoline) the differences in H-bond strength can only arise from the difference in distance and geometry of the H-bond that in turn is determined by the size and stereochemistry of the cy-cloalkadiene rings.
4.4.2 H-bond Geometry of the IMHB PnQ Phenols. Significant structural variations of the geometry of the H-bond across the series of IMHB phenols were observed by X-ray crystallography. The results are in excellent agreement with the ground state geometries that were calcu-lated by DFT. Suitable crystals for X-ray crystallography were obtained for P5Q-2I -the 2,4-diiodoviii analog of P5Q, P6Q and P7Q. Differences in the geometry of the H-bond within the series were analyzed on the basis of the proton donor-acceptor distances (dON) and the dihedral angle formed be-
4.12). Although only neutron diffraction allows the accurate assignment of crys-
tallographic proton positions, the hydroxyl protons were located in the elec-tron density map and their positions were allowed to refine freely. The O-H distance (dOH) varies according to the following trend: P5Q-2I (0.825 Å) < P7Q (0.913 Å) < P6Q (0.942 Å). The N···H distance (dNH) follows the com-plementary trend: P6Q (1.733 Å) < P7Q (1.874 Å) < P5Q-2I (2.049 Å). No specific trend was observed for the O- of 156.82º, 145.24º and 142.72º for P5Q-2I, P6Q and P7Q, respectively.
Of particular importance are variations of dON ( ON=0.30 Å)ix along the series in which P5Q dON = 2.881 Å (calculated from DFT) shows the largest, followed by P7Q with dON = 2.666(1) Å, and finally P6Q featuring the short-est dON = 2.567(2) Å indicating that the equilibrium proton donor-acceptor flows the trend P5Q > P7Q > P6Q. This trend is consistent with the trend in
vii A suitable comparison can be done considering the phenolic proton signal of 2,6-di-tert-butyl-4-methylphenol (BHT) in DCM-d2 = 5.00 ppm) and DMSO-d6 = 6.65 ppm) -a weak H-bond acceptor solvent.( Fulmer et al. Organometallics 2010, 29, 2176) viii P5Q-2I is a byproduct in the synthesis of P5Q-I, see chapter 7. ix ON = 0.30 Å is calculated using value for P5Q from DFT, and ON=0.26 Å using values from X-ray crystallography including dON = 2.826(4) Å for P5Q-2I.
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the H-bond strength P5Q < P7Q < P6Q that was estimated based on the chemical shift of the phenolic protons observed by 1H-NMR.
Figure 4.12 a) ORTEP views at 50% probability of P5Q-2I, P6Q, and P7Q. b) Side-on view. c) Key crystallographic parameters of P5Q-2I, P6Q, and P7Q.
These observations can be rationalized by analyzing the stereochemistry of the 1,3-cycloalkadienes and how these impact the spatial orientation of the ring-fused phenols and quinolines respect to each other. In the case of P5Q, the small (strained) internal angle of the 1,3-cyclopentadiene ring (ca. 109º for the diene carbons and 103º for the methylene) enforces the in-plane sepa-ration of the phenol and quinolone which results in the longest dDA of the series. The stretching of the dDA in P5Q as a result of the clocloalkadiene internal angles becomes apparent by comparison with the unbridged 2,2’-phenol-pyridine analog (i.e. without ring-fused clocloalkadiene). In the latter compound, the lack of any constraint allows the sp2 hybridized carbons to adopt regular 120º angles, resulting in calculated dDA = 2.555 Å (similar dDA have also been observed by X-ray crystallography).111 Likewise, the 1,3-cyclopentadiene of P5Q causes co-planarity between the phenol and quino-
= 0.0º). In the case of P6Q, the internal angles of the 1,3-cyclohexadiene ring (ca
119º on the diene carbons and ca. 110º in the methylenes) exhibit typical values for unstrained sp2 and sp3 hybridized carbons. This conformation promotes the closest proximity between the phenol and quinoline as evi-
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denced by the shortest dDA of the series. The cycloalkadiene of P6Q adopts the typical twisted conformation of 1,3-cyclohexadiene with staggered con-formations of the methylenes, resulting in a small dihedral angle between the phenol and the = 13.0º).
In the case of P7Q, the intermediate dDA between that of P5Q and P6Q does not result from the differences in internal angles of the cycloalkadiene (ca. 121º on the diene carbons and ca. 113º on the methylenes), but rather from the twisted boat conformation adopted by the 1,3-cycloheptadiene ring. This twisting gives rise to a significantly larger dihedral angle between the phenol and the = 36,4º). Thus, in the case of P7Q, the stretching of the dDA does not originate from in-plane separation of the phenol and the quinoline, but from their dihedral angle due to the twisted boat conformation of the cycloheptadiene.
4.5 Conclusions A feasible synthetic strategy has been developed to obtain IMBH PnQ phe-nols featuring doubly ring-fused cycloalkadienes of 5, 6 and 7 member rings between phenol and the quinoline. The designed synthetic routes proceed in high overall yields. The prepared IMHB PnQ phenols have a similar conjuga-tion pattern between the proton donor-acceptor moieties, while disclosing significant variations of the H-bond geometry with dDA spanning over 0.30 Å. The structural differences in the series result in a trend of the H-bond strength that has been separately stablished from the chemical shifts of the phenolic proton and the dDA. Moreover, the analysis of the stereochemical influence of the cycloalkadiene rings allowed the rationalization of the ob-served trend in H-bond strength.
Finally, it is important to highlight that the achieved degree of structural information for the IMHB PnQ phenols is indeed a cornerstone for the struc-ture-reactivity studies that follow hereafter.
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5. Excited State Proton Transfer and Tautomerization of IMHB PnQ Phenols.
This chapter describes the results of a combined spectroscopic and computa-tional study of the electronic excited state dynamics of IMHB PnQ phenols. The results are analyzed on the basis of structural differences in the H-bond geometry.
5.1 Background The acidity of hydroxyl and amine protons of aromatic molecules can be dramatically enhanced in the electronic excited state. Such changes in acidity (also referred to as photo-acidity) are derived from the intramolecular elec-tronic charge redistribution induced upon photon absorption.112,113 Given the simplicity of the reaction and the wide range of systems that can experience photo-acidity, it is not surprising that excited state proton transfer (ESPT) is regarded a fundamental photochemical reaction.114-116 Since the first experi-mental observation in the middle of the last century,117 excited state intramo-lecular proton transfer (ESIPT) reactions have been extensively investigat-ed.118-122 Several aspects contribute to the interest for ESIPT reactions: 1) Practical aspects: ESIPT can be triggered by optical pulses and its dynamics can be accurately monitored leaving aside complications of diffusional ef-fects. 2) Fundamental research: the complex dynamics of ESIPT can be in-vestigated experimentally, providing a suitable frame to compare experi-mental and theoretical work. 3) Applied science: ESIPT has been used in the development of technological applications (e.g. fluorescence imaging,123 laser dyes,124 OLEDs,125 optoelectronic materials,126 photo-protective addi-tives,127 solvation dynamics probes,128 protein binging-site probes129). Per-haps one of the most striking features of ESIPT is its ultrafast dynamics with reaction rates as fast as 30 fs and up to a few hundred fs, falling in the limit of barrierless adiabatic reactions.114
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Figure 5.1 General energy diagram of ESIPT and photo-induced tautomerization (Abs = absorption, Fl = fluorescence).
In the case of H-bonded systems with a conjugated pattern between the pro-ton donor-acceptor moieties, ESIPT typically yields an excited state tauto-mer photoproduct (T*, Figure 5.1). Asymmetric double minima potential energy surfaces (PES) have been used to rationalize tautomerizations be-tween two asymmetric proton transfer isomers, usually referred to as the enol and keto forms in the case of a hydroxyl proton donor system. If chang-es in acidity in the proton donor-acceptor moieties occur between the ground and electronic excited state, a reversal of the relative stability of the enol and keto forms between the ground and electronic excited state can be expected. This relates to the most important spectroscopic feature of the T* state pho-toproduct: its highly red-shifted fluorescence, also known as Stokes shift. Formation of the T* state photoproduct requires the H-bonded ground state enol form to undergo the following processes: 1) photon absorption to form an intramolecular charge-transfer state (ICT), leading to electronic charge redistribution that enhances the acidity of the proton donor motif providing the driving force for ESIPT, 2) adiabatic proton transfer on the electronic excited state PES, and finally 3) relaxation of the newly formed proton-transferred strained molecule by intramolecular vibrational redistribution (IVR), and excess energy dissipation to the solvent environment (vibrational cooling). The relaxation processes upon ESIPT causes rearrangement of the atomic positions and concomitant electronic redistribution, which typically involves bond-order alternation. Once the T* photoproduct is formed, (non-) radiative deactivation leads to electronic relaxation with significant back
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ICT. The electronic charge redistribution of the ground state tautomer (T) provides the driving force to close the cycle by back proton transfer on the ground state PES (Figure 5.1).
Certain systems that undergo photo-induced tautomerization exhibit a barrier for the ESIPT step. In this case, the rate of ESIPT drops relative to that of systems with barrierless ESIPT, and fluorescence from the enol form in the electronic excited state (N*) can be detected. Mechanistic studies of ESIPT are at the core of understanding the nature of this barrier. Different models and abundant spectroscopic evidence have been collected in order to elucidate the details for the mechanism of ESIPT. Two main models have been considered, their fundamental difference lies on whether the transfer-ring proton plays an active or passive role in the reaction coordinate.130 Compelling spectroscopic evidence on multiple model systems suggest that the transferring proton plays a passive role in the reaction. Instead, the ESIPT reaction coordinate couples with coherent vibrational motions associ-ated with low frequency in-plane skeletal deformations during and after pro-ton transfer (Figure 5.2).119,131-133 The in-plane skeletal deformations change the relative position of the atoms associated with the H-bond and modulate the proton donor-acceptor distance dDA. The observed negligible kinetic iso-tope effect kESIPT(H)/ kESIPT(D) (KIE) for the reaction correlates with the rear-rangement of the atomic positions of heavy atoms coupled to the reaction coordinate. Evidence for the ballistic proton motion model (i.e. with active role of the proton) has also been recently collected, demonstrating that the discussion is not resolved.134
Figure 5.2 Schematic in-plane skeletal deformations that assist ESIPT on the elec-tronic excited state of an arbitrary IMBH system. a) Electronic excited state enol form (N*) of the IMBH system, b) In-plane stretch along the linking bond of the proton-donor acceptor moieties and, c) In-plane bending mode between the proton-donor acceptor moieties.
Given the mechanistic relevance of ESIPT, most model systems have been studied with the aim to provide further insight into this fundamental step. Much less attention has been focused on the relaxation of the proton-transferred strained molecule. After ESIPT, the relaxation processes that follow lead to rearrangement of the atomic positions and bond-order alterna-tion to yield the T* photoproduct. It can be anticipated that bond order alter-
c-ceptor moieties, however direct experimental evidence in this regard is
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sparse. Conical intersections (CI), i.e. molecular configurations in which multiple electronic states are degenerate, have been calculated for ESIPT model systems in which the H-bonded molecule can explore a large confor-mational space with twist motthree state interactions (S1/S0 and S2/S1/S0, respectively) at the CI are regard-ed as an efficient competing non-radiative deactivation channel to the for-mation of the emissive T* photoproduct.135-138
Despite the interest in ESIPT and photo-induced tautomerization, system-atic studies on series of IMBH model systems have been limited to investi-gations on the effect of H-bond strength on the rate of ESIPT. This has been achieved in series of model systems in which variations of the H-bond strength are introduced by modulating the pKa of the proton donor-acceptor moieties with different EDG and EWG.139-141 The lack of a study in which a series of IMHB molecules is able to directly probe the influence of dDA has inspired us to investigate the dynamics in the electronic excited state of the IMHB PnQ phenols. As described in chapter 4, this series of phenols has the same proton donor-acceptor moieties while featuring significant varia-tions of the H-bond geometry due to the stereochemical influence of the cycloalkadienes of 5, 6 and 7 members (Figure 5.3).
Figure 5.3 a) Prototypical IMHB in a conjugated ring, (dDA) is the proton donor-
-acceptor moieties. b) Studied IMBH PnQ phenols.
5.2 Electronic Excited State Dynamics of IMHB Phenols Steady state fluorescence and transient absorption spectroscopy allows in-vestigating the electronic excited state dynamics of IMHB systems that un-dergo ESIPT and photo-induced tautomerization. As observed by steady state fluorescence, emission from the enol form (N*) results in an emission band with a small Stokes shift, whereas fluorescence from the keto form (T*) results in an emission band with a large Stokes shift (> 6000 cm-1). This case referred to as dual emission is exemplified in Figure 5.4a for an arbi-trary system. Kinetic information for the formation and decay of the enol (N*) and keto (T*) states can be extracted from the rise and decay of the
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stimulated emission (SE, negative amplitude) signals in transient absorption spectroscopy with subpicosecond time resolution. In addition, such kinetic information of the dynamics of the N* and T* states can be complemented by kinetic information of the rise and decay of the excited state absorption (ESA, positive amplitude) signals due to the precursor-successor type of mechanism that relates the N* and T* states in the experiment (Figure 5.4b).
Figure 5.4. a) Illustrative case of an arbitrary IMHB systems displaying dual emis-sion from the N* and T* states in the electronic excited state upon excitation into its ICT band. b) Illustrative scheme of the rise and decay of the excited state absorption (ESA, positive amplitude) and stimulated emission (SE, negative amplitude) signals at arbitrary wavelengths in the femtosecond transient absorption spectra. An optical pulse promotes an electronic transition (pump) and a delayed pulse of light probes changes in absorption (probe).
The dynamics in the electronic excited state of the IMHB PnQ phenols was studied by steady state fluorescence, and transient absorption spectroscopy with subpicosecond broad band detection (response function ca. 200 fs) in acetonitrile. Additionally, (TD)-DFT calculations with B3LYP/6-31G(d,p) with a PCM of acetonitrile provided structural insights and relative energies of the respective enol and keto forms in the ground and excited state. All the phenols have a S0 S1 -acetonitrile. Photo-excitation into this band generates the ICT state with enhanced acidity of the hydroxyl proton that provides the driving force for ESIPT.
5.2.1 Influence of Equilibrium Proton Donor-Acceptor Distance Comparison of the electronic excited state dynamics of P5Q versus P6Q allows to investigate the influence of the equilibrium proton donor-acceptor distance on the basis of the observed (dDA) on the rate of ESIPT since this pair of IMHB phenols disclose the largest difference in dDA NO = 0.30 Å). Importantly, both compounds have small dihedral angles between the phenol
= 13.0º) which enables to isolate the influence of equilib-rium proton donor-acceptor distance.
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The steady state fluorescence spectrum of P5Q shows emission from the enol (N*) and keto (T*) states. The emission band of the N* state shows a small Stokes shift whereas the emission band of the T* state shows signifi-cantly larger Stokes shift (13100 cm-1). Both emission bands arise from the same ground state structure as verified by their respective excitation spectra (Figure 5.5a). In agreement with the steady state fluorescence, the transient absorption spectrum of P5Q shows instantaneous SE from the N* state (sharp negative amplitude signal immediately after the pump optical pulse, monitored at 395 nm). The main time constant for the decay of the N* state corresponds to the kinetics of the ESIPT step (150 fs). The same time con-stant was observed for the rise of SE from the T* state –monitored at 700 nm– which confirms the precursor-successor type of mechanism that relates the N* and T* states. Decay of the T* state shows a time constant of ca.180 ps which corresponds to the return to the ground state (Figure 5.5b).
Figure 5.5. a) Absorption spectrum, steady state fluorescence spectrum and excita-tion spectrum of P5Q in acetonitrile at room temperature (Fl.= fluorescence). b) Kinetic traces at 395 and 700 nm of the time resolved femtosecond transient absorp-tion spectrum of P5Q in acetonitrile.
The steady state fluorescence spectrum of P6Q shows only one emission band with a large Stokes shift assigned to the emission from the T* state. The excitation spectrum of this emission band confirms that it arises from the enol form in the ground state (Figure 5.6a). In agreement with the steady state fluorescence, the kinetic trace at 395 nm of P6Q does not show any SE form the N* state, only instantaneous ESA from the T* state within the time resolution of the setup employed in the transient absorption experiment (< 100 fs)x. SE from the T* state can be detected at 700 nm. The decay of the T* state SE and ESA feature the same time constant (ca. 45 ps) correspond-ing to the return to the electronic ground state (Figure 5.6b). Additionally, in agreement with the shorter time constant for the decay of the T* state in P6Q
x A time resolution of < 100 fs is possible by applying deconvolution routines to the data.
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versus P5Q; in P6Q, the T* state emission band in the steady state fluores-cence is much weaker than the corresponding band for P5Q.
Figure 5.6 a) Absorption spectrum, steady state fluorescence spectrum and excita-tion spectrum of P6Q in acetonitrile at room temperature (Fl.= fluorescence). b) Kinetic traces at 395 and 700 nm of the time resolved femtosecond transient absorp-tion spectrum of P6Q in acetonitrile. * Peak of the Raman scatter from the solvent.
Therefore, comparing the electronic excited state dynamics of P5Q versus P6Q indicates that the longer equilibrium proton donor-acceptor distance in P5Q correlates with a barrier for the ESIPT step as only P5Q shows an emis-sion band in the steady state fluorescence and SE in the transient absorption spectra that arise from the N* state. In the case of P6Q, the rate of ESIPT is therefore much faster than in P5Q and cannot be resolved with the time reso-lution of the setup employed in the transient absorption experiment (< 100 fs). Due to nearly barrierless ESIPT in P6Q, the N* state has a very short lifetime and its emission cannot be detected in the setup employed for the steady state fluorescence. Despite their differences in the rate of ESIPT, both IMHB phenols undergo relaxation of the proton-transferred strained mole-cule to yield the fully relaxed T* state photoproduct (Figure 5.7).
Figure 5.7 Schematic proposed energy diagram for ESIPT and photo-induced tau-tomerization in a) P5Q and b) P6Q.
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5.2.2 Influence of the Dihedral Angle Between Proton Donor-Acceptor Moieties Comparison of the electronic excited state dynamics of P5Q and P6Q versus P7Q allows for an investigation of
= 36.4º) that is significantly larger than that in P5Q and P6Q, while its equilibrium proton donor-acceptor distance is intermediate to that of P5Q and P6Q.
The electronic excited state dynamics of P7Q is significantly different from that of P5Q and P6Q. The steady state fluorescence spectrum of P7Q does not show emission from neither the N* nor from the T* states under the same experimental conditions as those used to study P5Q and P6Q (i.e. ace-tonitrile solutions at room temperature). Absence of the T* state emission of P7Q at room temperature in a polar solvent resembles that of 2-(2’-hydroxyphenyl)pyridine, a related IMHB system without ring-fused cycloal-kadiene.142 Emission from the T* state of 2-(2’-hydroxyphenyl)pyridine is however observed at 77 K in 3:1 methylcyclohexane/isopentane. This is possible since the frozen glass formed under such experimental conditions restricts twis . Additionally, the nonpolar nature of the solvent reduces the interaction of the solvent with the weakened -bond after ESIPT. A similar exper-iment performed for P7Q using 3:1 methylcyclohexane/isopentane as solvent at temperatures down to 77 K did not show emission of the T* state at any of the temperatures investigated (Figure 5.8a).
In agreement with the steady state fluorescence, the transient absorption spectrum of P7Q does not show instantaneous SE from the N* state (sharp negative amplitude signal immediately after the pump optical pulse, moni-tored at 395 nm), only instantaneous ESA, indicating nearly barrierless ESIPT. Likewise, kinetic traces at 700 nm do not show SE from the T* state. The main time constant for the ESA decay is assigned to the return to the electronic ground state (1.6 ps). Importantly, the return to the electronic ground state in P7Q is much faster that that observed for P5Q and P6Q (Fig-ure 5.8b).
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Figure 5.8. a) Absorption spectrum of P7Q in acetonitrile and steady state fluores-cence spectra at various temperatures of P7Q in 3:1 methylcyclohexane/isopentane. b) Kinetic traces at 395 and 700 nm of the time resolved femtosecond transient ab-sorption spectrum of P7Q in acetonitrile. * Peak of the Raman scatter from the sol-vent.
The possibility of rapid non-radiative deactivation of P7Q before ESIPT –that is, non-radiative deactivation before the formation of the proton-transferred (N-H bound) strained molecule after formation of the ICT state– can be excluded based on the following facts: 1) the ICT state formed after photo-excitation enhances the acidity of the hydroxyl proton that provides the driving force for ESIPT, 2) the phenolic proton P7Q is H-bonded, with H-bond strength intermediate to that of P5Q and P6Q, 3) absence of emis-sion from N* state in the steady state fluorescence and absence of SE from N* state in the transient absorption spectrum, 4) the calculated favorable stability of the N-H bound form of P7Q in the electronic excited state. Therefore, after ESIPT in P7Q, non-radiative deactivation channels must out-compete the prototypical rearrangement of the atomic positions and bond order alternation that typically yield the T* state photoproduct after relaxa-tion of the proton-transferred strained molecule. This behavior can only be
Two possible scenarios could be considered to account for the influence
-radiative deactivation of P7Q. First, non-radiative deactiva-: this can be excluded since large-scale
twisting involves heavy atom movement which should be on the same time-scale as intramolecular vibrational relaxation –hundreds of femtoseconds– which is slower than instrument response function of the femtosecond setup used and therefore would have been observed. Further evidence against de-activatio
second scenario implies rapid non-radiative deactivation caused by a two state interaction (S1/S0) due to disto a-nation considering the large pre- = 36.4º), which becomes even larger in the calculated optimized geometry of the N-H bound electronic excited state of P7Q (ca. 60º). Additionally, indirect exper-
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-H bound electronic excited state of P7Q can be found in the structural analysis of the pattern anisole A7Q-Br, for which suitable crystals for X-ray crystal-lography were obtained (Figure 5.9). Like P7Q, A7Q-Br also adopts a twist-ed boat conformation of the 1,3-cycloheptadiene ring but with significantly
-Br also shows a larger barrier for conformational inter-conversion at room temperature compared to P7Q, as evidenced by differen-tiation of the enantiotopic protons of the 1,3-propylene fragment of A7Q-Br on the 1H-NMR timescale. Both effects are in part attributed to the repulsion of the valence free electron pairs of oxygen and nitrogen due to the absence of a H-bond in A7Q-Br.
Figure 5.9. ORTEP views at 50% probability of P7Q and A7Q-Br a) side-on view along the quinoline plane, b) side-on view along the C2 symmetry axis of the 1,3-cycloheptadienes, c) 1H-NMR of the alkyl protons of the 1,3-propyl fragment in DCM-d2 at room temperature.
-H bound electronic excited state can be expected, the efficient non-radiative deactivation that prevents the formation of T* state in the frozen glass can only be explained by a two state interaction (S1/S0) that occurs of ca. 35º. It is noteworthy
-H bound form of P7Q in the ground state (20.9º) is comparable to that of the enol form of P7Q in the electronic ground state, and therefore comparable to that in the Franck-Condon region. This introduces the possibility of molecular configurations of P7Q in which the S1 and S0 states are degenerate (Figure 5.10).
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Figure 5.10 Schematic proposed energy diagram for ESIPT decoupled from photo-induced tautomerization in P7Q.
5.3 Conclusions This study on the IMHB PnQ phenols allowed probing of key structural pa-rameters of the geometry of the H-bond that control the dynamics of excited state intramolecular proton transfer and the ability to form the relaxed tau-tomer state photoproduct. While most previous studies had focused on the mechanism of excited state intramolecular proton transfer, the series of IMHB phenols investigated herein is the first of its kind that provided exper-imental evidence that suggests that efficient non-radiative deactivation via conical intersections operate at relatively small dihedral angles between the proton donor-acceptor moieties. Hence, important design principles for the development of future technologies based on excited state intramolecular proton transfer and photo-induced tautomerization have been delineated.
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6. Bimolecular Proton-Coupled Electron Transfer of IMHB PnQ Phenols.
This chapter describes the results of a combined spectroscopic, electrochem-ical and quantum chemical calculations study of ground state proton-coupled electron transfer (PCET) reactions of the IMHB PnQ phenols. The results are analyzed on the basis of structural differences in the proton transfer distance for the formation of phenoxyl radicals in PCET reactions.
6.1 Background The quantum mechanical nature of electrons allows them to tunnel
through potential energy barriers that are several electron volts high and several nanometers long within less than a second.143-145 This phenomenon known as electron tunneling revolutionized our understanding of chemical transformations in which electron transfer (ET) is involved since molecular collisions are not required. This principle, however, could only be seized by chemists in many different fields thanks to the Marcus kinetic formulation of electron transfer between two weakly interacting redox centers at fixed dis-tance and orientation.58 In this formulation, the ET rate is expressed as a func c-tronic coupling strength between reactants and products at the transition state nuclear configuration (HAB), a parameter describing the extent of nuclear
Distance dependence studies reveal that the ET rate (kET) decays exponen-tially with increased distance of the electron donor and acceptor according to the expression: kET = kET° DA DA
0)). Here, (kET°) is the ET rate at close contact (dDA
0
distances of the electron donor and acceptor (dDAefficiency of long range electronic coupling of the redox centers across the tunneling barrier. For a specific i-cally takes values less than or close to 1 Å-1 depending on the electronic structure of the intervening medium or molecular bridge separating them.146-
148 Kinetic formulations for proton transfer (PT) in solution in different re-
gimes of adiabaticity including the quantum mechanical character of proton
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motion have also been formulated.149-151 In this formulation, adiabatic PT occurs in strongly H-bonded systems in which the proton free energy profile has a small PT barrier, whereas non-adiabatic PT occurs in weakly H-bonded systems by tunneling through the PT barrier. Some specific features of this PT kinetic formulation in the non-adiabatic limit include: 1) the reac-tion coordinate is identified as the solvent coordinate, rather than the proton coordinate, 2) as the solvent reorganizes the proton free energy potentials re-adjust in the proton reactant and product states 3) at the crossing point (tran-sition state), the proton reactants and product states are degenerate, 4) the specific shape of the proton free energy potential at the transition state de-pends on factors affecting the H-bond strength, 5) at the transition state in weak (long) H-bonds, PT occurs across the barrier through tunneling, 6) at the transition state in weak (long) H-bonds, the proton coupling (vibronic coupling) between the proton reactant and product states –qualitatively un-derstood in terms of the overlaps of the tails of the diabatic proton vibration-al wavefunctions in the two states– is strongly dependent on the proton tun-neling distance and decays exponentially according to: C = Cº
Qeq)). In this expression (Cº) is the vibronic coupling at the H-bond equilibrium distance (Qeq u-pling at different H-bond distances (Q).
- 35 Å-1,149 making the PT rate quite sensitive to the H-bond dynamics, in particular the proton tun-neling distance at the transition state. It is important to notice that the expo-nential dependence of the PT coupling resembles that of ET; however, the magnitude of the attenuation factor is significantly larger for PT due to the larger mass of the proton and in consequence the more localized character of its wavefunctions.
Figure 6.1. a) Schematic representation of electron or proton tunneling. D = donor, A = acceptor, dDA donor-acceptor distance. b) Illustrative correlation plot of the electron or proton tunneling rate versus the dDA.
The exponential dependence of the proton vibronic coupling on the proton tunneling distance have also been derived in kinetic formulations for con-certed electron-proton transfer reactions (CEPT, in which proton and elec-tron transfer occur in a single chemical step) incorporating the quantum me-
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chanical behavior of the active transferring proton and electron.152,153 As described in section 2.2, CEPT kinetic formulations capture the main fea-tures of separate quantum chemical formulations for ET and PT. In agree-ment with this, the CEPT rate is expected to be strongly sensitive to the H-bond dynamics according to the characteristic of PT in solution described above.
Only few groups have thus far embraced the challenge of experimentally verifying the predicted strong dependence of the CEPT rate on the proton tunneling distance. This has proven to be a particularly difficult task since ideally it requires isolating, and thus exclusively evaluating, the effect of the proton tunneling distance dependence of the CEPT reaction. This implies that ideally all other physical parameters affecting the CEPT rate must be kept constant along a series of model systems, which by extension implies high degree of control over structural parameters affecting the CEPT includ-ing for example the CEPT driving force, reorganization energies and H-bond frequency modes.
From a perspective of model system design, this requirements are very difficult to fulfill since structural variations aimed to modulate the proton transfer donor-acceptor distance are very likely to influence other parameters that will also influence the CEPT rate. At the same time, these obstacles to isolate the effect of the proton tunneling distance have made it difficult to draw general conclusions about the experimental evidence collected so far. Contributions in this area have been provided by the groups of Ham-marström and Mayer using redox active intramolecularly H-bonded (IMHB) phenols as model systems. The structural features of the IMHB phenols (Tyr-analogs) studied by Hammarström were described in section 4.1. Brief-ly, these are IMHB phenols in which a methylene fragment between the proton donor and acceptor was used to modulate the proton transfer distance, while introducing unwanted -conjugation within the series at the same time. These model systems exhibited a strong dependence of the PCET rate on promoting vibrations that modulate the proton transfer coordi-nate in the case of a (O)-carboxyl proton acceptor,101 and on correlations of the X-ray crystallographic oxygen to nitrogen distance (dON) in the case of (N)-pyridyl and (N)-benzimidazoyl proton-acceptors.102 These results con-trast to the weak dependence of the proton transfer distance observed by the Mayer group,154 in non- -conjugated IMHB phenols where the proton-acceptors are two different primary amine groups.
Aiming to extent these studies, the PCET rates of the PnQ phenols were studied. As described in chapter 4, the structural features of the PnQ phenols allow good isolation of proton donor-acceptor distance since large electronic differences related to donor-acceptor pKa’s and -conjugation are avoided, while the equilibrium proton donor-acceptor distance varies progressively through series according to P6Q < P7Q < P5Q.
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6.2 Kinetic PCET Studies
6.2.1 PCET Rates PCET reactions of the IMHB PnQ phenols were studied in bimolecular ex-periments in which ET from the phenols occurs intermolecularly to an oxida-tive reagent coupled to intramolecular PT of the phenolic proton to the quin-oline. The oxidative reagent used is a photo-generated homoleptic tris(bidentate)ruthenium(III) polypyridyl complexes [Ru(L)3]3+. This is achieved by photo-exciting [Ru(L)3]2+ by a nanosecond laser pulse to its 1MLCT excited state; this is followed by intersystem crossing (ISC) from the 1MLCT to yield the 3MLCT. This long-lived excited state can subsequently be oxidatively quenched in a bimolecular reaction with a sacrificial electron acceptor, methyl viologen (MV2+). This photo-induced electron transfer re-action yields the [Ru(L)3]3+ oxidant in the electronic ground state which is used to oxidize the IMHB PnQ phenols (Figure 6.3).
Figure 6.3. Photo-induced generation of the [Ru(L)3]3+ oxidant and subsequent bi-molecular PCET reaction with the IMHB PnQ phenols.
The rate of the oxidation coupled to deprotonation (PCET) reaction between [Ru(L)3]3+ and the IMHB PnQ phenols can be extracted from fits of kinetic traces in a spectroscopic transient absorption experiment at wavelengths suitable to monitor the reduction [Ru(L)3]3+ + e- [Ru(L)3]2+. This can be done in the spectral region of the 1MLCT transition band for the homoleptic tris(bidentate)ruthenium(II) polypyridyl complexes used, for instance at 450 nm, where changes in absorptivity of other formed or depleted species in the experiment are minimal. Using a large excess (ca. 1000 fold) of the PnQ with respect to photo-generated [Ru(L)3]3+, the fitted rate constants are evaluated under pseudo-first order conditions. Under the experimental conditions, the observed rate constant for the [Ru(L)3]2+ recovery, kobs, is much slower than a diffusion controlled reaction 1×1010 M-1s-1). In such case, the fitted rate
3
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constants correspond to kobs = Kd × kPCET × [PnQ], where Kd describes the ratio of diffusion and dissociation rate constants for formation and dissocia-tion of an encounter complex between the [Ru(L)3]3+ and PnQ, kd and k–d, respectively, kPCET is the rate of the PCET reaction and [PnQ] the phenol concentration. Under these conditions, it is not possible to separate Kd from kPCET; however, given the similar experimental conditions, it is valid to as-sume that differences in kobs within the series arise from differences in kPCET, due to the expected similar diffusion constants for the phenols. This allows the relative evaluation of kPCET within the series assuming Kd = 1 since only relative differences of kPCET within the series are relevant for this study. With this assumption, it is possible to fit the [Ru(L)3]2+ recovery kinetic traces to single exponential decays to obtain kobs = kPCET × [PnQ]. From this expression PCET rates were obtained for the IMHB PnQ phenols in a range of tempera-tures from ca. 0 to 50 ºC for the hydroxylic proteo and deutereo isotopes and the rates were fitted according to the Arrhenius equation (Figure 6.4).
Under comparable experimental conditions, the PCET rates for the IMHB PnQ phenols show significant differences along the series, differing by about one order of magnitude. For example, PCET rates (kPCET / M-1s-1) are (8.57 ± 0.1) ×106 for P5Q at 299K , (8.37 ± 0.02) ×107 for P6Q at 298K and, (2.72 ± 0.03) ×107 for P7Q at 297 K. Importantly, PCET rates decrease consistently with increase of the equilibrium proton donor-acceptor distance according to kPCET (P6Q > P7Q > P5Q) as can be observed in Figure 6.4a on the recovery kinetic traces at 450 nm under similar conditions of P5Q and P6Q, and the relative rates in the temperature and isotope dependence studies in Figure 6.4b.
Figure 6.4. a) Representative kinetic traces at 450 nm tracing the [Ru(bpy)3]2+ re-covery in the presence of P5Q and P6Q at 5 mM. No-PnQ = [Ru(bpy)3]2+ and MV2+
and no IMHB PnQ phenol. b) PCET rate constants of the IMHB PnQ phenols as a function of temperature and isotope.
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Linear Arrhenius correlations were observed in the range of temperatures studied, for each phenol with the respective hydroxylic proteo and deutereo isotopes. Small kinetic isotope effect (KIE) (k(H)/k(D)) that do not reflect the trend in proton donor-acceptor distance were observed. These are 1.17 ± 0.0.2, 1.35 ± 0.01 and 1.40 ± 0.04 for P5Q, P6Q and P7Q, respectively. In the case that proton tunneling only involves a transition between the ground state of the reactant and product, it is expected that the larger equilibrium proton donor-acceptor distance leads to larger KIE since this magnitude be-comes proportional to the overlaps of the hydrogen and deuterium ground state wavefunctions.63,155 However, in cases where proton transitions in-volves vibronic excited states the dependence of KIE with the overlaps of the hydrogen and deuterium wavefunctions is attenuated.156 This effect has also been observed experimentally in the related IMHB phenols studied by Mayer and co-workers,154 and further verified by quantum chemical calcula-tions.157 Given the functional similarities of the system studied by Mayer and the IMHB PnQ phenols, this is a plausible explanation for the shallow de-pendence of the KIE with the equilibrium proton donor-acceptor distance.
Additionally, the observed PCET rates are only consistent with a concert-ed mechanism (CEPT) on the basis of the expected rate that would be ob-served for the PCET process through the formation of the highly energetic intermediates of the PTET or ETPT mechanism (P-
nQ+H) and (P HnQ), re-spectively (Figure 6.5). The operating CEPT mechanism in the IMHB PnQ phenols agrees with the thermodynamic bias for the concerted process.55,57
Figure 6.5. Square scheme for PCET in the IMHB PnQ phenols.
6.2.2 PCET Driving Force As discussed above, in order to independently analyze the influence of the proton donor-acceptor distance, it is important to investigate the influence of
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other parameters affecting the PCET rate. Aiming to establish the driving force for the PCET reaction, electrochemical studies for the IMHB PnQ phe-nols were performed to evaluate the standard redox potential Eº for the cou-ple (PnQ +/PnQ). The specific conditions for the electrochemical measure-ments are dictated by the exhibited irreversible character of the oxidation coupled to intramolecular PT in the IMHB PnQ phenols. Such irreversible behavior is characteristic of highly reactive phenoxyl radicals formed on the PCET reaction which first undergo fast dimerization followed by polymeri-zation in the absence of any substituents the ortho- and para- positions.158 The dimer and other formed polymerization by-products are not electro-chemically active and their adsorption causes electrode passivation with shifts in the oxidation peak potential depending on the amount of passivation layer formed at the electrode’s surface. This prevents simple evaluation of the standard redox potential by cyclic voltammetry under normal condi-tions.159 Standard redox potentials can be extracted using cyclic voltammetry at low concentrations of phenol analyzing the shift of the oxidation peak potential at various scan rates according to the expression inserted in Figure 6.6b.160
Figure 6.6. a) Representative cyclic voltammograms for the IMHB PnQ phenols. b) Heterogeneous oxidation followed by dimerization of the phenoxyl radicals. c) Standard redox potentials for the IMHB PnQ phenols and the driving force for the PCET reaction using photo-generated oxidants [Ru(L)3]3+ (L = bpy or deeb).
The IMHB PnQ phenols disclose very similar standard redox potentials of the couple (PnQ /PnQ) that differ in less than 30 mV (Figure 6.6c). Such similarities arise from the consistent functionalization pattern of the phenols across the series. This is a particular distinctive feature of this series of phe-nols compared to previously studied systems that introduced variations of the proton donor-acceptor distance at the expense of substantial electronic differences along the series. In consequence, the IMHB PnQ phenols disclose similar driving force in PCET reactions with photo-generated oxidant rea-gents differing by less than 30 meV along the series. PCET reactions using the oxidants [Ru(bpy)3]3+ and [Ru(deeb)3]3+ (bpy = 2,2’-bipyridine and deeb
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= diethyl-(2,2'-bipyridine)-4,4'-dicarboxylate) show differences in the rates proportional to the differences in driving force (Figure 6.6c). Moreover, PCET reactions using the same oxidant, either [Ru(bpy)3]3+ or [Ru(deeb)3]3+, results in PCET rates that span over one order of magnitude within the IMHB PnQ phenols.
6.2.3 Dependence of the PCET Rate on the Proton Transfer Distance The effect of the proton transfer distance on the PCET rate can be quantita-tively analyzed accounting for differences in driving force by means of cor-relation plots of the PCET rate versus descriptors of the proton transfer dis-tance. In this study the analyzed descriptors are the calculated proton donor-acceptor distance dON, and proton tunneling distance (r0), where r0 here is defined as calculated distance between the proton position on the reactant state (PnQ, phenolic proton) and proton position in the product state (PnQ , N–H in the quinolinium cation, Figure 6.7, top). Calculated dON are 2.881, 2.577 and 2.2626 Å and r0 are 1.244, 0.716 and 0.856 Å for P5Q, P6Q and P7Q, respectively.
In this analysis, the correlation plots show excellent agreement with a lin-ear correlation according to equation 6.1 below. This expression has been derived to specifically seize the influence of the proton transfer distance on the PCET rate accounting for differences in the driving force of the reac-tion.102
ln(kPCET) + Gº/2RT = - (dON) + constant. (eq 6.1)
In the IMHB PnQ phenols it has been consistently found that the PCET rate increased with smaller dNO and r0, for rates obtained at two different driving forces, using oxidants [Ru(bpy)3]3+ or [Ru(deeb)3]3+ (Figure 6.7). In this analysis the slope of the linear fits (in Å-1 units) corresponds to the proton overlap exponential decay parameter the magnitude of which provides quantitative information of the influence of the proton transfer distances on the PCET rate.102,153 -values represent strong dependence of the PCET rate on proton transfer distance -1 would represents negligible dependence. In that limit case, other factors in-fluence the rate, for example the driving force, and would outweigh the in-fluence of the proton transfer distance. In correlations using dNO, -values of 7.5 and 9.2 Å-1 were obtained for PCET reactions with the oxidants [Ru(bpy)3]3+ and [Ru(deeb)3]3+, respectively. When the same kinetic infor-mation is used in correlation with r0 -values are 4.8 and 5.9 Å-1 with the oxidants [Ru(bpy)3]3+ and [Ru(deeb)3]3+, respectively.
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Figure 6.7. Driving force corrected correlation plots of the PCET rate and a) the proton donor acceptor distance dON and b) the proton tunneling distance r0. Filled diamonds correspond to rates determined using [Ru(deeb)3]3+ and unfilled circles with [Ru(bpy)3]3+.
In this analysis r0 is a better descriptor of the proton transfer distance since changes in the H-bond strength between the reactant and product states induce changes in the H-bond geometry that are not reflected by dON. Such changes become more important as the H-bond strength decreases. This is observed by the linear correlation of dON versus r0 which results in a slope greater than 1. In this approach the descriptors of the proton transfer are cal-culated from static structures that neglect the influence of the dynamic effect of vibration modes that modulate the proton transfer distance. These effects have been identified as important parameters that promote PCET.101,161
The observed -values for PCET reactions in the IMHB PnQ phenol are much smaller than the theoretically predicted values of 25–35 Å-1 from PT kinetic formulations in solution, which assume only ground state vibronic transitions. However, these -values clearly indicate a dependence of the PCET rate on the proton transfer distance. Additionally, the small -values suggest that here PCET involves accessible excited vibronic states also in cooperation with vibrational modes that compress the proton transfer dis-tance.101,156,157,161 These effects result in an enhancement of the proton wave-function overlap (in the ground and excited states) for the transition, which overall leads to an attenuated influence of the proton transfer distance com-pared to standard PT kinetic formulations in solution.
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6.3 Conclusions
The present study provides clear evidence of the dependence of the PCET rate on the proton transfer distance. This was possible due to the functional (similar proton donor and acceptor entities) and electronic consistency (simi-lar conjugation pattern between proton donor and acceptor) of the IMHB PnQ phenols. Additionally, this series has enabled the study of the widest range of proton tunneling distances in small molecule model systems; 0 = 0.5 Å in this study, compared to ca. 0.2 Å in previous studies. Importantly, the -values are smaller than expected from PT kinetic formulations in solu-tion that ignore the influence of PT transitions that involved vibronic exited states. This fact strongly suggests that the equilibrium proton transfer dis-tance is not the only parameter that determines the dependence of the PCET rate on the proton transfer distance, and that transitions that involve vibronic excited states and vibrational modes that compress the proton transfer dis-tance also take an important role in the modulation of the proton wavefunc-tion overlap that allows PT in CEPT reactions. These are significant contri-butions to understand PCET reactions from a fundamental perspective, with substantial implications for PCET reactions in biocatalysis and the design of functional PCET systems, such as catalysts for solar fuels production.
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7. Synthesis of Ruthenium(II) Polypyridyl Dyads Bearing IMHB PnQ Phenols
This chapter describes the synthesis and characterization of ruthenium(II) polypyridyl dyads that contain IMHB PnQ phenols. Different synthetic strat-egies are described to afford the desired dyads. Finally, a suitable method to synthetize the target dyads is developed and the complete synthesis of dyads of phenols P5Q and P6Q is presented.
7.1 Background In chapter 6, bimolecular PCET studies of the IMHB PnQ phenols have demonstrated the clear dependence of the observed rate of PCET on the pro-ton transfer distance. In these studies, efficient oxidative quenching of the photo-excited tris(bidentate)ruthenium(II) polypyridyl complexes yields a ruthenium(III) complex in the ground state that in turn acts as oxidant to the IMHB PnQ phenols by a CEPT mechanism. Due to the bimolecular nature of the process, the observed rate for the PCET reaction becomes interwoven with the mutual diffusion of the reactants to form an activated complex from which the PCET reaction takes place. PCET rates were compared within the series under pseudo first-order conditions with the reasonable assumption of similar diffusion properties of the IMHB PnQ phenols. Small -values sug-gest that the proton wavefunction overlap that enables CEPT is assisted by vibronic excited state transitions and vibrational modes that compress the proton transfer distance.
Due to the ring-fused polycyclic structure of the IMHB PnQ phenols, large conformational changes in solution arising from twisting along the dihedral angle between the proton donor-acceptor subunits are minimized compared to previously studied system. This offers the possibility of good isolation of the proton transfer coordinate, especially in the conformationally locked (coplanar) phenol P5Q. This feature makes the IMHB PnQ phenols a very suitable candidate for PCET pressure dependence studies in which the vibrational modes that compress the proton transfer distance can be studied.
A clear interpretation of the pressure dependence PCET rates requires the direct evaluation of the intrinsic, diffusion free, PCET rate constants. To consistently surpass inherent diffusion effects of in the bimolecular studies,
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it is necessary to advance to intramolecular systems to evaluate the intrinsic PCET rate constant, since the distance and mutual orientation of the electron donor-acceptor moieties are in principle well defined. This has motivated the synthesis of ruthenium(II) polypyridyl dyads featuring the IMHB PnQ phe-nols. In analogy to previously studied systems, the originally proposed ru-thenium(II) polypyridyl dyads (see Figure 5.2), also feature an alkyl amino-acid linker between the electron donor-acceptor moieties. As described in chapter 4, a feasible synthesis of the IMHB PnQ phenols required introduc-ing of a fragment suitable to be used as a linker in a subsequent synthetic sequence. Adapting the prepared IMHB PnQ phenols to the initially pro-posed ruthenium(II) dyads with an alkyl amino-acid linker results in the structures presented in Figure 7.1.
Figure 7.1 Ruthenium(II) polypyridyl dyads covalently attached to IMHB PnQ phe-nols via an alkyl amino-acid fragment (initially targeted linker).
7.2 Retrosynthetic Considerations Previously studied IMHB tyrosine analogs have been covalently attached to the ruthenium(II) polypyridyl complexes via an amide bond between the amine function of the aminoacid fragment and the carboxylic acid function of 4’-methyl-2,2’-bipyridine-4’-carboxylic acid. In a subsequent step, the tyrosine functionalized polypyridyl ligand is finally coordinated to a bis(bidentate)ruthenium(II) polypyridyl precursor to yield the desired dyads. Accordingly, a similar strategy to for the synthesis of the ruthenium(II) polypyridyl dyads of the IMHB PnQ phenols would require para- functional-ization of the phenols with an alkyl aminoacid fragment
Excluding biosynthetic routes for the synthesis of un-natural amino-acids,162,163 a limited number of synthetic routes for the construction of an alkyl amino acid function in the para- position of phenols have been report-ed. A retrosynthetic analysis of these strategies allows us to group them into two main categories according to the position where the key disconnection
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takes place (Figure 7.2). In the first category, the key disconnection occurs between C- -carbon of the alkyl amino-acid frag-ment. Suitable synthetic equivalents for this disconnection are coupled by Heck arylation.164-166 In the second category, the key disconnection occurs
- -carbons in the alkyl amino-acid fragment. In this case, suitable synthetic equivalents for this disconnection are coupled either by reacting suitable condensation partners (e.g. a p-phenolaldehyde and hippu-ric acid), or by addition of an organometallic reagent of the phenol that can undergo nucleophilic addition to N-tert-butylsulfinyl imino acetate.167,168
Figure 7.2 Retrosynthetic analysis for the construction of the alkyl amino-acid fragment. Disconnection (A): between C- -carbon of the alkyl amino-acid fragment. Disconnection (B): between the - and -carbons in alkyl amino-acid fragment.
In every case, the synthetic routes require protection/deprotection sequences of the hydroxyl proton as well as regioselective functionalization of the C-4 of the phenol with the appropriate functional group for the subsequent cou-pling step. Methods based on Heck arylation require further catalytic hydro-genation of the resulting double bond in the amino acid fragment and cleav-age of the tertiary alkyl-amine to yield the desired primary amine. Similar procedures need to be applied for the condensation of p-phenolaldehydes. On the other hand, addition of an organometallic reagent of the phenol and N-tert-butylsulfinyl imino acetate does not require a catalytic hydrogenation step; however, it requires a multi-step sequence to afford the phenol deriva-tive organometallic reagent and further cleavage of the tert-butylsulfinyl group to yield a primary amine. Adaptation of any of these strategies for the synthesis of the target dyads has, depending on the method, at least one or many drawbacks. In general, owing to the multistep sequences required, the reaction conditions of the individual synthetic steps can compromise the chemoselectivity of the reactions since the methods have been developed for
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simpler phenols that do not require ester protected carboxylic group and a primary amine for further amide linkage.
A different synthetic strategy to covalently attach the IMHB PnQ phenols and ruthenium(II) polypyridyl complexes was explored in the light of the above considerations. A method based on copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) has been previously employed for the covalent link-age of ruthenium(II) polypyridyl complexes and phenol.169 CuAAC affords a 1,4-disubstituted 1,2,3-triazole linker between a terminal acetylene substitut-ed ruthenium(II) polypyridyl complex and 4-azidophenol. This method pro-vides various advantages as compared to approaches described above. For example, it is compatible with unprotected hydroxyl protons of the phenol and requires functional groups on the ruthenium(II) polypyridyl photosensi-tizer and phenol that can in principle be successfully installed with guaran-teed chemoselectivity. Additionally, the 1,2,3-triazole linker does not disturb the electronic coupling between the photosensitizer and different electron donor and acceptor moieties.169 Therefore, CuAAC was identified as a suita-ble method for the synthesis of ruthenium(II) polypyridyl dyads featuring the IMHB PnQ phenols (Figure 7.3).
Figure 7.3 General scheme for the synthesis of ruthenium(II) dyads linked via a triazole ring formed using CuAAC (based on previously reported analog dyads).
7.3 Synthesis Azide functionalization in the para- position of the IMHB PnQ phenols was attempted by Ullmann-type coupling from aryl-halides using CuI as catalyst. The chosen method was previously shown to be highly versatile, allowing the azide functionalization of a wide range of aryl-halides including electron rich bromo-aryls under mild conditions.170 Multiple methods to brominate P5Q and P6Q in para- position were explored. Best yields were obtained by bromination of the intermediate anisoles A5Q and A6Q with NBS and HBF4·Et2O in acetonitrile at room temperature, followed by hydroxyl depro-tection with BBr3 at 65 ºC in CHCl3. In the case of P7Q, hydroxyl deprotec-
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tion of the intermediate anisole A7Q-Br under the same conditions afforded the desire para-bromo substituted phenol. The IMHB phenols P5Q-Br, P6Q-Br and P7Q-Br were prepared in 54%, 59% and 85% overall yields respec-tively, from their anisoles (Figure 7.4a). Unfortunately, Extensive attempts to optimize the reaction conditions for the Ullmann-type coupling of the para-bromo substituted PnQ phenols did not afford the desire para-azide substituted phenols (Figure 7.4b).
Figure 7.4 General schemes for: a) para-bromination or iodination of the IMHB PnQ phenols b) Ullman-type coupling of the para-bromo and iodo substituted IMHB PnQ phenols. c) ORTEP view at 50% probability of P6Q-Br.
Owing to the increased reactivity of iodo-aryls relative to their bromo coun-terparts, the para-iodo substituted IMHB PnQ phenols were prepared (Figure 7.4a). Iodination of the PnQ phenols was performed using NIS and HBF4·Et2O in acetonitrile at 100 ºC for 5 minutes under microwave irradia-tion by adaptation of related procedures.171,172 The desired IMHB phenols P5Q-I, P6Q-I and P7Q-I were prepared in 45%, 24% and 7% yields, respec-tively. In the case of P7Q-I the main product of the reaction is the ortho-, para- doubly iodinated phenol, suggesting that the para-iodo substituted phenol of P7Q is more reactive towards iodination than the starting material. This accounts for the poor (unusable) yield of the reaction. Unreacted start-ing material was also observed in the reaction mixture since one equivalent of NIS was used in all cases. In consequence, further optimization of the synthesis of P7Q-I is necessary.
With the IMHB phenols P5Q-I and P6Q-I in hand, Ullmann-type cou-pling to afford the para-azide substituted phenol of P5Q and P6Q was at-tempted again; however, the reaction with these substrates did not yield the desired product despite multiple efforts to optimize the reaction conditions (Figure 7.4b). Presuming the instability of the products, in-situ Ullmann-type coupling followed by CuAAC with the terminal acetylene substituted ruthe-nium(II) polypyridyl complexes reported by Aukauloo et. al.169 was attempt-ed by adaptation of a procedure reported for this type of transformation.173
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However, the desired dyads were not obtained, instead, the main product of the reaction corresponds to the ruthenium(II) polypyridyl complex bearing a mono-substituted 1,2,3- triazole ring.
In order to overcome the limitation on the synthesis of the para- azide functionalized IMHB PnQ phenols (PnQ-N3), different strategies were stud-ied. An attractive alternative strategy would be to exchange the functional groups in the substrates engaged in the CuAAC coupling. This implied func-tionalization of the ruthenium(II) polypyridyl complex with a azide func-tional group and functionalization of the IMHB phenols with a terminal acetylene. This was accomplished by Sonogashira coupling of the P5Q-I and P6Q-I with ethynyltrimethylsilane to afford the para- substituted TMS pro-tected acetylenic phenols P5Q- -TMS and P6Q- -TMS in 62% and 55% yield, respectively. Notably, the para-bromo substituted phenols did not engage in Sonogashira coupling under similar conditions. Trimethylsi-lylacetylene protodesilylation did not afford the desired products using con-ventional methods (e.g. fluoride or carbonate ions). Specifically, in the case of P5Q- -TMS it was identified that even mildly basic reagents will deprotonate the methylene fragment in the 1,3-cyclopentadiene ring to from the resonance stabilized cyclopentadienyl anion as intermediate in the for-mation of undesirable side-products. Suitable conditions for trimethylsilyla-cetylene protodesilylation were obtained using AgNO3 in a H2O/MeOH mix-ture followed by quenching with NH4Cl, to afford the phenols P5Q- -H and P6Q- -H in 95 % and 90 % yield, respectively (Figure 7.5). This method avoids the use to basic reagents and provides high chemoselectivity in the trimethylsilylacetylene desilylation of the IMHB phenols. In this case, desilylation proceeds by formation of an intermediate silver(I) acetylene complex that reacts with NH4Cl to form the terminal acetylene and AgCl.174
Figure 7.5 General scheme for the synthesis of para-substituted IMHB PnQ phenols with a terminal acetylene. (a) Iodination, (b) Sonogashira coupling, (c) TMS desi-lylation.
The para-substituted IMBH phenols P5Q-Y, P6Q-Y and P7Q-Y (Y=Br, I, --TMS and - -H) show a 1H-NMR splitting pattern of the signals in
the aromatic region consistent with that expected for a para-substituted [2,3]-fused ring phenol and a [2,3]-fused ring quinoline. Likewise, the alkyl fragments of the cycloalkadiene ring in the P5Q-Y, P6Q-Y and P7Q-Y IMHB phenols (i.e. methylene, 1,2-ethylene and 1,3-propylene, respectively)
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can be identified at low frequencies. The specific assignment of the 1H-NMR signals was done based on the assignment of the pattern in the IMHB PnQ phenols. In the case of P5Q- -TMS and P6Q- -TMS, the trimethylsi-lyl proton signals appeared at ca. 0.3 ppm, whereas in P5Q- -H and P6Q-
-H terminal acetylene proton signals appeared at ca. 3.2 ppm. 13C-NMR and a combination of mass spectrometry techniques allowed us to confirm the proposed structure of the para-substituted IMBH phenols.
The synthesis of the ruthenium(II) polypyridyl complexes functionalized with an azide functional group presented a different challenge since the ru-thenium(II) polypyridyl complex featuring the ligand 4-azido-2,2’-bipyridine has been reported to be unattainable in previous studies by Aukauloo et. al.169 This obstacle was successfully surpassed by functionalizing the ruthe-nium(II) polypyridyl complex by an alkyl-azide rather than an aryl-azide (like 4-azido-2,2’-bipyridine). This offered a strategy to circumvent the in-herent challenges of the synthesis of aryl-azides. To this end, a ruthenium(II) polypyridyl complex featuring the ligand 4-bromomethyl- -methyl- -bipyridine (Ru-Br) was prepared as precursor for azide functionalization. The ancillary ligands in the complex feature EWG carboxylate ester groups to influence the potential of the Ru3+/2+ redox couple in order to guarantee sufficient redox power of the oxidized ground state to oxidize the IMHB phenols in the dyads. The precursor Ru-Br was prepared in a multistep se-quence in 60% overall yield (Figure 7.6).
Figure 7.6 General scheme for the synthesis of the precursor [Ru(deeb)(dmb-Br)]2+ (Ru-Br) (PF6
- counterions are omitted).
Azide functionalization of the precursor Ru-Br was performed via a nucleo-philic substitution (SN2) using sodium azide. This method afforded the de-sired ruthenium(II) polypyridyl complex functionalized with an azide func-tional group (Ru-N3) in 75% yield (Figure 7.7).
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Figure 7.7 General scheme of the synthesis of the azide functionalized photosensi-tizer [Ru(deeb)(dmb-N3)]2+ (Ru-N3) (PF6
- counterions are omitted).
The ruthenium(II) polypyridyl complexes Ru-Br and Ru-N3 show 1H-NMR signals in the aromatic region consistent with that expected for heteroleptic ruthenium(II) diimine complexes of the type [Ru(L)2(L1)]2+ with L = diethyl-(2,2'-bipyridine)-4,4'-dicarboxylate (deeb) and L1 = 4-(bromomethyl)-4'-methyl-2,2'-bipyridine (dmb-Br) in the case of Ru-Br, and L1 = 4-(azidomethyl)-4'-methyl-2,2'-bipyridine (dmb-N3) ligand in the case of Ru-N3. The specific assignment of the 1H-NMR signals of the complex Ru-Br was done based on 1H-NMR signals of the free ligands deeb and dmb-Br, and the correlation of the coupled protons in the COSY 1H-1H spectrum of the complex. The assignment of the 1H-NMR signals of Ru-N3 was done based on the assignment for Ru-Br since the same splitting pattern and rela-tively similar chemical shift of proton signals prevail in the two complexes. In Ru-Br, the carboxylate ester proton signals in the deeb ligands show a chemical shift of ca. 4.4 ppm for the methylene protons and ca. 1.4 ppm for the methyl protons. In the case of the dmb-Br ligand, the methylene and methyl proton signals show a chemical shift of ca. 4.6 ppm and ca. 2.5 ppm, respectively. Similar chemical shifts for the substituents of the polypyridyl ligands in Ru-N3 were observed with respect to the precursor complex Ru-Br. Likewise, 13C-NMR and a combination of mass spectrometric techniques allowed us to confirm the structure the ruthenium(II) polypyridyl complexes Ru-Br and Ru-N3.
With the synthetic equivalents for CuAAC linkage via 1,2,3-triazole for-mation in hand (i.e. IMHB phenols P5Q- -H, P6Q- -H and Ru-N3 complex), the dyads of the respective IMHB PnQ phenols (Ru-tz-P5Q and Ru-tz-P6Q) were prepared adapting the conditions for CuAAC in a by-phasic solvent system.175 The dyads Ru-tz-P5Q and Ru-tz-P6Q were synthe-tized in 40-30% yield (Figure 7.8). The moderate yields in the synthesis of the dyads are in part associated with the formation of ruthenium(II) polypyridyl by-products resulting from the cleavage of the azido group in Ru-N3, which in turn results in extensive purification protocols using differ-ent chromatographic methods including semi-preparative HPLC.
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Figure 7.8 General scheme for the synthesis of ruthenium(II) dyads featuring IMHB phenols covalently linked via 1,2,3-triazole (PF6
- counterions are omitted).
The dyads Ru-tz-P5Q and Ru-tz-P6Q show 1H-NMR proton signals in the aromatic region consistent with those expected for heteroleptic ruthenium(II) diimine complexes of the type [Ru(L)2(L1)]2+ with L= deeb and L1= 4-(methyl-substituted)-4'-methyl-2,2'-bipyridine (dmb-Y) in which the dmb ligand is substituted by a 1,2,3-triazole bearing the IMHB PnQ phenols P5Q and P6Q. Every specific 1H-NMR signal for the ruthenium(II) complex, triazole linker and IMHB phenol in the spectra could be assigned. This was accomplished by integrating the information of the chemical shift of the signals for the precursor complex (Ru-N3) and the para-substituted IMHB PnQ phenols (PnQ-Y), the correlation of the coupled protons in the COSY 1H-1H spectra and the expected relative integration for the individual signals. In general, the aromatic region of the spectra shows the superimposed sig-nals of the IMHB PnQ phenols and the polypyridyl ligands, with some over-lap of specific signals. The proton signal of the 1,2,3-triazole ring appears at ca. 8.3 ppm and ca. 8.1 ppm for Ru-tz-P5Q and Ru-tz-P6Q, respectively. Formation of the 1,2,3-triazole ring also shifts the proton signal of the meth-ylene in the dmb derivative ligand to ca. 5.8 ppm in both dyads. The proton signals in the carboxylate ester of the deeb ligands and the methyl in the dmb derivative ligand remain at the same chemical shift relative to the pattern in the ruthenium(II) polypyridyl complex. The 1H-NMR signal for the P6Q phenolic proton appears at 15.1 ppm in Ru-tz-P6Q, whereas the signal for the same proton in Ru-tz-P5Q could not be identified due to residual H2O in the sample that promotes rapid exchange similarly to the pattern IMHB phe-nol P5Q. 13C-NMR and a combination of mass spectrometric techniques finally confirmed the structure of the ruthenium(II) polypyridyl dyads Ru-tz-P5Q and Ru-tz-P6Q.
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7.4 Conclusions and Outlook Different strategies to prepare ruthenium(II) polypyridyl dyads of the IMHB PnQ phenols were explored. A suitable synthetic strategy was developed in which the linkage was performed by a 1,2,3-triazole ring formed via Cu-AAC. This was accomplished by installing appropriate functional groups for CuAAC in the ruthenium(II) polypyridyl complex and the IMHB phenols moieties via multistep sequences implemented in moderate to high yields. The final Ru-tz-P5Q and Ru-tz-P6Q dyads and their synthetic precursors were fully characterized.
Although further synthetic efforts are required to afford the ruthenium(II) polypyridyl dyad of P7Q, this compound can be furnished once the yield to prepare the intermediate para- iodo P7Q is improved. To this end, different synthetic approaches can be envisioned. For example, using classical meth-ods to iodinate the intermediate 5-(3-methoxyphenyl)pentanoic acid pre-pared in the synthetic sequence to afford the IMHB phenol P7Q. This will afford the intermediate A7Q-I instead of its brominated counterpart upon Friedländer annulation with 2-aminobenzaldehyde (see Figure 5.10). Like-wise, different milder conditions to directly iodinate the IMHB phenol P7Q can be explored.
Temperature and pressure dependence studies of the intrinsic, diffusion free, rates of PCET will be conducted in ruthenium(II) polypyridyl dyads of the IMHB PnQ phenols. The dyads are unprecedented frameworks to con-front current theoretical models of PCET reactions and we expect to obtain previously unavailable experimental data, specifically regarding the depend-ence of the rate of PCET on vibrational modes that compress the proton tun-neling distance and enhance the proton wavefunction overlap that enables CEPT reactions.
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8. Summary and Outlook
The systems synthetized and studied in this thesis have proven to be useful as functional biomimetic models of Chlorophyll dimer (P680) and Tyrosine-161 (TyrZ) in PSII. Substitution of the lateral quinolinyl fragments of dqp by
-accepting fragments has demonstrated to be a very effective way to alter the electronic properties of the original [Ru(dqp)2]2+ . This strategy opened the possibility of ground and exited-state redox tuning in this type of complexes preserving suitable photophysical and topological properties for the ensemble of linear supramolecular rod-like arrangements for vectorial photo-induced electron transfer reactions. The observed redox properties of the complexes were analyzed on the basis of their electronic structure. This enabled a detailed understanding of the influence of substitut-ing the lateral quinolinyl fragments of dqp type ligands by stronger and
-accepting fragments isoelectronic to quinoline. A novel series of intramolecularly hydrogen bonded phenols with doubly
ring-fused cycloalkadienes of 5, 6 and 7 member rings between phenol and quinoline was synthetized. These phenols are an improved series of model systems to study distance dependent proton-coupled electron transfer reac-tions compared to previous studied systems. The IMHB phenols described herein enable the isolated study of effects that arise from differences in pro-ton transfer distance compared to those that are caused by other electronic effects that can influence the H-bond strength. The latter effects include
as, and differences in the conjugation pattern which induce differences in reso-nance assisted hydrogen bond. A detailed structural characterization of the phenols allowed the rationalization of the observed trend in the hydrogen bond strength on the basis of the stereochemical influence of the ring-fused cycloalkadienes.
Proton-coupled electron transfer studies of the phenols revealed compel-ling evidence for the dependence of the CEPT rate on the proton transfer distance. The observed dependence provides strong experimental evidence that suggest that vibronic exited states and vibration modes that compress the proton transfer distance take an important role in the modulation of the pro-ton wavefunction overlaps that allows CEPT reactions. This study indicated that the proton wavefunction overlap is therefore not a simple function of the equilibrium proton donor-acceptor distance.
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A suitable synthetic strategy to afford ruthenium(II) polypyridyl dyads featuring the phenols was successfully developed. These dyads will allow investigating the pressure and temperature dependence of the PCET rate in the IMHB phenols. This is possible since the dyads allow the direct evalua-tion of the intrinsic, diffusion free, PCET rate constants. This in turn opens the possibility of further studies aimed to investigate the influence of vibra-tional modes that compress the proton transfer distance and thereby modu-late the proton wavefunction overlap in CEPT reactions.
In addition, the excited state dynamics of the IMHB phenols was investi-gated. This study revealed important information of the influence of the pro-ton transfer distance as a critical hydrogen bond geometrical parameter that influences the rate of excited state intramolecular proton transfer. Further-more, it emerged that dihedral angle between proton donor and acceptor is the critical hydrogen bond geometrical parameter that influences formation of the tautomer excited state photoproduct. While theoretical formulations predict efficient excited state and ground state interactions via conical inter-sections are most efficient at dihedral angles close to 90º, this study provided important experimental evidence that suggest that efficient non-radiative deactivation pathways operate at much smaller twisted dihedral angles be-tween proton donor and acceptor. These finding underpin important design principles for technological applications based on excited state intramolecu-lar proton transfer and photo-induced and tautomerization.
This thesis combined multiple synthetic methodologies, electrochemical investigations, photophysical investigations, quantum chemical calculations and spectroscopic kinetic experiments to further the knowledge of proton and electron transfer reactions in the ground and excited state. Such knowledge is an important contribution from the perspective of fundamental science and for the development of artificial photosynthesis and other multi-ple technological applications that involve the type of reactions studied herein.
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Populärvetenskaplig sammanfattning på svenska
Människan har alltid varit beroende av solen som energikälla. Redan i de första biologilektionerna i skolan lär vi oss om symbiosen mellan växternas fotosyntes och djurens respiration (andning). Växterna å ena sidan använder energi från solen, koldioxid och vatten för att producera kolhydrater och syre, medan djuren å andra sidan använder syre, kolhydrater från växter som energikälla och genererar koldioxid och vatten. Växter och djur är alltså beroende av varandras biprodukter, och solen är energikälla för hela cykeln. Således är människan direkt beroende av växter för att få energi, och det innebär att människan indirekt är beroende av solen.
Mänskligt liv får sin energi från växter. Människans livsstil får framförallt sin energi från kol och olja, vilket även det kommer från växter. Det är all-mänt känt att råolja är utvunnen från jordens inre, en det är allt för lätt att ta för givet hur det kom dit från första början. Kanske är vi helt enkelt nöjda med att ha denna energikälla till vårt förfogande, men det blir allt mer up-penbart att den både förstör den naturliga symbiosen och heller inte är eko-logiskt hållbar. Kolet som utgör oljefyndigheterna härstammar från karbon-perioden, ca 360 till 286 miljoner år sedan. Under denna geologiska period var jorden täckt av vidsträckta skogar vilket möjliggjorde ackumulering av enorma mängder kolhaltig biomassa på jordens yta. Ryggradsdjur, mestadels amfibier och leddjur, existerade på jorden under denna tid, men de stora dinosaurierna som t.ex. Tyrannosaurus rex kom miljontals år senare, för 67 miljoner år sedan. Karbonperioden slutade med en massiv klimatförändring vilken ledde till en plötslig kollaps av regnskogar och mycket av det amfi-biska livet, endast små fickor av skog återstod. Nedbrytningen av växter och djur från denna kollaps skedde i jordens innandöme vid hög temperatur och tryck, vilket över miljontals år formade dagens kol, olja och naturgas. Dessa ”fossila bränslen” vilka används av den nutida människan för att möjliggöra vår livsstil har alltså väldigt lite att göra med dinosaurier och mycket mer att göra med växterna under karbonperioden. Dessa energitillgångar hade alltså inte varit möjliga utan fotosyntes som verkat för miljoner år sedan.
Enligt NASA är 97% av världens forskare överens om att de klimatför-ändringar som vi upplever idag är orsakade av den globala uppvärmning som är aktiverad av de höga nivåerna av utsläpp av växthusgaser. Av dessa gaser
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är CO2 (koldioxid) den huvudsakliga bidragaren. Ökningen av CO2 i jordens atmosfär är direkt kopplad till förbränningen av fossila bränslen ‘uppnådd fotosyntes’ bränslen). Det är ingen tvekan att människans livsstil har orsakat denna kraftiga variation av klimatförändring. Av denna anledning och de lika så viktiga politiska frågor som härrör från upphandlingen och använ-dandet av fossila bränslen, behöver vi skyndsamt ta itu med utveckling av nya teknologier för ren förnybar energi.
Den mest lovande teknologin skulle drivas av vad som redan driver oss – solen. Ett verkligt revolutionerande tillvägagångssätt skulle vara att ’artifici-ellt fotosyntetisera’ vår energi. Denna metod har potential att vara fri från kol och vara helt och hållet hållbar och förnybar. En teknologi baserad på konstgjord fotosyntes särskiljer sig från andra alternativa energislag, såsom vind, kärnkraft, och vattenkraft, i det att ett ”sol-bränsle” är producerat; det vill säga, energin kommer att lagras i kemiska bindningar på samma sätt som bränslen från ‘uppnådd fotosyntes’ är lagrad i kolväte-bindningar. Den extra fördelen med ”sol-bränslen” är att den mesta infrastrukturen redan är utfor-mad för bränslen snarare än elektricitet.
Utvecklandet och en storskalig implementering av artificiell fotosyntes är ett stort åtagande. Först och främst måste vi samla en fördjupad förståelse av de fundamentala principer som styr naturlig fotosyntes. Samtidigt som vi vet en hel del om naturlig fotosyntes är det fortfarande viktiga detaljer som är okända. I vissa fall har en hel del lärts från studier av konstgjorda molekyler som härmar väsentliga kemiska reaktioner som driver fotosyntesen. Denna avhandling representerar en sådan prestation, vari målet har varit att testa fysikaliska beteenden hos elektron- och protonöverföringar i system som är inspirerade av naturliga fotosyntetiska organismer.
Denna avhandling avser att bidra med utökad kunskap om hur ljus-absorption kan utlösa förflyttningar av elektroner och protoner. Dessa reakt-ioner är de som driver växternas fotosyntes. För att uppnå detta mål har jag studerat en serie oorganiska ljusabsorberande komplex baserade på ett ru-teniummetallcenter som efter ljusabsorption erhåller erforderlig energi för att förflytta elektroner. Jag har även studerat en serie organiska föreningar rela-terade till de som finns i fotoaktiva enzymer som genomgår protonkopplad elektronöverföring. När dessa två system är sammankopplade har vi möjlig-het att studera ljus-sensiterad elektronöverföring som inducerar en proton-kopplad elektronöverföring; detta härmar vissa av de fundamentala reaktion-erna i fotosyntes. Serien med ljusabsorberande molekyler är designad för att studera hur molekylens förmåga att ge eller ta emot elektroner påverkas av den absorberade ljus-energin. Serien med organiska molekyler användes för att studera hur avståndet som protonen behövde förflyttas påverkade hastig-heten för den proton-kopplade elektronöverföringsreaktionen. Dessa studier är i synnerhet relevanta för utvecklingen av konstgjord fotosyntes eftersom framtida teknologier kommer bero på effektiviteten hos dessa reaktioner.
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För dessa två studier har jag tillverkat (syntetiserat) nya oorganiska och organiska molekyler vilka undergår ljus-sensiterad elektronöverföring och proton-kopplad elektronöverföring. En betydande utmaning inom grund-forskning är ofta syntetiseringen av nya föreningar som är relevanta för stu-dien. För denna avhandling har en mängd nya strategier och tillvägagångs-sätt använts för syntetiseringen av varje förening. Syntesen av var och en av föreningarna i denna avhandling kräver ett flertal steg, som följer: omfat-tande efterforskning för att planera syntes-proceduren (retrosyntes), optime-ring av de bästa förhållanden för att erhålla så stort utbyte av syntesen som möjligt, beredning av föreningar för varje delsteg och isoleringen av de slut-liga önskade molekylerna. I de fall föreningarna är strukturellt unika krävs ofta hittills outforskade syntetiska metoder. I tillägg har varje förening och dess intermediära föreningar karaktäriserats med ett flertal tekniker för att säkerställa dess identitet. De viktigaste teknikerna för detta är röntgen-kristallografi och kärnmagnetisk resonans (NMR). Dessa två kraftfulla tek-niker ger detaljerad strukturell information om molekylerna (hur atomerna som utgör molekylerna är rumsligt fördelade och hur de är kopplade till varandra). Resultaten från detta används även senare för att förstå resultaten av andra typer av mätningar vilka ger information om fördelningen av elektroner i molekylen. Elektronfördelningen kan ändras när molekyler ab-sorberar ljus och även när en kemisk reaktion sker. Denna förändring av elektronisk struktur kan vara svår att tyda direkt, och kunskap av strukturen hos molekylerna (föreningarna) som studeras är av stort värde.
Serien av oorganiska molekyler användes sedan för att undersöka för-mågan att överföra elektroner vid bestrålning av synligt ljus. Två olika typer av processer studerades: först förmågan att överföra en elektron vid absorpt-ion av UV-ljus, följt av en protonöverföring i ett elektroniskt exciterat till-stånd, sedan även förmågan att överföra en elektron och en proton i ett elektroniskt grundtillstånd. Dessa processer kunde följas i realtid med hjälp av ultrasnabba spektroskopiska tekniker. Från UV-ljus experimenten fann vi att de organiska molekylerna genomgick protonöverföring inom en tidsskala av 0,000 000 000 000 1 och 0,000 000 000 000 01 sekunder (10-12 till 10-13 s). De olika hastigheterna berodde på den specifika strukturella särdragen för de olika oorganiska molekylerna. Protonkopplade elektronöverföringsreakt-ioner fanns äga rum med halveringstider som sträcker sig från 0.00001 till 0.0000001 sekunder, och skillnaden i hastighet kunde relateras till avståndet som protonen behövde förflyttas. Den fysikaliska information som studien av oorganiska och organiska molekyler har lärt oss har sedan kombinerats för att erhålla sambandet mellan dess struktur och egenskaperna: energin för elektronen som deltar i elektronöverföring samt de olika hastigheterna för elektron- och protonöverföring.
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Sammanfattningsvis, de viktigaste aspekterna detta arbete har bidragit med är utveklingen av procedurerna för syntetiseringen av dessa unika mo-lekyler. Molekylerna har å sin sida vidare möjliggjort studier av elektronö-verföring i ruthenium(II) polypyridyl-komplex, och inverkan av protonöver-föringsavståndet samt mekanistiska detaljer av den kopplade rörelsen av elektroner och protoner i vätebindande fenoler både i exiterat tillstånd och i grundtillstånd (med och utan bestrålning av UV ljus). Dessa upptäckter har korrelerats med strukturella parametrar hos molekylerna och möjliggjort generella slutsatser av om egenskaper för protoners och elektroners rörelse. Detta är av stor betydelse för utveklingen av konstgjord fotosyntes, och i själva verket även för många andra metaboliska processer i naturen.
Översatt av Jonas Petersson
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Resumen en Español
La humanidad siempre ha dependido del sol como fuente de energía. Una de las primeras lecciones de biología en el colegio nos enseña a cerca de la simbiosis que existe entre la fotosíntesis en plantas y la respiración aeróbica en animales. Esta simbiosis puede resumirse así: Las plantas usan dióxido de carbono, agua y energía proveniente del sol, para producir carbohidratos y oxígeno: Por su parte, los animales usan carbohidratos y oxígeno (provenientes de las plantas) para generar energía, y liberan dióxido de carbono y agua en el proceso. Por lo tanto, animales y plantas utilizan las sustancias producidas por el otro en sus funciones metabólicas vitales, donde el sol es la fuente primaria de energía. Esto significa que los humanos dependen de manera directa de las plantas como fuente de energía, lo que en consecuencia significa que dependen de manera indirecta del sol ya que este es la fuente directa de energía de las plantas.
Mientras que la energía para los procesos metabólicos que sostienen la vida de los humanos proveniente de las plantas, la energía que mantiene el estilo de vida de los humanos proviene principalmente de combustibles fósiles, por ejemplo para diversos procesos industriales y medios de transporte. A pesar de que es común saber que los combustibles fósiles son extraídos del interior de la tierra, pocas veces nos preguntamos cómo llegaron allí en primer lugar. La mayoría del tiempo basta con estar felices de tener esta fuente de energía a nuestra disposición. Sin embargo, cada vez es más claro que el uso de combustibles fósiles no solo está alterando rápidamente el equilibrio de diversos ecosistemas, sino que es bien sabido que esta fuente de energía no es inagotable, y por lo tanto es insostenible a largo plazo.
Los combustibles fósiles que usa nuestra sociedad se constituyen de hidrocarburos. El carbón que constituye dichos hidrocarburos almacenados en el interior de la corteza terrestre proviene del periodo geológico conocido como periodo Carbonifero, ocurrido hace 360 y 286 millones de años. En este periodo el planeta estaba cubierto por extensos bosques que permitieron la acumulación de inmensas cantidades de biomasa carbonacea en la superficie de la tierra. Animales vertebrados, principalmente anfibios y artrópodos también existieron durante este periodo. Los grandes dinosaurios como el Tiranosaurio Rex vinieron millones de años después, hace cerca de 67 millones de años. El periodo Carbonifero finalizó con un cambio climático severo que conllevó al colapso súbito de las selvas de la superficie
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terrestre y de mucha de la vida anfibia, en la cual solo pequeños bosque se sobrevivieron y ciertas especies que evolucionaron en forma de reptiles. Grandes cantidades de biomasa carbonacea fueron atrapadas en el la corteza terrestre e iniciaron su procesos de descomposición a inducidos por temperaturas y presiones elevadas. Estos procesos se han llevado a cabo durante millones de años han dado origen al petróleo, gas natural y carbón que extrae y consume nuestra sociedad para proveer energía y mantener nuestro actual estilo de vida. Así pues, el origen de estos “combustibles fósiles” tiene poco que ver con grandes dinosaurios y mucho más que ver con plantas, las cuales solo pudieron existir gracias a procesos fotosintéticos hace millones de años.
De acuerdo con la NASA, el 97% de la comunidad científica mundial concuerda que el cambio climático que experimentamos en nuestros días proviene de la tendencia de calentamiento global activada por los altos niveles de emisión de gases de invernadero. De estos gases, el dióxido de carbono (CO2) es un contribuidor mayoritario. El incremento de CO2 en la atmosfera de la tierra está directamente relacionado con el uso de combustibles fósiles o “combustibles fotosintéticos archivados” en el la corteza de la tierra. No hay marera de negar que los combustibles que mantienen el estilo de vida de nuestra sociedad han propiciado este acelerado cambio climático. Por este motivo, por su naturaleza no renovable y por asuntos geopolíticos de igual gravedad en la consecución y uso de combustibles fósiles, se hace necesario implementar con urgencia el desarrollo de nuevas tecnologías de energía renovable de bajo impacto ambiental.
La tecnología más prometedora será alimentada por la fuente de energía que ya nos alimenta: el sol. Una estrategia visionaria sería proveer energía a través de una forma artificial de fotosíntesis. Esta estrategia tiene el potencial de convertirse en una fuente completamente renovable, sostenible, con cero emisiones de carbono a la atmosfera y que además no dependería de la infraestructura de malla eléctrica. Una tecnología de fotosíntesis artificial se distingue de otras formas de “energías alternativas” tales como energía eólica, nuclear, hidroeléctrica, en cuanto a que produce un “combustible solar”. Esto significa que la energía solar podrá ser almacenada en enlaces químicos de manera similar a los “combustibles fotosintéticos archivados” en los que la energía es almacenada en enlaces hidro-carbono. La ventaja adicional de esta estrategia de “combustibles solares” es que la mayoría de nuestra infraestructura energética ha sido desarrollada para combustibles, especialmente combustibles líquidos.
El desarrollo e implementación a gran escala de fotosíntesis artificial requiere de un gran esfuerzo científico y de planeación de gobiernos y organizaciones internaciones. Para esto es de suma importancia acumular conocimiento detallado de los principios fundamentales que operan en organismos fotosintéticos. A pesar de que existe una gran cantidad de
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conocimiento de este proceso, hay aún detalles importantes que aún se desconocen. En ciertas áreas de investigación de en fotosíntesis una gran cantidad de conocimiento ha sido adquirido a través de moléculas sintetizadas en el laboratorio las cuales emulan reacciones químicas importantes determinantes en el funcionamiento de este proceso. Esta tesis constituye un esfuerzo de esa índole, el objetivo principal es examinar el comportamiento físico-químico de ciertas reacciones de transferencia de electrones y protones en moléculas inspiradas por procesos similares que ocurren en organismos fotosintéticos.
En particular, con esta tesis se busca incrementar el conocimiento de cómo la luz es capaz de iniciar el movimiento de electrones, y seguidamente iniciar el movimiento conjunto de protones y electrones. Este tipo de reacciones son de vital importancia en múltiples reacciones químicas que operan en la fotosíntesis. Para alcanzar este objetivo se han estudiado una serie de compuestos inorgánicos que capturan luz visible al ojo humano, los cuales se constituyen por un centro metálico de rutenio. Estas moléculas una vez absorbe luz visible adquieren la energía necesaria para transferir o recibir electrones. Así mismo, se han estudiado una serie de compuestos orgánicos relacionados a amino ácidos capaces de llevar a cabo reacciones de transferencia acoplada de electrones y protones. Cuando estos dos sistemas son estudiados simultáneamente se han logrado estudiar trasferencias de electrones iniciadas con luz visible que inducen reacciones la transferencia acoplada de electrones y protones. De manera muy similar a reacciones que se encuentran en la fotosíntesis. La serie de moléculas que absorben luz ha sido específicamente diseñadas para para investigas propiedades energéticas de dichas moléculas para transferir o recibir un electrón después de la absorción de luz. Las moléculas orgánicas fueron diseñadas para investigar cómo la distancia a la que se transfiere un protón afecta la velocidad de la transferencia acoplada de electrones y protones.
Para estos estudios se han sintetizado nuevos compuestos inorgánicos y orgánicos. Un gran reto en esta área de ciencia básica usualmente es la consecución de nuevas moléculas que revelen detalles desconocidos de reacciones este tipo de reacciones. Para esta tesis se han utilizado múltiples rutas sintéticas que fueron empleadas para la consecución de cada uno de estos compuestos nuevos, cada una empleado múltiples reacciones. Esto significó una detallada planeación de las diferentes rutas sintéticas de manera que la eficiencia de los procesos sintéticos fuese maximizada y así lograr los mejores rendimientos en la síntesis. Todos los compuestos sintetizados fueron estudiados para obtener información de la estructura molecular de los mismos. Estos estudios ofrecen información de la disposición relativa de los átomos en los compuestos y la energía de electrones que más fácilmente participan en reacciones químicas de transferencia de electrones iniciada por luz y transfería acoplada de electrones y protones. Así mismo diversos estudios fueron realizados para
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determinar la energía necesaria y la velocidad a la que ocurren este tipo de reacciones en los compuestos estudiados. Usando luz ultravioleta pudieron ser revelados detalles de reacciones de transferencia de protón cientos de veces más rápidas que una billonésima de segundo (picosegundos) en las moléculas orgánicas estudiadas. En las mismas moléculas, estudios de transferencia acoplada de protones y electrones ocurrieron mucho más lento, a velocidades cercanas a las mil millonésimas de segundo (nanosegundos).
Toda la información recolectada en estudios de la velocidad de estas reacciones, así como la energía requerida para las mismas fue interpretada en función de estructura molecular de los compuestos y finalmente comparada con modelos teóricos. Con esto fue posible contribuir al conocimiento de reacciones transferencia de electrones iniciada por luz y transfería acoplada de electrones y protones que pueden ser usadas para el entendimiento de este tipo de reacciones en organismos fotosintéticos. Por lo tanto, el conocimiento aportado contribuye al desarrollo nuevas tecnologías de energías renovables basadas en fotosíntesis artificial.
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Acknowledgements
First, I would like to express my deepest gratitude to Sascha Ott, my super-visor, always cool, ambitious and optimistic. Thank you for always been there to provide a very insightful advice, it always helped me to look at things differently and find pragmatic solutions. Many thanks for your trust on assigning me on a project in which I could exercise skills to potentially become an independent researcher, and your trust to let me explore scientific venues outside your labs.
I would also like to express my deepest gratitude to Professors Sternbjörn Styring and Leif Hammarström and Dr. Olof Johansson for giving me the chance to be part of the Swedish Consortium for Artificial Photosynthesis. I feel extremely fortunate, it has been a fantastic multidisciplinary experience that has expanded my vision beyond the limits of what I had ever dreamed before coming here. The enthusiasm of the scientific discussions at CAP was a source of inspiration and a good reminder of the value of what we do. In particular, to Prof Leif Hammarström for his very inspiring projects, leader-ship, and insightful discussions. I still keep my first copy of one of your early ruthenium-dqp papers with Olof from when I was still in Colombia –this chemistry was my first scientific motivation to come here.
Infinite thanks to the most special person I met in Sweden, my beloved collaborator Starla D. Glover. Thank you for making these years so much fun, livable and make me my days so happy. I have no way to tell you how much I owe you! I am entirely sure I would not have made it without you in my life. In any sense, definitively my luckiest finding over these years.
I would like to thank my collaborator, lab mate and buddy Todd F. Mar-kle for our collaboration, for so many times being the in-the-lab person to bounce ideas with, and for sharing so much knowledge on IMHBs, also for so many good times outside the lab. Many thanks to Burkhard Zeit for all the discussions around our joint project –I learned a lot in all of them–and also for your friendship. Also thanks to my collaborators on ruthenium-dqp com-plexes the Michael Jäger and Petter Persson.
Many thanks to all pass and present members of the Ott group, especially to my long-term office mates Elisabet Öberg and Sonja Pullen. You guys were very good friends and excellent listeners in and outside the office. Thank you for so many good times in dinners, fikas and trips. Also thanks to Anna Arkhypchuk for her friendship and for her strict rules about the lab that drove me crazy but made it the nice work place it is. Thanks to Travis, Reu-
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ben, Djawed, Marie-Pierre (how much did we struggle with the POMs pro-ject..., thanks for X-ray crystallography too), Yuri, Maryline, Micha and Stefanie, Xue-Li and Ming-Tian for your friendship, good mood in the lab, dinners and parties, and special thanks to those of you who help me when I broke my ankle. Thanks to Keyhan, Edgar (thanks for X-ray crystallog-raphy), Valentina, Hemlata, Maria, Bis, Shameemn, Daniel, Ben, Ulrika, Andy and Michele for your good mood in the labs. Thanks to the project students that worked with me Clara, Noemi and Malhi.
Especially, thanks to Andres Thapper for all these years of good mood at group meeting, dinners and parties and to Andreas Orthaber thanks for X-ray crystallography and an improving mood at parties.
Thanks to my colleagues and friends outside the synthesis group, Mo-hammad, Daniel Camsund, Allison, Jonas Petterson, Erik, Jonas Lissau, Daniel Streich, Patricia, Katrin, Luca, Felix and Ana Moranderira.
Thanks to Sven, Åsa, Sussane, Jessica and Anna and everyone in the de-partment for so many years of such nice work environment, it is amazing.
Also thanks the C. F. Liljewalch foundation for travel scholarships Thanks Ola, Claire and Andreas Hoess for such a nice friendship and ca-
maraderie and so many fun times. Gracias a mis amigos Colombianos en Uppsala Yeisson, Sole, Sara, Daniel, Luisa (y Thommas), Caro, Angélica y Tanai por tanto apoyo en los momentos difíciles y por tantos bonitos momentos en los que no la gozamos. En especial a mi parcero Yeisin por tanta parla que echamos, tantos Buenos momentos y tanta lagrima que me vio soltar en momentos en que necesite de un verdadero amigo.
Para terminar vuelvo al inicio de todo, a las personas que más amo, y a
quienes quiero agradecer infinitamente, mi Familia: Lina, Betty, Hugo, mi mamita Carmenza, David y Marce. Siempre nos hemos apoyado en cada paso y así ocurrió cuando decidí venir aquí. Incluso tu hijita fuiste quien con tu dedito diminuto oprimió enviar al correo que en un comienzo nos traería a Suecia. Nunca pararé de adorarlos y agradecerles infinitamente todo el valor que como familia esta experiencia nos ha constado. No creo que nunca nos hayamos adaptado del todo a esta lejanía que en los primeros años nos causó tanto dolor. Entre tanto apoyo que recibí nunca nos imaginamos que iba a ser tan difícil. Por eso no ha pasado un solo día, ni uno solo, en que no me sienta incompleto sin cada uno de ustedes. A Lina quiero decirte aquí que me desgarra no haber estado contigo todos estos años. Esa es sin lugar a dudas la tristeza más insondable e irreparable de mi corazón y que llevaré por siempre. Muchas veces me he arrepentido y pensado que no valió la pena por este libro y este título, sin embargo aquí están, terminé. Todo gracias a ustedes y para ustedes!
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Acta Universitatis UpsaliensisDigital Comprehensive Summaries of Uppsala Dissertationsfrom the Faculty of Science and Technology 1258
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 throughthe series 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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