Keywords: tweezer, cage, multi-switching receptor, host-guest chemistry, acridinium, porphyrin

Firstly, I would like to thank the members of the jury for agreeing to be a part of my thesis defense and taking the time to read and evaluate this work. Your joint understanding and cooperation in the organisation of the defense was and is very much appreciated.

It is perhaps redundant to say, but this work could of course not have been possible without the supervision and direction of my thesis supervisor: Prof. Valérie Heitz, and my secondary mentor: Dr. Henri-Pierre Jacquot de Rouville. Thanks to your joint expertise we were able to access a world of new compounds! We encountered many roadblocks along the way, and there were times where I felt as if these blocks were unsurmountable, but your support and advice kept the work going. Thank you for your guidance, your influence on my development as a researcher, and for the experience of being an LSAMM member, it's not one I shall soon forget! To the past (Sebastien, Ryan, Alexis, Charly, Etienne) and present (Stéphanie, Johnny, Sonia and Nahid) members of the LSAMM group: thank you for welcoming me to the group and to Strasbourg! When I first came to France, I did not speak much French. Now, I will leave…still not speaking much French, but with plenty of francophone friends. Thanks for all the discussions, the pastries, the drinks, the pots, and the general comradery and warmth. And to the CLAC and IFM group members, thanks for helping make the 8 th floor feel like a home from home. Thanks also and especially to Geneviève, who has been so kind in my time here and has been a massive help with all the administrative quirks of this project.

To the PIs and industrial partners that make up the NOAH-ITN: thank you all for your part in the development of NOAH, and for the many discussions and opportunities to further develop. Even with the unexpected force majeure that came in the form of COVID, you all managed to make sure that we, the ESRs, got as much from the project as possible. Thanks also to my NOAH secondment supervisors: Dr. Arno Wiehe, and Prof. Mike Ward, for accepting me into your groups, designing the secondment projects and being so helpful when COVID lockdowns struck during the secondments. Even with the circumstances, it was a true treat to be in Berlin and to return to Warwick. Thanks especially to Gemma, our project coordinator who kept NOAH running through it all. To the ESRs of NOAH: thank you all for the support both in and outside of science. We have been in a unique situation for the past 3.5 years and being able to share and discuss with you has made a heavy project lighter.

To our collaborators (Dr. Christophe Gourlaouen, Dr. Barbara Ventura, Daniel Sanchez-Resá, Prof. Xavier Barril and Dr. Dylan Serillon): thank you all for your input in this work, which truly formed the basis of our understanding of these compounds. Many thanks also to the people of the NMR service (Bruno, Maurice and Lionel), the MS service (Stéphanie and Hélène), and the X-Ray service (Lydia, Nathalie and Corrine), for all your help in the characterisations of these compounds.

To all of my friends, from the TMV crowd (who I've known for over a decade), to my Warwick friends (from Westwood, chemistry and WWRFC): thank you all for your support, and the many ways you all have helped me. You lent a listening ear, you arranged video call meet ups when I couldn't attend get-togethers in-person, you offered me accommodation when I came back to Warwick, and some of you even came to visit in my first year in Strasbourg when I was feeling most out of place. I am so grateful for all of you.

To my family, my brothers Aaron and Alex, and my mum Olubunmi: I am most grateful for the three of you. You have been the biggest support throughout this all, my first point of call for comfort, my go-to for gist. I would not have made it through this PhD without you. I didn't fully anticipate it, but the hardest part of this experience has been being away from you all.

To my mum especially, your words of comfort and prayer held me up when I most needed it.

Uruẹse!

To my dad, Augustin: my only sadness at the end of this all is that you won't be there to see it. A few years ago, I came to the realisation that your only true hopes for your children were that we took every opportunity that came our way; that we not only dreamed but pursued those dreams; and that we didn't let life pass us by. This is something I've tried to do ever since. I hope you're proud of me wherever you are.

Introduction

The importance of non-covalent interactions in holding together key structures in nature was not a fact well accepted until the mid-1900's, with the discovery of the impact of hydrogen bonding in DNA. 1,2 Since then, non-covalent interactions have been implicated in multiple key biological structures and processes. In the synthetic world, design and synthesis of molecules (hosts) capable of forming non-covalent interactions with other molecules (guests) to give host-guest complexes began in the 1960's, eventually birthing a new field: Supramolecular chemistry. The term supramolecular was coined by Jean-Marie Lehn, with the work of Pedersen (crown ethers), 3,4 Lehn (cryptands), [5][6][7] and Cram (spherands) 8,9 in molecular encapsulation forming the foundation of the field (Figure 1). Non-covalent interactions and molecular encapsulation were later extended to the self-assembly of molecular containers, 10,11 and further implicated in the efficient synthesis of mechanically interlocked molecules such as rotaxanes and catenanes. 12,13 Figure 1. Structures of the molecular containers first synthesised by Pedersen, 3,4 Lehn, [5][6][7] and Cram 8,9 respectively.

As the field has developed, and the toolkit of available recognition units expanded, focus has shifted from the synthesis and characterisation of host-guest complexes. Instead, research has become more focused on the encoding of advanced functions into hosts, such as controlled motion, catalysis, switchable physical properties etc. These advanced functions allow the application of such systems in areas such as molecular sensing and separation, controlled catalysis, and drug delivery among others. [14][15][16][17] Of prime importance to the development of these functional host systems, is their ability to respond to stimuli. The use of various stimuli such as light, redox, and chemical, brings about a change in properties for the host, which can sometimes be translated into a controlled change in properties for the guest. This can be a change in complexation (controlled uptake and/or release), catalysis of the guest, or further change in the electronic state or conformation of the guest.

In order to afford a responsive host, stimuli-responsive motifs must be incorporated into the host structure, either in conjunction with or as a recognition unit. Many stimuli-responsive motifs have been explored, including use of redox-responsive units such as viologen, 18 and TTF; [19][20][21] photo-responsive units such as azobenzene, 22,23 and diarylethene; 24,25 and chemically-responsive units such as hydrazone and amine/ammonium. 26 An often-used building block for functional hosts is that of the porphyrin, a fact not wholly surprising, given its properties.

The porphyrin and its derivatives (Figure 2), defined as an aromatic tetra-pyrrolic macrocycle with 18 delocalised -electrons, is a recognition motif prolific in nature. Famed for their photophysical properties, namely their intense absorption and emission, porphyrins have been used in development of dyes, photodynamic therapeutic agents, and artificial photosynthetic systems, [27][28][29][30] harking back to cytochrome P450 and chlorophyll. 31,[START_REF] Milgrom | The Colours of Life: An Introduction to the Chemistry of Porphyrins and Related Compounds[END_REF] As well as originating its photophysical properties, the large -conjugated system affords aromatic stability and robustness and the ability to form - interactions. In addition, the ability to coordinate different metals allows for further ligand coordination, as well as imbuing the molecule with its own metal specific properties. [START_REF] Zhang | Energy-Related Small Molecule Activation Reactions: Oxygen Reduction and Hydrogen and Oxygen Evolution Reactions Catalyzed by Porphyrin-and Corrole-Based Systems[END_REF] As such, porphyrin units have been used to synthesise host molecules in differing architectures including tweezers, capsules, macrocycles, and cages. [START_REF] Valderrey | Porphyrin Tweezer Receptors: Binding Studies, Conformational Properties and Applications[END_REF][START_REF] Durot | Multiporphyrinic Cages: Architectures and Functions[END_REF][START_REF] Mondal | Cyclic Metalloporphyrin Dimers: Conformational Flexibility, Applications and Future Prospects[END_REF][START_REF] Elemans | Porphyrin Cage Compounds Based on Glycolurilfrom Enzyme Mimics to Functional Molecular Machines[END_REF][START_REF] Percástegui | Coordination-Driven Assemblies Based on Meso-Substituted Porphyrins: Metal-Organic Cages and a New Type of Meso-Metallaporphyrin Macrocycles[END_REF]

Figure 2. Skeletal structures of the simplest porphyrin and two of its related derivatives, with an 18 pathway highlighted in purple (names for the carbon/proton positions are given).

The porphyrin unit is known to be electro and photo active, with unique spectroscopic signatures with regards to UV-Vis spectroscopy, fluorescence spectroscopy and voltammetry (Figure 3). [START_REF] Ishihara | Porphyrin-Based Sensor Nanoarchitectonics in Diverse Physical Detection Modes[END_REF] As such, it can be used as a photo and/or redox switch in stimuli responsive systems. Additionally, metalated porphyrin species are responsive to pH stimulus, allowing their exploitation as chemically responsive units. Furthermore, the presence of multiple points of functionalisation (namely the  and meso positions) allows for the appendage of other stimuli-responsive motifs, to form responsive supramolecular receptors.

Figure 3. Absorbance (in black) & fluorescence (in purple) spectra and cyclic voltammogram

for a free base meso tetrakisphenyl porphyrin in CH2Cl2. [START_REF] Ishihara | Porphyrin-Based Sensor Nanoarchitectonics in Diverse Physical Detection Modes[END_REF] This introductory chapter will give an overview of key works in the development of stimuliresponsive porphyrin-based hosts, highlighting their structural design and how it translates to their function. Specifically, host-guest systems where application of external stimuli to the host thereby affects the host-guest interaction or the state (conformational or electronic) of the guest will be explored. Therefore, systems without the presence of a guest will be regarded strictly as molecular switches and hence excluded from this bibliography, unless explicitly linked to a relevant system. Furthermore, the host and the guest will be herein defined as separate entities, that are only linked via non-covalent interactions. As such, stimuli-responsive self-locking systems will be mostly excluded, except in the case where a separate guest is present. Wavelength (nm)

Soret S0 → S2 Q S0 → S1  ≥ 10 5 M -1 cm -1

Potential (V vs. SCE)

(1, 0) (0, 0) (1, 0) (0, 0)

Responsive porphyrin hosts 1.Light stimulus to control the function of porphyrin hosts

Use of light stimulus has been well explored in molecular encapsulation, with the attachment of photo-switchable motifs to recognition units commonly exploited to afford controlled guest uptake and/or release. 22,23,[START_REF] Wezenberg | Highlight Review Light-Switchable Metal-Organic Cages[END_REF][START_REF] Qu | Photoresponsive Host-Guest Functional Systems[END_REF] In such cases, the photo-switchable unit is covalently appended to the recognition unit in a way that leads to conformational change in the host upon irradiation, impacting the host-guest interaction. An exemplary case is that of Aida et al. who explored how light stimulus could be used to control the conformation of a freely rotating guest. The group first reported on a porphyrin-less photo-switchable molecular scissor (1) consisting of a ferrocene hinge with attached azobenzene groups (acting as the switch) and additional opposing phenyl "blades" (Figure 4). [START_REF] Muraoka | Light-Driven Open-Close Motion of Chiral Molecular Scissors[END_REF] Via irradiation at 350 nm, the azobenzene group could be switched from the trans to the cis isomer at a ratio of 11:89. This change in conformation was then conferred to the ferrocene hinge, pivoting the opposing phenyl blades. [START_REF] Muraoka | Light-Driven Open-Close Motion of Chiral Molecular Scissors[END_REF] Based on this work, the Aida group then proposed a Zn(II)-porphyrin tweezer (2), [START_REF] Muraoka | Mechanical Twisting of a Guest by a Photoresponsive Host[END_REF] featuring the same scissor component, with the switching of the azobenzene groups, leading to a change in the orientation of the Zn(II)-porphyrin units (Figure 5). Control of the orientation of the porphyrin units could then be transferred to a ditopic rotor molecule upon its complexation to the two Zn(II)-porphyrin units of 2. Similarly to 1, the azobenzene group could be photo-induced to switch from the trans to the cis isomer via irradiation at 350 nm, at a slightly lower ratio of 22:77, as assessed spectroscopically. Back isomerisation could then be achieved via irradiation using visible light (> 420 nm). UV-Vis titrations of the trans and cis-enriched 2 in CH2Cl2 showed binding constants of 1.3 and 2.6 × 10 6 M -1 , forming 1:1 complexes in both cases. Using CD spectroscopic experiments, Aida and co-workers were able to show that due to hindered free rotation the guest became optically active after complexation, with its conformation switching upon irradiation of 2 (Figure 4). Additionally, the CD activity of 2 was seen to increase due to restriction in the host flexibility upon complexation of the guest.

Figure 5. Complexation of the freely rotating diamine (in red)

, and control of its conformation upon irradiation of 2. [START_REF] Muraoka | Mechanical Twisting of a Guest by a Photoresponsive Host[END_REF] In a similar vein, the Nolte group have recently reported a Zn(II)-porphyrin-glycoluril cage (3), [START_REF] Gilissen | Lightgated Binding in Double-motorized Porphyrin Cages[END_REF] featuring Feringa-type light switchable motors. [START_REF] Feringa | The Art of Building Small: From Molecular Switches to Motors (Nobel Lecture)[END_REF] Due to the multiple points of chirality (point, planar and axial) 3 was obtained as three isolatable enantiomer pairs (Figure 6), with one pair featuring the two motors facing outward (away from the cage, Figure 6a), another having one inward-facing and one outward-facing motor (Figure 6b), and the third featuring the two motors facing inward (towards the cage, Figure 6c).

For the in-in and out-out forms of 3, a stark difference in their affinities toward viologens could be seen, with the out-out cage having a binding constant 4.8 times larger than the in-in cage for the guest benzyl viologen (Ka = 3 × 10 5 vs. 6.3 × 10 4 M -1 in CHCl3/CH3CN (1:1)). Via irradiation of the motors at 365 nm, the in-in and out-out cages could be isomerised to metastable pseudo-identical versions of each other (≈ 75% conversion), with inversion of the helicity of the motor. This feature was exploited to afford light-controlled tuning of the guest complexation. Using time resolved fluorescence quenching spectroscopy, they were able to show that upon irradiation of a 1:1 [host-guest]:[host] solution ([3@viologen]:3), the fluorescence of the host changed. Since binding of the guest led to fluorescence quenching of the host, this amounted to a change in the affinity for the guest. In the case of the in-in cage, irradiation led to isomerisation to an out-out form. Thus, decrease in the 3 band was seen, in line with increased affinity for the guest. In contrast for the out-out cage, irradiation led to isomerisation to an in-in form. As such, the fluorescence band for 3 increased, in line with decreased affinity for the guest. and the binding constants for the respective structures in binding of benzyl viologen stated. [START_REF] Gilissen | Lightgated Binding in Double-motorized Porphyrin Cages[END_REF]

Redox and electrochemical stimulus to control the function of porphyrin hosts

Redox-switchable hosts can be afforded via appendage of redox-active motifs to recognition sites, or indeed via the use of redox-active motifs as recognition sites. [START_REF] Fukino | Redox-Responsive Molecular Systems and Materials[END_REF][START_REF] Kahlfuss | Redox-Controlled Intramolecular Motions Triggered by π-Dimerization and Pimerization Processes[END_REF][START_REF] Cai | Radical-Pairing-Induced Molecular Assembly and Motion[END_REF] In terms of porphyrinic hosts examples include the work of Bucher et al. of a porphyrin tweezer (4) featuring a short 3-carbon linker which utilises viologen groups as a redox-switch (Figure 7). [START_REF] Iordache | Redox-Responsive Porphyrin-Based Molecular Tweezers[END_REF] Due to the short length of the linker, coulombic repulsion between the viologen groups in 4 4+ disfavoured a closed conformation. This was most apparent in the tetracationic tweezer's unwillingness to internally ditopically bind DABCO to form the 1:1 complex. However, reduction of the viologen units allowed for the formation of the -dimer, causing 4 2+ to assume the closed u-conformation, with eclipsed porphyrin units (Figure 7). As such, upon reduction of the viologens, the tweezer readily internally bound DABCO forming the 1:1 complex in dimethyl formamide, with a binding constant of 8.2 × 10 4 M -1 as assessed via UV-Vis titrations.

Figure 7.

Chemical structures of 4 4+ , 4 2+ , and the internal complexation of DABCO to form 4 2+ @DABCO + . [START_REF] Iordache | Redox-Responsive Porphyrin-Based Molecular Tweezers[END_REF] Additionally, as redox-active recognition units, porphyrins can also be used directly as redox switches. The Weiss group reported a porphyrin pac-man type tweezer 5 (Figure 8), featuring a semi-flexible calixarene linker connecting two Zn(II)-porphyrin units. [START_REF] Jokic | Structural and Binding Features of Cofacial Bis-Porphyrins with Calixarene Spacers: Pac-Man Porphyrins That Can Chew[END_REF] The tweezer was shown to be able to bind ditopic ligands, with a binding constant of 1.6 × 10 8 M -1 (via UV-Vis spectroscopy in CHCl3) found for binding of DABCO by 5 forming the macrocyclic complex 5@DABCO. Furthermore, the ditopic nature of the binding of the guest was evidenced via UV-Visible and NMR spectroscopy.

In voltametric studies, the porphyrin units of 5 were shown to be reversibly oxidised at the same potential (Eox = 0.31 V) to form a bis(radical cation), with slight broadening of the oxidation wave due to the weak exitonic coupling between the two porphyrin units. However, upon addition of an equivalent of DABCO, the two porphyrin units were found to be oxidised at two distinct potentials, with one significantly cathodically shifted oxidation to form a single radical cation (at Eox = 0.14 V), and a second less shifted oxidation (at Eox = 0.29 V) to form the bis(radical cation). The different oxidation potentials were assigned to decoordination of DABCO from the second porphyrin upon oxidation of the first porphyrin, leading to a redoxinduced change from a ditopic binding of DABCO to a monotopic binding of DABCO. Thus, the group were able to show a "chewing" action in the binding of DABCO when applying electrochemical stimulus. upon oxidation of the porphyrin units. [START_REF] Jokic | Structural and Binding Features of Cofacial Bis-Porphyrins with Calixarene Spacers: Pac-Man Porphyrins That Can Chew[END_REF] More recently, the Lipke group reported the trigonal nanoprism 6.(Figure 9), with porphyrin walls, featuring (PtL2) 2+ at its apexes where L is either 2,2'-bipyridine (biPy, 6a) or Tetramethylethylenediamine (TMEDA, 6b). [START_REF] Dutton | The Influence of Redox-Active Linkers on the Stability and Physical Properties of a Highly Electroactive Porphyrin Nanoprism[END_REF] Electrochemical characterisation of the nanoprism via cyclic voltammetry, showed that the dodecacationic host could be reversibly reduced to a zwitterionic species with total charges of 9+, 6+, 3+ or 0, via single electron reductions of the biPy ligands (in the case of 6a) and/or successive single electron reductions of the porphyrin walls (in the case of 6a and 6b).

As Cp2Co was able to reduce the units, this was later exploited in the encapsulation of cationic Cp*2Co + in acetonitrile. [START_REF] Mansoor | Trapping, and Release of Organometallic Cations by Redox-Active Cationic Hosts[END_REF] Addition of 12 equivalents of Cp*2Co to 6a 12+ led to reduction of the host forming 6a 0 , and oxidation of Cp*2Co to form the cationic guest Cp*2Co + . 6a 0 was able to encapsulate Cp*2Co + to form the host-guest complex 6a 0 @Cp*2Co + . Upon reoxidation of the host via addition of 12.5 equivalents of AgBF4 or AgPF6, the kinetic product 6a 12+ @Cp*2Co + was formed at a yield of 90% as assessed via NMR, with the cationic charges (localised at the apertures of the nanoprism) impeding dissociation of the cation-in-cation host-guest species.

Accordingly, 6a 12+ @Cp*2Co + was shown to have a half-life of 17 days in solution (CH3CN, at 298 K), decomposing to the thermodynamic products: the free guest Cp*2Co + and the free host 6a 12+ , but a persistent stability as a solid. Using the yield, the group was able to estimate a binding constant of 1.3 × 10 3 M -1 , for the 6a 0 species. Interestingly, even in cases where 6a was only partially reduced, complexation of the guest could still be seen, albeit with reduced estimated binding constants compared to 6a 0 , at 10 and 50 times smaller for 6a 3+ and 6a 9+ respectively. In contrast, direct addition of Cp*2Co + to a solution of 6a 12+ was not observed to lead to uptake of the guest, showing that the uptake was indeed redox induced. Studies via VT NMR, comparing the BF4 and PF6 salts of 6a 12+ @Cp*2Co + , coupled with computational analysis showed that the cation-in-cation species was in part stabilised by interaction with the counterions.

Figure 9.

The redox-induced process by which 6a is able to encapsulate Cp*2Co + . [START_REF] Mansoor | Trapping, and Release of Organometallic Cations by Redox-Active Cationic Hosts[END_REF]

Chemical stimulus to control the function of porphyrin hosts

In the case of chemical stimuli, unsurprisingly, there are many different types of species that can be employed and different mechanisms by which control can occur. As with photo and electrochemical stimuli, a major mark of delineation is whether stimulus directly affects/alters the recognition site, or whether change is created in the recognition site via activation at a remote site. The direct alteration of a recognition site is dependent on the chemical species which the recognition site is sensitive to. Commonly, pH stimulus is used or in the case of metal-organic cages, change in the ligand:metal stoichiometries. Shionoya et al., presented a multi-chemical stimuli responsive receptor 7, comprised of tris bipyridyl porphyrin fragments linked via coordination of Zn(II) at the apexes (Figure 10). [START_REF] Endo | Multi-Stimuli-Responsive Interconversion between Bowl-And Capsule-Shaped Self-Assembled Zinc(II) Complexes[END_REF] The receptor could be switched between a bowl (with a formula of Zn4Porphyrin3X6, where X is a solvent ligand) or a capsule (with a formula of Zn4Porphyrin4). It was found that two guests, adamantane and an aryl sulfonamide derivative, preferentially bound to the capsule and bowl complex respectively. Furthermore, when in the presence of the opposite conformation, an induced fit would occur upon heating (at 70°C, in CH3CN), with partial switching to the preferred conformation. As such, when adamantane was added to the bowl, a partial change to the capsule would occur giving a ratio of 41:59 (bowl:capsule). Further addition of aryl sulfonamide to this solution led to a reversion to the bowl (at a ratio of 89:11 bowl:capsule), with adamantane being released.

Upon heating (at 70°C, in CH3CN) in the presence of different chemical stimuli, control of the conformation and hence further control of the guest encapsulated could be afforded. For example, due to the different ligand-metal ratios of the two forms, addition of metal could be used to trigger switching. Addition of 0.4 eq. of ZnOTf2 to the bowl was shown to allow formation of the capsule, while addition of a further 0.56 eq. led to reformation of the bowl.

Additionally, base/acid addition was used, with the bowl to capsule (1:9) transformation occurring upon addition of base due to the formation of the stable Zn(OH)2 complex, and the capsule to bowl (21:79) upon addition of acid (via reaction with Zn(OH)2 to form a more reactive complex, allowing reformation of the bowl).

Figure 10. The induced switch between the two states (bowl and capsule) upon addition of

Zn(OTf)2 to the Shionoya group's porphyrinic host 7, and the preferentially bound guests. [START_REF] Endo | Multi-Stimuli-Responsive Interconversion between Bowl-And Capsule-Shaped Self-Assembled Zinc(II) Complexes[END_REF] Although there exist many ways to chemically alter and thereby impact the activity of a recognition site, chemical stimulus as a remote-control in guest uptake is a more prominently employed mechanism, similarly reflected in the prominence of a specific remote-control process in nature: Allosteric regulation.

Allosteric Regulation

Taken from the Greek "allos stereos" meaning different objects, the term is commonly defined as conformational changes in a macromolecule brought about by binding of a molecule (an effector, so called due to its role of triggering change as a chemical stimulus).

These conformational changes lead to alterations in the binding ability/activity of/for a guest at a separate and distinct site. The process was first proposed in 1961 by Monod, Jacob and Changeux, [START_REF] Jacob | Genetic Regulatory Mechanisms in the Synthesis of Proteins[END_REF][START_REF] Monod | Conclusions: Teleonomic Mechanisms in Cellular Metabolism, Growth, and Differentiation[END_REF] in response to several observations in biology where biosynthetic pathways were regulated by their end-product, despite the end products being stereochemically different from their preceding substrates. [START_REF] Changeux | 50th Anniversary of the Word "Allosteric[END_REF] These observations, in addition to the non-Michaelis-Menten kinetics observed, were used as the first signifiers of the presence of different stereospecific binding sites on enzymes and proteins.

Further development of this model led to the publishing of a paper in 1965 which has become the foundation of this field, [START_REF] Monod | On the Nature of Allosteric Transitions: A Plausible Model[END_REF] the so-called Monod-Wyman-Changeux (MWC) or concerted model (Figure 11), which stipulated that several proteins and enzymes displayed allosteric regulation and that this process was achieved via the following key features:

1. The ability of the macromolecule to assume two conformations, a relaxed (R) and tense (T) state, which exist in equilibrium.

2. The ligand/effector preferentially binding to one state over the other, stabilising the preferred state and shifting the equilibrium.

In addition, the various ways allosteric regulation/control could appear in nature were described, based on:

1. The relationship between the effector and substrate

Homotropic

Effector and guest are the same chemical species

Heterotropic

Effector and guest are different chemical species 2. The observed effect brought about by binding of the effector:

Positive

Binding of the effector leads to conformational changes which increases affinity/activity at secondary site

Negative

Binding of the effector leads to a conformational change which decreases affinity/activity at the secondary site An alternative theory in contrast to the MWC model, is that of the Koshland-Nemethy-Filmer (KNF) model published a year later (Figure 12). This model postulated a stepwise induced-fit mechanism for positive allosteric control, where the secondary state was assumed upon binding of the effector, rather than due to preferential binding. [START_REF] Koshland | Comparison of Experimental Binding Data and Theoretical Models in Proteins Containing Subunits[END_REF] Hence, in opposition to the MWC model, the "tensed" state cannot be assumed without the presence and binding of the effector. The transport of oxygen by the blood is a long-studied process, and the action of the central protein "haemoglobin" is a well examined example of allosteric regulation which was central to the development of the MWC model. Haemoglobin is comprised of four subunits (two alpha and two beta) arranged in a globular quaternary structure with a heme molecule embedded in each subunit (Figure 13). The heme molecules (Fe(II) coordinated porphyrin) act as binding sites for oxygen molecules (as well as for the inhibitors: CO and NO).

Figure 13.

Crystal structure of deoxyhaemoglobin, [START_REF] Park | 1.25 Å Resolution Crystal Structures of Human Haemoglobin in the Oxy, Deoxy and Carbonmonoxy Forms[END_REF] and skeletal structures of the oxygen binding unit: heme, and the heterotropic effector 2,3-bisphosphoglycerate.

Haemoglobin is known to exhibit multiple allosteric pathways. [START_REF] Perutz | Stereochemistry of Cooperative Effects in Haemoglobin: Haem-Haem Interaction and the Problem of Allostery[END_REF] Homotropic positive allosteric regulation is shown where oxygen acts as both the effector and the guest. Binding of one oxygen molecule to a heme molecule leads to increased binding affinity at the remaining heme sites, with release of the oxygen molecules triggered in response to acidic pH stimulus. Additionally, heterotropic effects are also seen in the binding of oxygen via 2,3-Bisphosphoglycerate, which upon complexation increases the oxygen affinity of deoxyhemoglobin.

Enzyme regulation

Allosteric regulation has also been implicated in energy metabolism such as, in the synthesis of glucose-phosphate from glycogen, [START_REF] Barford | The Allosteric Transition of Glycogen Phosphorylase[END_REF] which is controlled via the enzyme Glycogen phosphorylase (Figure 14). Two key forms of the enzyme (a and b) exist in the liver and in muscles with the presence or lack of phosphorylation at a serine residue leading to different allosteric expressions. [START_REF] Berg | Phosphorylase Is Regulated by Allosteric Interactions and Reversible Phosphorylation[END_REF] In particular, the Liver Glycogen Phosphorylase in its phosphorylated form (Liver Glycogen Phosphorylase a) is known to exhibit negative heterotropic allosteric regulation, with binding of glucose inhibiting the enzyme and preventing formation of glucose-phosphate, thereby regulating the formation and concentration of glucose in the liver.

Figure 14. Crystal structure of a glycogen phosphorylase enzyme with bound carbohydrates

(represented in blue), [START_REF] Johnson | Refined Crystal Structure of the Phosphorylase-Heptulose 2-Phosphate-Oligosaccharide-AMP Complex[END_REF] and illustration of the phosphorylation of glycogen to form glucose phosphate.

Artificial allosteric Receptors

As can be seen in the presented biological examples, and as is intrinsic to the MWC and KNF model, the ability of the receptor to assume more than one conformational state i.e., the presence of some form of flexibility in the receptor structure, is needed in order to have an allosteric effect. Additionally, the ability to control the conformation via binding of guests is also required. Rebek named the basic requirements for the synthesis of an allosteric receptor as being the presence of an allosteric site, an active site, and a mechanism by which the two sites are coupled. [START_REF] Rebek | Allosteric Effects in Organic Chemistry. Site-Specific Binding[END_REF] The group of Rebek published in 1979 the first artificial allosteric receptor, in the synthesis of a two-dimensional receptor 8 featuring two recognition sites: a 2,2'-bipyridyl unit linked at its 3,3'-carbons to a crown ether motif (Figure 15). [START_REF] Rebek | Allosteric Effects in Organic Chemistry. Site-Specific Binding[END_REF] Using out of plane effects brought about by binding at either site, 8 was able to show negative allosteric control. Binding of transition metals (namely W(CO)4) by the bipyridyl, contorts the crown ether, thereby hindering binding of cations (such as Na + and K + ) and vice versa. The following year, Rebek and co-workers showed the ability of 8 to regulate the selectivity of ion-transport across a liquid membrane, with the ability to decrease the transport of K + ions across the membrane upon complexation of W(CO)4 by a factor of 5 compared to the transport of Na + . This presented an early example of an artificial receptor being used to model the functions of systems seen in nature.

Figure 15. Allosteric mechanism of the 1st allosteric receptor 8 reported by Rebek and co-

workers in 1979. [START_REF] Rebek | Allosteric Effects in Organic Chemistry. Site-Specific Binding[END_REF] The work of the Rebek group, was followed by the development of three-dimensional structures, with a number of motifs explored, [START_REF] Kremer | Artificial Allosteric Receptors[END_REF][START_REF] Shinkai | Positive Allosteric Systems Designed on Dynamic Supramolecular Scaffolds: Toward Switching and Amplification of Guest Affinity and Selectivity[END_REF][START_REF] Rizzuto | Strategies for Binding Multiple Guests in Metal-Organic Cages[END_REF] displaying key features important to the efficiency of biological allosteric receptors, and hence important to the development of sophisticated/advanced synthetic allosteric systems: 1) Large amplitude allosteric effects, 2) multiple pathways, 3) multi-dimensional translation of binding events, 4) catalysis and 5)

further control using other external stimuli . The use of porphyrin units as recognition sites was also considered, with the group of Kubo reporting the first heterotropic allosteric porphyrinic receptor in 1999 using a bis-porphyrin system connected by a biphenyl crown ether. [START_REF] Kubo | A new biphenyl-20-crown-6derived zinc(II) porphyrin dimer with a potentially heterotropic allostery[END_REF]

Large amplitude allosteric effects in controlled encapsulation

The ability to use allosteric control as a true on/off switch in the encapsulation of guests or tune the binding affinity for guests by more than 2 orders of magnitude is of great importance in the development of high efficiency host-guest systems. Such large amplitude binding effects have been seen in the work of Shinkai et al. who reported a C3 capsule (9) featuring three porphyrin units capped with two calixarene motifs (Figure 16). [START_REF] Kawaguchi | A Novel Porphyrin-Homooxacalix[3]Arene Conjugate Which Creates a C3-Symmetrical Capsular Space[END_REF] Via coordination to the three Zn(II)-porphyrin sites, the capsule was able to bind tris(2-aminoethyl)amine (TREN) forming a 1:1 host:guest complex at a binding constant of 1.72 × 10 5 M -1 in CHCl3. However, in the presence of NaClO4 the binding constant was shown to increase by almost 3 orders of magnitude (1.5 × 10 8 M -1 ). This was proposed to be due to binding of Na + ions by the calixarene caps leading to assumption of a more open conformation, presumably by interrupting intramolecular hydrogen bonding. The assertion was further supported by the effects of MeOH addition, where it was seen that titrations of TREN to 9 conducted in CHCl3/MeOH (9:1) gave a higher binding constant (2.63 × 10 6 M -1 ), instead of decreasing as typical in competitively coordinating solvents. In contrast, return to typical behaviour was seen for 9@Na + with the binding constant for TREN being lower in CHCl3/MeOH (1.11 × 10 7

M -1 ) compared to in CHCl3 (1.5 × 10 8 M -1 ).

Figure 16.

Structure of the Shinkai group's capsule 9 featuring three Zn(II)-porphyrins and two terminal calixarene units, and illustration of the binding of the effector and guest. [START_REF] Kawaguchi | A Novel Porphyrin-Homooxacalix[3]Arene Conjugate Which Creates a C3-Symmetrical Capsular Space[END_REF] Additionally, Ballester and co-workers were able to show on/off allosteric switching of guest uptake in a porphyrinic system. The group reported a Zn(II)-trisporphyrin featuring a central benzene tricarboxamide unit (10) able to bind up to three DABCO molecules (K13 = 2.2 × 10 15 M -3 in CHCl3, Figure 17). [START_REF] Ballester | DABCO-Induced Self-Assembly of a Trisporphyrin Double-Decker Cage: Thermodynamic Characterization and Guest Recognition[END_REF] When exposed to 1.5 equivalents of DABCO at millimolar concentrations, 10 formed a self-assembled molecular cage (102@(DABCO)3), with a stability constant of K23 = 8 × 10 27 M -4 found for the structure via UV-Visible titrations.

Using molecular modelling, the group found the cage had a binding cavity with a flexible height of up to 7 Å. As the upper end of the cavity height would allow binding of aromatic molecules, and the amide functional groups allowed formation of hydrogen bonds, the group investigated the ability of the cage to bind benzene-1,3,5-tricarboxamide guests. Conducting ITC measurements, an averaged binding constant of 1.4 × 10 4 M -1 was found for the guest tripentyl benzene carboxamide when titrated with 102@(DABCO)3. In contrast, in the absence of DABCO, 10 was not seen to bind the guest. ITC dilution measurements indicated dimerization of 10 at millimolar concentrations with a dissociation constant of 1.1 × 10 -3 M, but no uptake of the guest by the dimer was seen. Thus, 10 was shown to be able to form an allosteric supramolecular cage.

Multi-pathway allosteric regulation

Commonly in nature, allosteric proteins display multiple allosteric pathways, for example in the case of haemoglobin where it displays both heterotropic and homotropic allosteric control.

In order to design an artificial receptor with multiple levels of allosteric control, as seen with haemoglobin, multiple factors must be taken into account, making their design and synthesis even more non-trivial than simpler allosteric systems. For example, the Jang group were able to design and synthesise a porphyrin tweezer (11), [START_REF] Lee | Biindole-Bridged Porphyrin Dimer as Allosteric Molecular Tweezers[END_REF] which showed positive heterotropic binding of DABCO when chloride is bound or cooperative binding of chloride when DABCO is bound in THF (Figure 18). Utilising the free rotation about the biindole single bond, complexation of the effector fixed the positions of the two faces of the tweezer in a cofacial arrangement. Thus, binding of Cl -at the biindole bridge increased the binding constant for binding of DABCO by a factor of 12 (to Ka = 2.48 × 10 7 M -1 ), and similarly binding of DABCO by the Zn(II)-porphyrin units increased binding of Cl -by a factor of 9 (to Ka = 7.1 × 10 5 M -1 ).

Figure 18.

Allosteric mechanism of the biindole porphyrin tweezer 11 reported by Jang et al. [START_REF] Lee | Biindole-Bridged Porphyrin Dimer as Allosteric Molecular Tweezers[END_REF] However, when extending this work to form a multi-level allosteric host difficulties were found. The group designed and synthesised a porphyrin macrocycle (12), featuring two biindole bridges (Figure 19). [START_REF] Lee | An Indolocarbazole-Bridged Macrocyclic Porphyrin Dimer Having Homotropic Allosterism with Inhibitory Control[END_REF] In the absence of pre-coordination of DABCO, it was seen that there was positive homotropic allosteric control between the two biindole sites, with allosteric cooperativity in the binding of two fluoride ions (K2/K1 = 3.39), two acetate ions (K2/K1 = 24.5) or two azide ions (K2/K1 = 35.2). Similarly to 11, when DABCO was bound the binding affinity for the first anion significantly increased (by a factor of 74 in the case of fluoride). However, the binding of DABCO was found to switch off the homotropic allosteric effect between the two biindole sites. Thus, the biindole sites became non-cooperative with respect to one another, with K2/K1 ≈ 0.25 as expected for non-cooperative binding (in the absence of statistical correction). It was hypothesised that due to the intrinsic rigidity of 12, and further rigidification of the host upon complexation of DABCO, the binding of the first anion did not translate to a further pre-organisation of the host at the second anion binding site when DABCO is complexed. 73 The design of 13 included pyridine groups at the meso positions of the porphyrin units, with an approximate interplanar distance of 3.4 Å, allowing for binding of dicarboxylic acids of the right length (Figure 20). [START_REF] Takeuchi | A Strong Positive Allosteric Effect in the Molecular Recognition of Dicarboxylic Acids by a Cerium(IV) Bis[Tetrakis(4-Pyridyl)Porphyrinate] Double Decker[END_REF] Titration of (1R,2R)-cyclohexane-1,2-dicarboxylic acid (RR-CHDA) in CH2Cl2/EtOAc (30:1), was found to produce a sigmoidal curve, indicative of positive cooperative binding of multiple guests. Using the Hill equation, a Hill coefficient of 4 was found, indicating very strong cooperativity between the binding sites, with an estimated total binding constant of Ktot = 2.75 × 10 9 M -4 . Comparison of the host to a model featuring only one pyridinyl group on each porphyrin, showed that in the absence of multivalency, RR-CHDA could not be bound, underscoring the smaller binding constant for the first guest and the effects of cooperativity.

Figure 20. Skeletal representation of the allosteric mode of action for the Ce(IV)-porphyrin

dimer 13 reported by Shinkai and co-workers. [START_REF] Takeuchi | A Strong Positive Allosteric Effect in the Molecular Recognition of Dicarboxylic Acids by a Cerium(IV) Bis[Tetrakis(4-Pyridyl)Porphyrinate] Double Decker[END_REF] This work was further developed to create a prototype molecular spring (14), with the group reporting a cerium(IV) double decker featuring ferrocene hinges and 12 pyridine sites (Figure 21). [START_REF] Ikeda | A Preliminary Step toward Molecular Spring Driven by Cooperative Guest Binding[END_REF] The host was shown to be able to assume an open "extended" conformation, with a large distance between the ferrocene units (3.2 nm) and smaller distance between the cerium centres (1.3 nm), which could be contracted upon cooperative binding of the dicarboxylic acid guests. Titration of RR-CHDA, was shown to lead to a sigmoidal curve with a Hill coefficient of 2.1 and Ktot = 10 14 M -6 , suggesting cooperativity albeit to a lesser extent than seen for 13.

Nevertheless, changes in the NMR spectrum and in the CD spectrum showed the bound host assumed the contracted form upon guest complexation, with Fe-Fe distance shortened to 0.5 Å, and the Ce-Ce distance elongated to 3.5 nm according to computational models. More recently, examples of multi-directional translation of binding events have looked at the use of multiple effectors to simultaneously give rise to conformational changes, similar to the mechanism of the nicotinic acetyl choline receptor. [START_REF] Changeux | The Nicotinic Acetylcholine Receptor: A Typical 'Allosteric Machine[END_REF] This design has been used by the Heitz group, reporting a porphyrin cage (15) featuring triazole ligands embedded into the linkers (Figure 22). [START_REF] Djemili | Positive Allosteric Control of Guests Encapsulation by Metal Binding to Covalent Porphyrin Cages[END_REF][START_REF] Schoepff | Chemically Induced Breathing of Flexible Porphyrinic Covalent Cages[END_REF][START_REF] Kocher | Control of the Cavity Size of Flexible Covalent Cages by Silver Coordination to the Peripheral Binding Sites[END_REF] As - interactions were present between the porphyrin units, 15 assumed a collapsed conformation, with an interplanar distance of 3.77 Å measured in the XRD structure. Due to the strength of the interaction, 15 could not encapsulate guests pyrazine or NDI. However, upon addition of Ag + ions, the cage was shown to undergo an increase in cavity width to 9.5 Å, with the Ag + ions binding to the triazole groups and switching their spatial arrangement from anti-syn-anti-syn, to an all syn configuration. As such, 15@4Ag + was able to bind pyrazine, via ditopic coordination to the two Zn(II) metal centres, at a binding constant of 4.5 × 10 6 M -1 in CH2Cl2, amounting to an allosteric on/off control, with a very large amplitude. Similarly, coordination of Ag + ions was shown to allow the encapsulation of NDI, via - interactions (Ka = 95 M -1 in CH2Cl2).

The allosterically controlled encapsulation of NDI was also studied within the context of photophysics, where it was observed that a photoinduced electron transfer (from the Zn(II)porphyrin units to the encapsulated NDI) took place upon irradiation of the porphyrin units, amounting to an allosteric control of the photoinduced electron transfer.

Allostery within stimuli-responsive units and catalytic systems

The final key features in developing advanced allosteric receptors, more specifically when contemplating the application of such receptors, or more advanced functions, has been the ability to respond to additional stimuli, and/or allosterically control the catalytic activity of an active site.

The Mirkin group reported an early example of an allosterically controlled catalyst (16), designing a bis-Zn(II)-porphyrin macrocycle with two Rh(I) metal centres embedded within the linker fragments (Figure 23). [START_REF] Oliveri | Supramolecular Allosteric Cofacial Porphyrin Complexes[END_REF] By incorporating hemilabile chelating thioether ligands into its structure, it was possible to control the diameter of 16's aperture. In the presence of Cl -and CO ligands, the thioether was displaced, and the aperture of 16 was increased from 3.5 Å to 7 Å. Using this effect, the group were able to display tuneable catalysis of an acyl transfer reaction between pyridyl carbinol and N-acetyl imidazole, previously shown to be accelerated by trimetallic lewis acidic porphyrin assemblies. In terms of additionally stimuli-responsive allosteric systems, examples include the work of the Álvarez group, where the difference in behaviour between a free-base and metalloporphyrin was exploited in a less classical fashion to afford a switching in the behaviour of an octapodal pyrene porphyrin 17-2H (Figure 24). [START_REF] Ferrero | Dual-Tweezer Behavior of an Octapodal Pyrene Porphyrin-Based System as a Host for Fullerenes[END_REF] The receptor was shown to be able to bind fullerenes, forming a 1:2 complex, with binding of fullerene to both faces of the free-base porphyrin. A decrease in the 1:2 binding constants could be seen for the free base receptor (K1 = 1.4 × 10 4 M -1 , K2 = 3.5 × 10 3 M -1 for C70 and K1 = 1.49 × 10 3 M -1 , K2 = 3.71

× 10 2 M -1 for C60 in toluene) with K2/K1 = 0.25, in line with a non-cooperative system.

However, it was shown that upon complexation of Zn(II) a very strong negative cooperativity was seen, becoming an off switch for the second binding site, with only formation of the 1:1 complex observed for 17-Zn(II) (2.69 × 10 4 M -1 for C70 and 2.3 × 10 3 M -1 for C60 in toluene).

Thus, Zn 2+ was used as chemical switch to turn on/off cooperativity between the two binding sites, with the effect possibly arising from the changes in planarity of the porphyrin upon coordination of Zn 2+ indicated via UV-Vis spectroscopy. octapodal pyrene porphyrin hosts, with complexation of fullerene C60 and respective binding constants shown. [START_REF] Ferrero | Dual-Tweezer Behavior of an Octapodal Pyrene Porphyrin-Based System as a Host for Fullerenes[END_REF] The self-locking nano-switch 18 presented by the Schmittel group can be regarded as an example of a stimuli responsive catalytic allosteric system (Figure 25). [START_REF] Schmittel | A Reversible Nanoswitch as an ON-OFF Photocatalyst[END_REF] The receptor, comprised of three freely rotating arms, each incorporating a different recognition unit (a Zn(II)-porphyrin, pyrimidine-pyridine (py-pm) arm and phenanthroline respectively), was

shown to be able to assume two states. In its native state, the py-pm arm coordinates to the Zn(II)-porphyrin, blocking the porphyrin site. However, in the presence of Cu(I), the receptor is switched to its second state, with the phenanthroline unit and py-pm both coordinating the Cu(I) guest (Ka = 1.2 × 10 6 M -1 in CH2Cl2), leaving the Zn(II)-porphyrin free for coordination by guests. Diazastilbene hence coordinates to the Zn(II), at a binding constant 3000 times higher than in the absence of Cu(I) (Ka = 1.6 × 10 3 vs. 0.095 M -1 in CH2Cl2). Utilising its photosensitising properties, upon irradiation of the porphyrin (419 nm, 30 minutes) 18

(present at a 25 mol% catalyst loading) affords catalysation of the cis to trans isomerisation of the guest (28:72 ±4). [START_REF] Schmittel | A Reversible Nanoswitch as an ON-OFF Photocatalyst[END_REF] The successful use of porphyrins in all variations of stimuli-responsive systems as structural motifs, recognition sites and molecular switches exemplifies the power of the porphyrin building block in developing complex artificial receptors. Although a number of features key to the development of sophisticated responsive hosts have been achieved, there remain some areas to further develop. For example, in the development of multi-pathway allosteric systems which display simultaneously both homotropic and heterotropic control of guest encapsulation. Development of multi-dimensional allosteric systems featuring more than two enclosed binding pockets is also of interest. Likewise, development of hosts which achieve control using multiple different stimuli, especially further development of multi-state hostguest systems, is worthwhile due to the widened applications that may be afforded.

Therefore, design and synthesis of a multi-responsive allosteric host capable of heterotropic binding of effectors and guests, would be of interest. In order to form a heterotropic allosteric system, the porphyrin unit must be coupled to another recognition group. Additionally, coupling with a stimuli-responsive motif could afford further mechanisms by which control of the host-guest properties is obtained. As such, pairing with a recognition motif able to bind guests and respond to different stimuli could be explored to achieve this system. An example of one such motif is that of the N-substituted acridinium.

N-substituted acridinium units in molecular encapsulation

Acridiniums are a class of cationic heterocycle, consisting of an anthracenic structure, with a central pyridyl ring. The extended aromatic structure gives the compounds strong optical properties which have been utilised in DNA labelling and in photoredox catalysis, exploiting the electrochemical properties of the motif. [START_REF] Li | Across the Board: Yang Li on Visible-Light Photoredox Catalysis[END_REF][START_REF] Joshi-Pangu | Acridinium-Based Photocatalysts: A Sustainable Option in Photoredox Catalysis[END_REF][START_REF] Arnold | Assay Formats Involving Acridinium-Ester-Labeled DNA Probes[END_REF] Yet of more particular interest, the electrodeficient aromaticity has led to the use of acridiniums as recognition sites, with its stimuliresponsive nature exploited to afford control of guest uptake and release. Similarly to the porphyrin, the acridinium is multi-responsive. Addition of nucleophiles leads to acridane formation, with photo-triggered release of the nucleophile. In addition, N-substituted acridinium can be reduced via electrochemical means to give a radical species which is easily re-oxidised to the acridinium species (Figure 26). [START_REF] Zhou | Mechanistic Study of the Photochemical Hydroxide Ion Release from 9-Hydroxy-10-Methyl-9-Phenyl-9,10-Dihydroacridine[END_REF][START_REF] Koper | Electrochemistry of the 9-Phenyl-10-Methyl-Acridan/Acridinium Redox System; a High-Potential NADH/NAD + Analogue[END_REF][START_REF] Jacquot De Rouville | N-Substituted Acridinium as a Multi-Responsive Recognition Unit in Supramolecular Chemistry[END_REF] Figure 26. Representation of the structures formed upon application of different stimuli to a 9-phenyl N-methyl acridinium.

N-substituted acridinium-based receptors

The earliest example of acridinium based receptors is that of Lehn et al. of a bisacridinium cavitand 19a featuring acetylene linkers and its related precursor tweezer 19b (Figure 27). [START_REF] Claude | Binding of Nucleosides, Nucleotides and Anionic Planar Substrates by Bis-Intercaland Receptor Molecules[END_REF] The water-soluble cavitand was shown to be able to bind anionic and neutral planar guests (logKa = 3 -6), forming 1:1 complexes, with observed hypochromic shifts in the UV-Vis spectra consistent with a - stacking structure. The effect was shown to be larger the more stable the host-guest complex, with binding constants seemingly dependent on the aromatic surface area of the guest as opposed to electron density. Interestingly, it was found that the acetylene bridges hindered binding, due to their rigidity, and the distance within the cavity. As such, the acyclic precursors had binding constants 10-100 times larger compared to the cavitands (logKa = 4 -7), highlighting the importance of linkers in determining the efficacy of guest binding. In actuality, the crystal structure of 19a, showed the cavity to have a height of 7.5 Å (with a width of 4 Å), slightly larger than optimal for - interactions (2 × 3.5 Å). [START_REF] Claude | Binding of Nucleosides, Nucleotides and Anionic Planar Substrates by Bis-Intercaland Receptor Molecules[END_REF] Since then, other acridinium based receptors have been synthesised which utilise the stimuliresponsiveness of the acridinium to afford controlled encapsulation of the guests. In the work of Yoshizawa et al., [START_REF] Yazaki | Polycationic-Shelled Capsular and Tubular Nanostructures and Their Anionic-Guest Binding Properties[END_REF] acridiniums were used to form water-soluble metal-organic capsules, able to encapsulate trifluoroborate-appended cycloalkanes. Yoshizawa then went on to develop a wholly organic water-soluble macrocycle 20 (Figure 28), able to bind long hydrophilic molecules featuring steroid or coumarin motifs, with switchable release upon addition of base. [START_REF] Kurihara | A Switchable Open/Closed Polyaromatic Macrocycle That Shows Reversible Binding of Long Hydrophilic Molecules[END_REF] The crystal structure of 20 revealed a cylindrical structure with a 1 nm long cavity. Upon addition of excess aqueous NaOH or NaHCO3, 20 was converted to the acridane derivative 20-OR, with XRD structure showing a collapsed structure. Upon addition of aqueous HCl, the receptor 20 was recovered, with a fatigue cycle showing no major loss in conversion after 5 cycles. Binding constants and thermodynamic parameters were found via ITC for the guest CHAPS (Ka = 7.3 × 10 3 M -1 ). Via NMR spectroscopy, the binding of the guest was found to proceed via encapsulation of the recognition group of the guest molecule, (with the rest of the guest lying outside the receptor). This suggested possible use of the receptor in binding longer biomolecules and polymers. Similarly, the successive release and reuptake of the guest via addition of base then acid was shown via NMR spectroscopy.

Figure 28.

Structure of the acridinium nano-capsule (20) reported by the Yoshizawa group, and the neutral acridane structure (20-OR) formed upon exposure to base. [START_REF] Kurihara | A Switchable Open/Closed Polyaromatic Macrocycle That Shows Reversible Binding of Long Hydrophilic Molecules[END_REF] More recently, our own research group has reported on a series of tweezers and macrocycles, showing binding of various aromatic molecules, and their switchable release upon addition of nucleophiles/base, or reduction of the acridinium. Building on previous work reporting the design and study of bis-acridinium tweezers, [START_REF] Gosset | A Chemically-Responsive Bis-Acridinium Receptor[END_REF] a bis-acridinium macrocycle 21 featuring a semi-rigid bipyridylphenyl spacer was reported (Figure 29). [START_REF] Hu | A Bis-Acridinium Macrocycle as Multi-Responsive Receptor and Selective Phase-Transfer Agent of Perylene[END_REF] The macrocycle was shown to be able to bind polyaromatic molecules, with the highest binding constant being found for perylene (Ka = 1.2 × 10 3 M -1 in CH2Cl2 or C2H4Cl2). Significantly, the multi-responsive behaviour of the acridinium units was utilised to tune the binding affinity of the macrocycle, with release of the guest upon addition of OH -evidenced via UV-Vis spectroscopy. As with Yoshizawa's system, re-aromatisation via addition of TFA led to re-encapsulation of the guest, recovering the host-guest spectral features. Electrochemical reduction of the acridinium was shown to lead to a dramatic decrease in binding affinity for perylene, (by two orders of magnitude, to Ka = 55 M -1 ) Thus, a multi-responsive control in the guest uptake and release was shown, utilising electrochemical and chemical stimuli. response to different stimuli. [START_REF] Hu | A Bis-Acridinium Macrocycle as Multi-Responsive Receptor and Selective Phase-Transfer Agent of Perylene[END_REF]

Protonated acridines as guests for porphyrinic hosts

Although the pairing of the two motifs opens many perspectives, the coupling of porphyrin and acridinium has not been well explored, with no published examples of metalloporphyrins and acridiniums within a host-guest system, and limited examples of acridinium and free base porphyrin as units within the same system. Most papers involving the two units have focused on the use of the protonated acridine as guests for bis-porphyrin receptors, more specifically bisporphyrin clips. [START_REF] Wada | A New Strategy for the Design of Water-Soluble Synthetic Receptors: Specific Recognition of DNA Intercalators and Diamines[END_REF][START_REF] Mizutani | Molecular Recognition of DNA Intercalators at Nanomolar Concentration in Water[END_REF] The photodynamics of such host-guest complexes were first explored by the group of Fukuzumi, reporting a bis free-base porphyrin clip 22 featuring a diphenyl oxide spacer (Figure 30). 22 was shown via UV-Vis and Fluorescence spectroscopy to be able to bind a simple acridinium (the protonated acridine, AcrH) in a cofacial manner with a binding constant of 9.7 × 10 4 M -1 in benzonitrile. Upon irradiation of the complex, electron transfer from the porphyrin to AcrH was observed to occur, verified via laser photolysis and fluorescence decay experiments, with the charge separated state being long-lived at low temperatures. Similarly, Rath and Chaudhray later explored the encapsulation of AcrH by a bis porphyrin clip 23 featuring a rigid pyrrole linker (Figure 30), able to complex AcrH in dichloromethane with a binding constant of 1.4 × 10 4 M -1 . [START_REF] Chaudhary | Encapsulation of TCNQ and the Acridinium Ion within a Bisporphyrin Cavity: Synthesis, Structure, and Photophysical and HOMO-LUMO-Gap-Mediated Electron-Transfer Properties[END_REF] Here, similarly to the host-guest complexes of Fukuzumi, photoinduced electron transfer was observed, leading to an efficient fluorescence quenching, with 95% quenching of the porphyrin emission, when exciting the Qband of the porphyrin.

Figure 30.

Host-guest complexes studied by the Fukuzumi group (22@AcrH), [START_REF] Wada | A New Strategy for the Design of Water-Soluble Synthetic Receptors: Specific Recognition of DNA Intercalators and Diamines[END_REF][START_REF] Mizutani | Molecular Recognition of DNA Intercalators at Nanomolar Concentration in Water[END_REF] and Rath & Chaudray (23@AcrH). [START_REF] Chaudhary | Encapsulation of TCNQ and the Acridinium Ion within a Bisporphyrin Cavity: Synthesis, Structure, and Photophysical and HOMO-LUMO-Gap-Mediated Electron-Transfer Properties[END_REF]

N-substituted acridiniums covalently linked to porphyrins

Examples of covalently linked porphyrin-acridinium systems are limited to work by Fukuzumi et al. in the synthesis of the porphyrin-acridinium triad 24 (Figure 31). 100 Similar to 22@AcrH and 23@AcrH, the triad was shown to have quenched fluorescence for both the acridinium and porphyrin due to photoinduced electron transfer. This property was exploited to develop a fluorescence sensor for one-electron reductants such as superoxide, utilising the ability to reduce the acridinium (forming the radical species), and thereby restore the fluorescence of the porphyrin.

Aims and Objectives

This thesis has aimed to synthesise a family of receptors incorporating the N-alkylated acridinium and the porphyrin as recognitions sites, for the controlled encapsulation of guests.

Moreover, in order to take advantage of the different non-covalent interactions that a metalloporphyrin can use to stabilise guest molecules (both metal-ligand coordination and - interactions), the design of the receptors incorporated Zn(II)-metallated porphyrins.

Different receptor architectures were designed via exploitation of the multiple functionalisation points of the porphyrin, with formation of the receptors via linking of the two halves of the receptor using flexible linkers (Figure 32). Specifically, a tweezer could be afforded via linking of two porphyrin acridinium conjugates (featuring one N-alkylated acridinium substituent per porphyrin) with one linker group. Similarly, a cage could be obtained by forming four linkers between two porphyrin acridinium conjugates (with four Nalkylated acridinium substituents per porphyrin).

It was hypothesised that such systems would show positive heterotropic allosteric control (Figure 32). In the case of the tweezer, binding of an effector by the porphyrin units, would pre-organise and rigidify the receptor, translating to increased binding affinity at the acridinium site. Given that the acridinium is known to bind planar aromatic guests, effective pre-organisation for binding at the acridinium site, is thus afforded when using an effector which gives a cavity height of approximately 7 Å upon coordination.

h' h h

Additionally, in the case of the cage, as there are four acridinium sites surrounding the porphyrin, binding of the effector would pre-organise for binding of up to four aromatic guests.

Control in the uptake and release of guests may additionally be achieved via exploitation of the multi-stimuli responsive natures of the porphyrin and acridinium units. More specifically, by exploiting the effects of chemical stimulus (on the acridinium units), and the effect of redox stimulus (on both units) on the binding abilities of the two recognition motifs. In order to meet these aims, an efficient means of synthesis had first to be identified. As there were limited examples of porphyrin-acridinium conjugates in the literature, focus was first placed on the covalent attachment of the two motifs, aiming to find an effective route to synthesis of conjugates. The syntheses of the porphyrin-conjugates and the subsequent studies into their properties are detailed in chapter two. Lastly, chapter four covers the synthesis of the cage receptor, and similarly discusses the studies into the host-guest properties of the cage and the effect of chemical stimulus.

Introduction

We first examined the synthetic routes to obtain novel conjugates, aiming to probe the synthetic feasibility of covalent attachment of porphyrin and acridinium units, and to further explore the binding properties.

Design

In order to afford an allosteric system, key factors must be considered, specifically as they pertain to the efficiency of the allosteric effect. Of high importance is the spacer between the allosteric and active site. Typically, efficient translation of the effects of binding the effector to the secondary binding sites requires a rigid spacer, as use of a flexible spacer can lead to poor translation or loss of the pre-organisation. A convenient spacer used in some examples shown in Chapter 1, is that of a phenyl ring (Figure 1). As a rigid aromatic spacer, it allows translation of rigidification/pre-organisation to the secondary site. Additionally, as a small spacer (relative to the active units) encumbering steric interactions are unlikely to be seen upon pre-organisation of the receptor. Finally, due to steric repulsion between the phenyl protons and that of the beta pyrrolic protons and the 1/8 acridinium protons, use of the phenyl spacer should allow for the two motifs to be within the same plane, maximising the effect of the binding activated pre-organisation.

Due to the large differences in polarity between the two recognition units, use of solubilising groups must also be considered in the design of the conjugates, to allow solubility in organic media. This can be aided in several ways, such as 1) via use of a non-coordinating counter anion such as PF6 and/or 2) via use of solubilising alkyl groups at key functionalisation points.

In the latter case, use of solubilising R groups in the AB3 conjugate is possible. Specifically, the group di-tert-butyl benzene is known to enhance the solubility of porphyrins, and as such was chosen.

Figure 1.

Illustration of a porphyrin-acridinium conjugate, featuring a phenyl spacer perpendicular to the two active units, and the di-tert-butyl benzyl R group.

General routes in porphyrin synthesis and functionalisation

Synthesis of porphyrins has been known since the early 1900s with the first reported syntheses given by Hans Fischer. 1,2 Generally, synthesis is achieved via condensation of pyrroles and aldehydes in the presence of acid and oxidants. Two major methodologies commonly utilised are the Adler-Longo method and the Lindsey method. The Adler-Longo method, 3 building on early work by Rothemund, 4 achieves porphyrin condensation via refluxing of aldehydes and pyrroles in propionic acid, while utilising atmospheric oxygen as the oxidant. The second methodology by Lindsey, et al. (Figure 2) consists of a two-step reaction, the 1 st step being condensation of aldehydes and pyrroles in the presence of TFA or BF3•OEt2, to reversibly form the porphyrinogen macrocycle at equilibrium, and the following 2 nd step, an oxidation using DDQ or chloranil to irreversibly form the porphyrin. [5][6][7][8] By carefully monitoring the position of the equilibrium for different aldehydes between the starting materials, side products and the porphyrinogen, Lindsey and co-workers were able to achieve yields as high as 60% in the synthesis of A4 porphyrins. 8,9 Additionally, although the Adler-Longo method is simpler, the Lindsey method can be advantageous for aldehydes which show poor solubility in propionic acid and/or have acid sensitive substituents. By using functionalised aldehydes, or -functionalised pyrroles, meso or beta substituted porphyrins respectively are readily obtained. Further functionalisation at the peripheries of a porphyrin can also be achieved via different organometallic methodologies. 10 Most commonly, halogenated (or halogenated aryl) porphyrins are used as synthons in metalhalogen exchange reactions or palladium cross coupling reaction, allowing pairing of porphyrins with wide ranging motifs.

General routes in acridinium synthesis and functionalisation

Acridiniums can be readily accessed using the synthon acridone. The molecule has two key functionalisation points: the carbonyl, and the amine. Stepwise functionalisation at these points allows for the synthesis of acridinium species, with different substituents (Figure 3). In the case of the amine site, alkylation and Ullman amination have been previously reported. 11,12 The substituted acridone can then be reacted at the carbonyl position with organometallic nucleophiles, furnishing an intermediate acridanol species which is readily aromatised to the acridinium upon acid hydrolysis. 4). 13 The synthesis of the species was achieved using a formyl functionalised acridinium (25), in turn synthesised via bromination of the photoredox catalyst mesityl methylacridinium followed by a Sommelet reaction to give the cationic aldehyde. Condensation of this species with a 2,2'-dipyrromethane then allowed for the synthesis of the porphyrin-acridinium triad. Although this synthetic route was successful, the yield was very low for the final porphyrin condensation step at 3%. (synthesised from the 9-mesityl-10-methylacridnium species).

Attempted synthesis of an AB3 monoacridinium porphyrin conjugate via Br-Li exchange

Given the typical porphyrin and acridinium synthetic routes and methods of functionalisation, it was proposed that porphyrin-acridinium conjugates may be synthesised via Br-Li exchange of a bromo-aryl functionalised porphyrin. Bromo-aryl porphyrins had been previously shown by the group of Hirel to be useful in the synthesis of carbonyl functionalised porphyrins via such reactions. 14 In the published work specific conditions were used differing from standard procedure for bromo-lithium exchange using n-BuLi; Et2O at -50 °C was used as the solvent, with THF found to lead to the synthesis of unidentifiable side products and not the desired molecule. In addition, due to the presence of the two internal NH of the porphyrin a two equivalent excess had to be employed, to account for the deprotonation and Li coordination of the internal nitrogen atoms. Taking into account the conditions of the published reaction, a synthetic route was devised to couple a bromo-phenyl functionalised porphyrin and an Nmethylated acridone to form a porphyrin-acridinium conjugate (Figure 5). Using the Adler and Longo procedure a mono-bromo phenyl "AB3" porphyrin (26-2H) was synthesised at a yield of 7%, 15 utilising di-tert-butyl benzyl as the B substituent for its solubilising effects (Figure 6). The obtained porphyrin was then reacted with three equivalents of n-BuLi under dilute conditions in Et2O at -50°C, to form the lithiated species, before addition of two equivalents of N-methyl acridone. It was believed that in this reaction an intermediate porphyrin-acridanol would be formed (Figure 6), which could then be hydrolysed to the acridinium under acidic conditions similarly to the work of Hirel et al.

However, it was found that the reaction did not proceed, with return of the starting material:

1 H NMR spectroscopy showed no change in the spectrum, suggesting the lithiated species was not formed. To prevent coordination to the internal nitrogen atoms and outlaw its possible effects, the porphyrin was metalated using Zn(OAc)2, forming the Zn(II)-porphyrin (26-Zn), and the reaction was repeated using the same conditions as stated above. However, similarly to 26-2H, the reaction was not observed to proceed, with the 1 H NMR spectrum of the obtained product appearing similar to the starting material. Therefore, it was concluded that the porphyrin could not be coupled to the acridinium via this method using the published conditions. Later literature analysis revealed that previous works had used higher temperatures of -10 -0 °C and a larger excess of n-BuLi (6.7 equivalents of n-BuLi) to achieve functionalisation of AB3 bromo aryl porphyrins, 16,17 suggesting that more forcing conditions may have been necessary to achieve synthesis of the conjugate. However, these works were found after development of other synthetic routes; thus, the alternative conditions were not explored.

Synthesis of an AB3 monoacridinium Zn(II)-porphyrin conjugate via palladium cross coupling

Having been unsuccessful in synthesis of conjugates via Br-Li exchange, we next turned to another common synthetic route: palladium catalysed cross coupling, probing its efficacy using 26-Zn. It was proposed that via reaction of 26-Zn with an acridane boronic ester followed by a subsequent oxidation, a diphenyl-spaced porphyrin acridinium conjugate could be afforded (Figure 7). In turn, the acridane boronic ester could be synthesised via palladium cross coupling of a bromo-aryl acridane species.

Figure 7. Retrosynthesis for the synthesis of a monoacridinium porphyrin conjugate (30•PF6) via palladium catalysed cross coupling.

Although functionalisation of acridiniums with boronic esters is theoretically feasible the charged nature of an acridinium boronic ester would make its isolation from the bromophenyl acridinium difficult. As such the acridane form was preferred, with a similar species synthesised and successfully isolated by our research group in previous work. 18 A bromo phenyl acridinium (28•PF6) was first synthesised from 1,4-dibromo benzene, and methyl acridone (27) via bromo-lithium exchange (Figure 8). Once in hand, 28•PF6 was then reacted with five equivalents of LiAlH4 (reducing the species to the air-sensitive acridane) and a palladium catalysed cross coupling reaction performed to obtain the boronic ester 29. This was then reacted in a second Pd-catalysed cross coupling with 26-Zn to form an acridaneporphyrin. Due to the sensitivity of the acridane, oxidation was immediately carried out using 1.5 equivalents of DDQ to successfully synthesise the biphenyl model 30•PF6 at a yield of 67% for the final two steps. To confirm the coupling of the porphyrin and phenyl acridinium units, the compound was characterised via NMR ( 1 H and 13 C), UV-Vis spectroscopy and mass spectrometry. In the 1 H NMR characteristic peaks were seen alluding to the presence of an acridinium and a porphyrin. Two doublets at 9.08 and 9.06 ppm (with 3 J = 4.6 Hz) were observed as well as a singlet at 9.02 ppm, consistent with the pyrrolic protons for an AB3 porphyrin (Figure 9a).

Additionally, in the aromatic region two doublet of doublet of doublets and two doublet of doublets are seen, consistent with the splitting pattern of the acridinium. The absence of a peak between -2 --3 ppm also confirmed that the porphyrin remained metalated. In the 13 C NMR spectrum (Figure 9b), a tell-tale peak was observed at 163 ppm, assigned to the C9 carbon of the acridinium, with resonance of the positive charge to this position causing the highly deshielded peak. In the UV-Vis spectrum of the conjugate (Figure 10) a clear and distinct Soret band at 426 nm ( = 541 000 L mol -1 cm -1 ) was seen, with the Q-band appearing at 554 (21 600) and 596 nm (8 260). A right-hand shoulder was also observed at the Soret band (450-500 nm), likely due to overlap of an acridinium-centred (- transition) absorbance band. Furthermore, absorption bands observed at 348 (20 900) and 362 nm (30 200) were in-line with an acridinium-centred -* transition band. Finally, ESI-TOF mass spectrometry gave a mass spectrum with a major mass ion peak equivalent to the calculated monoisotopic mass for the conjugate minus the counterion ([M] + at m/z = 1280.6458 corresponding to a chemical formula of C88H90N5Zn). The simulated isotopic pattern for the chemical formula was also seen to be in good agreement with that obtained experimentally.

Thus, porphyrin and acridinium units could be coupled via palladium cross coupling, with moderate to high yields for each of the 6 steps. However, this route presented some drawbacks. 30•PF6 featured a diphenyl spacer, in contrast to the initial design. Such a spacer was not ideal due to the potential impact and limit in the efficacy of translation of binding events across the conjugate. Additionally, although the use of the acridane 29 is advantageous for purification, it has a low stability compared to the acridinium, being highly prone to oxidation and therefore sensitive to oxygen. This is due to the gain in aromaticity upon formation of the acridinium. Thus, synthesis of 29 at large scales (and consequently synthesis of the conjugates) might be hindered. As such, in order to afford the single phenyl spaced conjugate in an efficient manner, attention was turned to a third synthetic pathway taking inspiration from the previous work of the Fukuzumi group: porphyrin condensation using a formyl phenyl acridinium.

Synthesis of acridinium porphyrin conjugates via porphyrin condensation

Although the yield achieved by the Fukuzumi group had been low (Figure 4), the route presented some key advantages over palladium catalysed cross coupling which encouraged its pursuit: 1) as the key reactant would be a formyl functionalised acridinium, it would likely be stable in air compared to 29, in turn allowing the ability to synthesise the reactant in largescale without fear of degradation. 2) As porphyrin condensation served as the last step, the intermediate could be used to synthesise an entire family of conjugates using one key building block, in contrast to the two previous routes which would require differing porphyrin precursors for each conjugate.

As such, keeping within our design for the conjugates, a synthetic scheme was devised aiming to synthesise conjugates 33•PF6 and 35•2PF6 from a common novel formyl phenyl acridinium building block, which could in turn be synthesised using cheap and commercially available synthons (Figure 11).

Synthesis of the formyl phenyl acridinium 32•PF6

Starting from 4-bromo-benzaldehyde dissolved in toluene, a protection step was carried out, reacting the aldehyde with pinacol in the presence of a catalytic amount of para-tosylic acid (pTsOH) under refluxing conditions to form the dioxolane analogue (31). 19 This protection served to prevent reaction of the aldehyde during the lithiation reaction. With the protected species in hand, the metal halogen exchange was then performed by reacting with n-BuLi, at -78 °C. The lithitated intermediate was then reacted with one equivalent of N-methyl acridone, forming a phenyl-acridanol intermediary species, followed by an acid workup to dehydrate (and thus aromatise) the heterocycle as well as deprotecting the aldehyde in one step. The formed N-methyl formyl-phenyl acridinium chloride salt (32•Cl) was then exchanged to the PF6 salt in an anion metathesis, giving 32•PF6 at a yield of 78% after purification via precipitation from Et2O (Figure 12). The formation of the aldehyde was confirmed via characteristic peaks for the formyl group in the 1 H (10.25 ppm) and 13 C (193.3 ppm) NMR spectra, with further structural confirmation given by ESI-TOF mass spectrometry.

Synthesis of the AB3 monoacridinium Zn(II)-porphyrin conjugate 33•PF6

Having successfully synthesised the novel reactant, the synthesis of a monoacridinium porphyrin was attempted via porphyrin condensation (Figure 13). Following the Lindsey procedure, 32•PF6 was reacted with 3,5-di-tert-butyl benzaldehyde and pyrrole in the presence of TFA, to statistically form the monoacridinium porphyrinogen. This was then oxidised via DDQ, and metalated with Zn(II) to obtain the monoacridinium porphyrin 33•PF6

after purification via column chromatography, at a yield of 12%. Additionally, the UV-Vis spectrum for 33•PF6 (Figure 15) was shown to be similar to that of 33•PF6 (Figure 8), with features corresponding to the Zn(II)-porphyrin and to the acridinium at similar absorbance maxima and extinction coefficients. Additionally, the mass spectrum showed a major mass ion peak in agreement with that calculated for the conjugate minus the with a similar isotopic pattern to that simulated. In the absence of the solubilising tBu groups, and due to increased - stacking interaction, Furthermore, the mass spectrum obtained showed a major mass ion peak equal to that calculated for 35 2+ with an isotopic pattern complementary to the simulated spectrum ([M] 2+ at m/z = 454.1268 corresponding to a molecular formula of C60H40N6Zn 2+ ). Similarly, the UV-Vis spectrum of the conjugate contained transition bands consistent with the acridinium (at 348 and 362 nm) and Zn(II)-metalated porphyrin (Soret band at 411 nm and Q-bands at 545 & 586 nm) units (Figure 18). Thus, it was concluded that porphyrin acridinium conjugates were most easily afforded via porphyrin condensation, with the ability to access a family of conjugates directly from the powerful building block 32•PF6.

Study of the A2B2 bisacridinium Zn(II)-porphyrin conjugate 35•2PF6

To further investigate the properties of the conjugates, more specifically 35•2PF6, Further calculations allowed the simulation of a theoretical absorption spectrum (Figure 20), which showed similar spectral features to that obtained experimentally. Namely, an intense band at 406 nm (similar to the experimental value of 411 nm), and three smaller bands at 332, 512 and 610 nm respectively (consistent with the experimental values of 362, 545 and 586 nm). The band at 406 nm was found to be composed of overlapping transition bands, with absorbance maxima at 397 and 406 nm for the two porphyrin-centred -* transitions, and at 408 nm for the comparatively lower intensity acridinium-centred -* transitions. The band at 332 nm, was composed of two acridinium -* transitions, and the band at 512 nm, composed of two porphyrin-based -* transitions. Interestingly, the lowest energy transition at 610 nm was shown to be due to a charge transfer from the porphyrin to one of the acridinium units. The charge transfer transition was further probed, investigating the properties of the chargeseparated state via calculations in the presence and absence of an imposed C2 symmetry. In the symmetry optimised structure, it was found that the structure became significantly distorted upon relaxation of the excited state, with decrease in the dihedral Phenyl-Acridinium angle to 77.2°, and an even larger decrease for the Phenyl-Porphyrin dihedral angle to 59.9°. The optimised structure was calculated to emit at 693 nm. When C2 symmetry was not imposed, the structure was observed to undergo more significant distortion, with curving of the structure (Figure 21). Due to the lack of symmetry, delocalisation was not preserved, leading to localisation of the electron on one of the two acridinium units, thus generating two minima. The barrier between the two minima was calculated to be very low, at 302 cm -1 , allowing free oscillation of the exciton, and giving rise to an averaged symmetrical conformer.

Figure 21. Schematic representation of the energy diagram for the relaxation of 35•2PF6 from

the charge separated state to the ground state.

Electrochemical Study

The electrochemical properties of the molecule were next investigated via cyclic voltammetry (Figure 22). Although the compound showed good solubility in acetonitrile, it was found that in the presence of TBAPF6, the solubility was drastically reduced. As such, cyclic voltammograms were recorded in another polar solvent with a similar dielectric constant:

DMF (r = 35.94 vs. 36.71 for CH3CN).

Typically, within a 1.5 to -1.6 voltage window a Zn(II)-porphyrin exhibits two reversible ringcentred single electron oxidations and a reversible ring-centred reduction. 21,22 In contrast, the phenyl acridinium typically exhibits two reductions, one reversible wave and an irreversible wave at a more negative potential. 23 However, deviations from typical behaviour could be seen for 35•2PF6. Scanning within the 1 to -1 voltage window (Figure 22) revealed a reversible wave in the cathodic regime (Ered = -0.475 V vs SCE and E1/2 = -0.442 V vs SCE) and an irreversible wave in the anodic regime (Eox = +0.949 V vs SCE), with similar peak current (I = 7.3 A), suggesting an equal number of electrons in the two processes. The equal peak heights of the two peaks was further confirmed via rotating disk electrode (RDE) measurements in benzonitrile. The reversible wave was assigned to the one electron reductions of the two acridinium fragments (2Acr + + 2e -⇄ 2Acr • ), with the two acridinium units not expected to be in electronic communication with one another, and hence to be reduced at the same potential. This was further supported by the degeneracy of the LUMOs calculated computationally. Given the peak height, the irreversible wave could then be assigned to a bi-electronic oxidation of the porphyrin to give a dicationic porphyrin (Por→Por 2+ + 2e -), with irreversibility likely due to chemical reaction of the formed dication porphyrin unit with either solvent molecules or with the non-oxidised porphyrin to form oligomers. [24][25][26][27] Based on these values, an estimate for the HOMO-LUMO gap was obtained equalling 1.39 eV, smaller than that calculated computationally (2.3 eV, Figure 19).

When expanding the voltage window to 1.5 to -1.6, two additional peaks were observed in the cathodic regime (Ered = -1.34 V vs SCE and Ered = -1.43 V vs SCE), at smaller current heights than see for the two premier waves. Based on the electrochemistry of porphyrins and acridiniums, 22,23 it was determined that the two peaks belonged to reduction of the "acridinium" radical to form a carbanion (Acr • + e -→Acr -) and a reduction of the porphyrin to form a radical anion (Por + e -→Por •-). Formation of the carbanion was further supported by the reduced intensity of the acridinium re-oxidation peak (Eox = -0.409 V vs SCE). The carbanion is known to be highly reactive, reacting with solvent molecules, leading to a reduced amount of the species in the solution. 23 However, due to the close Ered values it could not be said with certainty which peak belonged to which of the two processes (i.e., whether Ered = -1.34 V belonged to the porphyrin reduction and Ered = -1.43 V to the acridinium radical reduction, or vice versa). 1). When exciting at 543 nm (selectively exciting the porphyrin), at both room temperature and at 77 K strong quenching of the emission of both the porphyrin and acridinium units of 35•2PF6 (Figure 23)

was observed, with emission quantum yield smaller than could be measured via steady state experiments (<0.0001). When compared to the emission quantum yield found for Zn-bP (0.035) and for 32•PF6 (0.045), this accounted for a near quantitative quenching of emission. corresponding to the formation of the -radical cation Zn-porphyrin and the radical acridinium species. 28 In contrast, the two models ZnbP and 32•PF6 were found to both form triplet excited states. The kinetics of the process was confirmed to be ultra-fast, with formation of the charge-separated (CS) state in 0.3 ps when exciting at 560 nm, and even faster at less than 0.3 ps, when exciting at 360 nm, with a lifetime of approximately 0.7 ps.

The energy of the charge-separated state (1.39 eV) was approximated as Eox -Ered, using the oxidation potential of the porphyrin unit (Eox = 0.949 V vs. SCE) and the reduction potential of the acridinium unit (Ered = -0.475 V vs. SCE). Based on the collected data, an energy level diagram was obtainable which confirmed that the photoinduced electron transfer was thermodynamically favourable, with the CS state being a lower lying excited state than the triplet excited states of the acridinium and porphyrin (Figure 24).

Choice of effector and guest

The use of porphyrins allows flexibility in the choice of effector, as both metal-ligand coordination, and - interactions can be formed. As metal-ligand coordination is a stronger interaction, preference is given to ditopic ligands as an effector, to ensure effective preorganisation of the receptor. To a similar end, the size and length of the effector will inform the shape and size of the guest binding cavity, as such effectors of suitable length must be chosen. We chose to bind polyaromatic molecules at the acridinium sites, and thus an approximate interplanar distance of 7 Å was required, accounting for the - interaction above and below the guest, (typically 3.5 Å). The most suitable effector for this was determined to be DABCO, being approximately 2.7 Å long giving an approximate interplanar Zn-Zn distance of 7 Å when internally complexed as seen in crystal XRD structures of hostguest porphyrin receptor@DABCO complexes. 29 Furthermore, DABCO was effective in preorganising for the binding of aromatic guests in the porphyrin cage 102@(DABCO)3 (Chapter 1, section 2.2.1). 30 Additionally, as a ditopic ligand bound via metal-ligand coordination, use of DABCO ensures no competition between the effector and the guest, a risk that may be present if an aromatic effector were used.

Binding of DABCO

Thus, the binding ability of 35•2PF6 with regards to DABCO was investigated via 1 H NMR spectroscopy. 0.5 equivalents of DABCO were added to one equivalent of 35•2PF6 in acetonitrile at a five millimolar concentration (Figure 25). The 1 H NMR spectrum of the solution showed clear upfield shifts of the porphyrin protons (Hmeso = 0.4 ppm, Hpy1-2 = 0.3 ppm), suggesting increased electronic shielding, synonymous with an induced magnetic field effect from increased proximity between the conjugates. In addition, a broad peak associated to DABCO was seen at -3.8 ppm, significantly shifted upfield from the chemical shift of free DABCO (2.7 ppm), in accordance with the formation of the sandwiched complex.

In contrast, the acridinium protons were not observed to be as upfield shifted as the porphyrin protons (H1/8 = 0.1 ppm), likely due to both the smaller induced anisotropic magnetic field of the acridinium, and the ability of DABCO to act as a rotor making the acridinium units not as eclipsed as the porphyrin units.

Binding of Pyrene

The ability of the sandwiched complex to bind pyrene was then explored, with an equivalent of pyrene added to the solution. The 1 H NMR spectrum of the solution showed little change to the peaks associated with the porphyrin (Figure 26). However, noticeable upfield shifts were seen for the acridinium peaks (H4/5 = 0.1 ppm, H3/6 = 0.06 ppm and H(1/8 & 2/7) = 0.05 ppm), again suggesting an increase in electronic shielding associated to binding of pyrene via - interactions. The peak associated with DABCO was also seen to be shifted upfield to -4.4 ppm, suggesting an overall stabilisation of the complex upon addition of pyrene, further supporting binding of pyrene. In addition, the pyrene peaks were seen to be shifted upfield in comparison to the 1 H NMR spectrum of free pyrene, assigned to an induced magnetic field effect experienced upon binding by the acridinium units. Furthermore, evidence of an allosteric process was given by the control 1 H NMR experiment of 35•2PF6 and pyrene without DABCO in the same conditions, which showed little to no change in chemical shifts, suggesting that in the absence of pre-organisation via DABCO complexation, the acridinium units could not bind pyrene (Figure 27). Therefore, it was concluded that the bisacridinium porphyrin was capable of forming a supramolecular receptor, with addition of DABCO resulting in the formation of a sandwiched Zn(II)porphyrin-DABCO-Zn(II)porphyrin complex, able to bind pyrene at the acridinium sites.

Conclusion

In conclusion, two effective synthetic pathways were found for connecting a porphyrin unit to acridinium unit(s). In particular, synthesis via porphyrin condensation using a novel and powerful reactant was found to be most efficient, allowing gram-scale synthesis of the stable key intermediate, and synthesis of different acridinium-porphyrin conjugates. Via this route, two conjugates were successfully synthesised and characterised, an AB3 and A2B2 conjugate.

The properties of the A2B2 conjugate with regards to its photophysics and electrochemistry have been studied, with key peculiar properties found. Via cyclic voltammetry, the porphyrin was shown to undergo an uncommon bi-electronic oxidation. In addition, the conjugates were all observed to have highly quenched fluorescence, with photoinduced electron transfer evidenced for the bisacridinium Zn(II)-porphyrin conjugate via transient absorption spectroscopy. Finally, the ability of the A2B2 conjugate to bind DABCO and form a sandwiched complex was exhibited via 1 H NMR spectroscopy, with the complexes ability to bind pyrene further probed. Revealing upfield shifts in the spectrum supported binding of pyrene by the sandwiched complex at the acridinium site, consistent with the hypothesis that positive allosteric control can be exhibited in porphyrin-acridinium systems.

Introduction

Having identified an efficient synthetic pathway for the coupling of porphyrins and acridiniums and established the exhibition of positive allosteric control in the binding of guests, we then looked to the synthesis of covalently attached porphyrin-acridinium conjugates. As the porphyrin-acridinium conjugates had been afforded with the acridinium at the meso substituents, the presence of up to four acridinium units per porphyrin was allowed, making the synthesis of different receptors possible including tweezers, macrocycles, cryptands and cages. However, due to their relative simplicity in comparison to the other architectures, the synthesis of molecular tweezers was first attempted.

Design and rationalisation of a porphyrin-acridinium tweezer

Molecular tweezers can be defined as a class of receptors featuring two recognition units, joined by a single linker. The first reported tweezer was given by Whitlock, 1 with countless tweezers reported since. [2][3][4][5] Tweezers can be grouped into three general classes based on the rigidity of the linker, whether it is: 1) Rigid: Where minimal flexibility is present, typically in the form of a few rotatable bonds, such as in the Jang groups' biindole bridged tweezer 11 (Chapter 1, section 2.2.2). 6 2) Semi-flexible: Where partial flexibility is seen, such as in the Weiss group's pac-man tweezer 5 (Chapter 1, section 1.2). 7 3) Flexible: Where full flexibility is seen, allowing for a larger range of accessible conformations.

The rigidity of the linker greatly informs the binding properties of the tweezer and its selectivity towards different guests. Use of rigid linkers can allow for higher binding constants in complexation. However, within the context of allosteric control a flexible linker can be preferrable to afford a larger allosteric effect. Thus, a flexible linker was proposed in the design of the porphyrin-acridinium tweezer (Figure 1). In synthesising covalent molecular tweezers, there are two general approaches. The first is a termolecular reaction where two tweezer fragments are reacted with a doubly functionalised linker fragment to afford the tweezer. The second approach is direct attachment of two fragments which are functionalised with a group that can be reacted together to form the tweezer in a bimolecular reaction. The latter is preferrable as the reaction allows for the formation of only one product in contrast to the former. Given the two-step functionalisation required to synthesise an acridinium from an acridone (Chapter 2, section 1.3), attachment of a "linker" group to the acridinium was possible and so synthesis via the second route was pursued.

Attachment of the linker as part of the functionalisation of the acridinium was advantageous in minimising the number of synthetic steps. However, it presented some considerations.

Namely, the linker group used would need to be robust to the conditions of both the synthesis of the acridinium (where strong nucleophiles are used) and of the porphyrin (where acid catalysts are used). Additionally, as the linking of the two halves of the receptors would be the last synthetic step, care also had to be taken in the choice of linking reaction. As previously discussed (Chapter 1, section 3), the acridinium is sensitive to nucleophilic addition.

Additionally, the Zn(II)-porphyrin is readily demetallated when exposed to strong acids.

Although the acridinium can be easily reformed via addition of acid, and the free base porphyrin is facile to remetallate, to avoid any issues high yielding linking reactions with mild conditions (without use of acids or bases/nucleophiles) were preferred. With these requirements in mind, and due to the ease of N-alkylation of the acridone synthon, alkenyl chains were chosen as the flexible linker, with formation of the receptor via olefin metathesis.

Alkene metathesis and retrosynthesis of a porphyrin-acridinium tweezer

The catalysis of olefin metathesis has been known since 1955, and is commonly used in ring closing, ring opening and cross metathesis. 8 The three most utilised catalysts are the 1 st and 2 nd generation Grubbs' catalysts, 9 and Schrock's catalyst (Figure 2). 10 In the presence of the catalyst, olefin metathesis is reversible, putting the reaction under thermodynamic control and allowing accumulating formation of the most stable product. The Grubbs' catalysts specifically are known to have high functional group tolerance as well as being less air and moisture sensitive than the Schrock catalyst. Thus, they can be used with a wide array of substituents, making use of the Grubbs' catalysts preferrable for synthesis of receptors.

Accordingly, the Grubbs' catalysts (both generations) have been used to synthesise a number of molecular receptors and mechanically interlocked molecules. [11][12][13][14][15][16][17][18][19][20][21]

Figure 2. Structures of the olefin metathesis catalysts.

The main consideration in Grubbs catalysed olefin metathesis is the solvent used. As dissociation of the tris cyclohexyl phosphine ligand is a key factor in the mechanism for both catalysts (forming the active species), 22,23 coordinating solvents will block the active site of the catalyst. Most commonly, dichloromethane is used as the solvent in Grubbs catalysed alkene metathesis, due to its suitably low polarity. As the monoacridinium porphyrin conjugate 33•PF6 showed solubility in CH2Cl2, it was expected that attachment of an alkenyl chain to the structure would also provide a suitably soluble tweezer precursor, which could be derivatized to the tweezer (Figure 3).

The final consideration for the design and synthesis of the tweezer was in the length of the alkenyl chain. Previous work within our research group had revealed the importance of chain length in determining the efficiency of the alkene metathesis. Specifically, in the synthesis of the bis acridinium macrocycle 21 (Chapter 1, section 3.1) via alkene metathesis; using a hexenyl or octenyl functionalised acyclic precursor was found to lead to a mixture of products, with the decenyl functionalised analogue proceeding efficiently to the macrocycle. 14 Thus, to ensure efficient synthesis of the porphyrin-acridinium receptors a decenyl functionalisation was chosen for the tweezer precursor.

Synthesis of a mono(N-decenyl)acridinium porphyrin tweezer precursor

In order to afford the decenyl functionalised formyl phenyl acridinium, alkylation of the starting synthon, 9-(10H)acridone was first performed via deprotonation using NaH, and the nucleophilic species then reacted with 10-bromo-decene, giving the N-decenyl acridone (36) at a yield of 70% after purification (Figure 4). The N-decenyl formyl phenyl acridinium was then synthesised via the same synthetic route as followed for 32•PF6 (Chapter 2, section 4.1), obtaining the product at a moderate yield of 65%. Formation of 37•PF6 was confirmed via NMR spectroscopy (Figure 5) and mass spectrometry. The formed 37•PF6 was then used in the same general procedure as followed for the mono(Nmethyl)acridinium porphyrin conjugate 33•PF6 (Chapter 2, section 4.2), to afford the monoacridinium porphyrin 38•PF6 (Figure 6). In contrast to the previous conjugates, it was found that 38•PF6 could not be easily isolated from the side products via column chromatography alone. However, when coupled with crystallisation, a pure product could be obtained, with a yield of 12%. The NMR spectra of the N-decenyl conjugate 38•PF6were observed to look much the same as the N-methyl conjugate 33•PF6, except for the presence of additional peaks in the alkyl region and peaks associated to the alkene group (Figure 7). Additionally, in accordance with a change from a methyl to a methylene group, the multiplicity of the nitrogen adjacent alkyl changed from a singlet to a multiplet in the 1 H NMR spectrum. 13 C NMR (125 MHz, CD2Cl2, 298 K) spectrum of the conjugate 38•PF6.

Mass spectrometry was seen to give a major mass ion peak in agreement with the chemical formula of the conjugate without the counter ions ([M] + at m/z = 1328.7402 corresponding to a molecular formula of C91H102N5Zn + , Figure 8). An additional peak at m/z = 664.3711 (30% intensity of the major mass ion peak) was seen assigned to a 2+ charged species of the same chemical formula as the major mass ion peak, indicating oxidation of the species during ionisation to form a radical-dicationic species.

Synthesis and characterisation of the porphyrin-acridinium tweezer 39•2PF6

With the tweezer precursor 38•PF6 in hand, synthesis of a tweezer via olefin metathesis was then attempted. Employing the Grubbs (I) catalyst at a 10 mol% loading, olefin metathesis was carried out on 38•PF6 (Figure 10), obtaining the tweezer 39•2PF6 at a yield of 77% after purification via column chromatography. indicating formation of both the trans and cis alkene isomers. This was further supported by the observable shoulder peak seen for the allylic methylene protons at 2.15 ppm, with the relative integrals giving a 3:1 ratio of trans:cis. Additionally, no other significant changes to the aromatic or aliphatic peaks were seen, suggesting that there was no interaction between the two linked faces of 39•2PF6, in accordance with the use of a highly flexible linker, and the presence of bulky meso aryl groups on the porphyrin units. Similarly, in the 13 C NMR spectrum (Figure 11b) only one peak could be seen for the alkene carbons (losing the two distinct alkenyl carbon peaks seen for 38•PF6) with the remaining peaks remaining mostly unchanged. Thus, successful metathesis was concluded. Finally, UV-Vis spectroscopy showed that covalently linking the monomers led to higher extinction coefficients for all bands by a factor of approximately 2.4, supporting the presence of two porphyrin and two acridinium units (Figure 13). In accordance with the NMR spectra, no hypsochromic or bathochromic shifts could be seen for any of the absorbance bands, when comparing to the precursor 38•PF6. To corroborate these results, DOSY experiments were conducted, with clear differences in the diffusion of 39•2PF6 seen in the presence and in the absence of DABCO. In the absence of DABCO, 39•2PF6 was shown to diffuse as a single species with a diffusion coefficient of 3.8 × 10 -6 cm 2 s -1 . Upon addition of DABCO, a single diffusing species was similarly seen, with the DABCO peak diffusing with the same coefficient as those of 39•2PF6, in agreement with formation of DABCO@39•2PF6. The complex had a larger diffusion coefficient of 4.5 × 10 -6 cm 2 s -1 , giving a hydrodynamic radius of 1.11 nm when assuming a spherical model (Table 1).

The energy minimised (MMFF, Spartan'20, Wavefunction, Inc., Irvine, CA) structure of DABCO@39•2PF6, was shown to extend outside of a sphere with a 1.11 nm radius, most specifically for the alkenyl chain. This is likely due to the flexibility of the alkenyl linker, and the deviation from a spherical shape. In addition, UV-Vis titrations were used to determine the binding constant (Figure 16). Wavelength (nm) 0 eq. 0.2 eq. 0.4 eq. 0.6 eq. 0.8 eq. 1 eq. 1.2 eq.

1.4 eq. 1.6 eq.

1.8 eq. 2 eq.

2.2 eq. 2.4 eq.

2.7 eq. 3 eq.

3.5 eq. 4 eq. 12 eq. 20 eq. 60 eq. 100 eq. 140 eq. 200 eq. 260 eq. 320 eq. Wavelength (nm) 0 eq. 1 eq. 2 eq. 3 eq. 4 eq. 5 eq. 6 eq. 8 eq. 10 eq. 12 eq. 14 eq. 16 eq. 18 eq. 20 eq. 22.5 eq. 25 eq. 30 eq. 35 We then looked to explore the ability of the DABCO@39•2PF6 complex to bind polyaromatic molecules, assessing the efficacy of DABCO as an effector for allosterically enhanced binding of polyaromatic molecules. A binding experiment was first carried out for the macrocyclic complex with perylene (Figure 18), with addition of 1 equivalent of perylene to a 1 millimolar solution of DABCO@39•2PF6 in CD2Cl2 leading to no major change to the 1 H NMR spectrum.

HC=

Switching to the polyaromatic molecule pyrene (Figure 19), addition of one equivalent to the DABCO@39•2PF6 solution at the same concentration, gave rise to a slight broadening of all peaks associated with 39•2PF6. However, no significant upfield shifts were seen. Addition of a further equivalent of pyrene was not seen to lead to further change, and an increase in concentration to five millimolar did not have significant impact. As a result, it was concluded that there was not a strong interaction between pyrene and DABCO@39•2PF6. would disfavour the eclipsed conformation required to have efficient - interaction with a polyaromatic guest at the acridinium binding site (Figure 20). This hypothesis was supported by computational studies (carried out by Dr. Dylan Serillon, University of Barcelona), modelling the interaction of 39•2PF6 with DABCO, showing unfavourable interactions between the aryl substituents upon complexation of DABCO when in an eclipsed conformation.

Figure 20. Illustration of the off-set conformation, the steric interactions encountered when the di-tert-butyl groups are close to one another, and the computed energy-minimised (Spartan'20) three-dimensional model of the off-set conformation

To assess whether any change in behaviour was observed in the absence of DABCO, a 1 H NMR spectrum was recorded for a millimolar solution of 39•2PF6 with an equivalent of pyrene in CD2Cl2 (Figure 21). However, as seen with DABCO@39•2PF6 little change was seen in the spectra, with no broadening or shifts of the peaks. As such it was concluded that 39•2PF6 could not bind poly aromatic guests in the absence of an effector. To avoid steric interactions between the faces of 39•2PF6, the larger effector 4,4'-bipyridine (biPy) was explored, with the ligand having a length more than twice that of DABCO (7.1 Å vs.

2.7Å, Figure 22), ensuring no steric interactions between the two faces of the receptor upon complexation of the ligand. Evidence of complexation of biPy was further given via 1 H DOSY NMR (Figure 24), which showed a single diffusing species with the same diffusion coefficient (D = 3.8 × 10 6 cm 2 s -1 ) for both the biPy protons and the protons of 39•2PF6 (similar to that found for 39•2PF6 alone, Table 3), giving a hydrodynamic radius of 13.2 Å when using a spherical model. The energyminimised model of biPy@39•2PF6 was shown to be in agreement with the DOSY experiments, being close in size to a superimposed sphere (with 1.32 nm radius). Similarly to DABCO@39•2PF6, the alkenyl chain was shown to partially extend outside the sphere (Figure 24). bathochromic shifting, with a second local isosbestic point at 433 nm (Figure 25). Fitting to a 1:2 model gave averaged binding constants of K11 of = 1.8 (± 0.1) ×10 5 L mol -1 , and K12 = 799 (± 130) L mol -1 . The 1:1 value was again found to be similar to binding constants found for other porphyrin tweezers with flexible/semi-flexible linkers. 24,25 For comparison, UV-Vis titration with 33•PF6 at five micromolar in CH2Cl2 were conducted (Figure 26). As seen with DABCO, addition of increasing equivalents of biPy (up to 2000 equivalents) led to larger bathochromic shifts (6 nm) than seen in the 1:1 process of 39•2PF6, with a single isosbestic point at 430 nm supporting formation of one species as expected.

Fitting to a 1:1 binding model gave an averaged binding constant of 3.85 (± 0.15) × 10 3 M -1 , 47 times smaller than that seen for biPy@39•2PF6 (Table 4). Wavelength (nm) 0 eq. 0.5 eq. 1 eq. 2 eq. 3 eq. 4 eq. 5 eq.

6.5 eq. 8 eq. 11 eq. 13 eq. 17 eq. 21.5 eq.

25.5 eq. 37.5 eq. 87.5 eq. 187.5 eq. Wavelength (nm) 0 eq. 20 eq. 40 eq. 60 eq. 80 eq. 100 eq. 125 eq. 150 eq. 175 eq. 200 eq. 325 eq. 450 eq. 600 eq. 750 eq. 1000 eq. 1500 eq. 2000 eq. The efficacy of the pre-organisation with biPy for the complexation of polyaromatic guests was probed. Due to the larger size of biPy relative to DABCO (Figure 22) it was expected that the complex should be able to bind aromatic guests such as ferrocene, which was previously utilised as a template to form the tetracationic molecular square Cyclobis(paraquat-4,4'biphenylene) by the Stoddart group, 26,27 and similarly explored by the group as an allosteric guest. 28 Additionally, biPy@39•2PF6 may be able to bind polyaromatic molecules such as pyrene or perylene or alternatively two polyaromatic hydrocarbons in a double-decker stacked formation.

When studying the ability of biPy@39•2PF6 to bind taller aromatic guests, ferrocene was found to be a poor guest for the receptor likely due to its small aromatic surface area, with seemingly no significant association between biPy@39•2PF6 and guest, as assessed via 1 H NMR spectroscopy.

However, addition of pyrene to a two millimolar solution of biPy@39•2PF6 (with 1 eq. of biPy giving 88% complex) in CD2Cl2 was seen to lead to changes in the 1 H NMR spectrum (Figure 27). Addition of 12 equivalents of pyrene led to small upfield shifts of the acridinium peaks, with the most clearly defined being for the NCH2 protons (NCH2= -0.070 ppm). This suggested possible increased electronic shielding of the acridinium protons upon addition of pyrene, in line with an acridinium-pyrene - interaction, as opposed to the expected downfield shift in the case of a CH- interaction. The peaks of the pyrene protons were also observed to be upfield shifted by 0.02 ppm. Furthermore, upfield shifts of the biPy peaks (H ppm= -0.052 ppm) were also seen as well as sharpening of the aromatic peaks associated to 39•2PF6, suggesting a possible stabilising effect on the complex. Upon further addition of pyrene (up to 50 equivalents), downfield shifts of the porphyrin protons were observed. This could suggest a reduction in the tilting motion of the porphyrin units, reducing the contribution of the induced magnetic field effect on the chemical shifts of the pyrrolic protons. Alternatively, the downfield shift may be due to an anisotropic magnetic field effect from the bound pyrene molecules on the pyrrolic protons. biPy@39•2PF6 after addition of 12 eq. of pyrene and c) biPy@39•2PF6 after addition of 40 eq. of pyrene.

To further probe the binding of pyrene, a 1 H NMR titration was performed with up to 360 equivalents of pyrene added to the solution. Fitting to a 1:1 binding model gave a low binding constant of <2 M -1 , while fitting of the curve to an instantaneous 1:2 binding model gave a binding constant of 25 M -2 (Figure 28). 5. Studies on the switchable nature of the porphyrin-acridinium tweezer

39•2PF6

In addition to the binding properties of 39•2PF6, studies into its switchable properties were also conducted. As discussed in Chapter 1, both the acridinium and the porphyrin are multiresponsive unts. Thus, investigations into the effect of chemical and redox stimuli on the properties of 39•2PF6 were conducted.

Study of the effects of chemical stimulus in the form of nucleophiles

As shown with the Yoshizawa group's macrocycle 20, 29 and our research group's macrocycle 21, 14 the acridinium is chemically responsive via nucleophilic addition to the C9 position.

Therefore, the ability of the tweezer to respond to chemical stimuli in the form of hydroxide ions was first probed.

NMR and Mass spectrometry studies of the chemo-switching process

Addition of 2.2 equivalents of TBAOH (40 wt.% in methanol) to a millimolar solution of 39•2PF6 in CD2Cl2, was seen to lead to dramatic changes in the 1 H and 13 C NMR spectra. Large upfield shifts were observed for all acridinium/acridanol protons in the aromatic region of the 1 H NMR spectrum, in-line with loss of aromaticity upon sp3 hybridisation of the C9 position (Figure 29a). In addition, the NCH2 protons were similarly upfield shifted ( = -1.2 ppm), due to the loss of the electron withdrawing nature of the acridinium, and no longer being in the direct periphery of an aromatic system (and as such experiencing a weaker anisotropic magnetic field effect). In contrast, the pyrrolic protons were not observed to be as upfield shifted, with the pyrrolic protons closest to the acridinium/acridanol unit seen to be most affected (Hpy1 = -0.3 ppm), emphasising that the reaction with the nucleophile was localised to the acridinium.

Similarly, in the 13 C NMR spectrum (Figure 29b) large upfield shifts were seen for the 9-carbon due to the change in hybridisation from sp 2 to sp 3 (C9= -85 ppm), consistent with a dearomatisation of the acridinium to form the acridanol (Figure 29).

UV-Vis study of the chemo-switching process

Due to the large change in aromaticity upon nucleophilic addition, UV-Vis spectroscopy could be used to follow and confirm the formation of the acridanol species, with the phenyl acridanol known to have a -* transition absorbance band at a wavelength significantly bathochromically shifted compared to the phenyl acridinium. 30 Accordingly , it was observed that addition of 2.2 equivalents of TBAOH to 39•2PF6 led to a flattening of the acridinium -* bands, (max = 363 & 348 nm) and the rise of a new bathochromically shifted band at around 300 nm, in-line with formation of the acridanol species (Figure 31). However, upon subsequent addition of 2.2 equivalents of TFA, flattening of the acridanol band and recovery of the acridinium -* bands and was seen, with a similar absorbance intensity to the band prior to addition of the nucleophile. This indicated near quantitative conversion back to the acridinium. Additionally, no demetallation of the Zn(II)-porphyrin units could be observed for the Q-bands, in accordance with the higher reactivity and acid-sensitivity of the acridanol relative to the Zn(II)-porphyrin. Via a fatigue cycle, it was found that no significant drop in conversion was seen after five cycles, indicating a robust species. (Figure 31).

Fluorescence study of the chemo-switching process

In addition, the effects of chemical stimulus were probed via fluorescence spectroscopy with no fluorescence seen for 39•2PF6 upon excitation of the Zn(II)-porphyrin Q-band (at 562 nm).

Transient absorption spectroscopy experiments conducted by collaborators Dr. Barbara Ventura and Daniel Sanchez-Resá, showed that the spectra of 39•2PF6 contained features corresponding to both the radical cation Zn(II)-porphyrin and the acridinium radical species.

This was in accordance with photoinduced electron transfer from the Zn(II)-porphyrin to the acridinium, forming the charge-separated state (Figure 32). This species was again observed to be short-lived, relaxing to the ground state within 1 ps.

Effects of chemo-switching on the binding of biPy

The ability of 40 to bind biPy was assessed via NMR and UV-Vis spectroscopy. Addition of an equivalent of biPy to a millimolar solution of 40 in CD2Cl2 gave rise to similar changes in the 1 H NMR spectrum as seen previously with 39•2PF6 (Figure 34). The biPy protons were significantly shifted with respect to free biPy (HbiPy- = -6.4 ppm, HbiPy- = -2.7 ppm), in accordance with its binding to the two Zn(II)-porphyrin units. Additionally, upfield shifts could DOSY NMR further confirmed the complexation of biPy (Figure 35), which diffused with the same diffusion coefficient as 40 (4.05 × 10 -6 cm 2 s -1 ). The diffusion coefficient for the complex was slightly larger than found for 40 alone (3.75 × 10 -6 cm 2 s -1 , Table 5) in contrast to 39•2PF6, with a hydrodynamic radius of 1.24 nm calculated for biPy@40. As with biPy@39•2PF6, the energy minimised (Spartan'20) structure biPy@40 was shown to agree with the DOSY experiments, being close in-size to a superimposed sphere of the same radius (1.24 nm), with the flexible alkenyl chain partially extending past the radius of the sphere (Figure 35). UV-Vis titrations in CH2Cl2 at micromolar concentrations (Figure 36) revealed little difference between biPy@39•2PF6 and biPy@40. Addition of up to 488 equivalents of biPy was seen to lead to similar changes in the Soret band, with an initial bathochromic shift by 3 nm upon addition of up to 11 equivalents (local isosbestic point at 427 nm), and further bathochromic shifts upon addition of further excess (second local isosbestic point at 432 nm). Accordingly, association constants similar to those found for 39•2PF6 (Table 6), were found for both the Wavelength (nm) 0 eq. 0.5 eq. 1 eq. 2 eq.

3 eq. 4 eq. 5 eq. 6 eq. 7 eq. 8 eq. 11 eq. 13 eq. 17 eq. 21 eq.

25.5 eq. 37.5 eq 87.5 eq 287.5 eq.

Molefractions [G]/[H]

Host Host:Guest Host:2(Guest) max = 429 nm max = 426 nm max = 430 nm

Study of the effects of redox stimulus

Initial cyclic voltammograms of 39•2PF6 showed, a reversible oxidation wave for the two porphyrin units at E1/2 = 0.750 V vs. SCE, and a reversible wave for the reduction of the two acridinium units at E1/2 = -0.535 V vs. SCE (Figure 37a). Upon addition of an equivalent of biPy (Fig. 37b), a notable cathodic shift was seen for the oxidation wave (E1/2 = -57 mV). This was assigned to the donation of electron density from biPy upon coordination to the Zn(II)porphyrin, which would decrease the required potential to oxidise the porphyrin.

The redox properties of 40 were also investigated, to quantify the effects of the acridinium relative to the acridanol, and further probe the effect of ligand coordination in mediating the ease with which the porphyrin species is oxidised. Initial recorded cyclic voltammograms showed, similarly to 39•2PF6, the presence of a reversible wave for the porphyrin (Figure 37c).

Regarding the porphyrin, it was found that switching to the acridanol species significantly increased the ease of oxidation of the porphyrin by approximately 48 mV. Addition of biPy was shown to have a similar effect as seen for 39•2PF6 (Figure 37d), with coordination of biPy increasing the electron density of the porphyrin components. However, the shift was to a lower degree (E1/2 = -19 mV) than seen for 39•2PF6, thought to be due to the absence of the electron withdrawing acridinium moiety. A thermodynamic cycle was used to quantify the oxidation effect on the biPy binding constants (Figure 38), with decreased binding constants found for both tweezers (Table 7).

However, the extent of this decrease was not equivalent for the two tweezers. For the oxidised form of the porphyrin-acridinium tweezer (39 4+ ) the binding constant was estimated as 2.1 × 10 3 M -1 (approximately 86 times larger than that found for 39•2PF6 (Ka = 1.8 × 10 5

M -1 ). In contrast, for the oxidised form of the porphyrin-acridanol tweezer (40 2+ ) the binding constant was estimated to be 3.1 × 10 4 M -1 , 4.5 times smaller than that found for 40 (Ka = 1.4

× 10 5 M -1 ).

-1 -0.5 0 0.5 1 This feature amounted to a remote control of biPy binding via chemical and redox stimuli at the acridinium/acridanol site, illustrating the differing properties of the eight distinct states accessible from 39•2PF6 (Figure 39). As such, the binding and switching studies showed that 39•2PF6 is a flexible and complex multi-responsive receptor, able to bind DABCO or biPy, respond to chemical and/or redox stimulus, and further use stimuli to control and tune binding affinity.

Potential (V) vs. SCE

Conclusions

In conclusion, a porphyrin-acridinium tweezer has been successfully synthesised via olefin metathesis. Due to the flexible linker, the tweezer is able to bind both DABCO and 4,4'bipyridine to form macrocyclic complexes at binding constants 20 and 40 times higher than the related mono acridinium porphyrin conjugate. The ability of the macrocyclic complexes to encapsulate pyrene were probed for both, with DABCO found to be a poor effector for the tweezer due to the presence of steric clashes.

In addition, the multi-stimuli responsive nature of both moieties has been exploited, with the ability to form a neutral tweezer via addition of nucleophiles. This was not initially seen to affect the binding properties with regards to complexation of 4,4'-bipyridine. However, when combining chemical and redox stimulus, the ability to remotely control the binding of 4,4'bipyridine was revealed with dearomatisation of the acridinium shown to tune and lessen the effect of oxidation, leading to characterisation of a multi-state system.

SYNTHESIS AND STUDY OF THE CAGE RECEPTOR

Introduction

Having synthesised the tweezer successfully via alkene metathesis and evidenced the role of the acridinium units in modulating the properties of the host, attention was turned to synthesis of the cage. As stated and shown with the syntheses of 33•PF6 and 35•2PF6 (Chapter 2, section 4), synthesis via porphyrin condensation allows for the direct attainment of differently meso substituted conjugates. Thus, focus was placed on the synthesis of a tetrakis alkene-functionalised acridinium porphyrin conjugate which would enable synthesis of a molecular cage via olefin metathesis (Figure 1).

Figure 1. Retrosynthetic scheme for the synthesis of an octaacridinium porphyrin cage (42•8PF6) via olefin metathesis of a tetrakisacridinium porphyrin conjugate (41•4PF6).

In direct contrast to molecular tweezers, molecular cages have three-dimensional enclosed cavities. Despite this, the general allosteric mechanism envisioned for the porphyrinacridinium tweezer would apply for the porphyrin-acridinium cage. Additionally, as a multitopic host with multiple acridinium binding sites, the cage could potentially bind up to four polyaromatic molecules (when using DABCO as an effector). Finally, as the cage would feature more acridinium units than the tweezer, the response of the host to different stimuli (chemical and redox) would be more pronounced, with the eight acridinium units giving a larger cumulative effect than the two of the tweezer.

Synthesis of an A4 porphyrin-acridinium conjugate via porphyrin condensation

Using the same general porphyrin condensation methodology as used for previous conjugates (Chapter 2, section 4 and Chapter 3, section 2), synthesis of the tetrakisacridinium porphyrin conjugate was pursued via reaction of the formyl functionalised (N-decenyl)acridinium 37•PF6

with pyrrole in the presence of TFA, followed by oxidation using DDQ (Figure 2).

Figure 2. Illustrative scheme for the synthesis of the tetrakis acridinium porphyrin conjugate 41•4PF6.

As with the tweezer precursor 38•PF6, it was observed that the conjugate could not be easily isolated from pyrrolic oligomeric side products via column chromatography alone.

Fortunately, due to the limited solubility of the conjugate in chloroform, and the contrasting higher solubility of the side products, precipitation of the conjugate from chloroform could be used to further isolate the conjugate. Thus, purification via combined column chromatography and precipitation followed by metalation afforded the product 41•4PF6 at a yield of 34%.

Advantageously for olefin metathesis, and despite the higher number of acridinium units, 41•4PF6 showed good solubility in dichloromethane. The 1 H NMR spectrum in CD2Cl2 showed the presence of the expected singlet for the eight pyrrolic protons, reflecting the higher symmetry (D4h) of the conjugate compared to 38•PF6 and 39•2PF6 (Figure 3a-i). This was similarly reflected in the 13 C NMR spectrum (Figure 3b) by the appearance of a lone peak at 150 ppm for the alpha pyrrolic carbons of the porphyrin, in contrast to the four peaks seen for 38•PF6 and 39•2PF6 (Chapter 3, section 3: Figure 11). Interestingly, the 1 H NMR spectrum was observed to dramatically change in CD3CN (Figure 3a-ii), more specifically with regards to the acridinium protons, which were seen to be narrower and more widely spread in the aromatic region, whereas in CD2Cl2 the acridinium peaks were comparatively broadened and overlapped in the case of the 3/6 and 4/5 protons. The 4/5 and NCH2 protons were observed to be the most changed, being upfield shifted in the CD2Cl2 spectrum (H4/5 = 0.21 ppm and NCH2 = 0.05 ppm). Additionally, needle-like crystals were prepared via vapour diffusion of Et2O into a solution of 41•4PF6 in CH3CN and analysed via X-ray diffraction (Figure 5). Due to the high flexibility of the alkenyl chains, disorder in two of the chains could not be removed, limiting the quality of the structure obtained. Regardless, the structures of the active units were still clearly seen and well-resolved, with the presence of the phenyl acridinium units at the meso position of the porphyrin, and a general co-planarity between the acridinium and porphyrin units. In contrast, as calculated for 35•2PF6, the phenyl spacers were found to be perpendicular to the active units (average dihedral angle = 60°). The cell unit was calculated to have a triclinic space group (P 1 ̅ (No. 2)), with the compound packing as sheets, at a 45° angle to the b and a axes of the cell unit.

When observing the packing of the crystal, it was found that there were short contact interactions between the porphyrin unit and the acridinium unit of two separate stacked conjugates at average lengths of 3.5 Å, suggesting - interactions between the porphyrin and acridinium in the solid-state structure.

Synthesis of a porphyrin-acridinium cage via olefin metathesis

As 41•4PF6 had four alkenyl chains, different products could be formed including oligomers. Thus, we first explored the suitability of different ditopic ligands to act as templates for the cage, via formation of sandwiched complexes, to favour intramolecular ring-closing reactions versus oligomer formation.

Since complexation of ligands to the active form of the Grubbs' catalyst blocks the active site of the catalyst, it was necessary to use a template with a high binding constant for the Zn(II)porphyrin. As DABCO has a binding constant for monomeric porphyrins typically in the order of 10 5 M -1 for a 1:1 complex, 1 and had been successfully used in similar porphyrin cage syntheses, 2,3 the use of DABCO was first explored, via addition of 0.5 equivalents of DABCO to a millimolar solution of 41•4PF6 in CD2Cl2. However, it was found that addition of DABCO led to precipitation of 41•4PF6 forming a complex insoluble in non-polar solvents.

In contrast, when exploring the typically less strongly binding biPy (Ka ≈ 10 3 -10 4 M -1 ) 4,5 as a template, addition of half an equivalent of biPy to a millimolar solution of the conjugate in CD2Cl2 did not lead to any precipitation. Furthermore, the 1 H NMR spectrum of the solution showed key changes suggesting formation of the sandwiched complex, including upfield shifts of both the pyrrolic (Hpy = -0.25 ppm) and acridinium protons (H1-8 < -0.1 ppm), in-line with an induced magnetic field effect (Figure 6). In addition, broad peaks at 5.1 and 2.5 ppm were seen, assigned to the complexed biPy beta and alpha protons respectively. As with the tweezer, the synthesis of the cage was achieved via olefin metathesis using Grubbs' 1 st generation catalyst for its high functional group tolerance and relative stability. catalyst load of 20 mol% (as assessed via TLC), the cage formed was not fully closed, with only three of the four links made (as assessed via mass spectrometry). Thus, in order to form the fully closed cage, a second catalyst loading was required, with reaction for 16 hours after the initial catalyst loading, and a further eight hours after the second catalyst loading completing the four required metathesis reactions.

After testing different eluents for purification via column chromatography, it was found that a solution of 80:5:15 CH2Cl2/CH3OH/CH3CN (0.02 M KPF6) gave good results, with KPF6

decreasing adherence of the cage to the stationary silica phase, while the polarity of the eluent gave a suitable retention factor (Rf) value of < 0.5.

To remove biPy further purification was required. Fortunately, removal of the template was achievable via subsequent column chromatography using a CH3CN KPF6 (0.04 M) solution as the eluent. The combination of the two chromatographic methods allowed for the isolation of the cage 42•8PF6 at a yield of 49%.

Curiously, 42•8PF6 showed much reduced solubility compared to the conjugate in CH2Cl2 (Figure 7), with 1 H NMR spectra in the deuterated solvent returning poorly resolved broadbase peaks in the absence of the template, which were hard to distinguish from one another.

However, a peak assignable to the pyrrolic protons was seen (9.39 ppm), and the lack of terminal alkene peaks notable. Additionally, broad peaks for the CH2 protons were observed in the alkyl region. Although the cage showed high solubility in polar solvents such as CD3CN, DMSO and DMF, 1 H NMR spectra in these solvents returned even broader peaks. Thus, intramolecular parallel offset - interaction between the porphyrin units was indicated, with seemingly no interaction between the porphyrin and acridinium units in solution. The cage was unambiguously detected via mass spectroscopy as major mass ion peaks, at different multiple charges (Figure 9). The highest intensity peak was seen to be a 7+ charged To further confirm the complexation of biPy, DOSY NMR spectra were recorded for the solution (Figure 11), where it was found that the cage and bipyridine ran at similar diffusion coefficients (2.80 × 10 -6 cm 2 s -1 ), further supporting complexation of biPy by the cage. Due to the mixed solvent system used (CD2Cl2/CD3CN (9:1 v/v)), the true viscosity of the solution is not known. However, if assuming a viscosity close to or equivalent to the major solvent (CD2Cl2 = 4.353 × 10 -4 Pa s), a hydrodynamic radius of 17.9 Å is calculated based on a spherical model, equivalent to a volume of 24023 Å 3 . This was in-line with what was expected based on the dimensions of the crystal structure cell unit of 41•4PF6 (b axis = 17.9 Å, Figure 5), as well as being an expectedly larger complex compared to the biPy@39•2PF6 complex (Table 1). Additionally, an energy-minimised structure of biPy@42•8PF6 was seen to agree with the derived radius, having a similar size to that of a superimposed sphere (with radius = 1.79 nm). UV-Vis titrations were conducted to ascertain the binding constant for formation of the complex (Figure 12). Addition of increasing amounts of biPy (up to 10 equivalents) to a solution of the cage in CH2Cl2 (0.1% CH3CN) led to hyperchromic shifting by a factor of 1.3 inline with removal of the - interaction between the porphyrin units. In contrast, no major changes were seen for the acridinium-centred band at 348 -364 nm, supporting interaction with the porphyrin and not the acridinium units, as expected. Slight decrease in the band width was also observed for the Soret band (in-line with a rigidification of the cage) and an isosbestic point at 423 nm, supporting the formation of a single 1:1 host:guest complex.

Fitting to a 1:1 model gave an averaged binding constant of 4.2 (± 0.7) × 10 6 M -1 , around 23 times larger than that seen for the tweezer 39•2PF6 (at 1.8 × 10 5 M -1 ), as expected for a less flexible species (in comparison to the tweezer).

Study of the complexation of DABCO by 42•8PF6

The ability of 42•8PF6 to bind DABCO was also explored. As was the case for biPy, addition of one equivalent of DABCO to a solution of the cage in CD3CN, gave a 1 H NMR spectrum with narrow peaks for the cage in contrast to that seen for the free cage (Figure 13). A narrow peak for DABCO could be seen at Wavelength (nm) 0 eq. 0.1 eq. 0.2 eq. 0.3 eq. 0.4 eq. 0.5 eq. 0.6 eq. 0.7 eq. 0.8 eq. 0.9 eq. 1 eq.

1.1 eq. 1.2 eq.

1.3 eq. 1.4 eq.

1.5 eq. 2 eq. 3 eq. 4 eq. 5 eq. 7 eq. 10 eq. Using NOESY NMR (Figure 14a), a through space correlation could be seen between the DABCO protons and the pyrrolic protons of the porphyrin units. DOSY NMR recorded in acetonitrile showed all peaks to move with a similar coefficient (D = 3.65 × 10 6 cm 2 s -1 ), further supporting complexation of DABCO (Figure 14b). Using the diffusion coefficient and the viscosity of acetonitrile (3.57 × 10 -4 Pa s), a hydrodynamic radius of 16.7 Å was calculated, with an approximate volume of 19660 Å 3 when assuming a spherical model. This was in good agreement with that calculated for the biPy@42•8PF6 complex, and with the DABCO@39•2PF6 complex (Table 2), being expectedly larger than the latter complex, given the larger aromatic surface area of the tetrakisacridinium porphyrin unit. Additionally, an energy-minimised structure of DABCO@39•2PF6 was seen to have a similar size to that of superimposed sphere with a radius of 1.67 nm.

Table 2. Diffusion coefficients and hydrodynamic radii for the DABCO complexes of 42•8PF6

and 39•2PF6. UV-Vis titrations were caried out at micromolar concentrations in CH3CN (Figure 15). Addition of increasing equivalents of DABCO to the 42•8PF6 solution was seen to lead to a large hypsochromic shift from 439 nm to 426 nm, in addition to a slight decrease in the band width, consistent with a constriction in flexibility. In addition, an isosbestic point could be seen at 432 nm suggesting formation of one complex. As such, the obtained curve was fit to a 1:1 binding model, with an averaged binding constant of 4.5 (±0.2) × 10 5 M -1 obtained. Wavelength (nm) 0 eq 0.5 eq 1 eq 1.5 eq 2 eq 2.5 eq 3 eq 3.5 eq 4 eq 4.5 eq 5 eq 6 eq 7 eq 8 eq 9.5 eq 11.

Species

Preliminary investigation into the allosteric binding of pyrene

Having evidenced the formation of the DABCO@42•8PF6 complex, attention was turned to the capacity of the complex to bind polyaromatic molecules. Due to the poor solubility of the complex in other solvents CD3CN was used, despite the somewhat limited solubility of poly aromatic hydrocarbons in this solvent. Adding 5 equivalents of pyrene to a solution of the DABCO@42•8PF6 complex in CD3CN, was seen to lead to significant changes to the 1 H NMR spectrum (Figure 16), namely upfield shifts of the pyrene molecule by 0.04 ppm, and upfield shifts of the NCH2 (-0.064 ppm) and 4/5 (-0.092 ppm) protons of the acridinium, indicating an induced magnetic field effect in-line with binding of the pyrene molecules via - stacking interactions. However, due to the limited solubility of poly aromatic hydrocarbons in acetonitrile, studies in this solvent were limited. Thus, in order to allow study in non-polar solvents (such as dichloromethane) anion metathesis was performed.

Synthesis, characterisation, and study of the cage BArF salt (42•8BArF)

Due to the high solubility and non-coordinating properties, 42•8PF6 was exchanged to the BArF analogue, with anion metathesis conducted using NaBArF in CH2Cl2 to give 42•8BArF in quantitative yields (Figure 17). Full exchange to BArF was confirmed via 19 F NMR, showing a lone singlet for the BArF molecules.

Figure 17. Synthesis of the cage 42•8BArF via anion metathesis of 42•8PF6.

Upon formation of the BArF salt, immediate distinctions could be seen. The cage showed significantly improved solubility in CH2Cl2 compared to the PF6 salt, with the ability to see narrow peaks in the 1 H NMR spectrum (Figure 18b). Additionally, separate peaks were noticeable for the inward facing and outward facing meta and ortho phenyl protons. When comparing the cage to the BArF analogue of the cage precursor 41•4BArF (Figure 18a), it was found that many of the peaks were significantly upfield shifted, including for the BArF counterion, suggesting a possible interaction between the cage and the counterion. Small shoulder peaks were also seen in the aromatic region of the spectrum, most noticeably for the pyrrolic protons. It was hypothesised that this may be due to slow conversion (relative to the NMR timescale) to conformations of the cage with wider apertures (indicated by their downfield shifted chemical shifts relative to the more intense peaks). Investigation of this assertion was limited due to the low boiling point of CH2Cl2 (hindering variable temperature NMR experiments), and the return to broadness seen in the NMR spectra when using alternative solvents (including CHCl3 and CD3CN). However, when exploring the binding of ditopic ligands, the resulting spectra of the complexes was seen to give a single set of peaks in the aromatic region, supporting the presence of one species in solution. DOSY NMR spectra were recorded for NaBArF, the cage precursor 41•4BArF and the cage 42•8BArF. A diffusion coefficient of 2.92 × 10 -6 cm 2 s -1 was found for the major peaks of the cage 42•8BArF, corresponding to a hydrodynamic radius of 17.2 Å (Figure 19). The BArF -ions were not observed to have a diffusion coefficient the same as the cage (3.77 × 10 -6 cm 2 s -1 ), however the diffusion coefficient measured was less than half the value for NaBArF (8.38 × 10 -6 cm 2 s -1 , Table 3). Thus, interactions between the cage and the BArF -counterions were concluded to take place, and the difference in the broadness of the 1 H NMR peaks in comparison to 42•8PF6 partly ascribed to this interaction. However, the exact nature of the interaction and its localisation could not be ascertained, although the upfield shift did suggest shielding via an induced magnetic field. 6. Binding Studies of the cage with BArF as the counter ion (42•8BArF)

Study of the complexation of biPy

To further investigate the effects of anion metathesis, the ability of 42•8BArF bind biPy was probed. Addition of an equivalent of biPy to a millimolar solution of the cage in CD2Cl2 was seen to lead to resolution of the pyrrolic protons in to one singlet for the 16 pyrrolic protons, upfield shifted by 0.094 ppm compared to the major pyrrolic proton of 42•8BArF (Figure 21).

The difference in chemical shifts between the outward and inward-facing meta and ortho phenyl protons was also seen to become smaller. This suggested a decreasing anisotropic magnetic field effect, that might be seen with a widening of the cage aperture upon complexation of biPy. A slight downfield shift of the BArF -ions' protons was also observed suggesting an interruption or reorganisation of the interaction between the BArF -ions and the cage. This trend was also seen in the 19 F NMR spectrum, which showed a slight downfield shift by 0.06 ppm (from -62.89 to -62.83 ppm). Tell-tale narrow upfield shifted protons could also be seen for biPy at 4.9 and 2.4 ppm for the beta and alpha biPy protons respectively, indicating internal complexation of biPy by the cage. As similarly seen with the tweezer 39•2PF6, upfield shifts of the acridinium protons were also observed, although to a lesser extent (H4/5 = 0.045 ppm, vs 0.1 ppm for biPy@39•2PF6). the biPy@42•8BArF complex formed upon addition of an equvalent of bipy to the solution.

The cage and biPy were observed to have the same diffusion coefficient (2.85 × 10 -6 cm 2 s -1 ) via DOSY NMR, with an approximate hydrodynamic radius of 17.6 Å (Figure 22). This value was similar to that obtained for the biPy@42•8PF6 complex, and slightly larger than that obtained for the free cage. The BArF -ions were still found to diffuse at a similarly slower rate (3.71 × 10 -6 cm 2 s -1 ) in comparison to NaBArF, suggesting that the interaction between the cage and counterions remained, with the downfield shift of the BArF protons indicating a possible change in the arrangement of the interaction. Additionally, as was seen with biPy@42•8PF6, the energy-minimised structure of the complex was found to be similar in size to a sphere of radius = 1.76 nm (Figure 22). nm (from 1.1 to 10 eq.). However, fitting to a 1:2 binding model was not observed to give a better residual error than the 1:1 model. One possible hypothesis indicated by the closeness of the two isosbestic points is that they may be due to a displacement of BArF -ions. Via fitting to a 1:1 model an averaged binding constant of 1.3 (±0.2) × 10 7 M -1 was found, 72 times larger than that found for 39•2PF6, and three times larger than that found for 42•8PF6. Wavelength (nm) 0 eq 0.1 eq 0.2 eq 0.3 eq 0.4 eq 0.5 eq 0.6 eq 0.7 eq 0.8 eq 0.9 eq 1 eq 1.1 eq 1.2 eq 1.3 eq 1.4 eq 1.5 eq 1.6 eq 5 eq

Study of the complexation of DABCO

Formation of the 1:1 DABCO@42•8BArF complex was also explored via NMR spectroscopies.

Addition of one equivalent of DABCO to a millimolar solution of 42•8BArF in CD2Cl2 gave (similarly to biPy) a single set of peaks, with a singlet for the 16 pyrrolic protons. The pyrrolic protons were seen to be upfield shifted by 0.29 ppm relative to the most intense pyrrolic peak of the cage (Figure 24). In addition, an upfield shifted peak was observed for the DABCO protons at -4.1 ppm (compared to free DABCO at 2.7 ppm), indicating internalisation and complexation at the Zn(II)-porphyrin site. Distinction from the biPy@42•8BArF spectrum was seen in the phenyl protons, with the difference in chemical shift between the inward and outward-facing ortho protons increasing relative to the spectra of 42•8BArF. However, this was not seen for the meta protons where the difference in chemical shift was seen to become smaller. This could be due to the unequal anisotropic effects of the acridinium and porphyrin units. The large difference between the inward and outward-facing protons seen for DABCO@42•8BArF was in direct contrast to that seen for the complex DABCO@42•8PF6,

where little separation was seen between the inward and outward-facing protons (Figure 13).

Interestingly, downfield shifts of the BArF protons could again be seen upon addition of DABCO (HBArF = +0.093 ppm), with the difference being larger than seen with biPy@42•8BArF. The 19 F NMR followed the trend, with a downfield shift by 0.14 ppm suggesting a possible rearrangement of the intermolecular BArF-cage interaction. NOESY NMR confirmed binding of DABCO, with correlation between the pyrrolic protons and DABCO, and additionally between the inward-facing ortho protons and DABCO (Figure 25). DOSY NMR experiments showed all peaks (excluding the BArF protons) to diffuse with the same diffusion coefficient (2.86 × 10 6 cm 2 s -1 ), giving a calculated hydrodynamic radius of 17.5

Å, and volume of 22543 Å 3 using a spherical model, slightly larger than that obtained for DABCO@42•8PF6 (Table 5). In addition, as with biPy@42•8BArF, interaction between the cage and the BArF -ion appeared to still be present, with a diffusion coefficient of 3.65 × 10 -6 cm 2 s -1 found for the BArF -ions, suggesting that the downfield shifts seen in the 1D spectra were due to rearrangement of the interaction between the cage and the BArF -ions. UV-Vis titrations in CH2Cl2 revealed hyperchromic shifts of the Soret band by a factor of 1.2, with a smaller shift in the absorbance maxima wavelength (Figure 27). A general thinning of the Soret band was also observed, in-line with a less conformationally flexible complex. In contrast to what was found with biPy, a single isosbestic point was observed at 419 nm, supporting formation of one complex. Fitting to a 1:1 model gave a binding constant of 1.2 (±0.2) × 10 7 M -1 , similar to that obtained for biPy.

Table 5. Diffusion coefficients and hydrodynamic radii of the

Studies of the allosteric binding of pyrene

Taking advantage of the increased solubility in CD2Cl2, the DABCO@42•8BArF complex was then assessed for its ability to bind pyrene via NMR titrations (Figure 28). Addition of increasing equivalents of pyrene to a sub millimolar solution of DABCO@42•8BArF was seen to lead to increasing upfield shifting of the acridinium protons, with a flattening of the 4/5 and NCH2 protons of the acridinium. Downfield shifting of the alkene and the allylic methylene protons was also seen, possibly due to their proximity to the amplified magnetic field at the periphery of the aromatic guest. Likewise, the inward-facing ortho protons were also increasingly downfield shifted. Interestingly, only a single set of peaks could be seen for the Wavelength (nm) 0 eq. 0.25 eq. 0.5 eq. 0.75 eq.

1.2 eq. 1.4 eq.

1.6 eq. 1.8 eq.

2.0 eq. 2.2 eq.

2.4 eq. 2.6 eq.

2.8 eq. 3 eq.

Molefractions [G]/[H]

Host Host:Guest max = 427 nm acridinium sites, faster than the NMR time scale. In addition, although the majority of the peaks were seen to shift in one direction throughout the titration, the DABCO protons were seen to initially shift upfield (up to 100 equivalents), before plateauing and then shifting downfield, approaching its original chemical shift. This effect could be due to either an initial stabilisation then destabilisation upon uptake of pyrene guests, or due to increasing anisotropic magnetic field effects from the bound pyrene molecules on the DABCO protons (downfield shift) balanced against the stabilisation of the structure (upfield shift). The obtained titration curve was not observed to have a sigmoidal shape, commonly seen for positively cooperative systems, 6,7 indicating that positive homotropic cooperativity was not present between the acridinium sites. Instead, a hyperbolic curve was seen for most protons (excluding DABCO), with increasing linearity in the curve at higher equivalents of the guest (Figure 29). The shape of the curve presented some uncertainty in whether there was a presence/lack of cooperativity between the acridinium units (i.e. whether negatively cooperative or non-cooperative). The stoichiometry of the host-guest species formed at the end of the titration could not be determined directly, with continuous variation plots unsuitable due to its unreliability in higher stoichiometry host:guest systems. 8 Due to the complexity of the system and difficulties in the analysis of the titration data, it could not be said directly which binding model was most accurate. Thus, further investigation of the binding of the polyaromatic molecules by the complex is needed, using new methods to ascertain the final stoichiometry.

Figure 29. Titration curves obtained for the alkene and DABCO protons.

In the absence of the effector DABCO, no significant changes were seen in the 1 H NMR spectrum of the cage upon addition of 30 equivalents of pyrene at the same sub-millimolar concentration (Figure 30), in contrast to the upfield shift of approx. 0.3 ppm for the NCH2 protons seen with the DABCO@42•8BArF complex at the same number of equivalents of pyrene. Additionally, no significant shifts were seen for the pyrene proton peaks, indicating little to no interactions taking place between the guest and 42•8BArF, and that DABCO was an effective effector for realising interaction within the interior of the cage. Thus, it was concluded that an allosteric system had been achieved.

Effect of chemical stimulus in the form of nucleophilic addition

As seen with the tweezer, addition of nucleophiles can drastically alter the properties of the receptor. As such it was expected that due to the presence of more acridinium units, an even more pronounced change in the properties of the cage would be seen upon dearomatisation of the eight acridinium units.

NMR and mass spectrometry studies

The effects of nucleophilic addition were first explored via NMR spectroscopy, with addition of 8.4 eq. of KOH to a solution of 42•8PF6 in CD2Cl2/CD3CN (5%) leading to very broad peaks, similar to 42•8PF6. Via evaporation of the solvent and taking up of the resultant solid in CH2Cl2/CH3OH (1:2) exchange of the OH groups to the methoxy group could be afforded, taking advantage of the reversible nature of the C-OH bond. The NMR spectrum of the resultant species was found to also be broad but more easily assigned (Figure 31a), with clear upfield shifts for the NCH2 protons (NCH2 = -1.5 ppm). Additionally, the 13 C NMR spectrum showed a highly upfield shifted peak for the 9-carbon of the acridane species at 78 ppm (C9 = -85 ppm, Figure 31b) as seen when the same reaction was performed on 39•2PF6 (Chapter 3, section 5.1). Further characterisation of the cage via DOSY experiments is currently underway, to verify the size and the singularity of the species. Analysis of the cage via ESI mass spectrometry gave a complex spectrum due to the multiple charged and radical species that could be formed as well as the replacement of the OMe groups with ionisation fragments of the solvent (Figure 32). Singly charged derivatives of the cage were not observed, however a number of low intensity 5+, 6+ and 7+ charged species were found. The major mass ion peak was found to be a 6+ species with loss of all methoxy groups and addition of a hydrogen atom ([M-8OMe+H] 6+ at m/z = 629.31).

UV-Vis study

To further explore the effects of chemical stimulus, a fatigue study was conducted via UV-Vis spectroscopy, adding 8.4 eq. of TBAOH, followed by TFA to a solution of 42•8PF6 (Figure 33).

As with 39•2PF6, addition of the nucleophile led to flattening of the acridinium transition bands, and the appearance of a new band at around 293 nm. Additionally, the lower energy - acridinium-centred transition band at around 450 nm was flattened, with the broad right-hand shoulder of the Soret band disappearing. Similarly, the Q-band was seen to narrow, most especially for the last peak at 600 nm, which is likely due to the change in nature of the transition for 43 versus 42•8PF6. In the latter case, the lowest energy transition band is likely due to charge transfer from the HOMO localised on the porphyrin to the octo-degenerate LUMOs localised on the eight acridinium units, as calculated and found (electrochemically) for the bisacridinium porphyrin 35•2PF6 (Chapter 2, section 5). In contrast, for 43 the HOMO and LUMO are likely both localised on the porphyrin units. Additionally, the intensity of the Soret band was seen to increase after addition of TBAOH.

Upon addition of 8.4 equivalents of TFA, the acridinium spectral features were recovered, with the acridinium-centred -  transition bands reappearing, and the Q-band becoming broadened again. The Soret band was not observed to decrease in intensity, however this was ascribed to an anion metathesis from the PF6 -counter anion to the more strongly coordinating TFA -counter anion. Repeat of this cycle nine times, was not seen to lead to any significant loss in conversion or recovery, showing that the acridinium units are robust.

Additionally, no demetallation of the Zn(II)-porphyrin units could be observed, consistent with a much more reactive and acid-sensitive acridanol species, compared to the metalloporphyrin, as was seen in the chemo-switching study of the tweezer 39•2PF6 (Chapter 3, section 5.1.2).

Figure 33.

Overlayed UV-Vis (CH2Cl2, l = 0.5 cm, 298 K) spectra, showing the changes in the spectra upon addition of TBAOH (8.4 eq.) to 42•8PF6 (c = 10.0 M) followed by addition of TFA (8.4 eq.). The change in absorbance for the acridinium-centred (364 nm) and acridanol-centred (293 nm) bands upon addition of TBAOH followed by TFA are given for 10 cycles.

Binding study of the octaacridane porphyrin cage

As the presence of eight acridinium units was expected to lead to a more pronounced response to chemical stimuli, the effects of nucleophiles on the binding ability of the porphyrin unit were next probed. Addition of 8.4 equivalents of KOH in CH3OH, to a solution of biPy@42•8PF6 was seen to lead to significant changes to the NMR spectrum (Figure 34). Compared to the biPy@42•8PF6 spectrum, the peaks of biPy@43 were observed to be slightly broadened, but significantly less broad than the spectrum of 43, with more distinct peaks for the phenyl ortho protons.

Upfield shifts of all protons relative to the biPy@42•8PF6 were seen, as well as an upfield shift of the pyrrolic protons relative to 43 (by 0.13 ppm). In addition, larger downfield shifts of the acridane protons were seen (by 0.21 ppm). Curiously, peaks for the beta protons of biPy were not observed at the chemical shift seen for biPy@42•8PF6 (4.95 ppm), with possible overlap with nearby peaks. Further investigation and characterisation of this complex via 1 H DOSY NMR experiments are currently underway to confirm complexation of biPy.

UV-Vis study of the complexation of bipy

To ascertain the binding constant, UV-Vis titrations were carried out (Figure 35). Addition of increasing equivalents of biPy, was seen to lead to bathochromic and hyperchromic shifts as seen for 42•8BArF. The presence of one isosbestic point at 428 nm supported formation of a 1:1 species, thus the data was fit to a 1:1 binding model. It was found that the binding affinity was significantly decreased relative to 42•8BArF and even to 42•8PF6, with a binding constant of 1.0 (± 0.2) × 10 6 M -1 . This value was 13 times smaller than that obtained for 42•8BArF and 4 times smaller than that obtained for 42•8PF6, indicating a significant decrease in the binding ability due to addition of nucleophiles (Table 6). Thus, remote controlled binding of biPy was afforded via chemical stimulus, in a mechanism slightly different to the tweezers 39•2PF6 and 40 where such large differences in the binding affinity were not seen until the addition of electrochemical stimulus.

The difference in behaviour was ascribed to the presence of a larger number of acridinium/acridanol units giving rise to larger cumulative differences in the two cage structures. For example, the loss of the electron withdrawing effect from the acridinium on the porphyrin is larger for the octacationic cage versus the dicationic tweezer. Additionally, the difference in conformational flexibility between the neutral and charged cage may be more pronounced than for the neutral and charged tweezer, which remain highly flexible in either form.

Conclusion

In conclusion, informed by our work in the synthesis of porphyrin-acridinium conjugates, and by the successful synthesis of a porphyrin-acridinium tweezer, an octacationic porphyrinacridinium cage was synthesised via olefin metathesis, and studied as both a PF6 and BArF salt. The counter anion was shown to dramatically affect the solubility of the cage, as well as impacting whether parallel offset - intramolecular interactions were present between the Zn(II)-porphyrin units.

Wavelength (nm)

0 eq 1 eq 2 eq 3 eq 4 eq 5 eq 6 eq 7 eq 8 eq 9 eq 10 eq 11 eq 12 eq 14 eq 16 eq 18 eq 20 eq 40 eq

General conclusions and perspectives

In this project, we first successfully identified an efficient route to synthesis of meso substituted porphyrin-acridinium conjugates, using a novel formyl phenyl acridinium reactant. This synthetic route was used to synthesise conjugates with one or two acridinium meso substituents. Furthermore, the properties of these novel conjugates were investigated, with photoinduced electron transfer implicated in the observed quenched fluorescence of the bisacridinium porphyrin species.

The synthetic pathway was extended to the synthesis of receptors, with synthesis of both a porphyrin-acridinium tweezer and cage. The capacity of the two receptors to bind differing ditopic ligands (specifically DABCO and 4,4'-bipyridine) was investigated, with binding constants in the range of 10 5 -10 6 M -1 found for the 1:1 macrocyclic host-guest complexes of the tweezer, and in the range of 10 6 -10 7 M -1 for the 1:1 complexes of the cage. The ability to pre-organise for binding of polyaromatic guests via ditopic coordination of DABCO was probed in the case of both the cage and the tweezer. For the tweezer, DABCO was found to be a poor effector. However, for the cage DABCO was seen to act as an effective on/off switch for encapsulation of the poly aromatic guest, thus giving rise to a positive heterotropic allosteric control of aromatic guest uptake.

Additionally, the effect of different stimuli on the binding abilities of the two receptors has been explored, with chemical stimulus seen to change the photophysical properties of the receptors due to changes in aromaticity upon nucleophilic addition to the acridinium. For the tweezer, the effects of nucleophilic addition were seen to extend to a change from a photoinduced electron transfer process (seen with the porphyrinacridinium tweezer) to an energy transfer (for the porphyrin-acridanol tweezer). Finally, the ability to remotely-control the binding of 4,4'-bipyridine at the porphyrin site via nucleophilic addition was evidenced in both receptors, and in the case of the tweezer, shown to proceed via the coupling of redox and chemical stimulus.

As such, the presented studies lead to the conclusion that we have successfully met our aim to synthesise novel receptors, which are able to bind different guests, control binding of guests via an allosteric mechanism and furthermore, respond to multiple different stimuli, thus having more than one control mechanism for the binding of guests.

Finalisation of the allosteric study is required, specifically in determining the stepwise binding constants for uptake of the aromatic guests. This will thereby establish whether there is any cooperativity between the acridinium binding sites and moreover, whether the cage shows multi-pathway allosteric control. Additionally, the ability to bind different polyaromatic molecules has not yet been fully investigated, with our work focusing on pyrene due to its relatively high solubility. Thus, titration of the hosts with other aromatic species such as perylene, pentacene, coronene etc., should be studied.

These studies will also aid in determining the features that most effect the strength of the binding interaction with the receptors.

Further investigations are also underway to complete the stimuli response study of the cage, most especially with regards to the effects of electrochemical stimuli, and whether the effects seen for the tweezer in the binding of 4,4'-bipyridine are similarly seen for the cages. Additionally, photophysical studies on the porphyrin-acridinium and porphyrin-acridanol cage are needed to establish whether similar changes in behaviour are seen upon nucleophilic addition as seen with the tweezer. Furthermore, full studies into the effects of chemical stimulus in the binding of polyaromatic molecules should be completed to confirm whether the acridane species displays no affinity for polyaromatic molecules, and to assess the affect if any on the binding of DABCO, and how this may further impact the binding of polyaromatic molecules.

As this work has been wide-ranging, covering the synthesis of novel porphyrin conjugates, receptors of different architectures and control of molecular encapsulation via different stimuli, many perspectives are opened for further research. For example, to complete the family of receptors, the synthesis of the macrocycle and cryptand structures can also be attempted, with investigations into their properties and encapsulating abilities, and comparison to the tweezer and cage, providing further insight into the impact of the structure on the properties of the cage.

Experimental Section

Materials and methods DOSY experiments were conducted on the 600 MHz Bruker Avance III Spectrometer, equipped with a Bruker BBI probe (developing a pulse field gradient of 5 G cm -1 A -1 ).

The diffusion NMR data of the samples (thermostated at 298 K) were acquired using a

UV-Visible spectroscopic methods

UV-Visible spectra were performed via a Biotek UVIKON XL UV/VIS Spectrophotometer, using quartz cuvettes of 0.1, 0.2, 0.5 or 1 cm path length, with absorbance maxima wavelengths given in nm, and corresponding molar extinction coefficients given in L mol -1 cm -1 .

Mass spectrometric methods

Accurate mass were obtained by way of high resolution ESI mass spectrometry using a Bruker MicroTOF(II) focus spectrometer.

Electrochemical Methods

Electrochemical experiments were acquired on an EG&G Princeton Applied Research Potentiostat/Galvanostat (Model 273A). Cyclic Voltammetry experiments were performed using a Pt working electrode (0.071 cm 2 ). The electrode surface was polished routinely with a 0.05 μm alumina-water slurry on a felt surface immediately before use.

The counter electrode was a Pt coil and the reference electrode was a saturated calomel electrode (SCE). Samples were prepared in dichloroethane (Acros organics, +99%), dimethylformamide (Fischer, 99.5%) and benzonitrile (Fluka, > 99%), using 0.1 mol L -1 tetrabutylammonium hexafluorophosphate (TBAPF6, Sigma Aldrich, +99%) as supporting electrolyte.

10-Methyl-9(10H)-acridone (27) 3

To a solution of 9(10H)-acridone (976 mg, 5 mmol) in anhydrous DMF (40 mL) cooled to 0°C, was added 60 wt. % NaH dispersion (500 mg, 12.5 mmol, 2.5 eq.). The solution was stirred for 30 minutes before adding MeI (0.78 mL, 12.5 mmol, 2.5 eq.). The mixture was then heated to 60°C and left to stir overnight, before precipitating from H2O (500 mL), affording 27 as a pale-yellow precipitate (1.03 g, 98%).

9-(4-bromophenyl)-10-methylacridin-10-ium hexafluorophosphate (28•PF6)

To a solution of 1,4-dibromobenzene (1.13 g, 4.78 mmol) in anhydrous THF (40 mL), cooled to -78°C. was added dropwise 2.5 mol L -1 n-BuLi in hexanes (1.91 mL, 4.78 mmol, 1 eq.). The solution was stirred for 30 minutes before addition of 27 (1 g, 4.78 mmol, 1 eq.). The reaction mixture was left to stir overnight at room temperature. 37 wt.% aqueous solution of HCl (15 mL) was added to the resulting solution and left to stir for 30 minutes. The acidified solution was poured slowly into an aqueous solution of KPF6 (6 g, 150 mL). The resulting precipitate was taken up in CH3CN (25 mL) and precipitated from Et2O (500 mL) giving 28•PF6 as a dark yellow solid (1.73 g, 73%). To a solution of 28•PF6 (400 mg, 0.809 mmol) in anhydrous THF (40 mL) cooled to 0°C, was added LiAlH4 (154 mg, 4.06 mmol, 5 eq.). The resulting mixture was stirred overnight at room temperature, before filtering twice on a plug of SiO2 (CH2Cl2). To a solution of the resulting intermediate in anhydrous degassed DMF (10 mL) was added Bis(pinacolato)diboron (207 mg, 0.814 mmol, 1.01 eq.), Pd(dppf)Cl2 (26.7 mg, 0.033 mmol, 4 mol%) and KOAc (230 mg, 0.33 mmol, 0.4 eq.). The mixture was stirred overnight at 80°C, and the solvent evaporated. The crude product was purified via column chromatography (SiO2, CH2Cl2), giving 29 as a white solid (322 mg, 81%.).

5-(9-([1,1'-biphenyl]-4-yl)-10-methylacridin-10-ium))-10,15,20-tris(3,5-di-tertbutylphenyl)porphyrin-Zn(II) hexafluorophosphate (30•PF6)

To a solution of 26-Zn (100 mg, 0.091 mmol) and 29 (40 mg, 0.1 mmol, 1.1 eq.) in degassed anhydrous DMF (10 mL) was added Pd(PPh3)4 (5 mg, 4.6 μmol, 5 mol %) and K3PO4 (58 mg, 0.27 mmol, 3 eq.). The reaction mixture was heated to 80°C and left to stir for 72 hours, before evaporation of the solvent. The crude solid was purified via column chromatography (SiO2, CH2Cl2/petroleum ether, 100:0 to 45:65), to obtain the intermediate as a pink solid. The obtained pink solid was dissolved in CH2Cl2 (15 mL) and DDQ (26 mg, 0.114 mmol, 1.25 eq.) added to the solution. The mixture was left to stir overnight before washing with H2O (3 × 20 mL). The solvent was evaporated to give a solid which was taken up in THF (10 mL) and added dropwise to an aqueous solution of KPF6 (6 g, 150 ml). The crude product was purified via column chromatography (SiO2, CH2Cl2/CH3CN, 94:6, Rf = 0.35) giving 30•PF6 as a deep pink solid (79 mg, 67%). ether/ethyl acetate, 9:1, Rf = 0.62), giving the desired product 31 as colourless crystals (13.6 g, 88%).

9-(4-formylphenyl)-10-methylacridin-10-ium hexafluorophosphate (32•PF6)

To a solution of 31 (1.28 g, 4.50 mmol, 1.2 eq.) in anhydrous THF (50 mL) at -78°C, was added dropwise 2.5 mol L -1 n-BuLi in hexanes (1.50 mL, 3.75 mmol, 1 eq.). After stirring for one hour, 27 (792 mg, 3.75 mmol, 1 eq.) was added. The resulting mixture was stirred for an additional 16 hours at room temperature. 37 wt.% aqueous solution HCl (50 mL) was added dropwise, and the solution left to stir for 30 minutes, after which it was added dropwise to an aqueous solution of KPF6 (6.00 g, 150 mL). The resulting solid was dissolved in CH3CN (20 mL) and precipitated from Et2O (500 mL) to give 32•PF6 as a yellow solid (1.25 g, 78%). 1 mL of the host solution was added to a cuvette (l = 0.5 cm) and small aliquots of the guest solution added to the solution, with UV-Vis spectra recorded after each addition.

The absorption values (at wavelengths 415 -432 nm) for each recorded spectrum were compiled in an excel file, the data corrected for dilution (< 5% dilution of initial concentration at end point of titration)) and the data analysed using the BindFit titration program (http://supramolecular.org). Fitting to a 1:1 binding model was observed to be most accurate, with a value of 3.85 (± 0.15) × 10 3 L mol -1 obtained.

For the UV-Vis titration with DABCO, two solutions were prepared: Host Solution: 33•PF6 (54.1 g, 40 nmol) in CH2Cl2 (20 mL) Guest Solution: DABCO (4.49 mg, 80.0 mol) in CH2Cl2 (10 mL) Small aliquots of the guest solution were added to the host solution (2 mL in a 1 cm quartz cuvette), and UV-Vis spectra recorded after each addition. The absorption values (at wavelengths 425 -435 nm) for each recorded spectrum were compiled in an excel file, corrected for dilution (< 3% dilution of initial concentration at end point of titration) and the data analysed using the BindFit titration program (http://supramolecular.org).

Fitting to a 1:1 binding model was observed to be most accurate, with a value of Ka = 1.06 (± 0.03) × 10 5 L mol -1 obtained.

di(1H-pyrrol-2-yl)methane (34) 5

To a solution of paraformaldehyde (649 mg, 21.6 mmol) in degassed pyrrole (150 mL, 2.16 mol, 100 eq.) was added InCl3•4H2O (635 mg, 2.16 mmol, 0.1 eq.). The resulting mixture was stirred at 55°C for 2.5 hours. The mixture was allowed to cool to room temperature, pulverised NaOH (4.32 g, 0.108 mol, 5 eq.) added and stirred for a further hour. The mixture was filtered through celite and excess pyrrole recovered via rotary evaporation, giving a brown oil which was washed with petroleum ether/EtOAc (8:2, 5 × 50 mL), filtered and the solvent evaporated. The crude product was purified via column chromatography (SiO2, CH2Cl2/petroleum ether/EtOAc 2:7:1, Rf = 0.40) giving 34 as an off-white solid (1.83 g, 58%). To a solution of 32•PF6 (554 mg, 1.25 mmol, 1 eq.) and 34 (183 mg, 1.25 mmol, 1 eq.) in degassed CH2Cl2 (250 mL) was added TFA (60.0 L, 0.75 mmol, 0.6 eq.). The solution was left to stir in the dark for four hours, before neutralising with Et3N (2 mL). Following removal of the solvent, the resultant solid was taken up in CH3CN (100 mL) and DDQ (426 mg, 1.88 mmol, 1.5 eq.) added to the solution. After stirring for one hour, purification was carried out via column chromatography (SiO2, acetone/aq. KPF6 soln., 100:0 to 95:5, Rf = 0.36) giving a purple solid. The solid was re-dissolved in CH3CN (50 mL) and a solution of Zn(OAc)2•2H2O (137 mg, 0.625 mmol, 0.5 eq.) in CH3OH (10 mL) added. The mixture was heated to reflux for one hour, before evaporating the solvent.

The resulting crude solid was triturated with CH3OH (50 mL), and then taken up in CH3CN (50 mL) and precipitated from Et2O (250 mL) to give 35•2PF6 as a dark purple solid (214 mg, 29%.). orange oil which was purified via column chromatography (SiO2, CH2Cl2/acetone, 100:0 to 99:1, Rf = 0.36), giving 36 as a pale-yellow solid (934 mg, 70%).

10-(dec-9-en-1-yl)-9-(4-formylphenyl)acridin-10-ium (37•PF6)

To a solution of 31 (770 mg, 2.7 mmol, 1.2 eq.) in anhydrous THF (30 mL), cooled to -78°C, was added 2.5 mol L -1 n-BuLi in hexanes (0.9 mL, 2.25 mmol, 1 eq.). The solution was stirred for one hour before addition of 36 (750 mg, 2.25 mmol, 1 eq.), and the resulting mixture stirred for an additional 16 hours at room temperature. 37 wt.% aqueous solution of HCl (30 mL) was added and the solution left to stir for 30 minutes, after which it was added dropwise to an aqueous solution of KPF6 (6 g, 150 mL), giving a yellow oil which was isolated via extraction using CH2Cl2 (3 × 100 mL). The organic layer was then washed with H2O (3 × 100 mL). The solvent was evaporated, and the resultant residue taken up in minimal CH3CN (10 mL) and precipitated from Et2O (500 mL) to give 37•PF6 as a yellow solid (0.829 g, 65%). To a solution of 37•PF6 (284 mg, 0.5 mmol), 3,5-di-tert-butylbenzaldehyde (328 mg, 1.5 mmol, 3 eq.) and pyrrole (0.139 mL, 2 mmol, 4 eq.) in degassed CH2Cl2 (120 mL) was added TFA (0.23 mL, 3 mmol, 6 eq.). The solution was stirred in the dark for three hours before neutralising with Et3N (4 mL) and evaporating the solvent. The resultant solid was taken up in CH2Cl2 (100 mL) and DDQ (342 mg, 1.5 mmol, 3 eq.) added, before stirring for a further hour. To the mixture was added acetone (25 mL) and the solution filtered through a plug of SiO2. The solvent was evaporated, and the resultant solid taken up in CH2Cl2 (100mL). Zn(OAc)2•2H2O (110 mg, 0.5 mmol, 1 eq.) in CH3OH (10 mL) was added to the solution, which was then heated to reflux for one hour, The solvent was evaporated, and purification carried out via column chromatography (SiO2, CH2Cl2/acetone, 98:2, Rf = 0.36) followed by crystallisation from acetone/petroleum ether (1:4), giving 38•PF6 as a purple crystalline solid (92 mg, 12%).

UV-Vis titration:

Host Solution: 39•2PF6 (58.5 g, 20 nmol) in CH2Cl2 (20 mL).

Guest Solution: DABCO (8.97 mg, 80.0 mol) in CH2Cl2 (10 mL).

2 mL of the host solution was added to a 1 cm cuvette, and small aliquots of the guest solution added directly to the cuvette, with UV-Vis spectra recorded after each addition.

The absorption values (at wavelengths 420 -435 nm) for each recorded spectrum were compiled in an excel file, corrected for dilution (< 3% dilution of initial concentration at end point of titration) and the data analysed using the BindFit titration program (http://supramolecular.org). Fitting to a 1:2 binding model was observed to be most accurate, with values of K11 = 2.0 (± 0.3) × 10 6 L mol -1 and K12 = 6.0 (± 0.7) × 10 3 L mol -1 obtained.

(Porphyrin-acridinium tweezer)@4,4'-bipyridine complex (biPy@39•2PF6)

To a solution of 39•2PF6 (3.33 mg, 1.14 mol) in CD2Cl2 (0.55 mL) was added a solution of 4,4'-bipyridine (0.178 mg, 1.14 mol) in CD2Cl2 (50 L). The mixture was manually stirred, and formation of the biPy @39•2PF6 complex assessed via 1 H NMR spectroscopy.

UV-Vis titration:

Host Solution: 39•2PF6 (30.9 g, 10.6 nmol) in CH2Cl2(20 mL) Guest Solution: 4,4'-bipyridine (3.1 mg, 19.8 mol) in CH2Cl2 (5 mL) Small aliquots of the guest solution were added to the host solution (0.15 mL in a 0.1 cm cuvette) with the host concentration kept constant, and UV-Vis spectra recorded after each addition. The absorption values (at wavelengths 415-435 nm) for each recorded spectra were compiled in an excel file and the data analysed using the BindFit titration program (http://supramolecular.org). Fitting to a 1:2 binding model was observed to be most accurate, with averaged values of K11 = 1.8 (± 0.1) × 10 5 L mol -1 and K12 = 799 (± 130) L mol -1 obtained.

Porphyrin-acridanol tweezer (40)

To a solution of tweezer 39•2PF6 (22.5 mg, 7.69 mol, 1 eq.) in CH2Cl2 (4 mL), was added an aliquot of 40 wt. % TBAOH in Methanol (12.1 L, 16.9 mol, 2.2 eq.). After 30 minutes stirring in the dark, the solution was washed with H2O (3 × 10 mL) the solvent evaporated and the solid triturated with methanol. The desired product 40 was obtained as a purple solid (18 mg. 88%).

UV-Vis titration:

Host Solution: 40 (30.6 g, 11.5 nmol) in CH2Cl2 (20 mL).

Guest Solution: 4,4'-bipyridine (3.3 mg, 21.1 mol) in CH2Cl2 (5 mL).

Small aliquots of the guest solution were added to the host solution (0.15 mL in a 0.1 cm cuvette) with the host concentration kept constant, and UV-Vis spectra recorded after each addition. The absorption values (at wavelengths 415-435 nm) for each recorded spectrum were compiled in an excel file and the data analysed using the BindFit titration program (http://supramolecular.org). Fitting to a 1:2 binding model was observed to be most accurate, with averaged values of K11 = 1.4 (± 0.3) × 10 5 L mol -1 and K12 = 870 (± 200) L mol -1 obtained.

Determination of binding constants for oxidised species (Ka-Ox)

Given the Nernst equation(s):

1) 𝐸 1 = 𝐸 1 0 + 𝑅𝑇 𝑛𝐹 ln ( [𝑀 0 ] [𝑀 2•+ ] ) 2) 𝐸 2 = 𝐸 2 0 + 𝑅𝑇 𝑛𝐹 ln ( [𝑐 0 ] [𝑐 2•+ ]
)

And defining the binding constant(s) as:

3) 𝐾 𝑎-𝑅𝑒𝑑 = [𝑐 0 ] [𝑀 0 ][𝑏𝑖𝑃𝑦] 4) 𝐾 𝑎-𝑂𝑥 = [𝑐 2•+ ] [𝑀 2•+ ][𝑏𝑖𝑃𝑦]
The following equations can be obtained:

5) a) 𝐸 1 -𝐸 2 = 𝐸 1 0 -𝐸 2 0 + 𝑅𝑇 𝑛𝐹 ln ( [𝑀 0 ][𝑐 2•+ ] [𝑀 2•+ ][𝑐 0 ] ) b) 𝐸 1 -𝐸 2 = 𝐸 1 0 -𝐸 2 0 + 𝑅𝑇 𝑛𝐹 ln ( 𝐾 𝑎-𝑂𝑥 𝐾 𝑎-𝑅𝑒𝑑 )
Assuming that the system is in thermodynamic equilibrium:

𝐸 1 = 𝐸 2
Equation (5b) can be rearranged to give:

𝐾 𝑎-𝑂𝑥 = 𝐾 𝑎-𝑅𝑒𝑑 exp ( 𝑛𝐹 𝑅𝑇 × (𝐸 2 0 -𝐸 1 0 )
For biPy@39•2PF6: Ka-Red = 1.8 ×10 5 L mol (Porphyrin-acridinium cage)@biPy complex hexafluorophosphate (biPy@42•8PF6)

A solution of 4,4'-bipyridine (85.9 g, 0.55 mol) in CH3CN (0.1 mL) was added to 42•8PF6

(2.71 mg, 0.55 mol) and the mixture dried under vacuum. The solid was then dissolved in CD2Cl2/CD3CN (0.55 mL, 9:1 v/v) and manually stirred.

UV-Vis titration:

Host Solution: 42•8PF6 (99.0 g, 20.1 nmol) in CH2Cl2 [0.1% CH3CN] (20 mL).

Guest Solution: biPy (0.624 mg, 4.00 mol) in CH2Cl2 [0.1% CH3CN] (10 mL).

Small aliquots of the guest solution were added to the host solution (2 mL in a 1 cm cuvette), and UV-Vis spectra recorded after each addition. The absorption values (at wavelengths 423 -435 nm) for each recorded spectrum were compiled in an excel file, corrected for dilution (< 3% dilution of initial concentration at end point of titration) and the data analysed using the BindFit titration program (http://supramolecular.org).

Fitting to a 1:1 binding model was observed to be most accurate, with an averaged value of Ka = 4.2 (± 0.7) × 10 6 L mol -1 obtained.

Porphyrin-acridinium cage@biPy complex tetrakis[3,5bis(trifluoromethyl)phenyl]borate (biPy@42•8BArF)

To a solution of cage 42•8BArF (5.87 mg, 0.55 mol) in CD2Cl2 (0.5 mL) was added a solution of 4,4'-bipyridine (85.9 g, 0.55 mol) in CD2Cl2 (50 L), and the resulting solution manually stirred. (Porphyrin acridane cage)@biPy complex (biPy@43)

To a solution of 42•8PF6 (2.71 mg, 0.55 mol) in CD2Cl2/CD3CN 9:1 (0.5 mL) was added biPy (85.9 g, 0.55 mol, 1 eq.). The resultant solution was manually stirred then an aliquot of KOH (0.259 mg, 4.62 mol, 8.4 eq.) in CH3OH (10 L) added, and manually stirred once more. The resulting solution was evaporated and triturated with H2O to remove residual salts, dried under vacuum, then re-dissolved in CD2Cl2 (0.55 mL). For the UV-Vis titration, two solutions were prepared:

Host Solution: 43 (38.2 g, 9.51 nmol) in CH2Cl2 (20 mL).

Guest Solution: biPy (5.94 mg, 38.0 mol) in CH2Cl2 (10 mL).

Small aliquots of the guest solution were added to the host solution (2 mL in a 1 cm cuvette), and UV-Vis spectra recorded after each addition. The absorption values (at wavelength 425 -435 nm) for each recorded spectrum were compiled in an excel file, corrected for dilution (< 3% dilution of initial concentration at end point of titration) and the data analysed using the BindFit titration program (http://supramolecular.org).

Fitting to a 1:1 binding model was observed to be the most accurate, with an averaged value of Ka = 1.0 (± 0.2) × 10 La lumière est un stimulus non-invasif, rapide offrant une haute-sensitivité (Figure 1). 4), 3 du groupe de Weiss ( 5) 4 et du groupe de Lipke ( 6). 5 L'utilisation d'un stimulus chimique dans des systèmes hôte-invité peut prendre deux aspects. Le premier aspect concerne la modification chimique de l'hôte comme dans les travaux du groupe de Shionoya (Figure 3). Ils ont utilisé plusieurs stimuli chimiques différents pour changer la conformation et donc les capacités d'interaction de leur hôte porphyrine 7. 6 11) et (12) du groupe Jang. 10,11 Des exemples d'hôtes synthétiques affichant une translation multidirectionnelle des événements de liaison ont été réalisés par le groupe de Shinkai (13). 12,13 Leur récepteur est composé de complexes de type double-decker de Ce(IV) fonctionnalisé par des unités pyridyles. L'interaction d'un premier ligand dicarboxylate avec deux des unités pyridines rigidifie la structure de la molécule augmentant ainsi l'interaction avec d'autres ligands dicarboxylates. Notre propre groupe de recherche a également décrit une cage covalente à base de porphyrine (15) possédant des triazoles intégrés dans les espaceurs. L'espace de la cavité de ce récepteur s'ouvre après coordination d'ions Ag + jouant le rôle d'effecteur ce qui permet la coordination du ligand pyrazine entre les porphyrines. 14,15 Figure 6. Structures des hôtes allostériques multidirectionnels, les doubles étages de porphyrine de Ce(IV) (13) du groupe 12,13 Shinkai et la cage de porphyrine du groupe Heitz (15). 14,15 Les travaux du groupe de Mirkin ont mis en évidence l'action du récepteur 16 à base de porphyrines macrocycliques dans un contrôle allostérique en catalyse (Figure 7). 16 Les centres métalliques Rh périphériques interagissent avec des ions chlorures ce qui ouvre la cavité du récepteur permettant ainsi la catalyse. De plus, le groupe de Schmittel a exploité à la fois le contrôle allostérique et la capacité de photosensibilisation des unités de porphyrine pour fournir un photocatalyseur allostérique 18. 17 19), 18 du groupe de Yoshizawa ( 20) 20 et de notre groupe de recherche (21). 19 L'utilisation d'unités porphyrines avec des fragments acridinium dans des systèmes hôte-invité a été limitée à l'encapsulation d'acridines protonées (AcrH) dans des récepteurs porphyrines, tels que ceux du groupe de Fukuzumi ( 22) et de Rath & Chaudhary (23) (Figure 9). 21,22 Cependant, les unités de reconnaissance acridinium et Enfin, nous nous sommes tournés vers une troisième voie de synthèse (Figure 13). Elle fait intervenir un acridinium fonctionnalisé par un formyle (32•PF6). Cet intermédiaire de synthèse est stable à l'air. Ce réactif clé est synthétisé via un échange métal-halogène en utilisant des synthons bon marché et disponibles dans le commerce. La réaction du 4-bromobenzaldéhyde en présence de BuLi sur l'acridone 31 permet la formation de l'acridinium 32•PF6. Ce composé peut être ainsi obtenu à l'échelle du gramme avec un rendement de 78%. Les effets de stimuli chimiques ont également été exploités. L'ajout de TBAOH a conduit à la désaromatisation des unités acridiniums formant l'espèce neutre acridanolporphyrine 40 (Figure 21). Ce processus a été suivi par spectroscopies RMN ( 1 H, 13 C), UV/Vis, de fluorescence. La forme de la pince moléculaire permet de complexer la bipy et les dosages suivi par spectroscopie UV/Vis ont montré une constante d'association de 1,4 (± 0,3) × 10 5 M -1 pour la formation du complexe 1:1 biPy@39•2PF6. A partir du complexe biPy@(41•4PF6)2, la synthèse de la cage 42.8PF6 a été réalisée avec un rendement de 49% (Figure 24).

Les caractéristiques de

Figure 4 .

 4 Figure 4. Skeletal diagram of 1. The photo-active unit (azobenzene) is highlighted in orange.[START_REF] Muraoka | Light-Driven Open-Close Motion of Chiral Molecular Scissors[END_REF]

Figure 6 .

 6 Figure 6. A side-on representation of the three enantiomeric pairs of 3, with the variation in the motor positioning for the three general forms (a) out/out, b) out/in and c) in/in) shown

Figure 8 .

 8 Figure 8. Structure of the Weiss group's Pacman tweezer 5 and the change in coordination

Figure 11 .

 11 Figure 11. Illustration of the MWC model of heterotropic allosteric regulation.

Figure 12 . 2 . 1 .

 1221 Figure 12. Illustration of the KNF model of heterotropic allosteric control.

Figure 17 .

 17 Figure 17. Structure of the trisporphyrin 10 and the cage it forms upon coordination of DABCO, allowing encapsulation of a guest.[START_REF] Ballester | DABCO-Induced Self-Assembly of a Trisporphyrin Double-Decker Cage: Thermodynamic Characterization and Guest Recognition[END_REF]

Figure 19 .

 19 Figure19. The allosteric effects displayed by the Jang group's porphyrin macrocycle 12, with the binding constants for binding of the different anions shown before (in black) and after (in blue) complexation of DABCO).[START_REF] Lee | An Indolocarbazole-Bridged Macrocyclic Porphyrin Dimer Having Homotropic Allosterism with Inhibitory Control[END_REF]

Figure 21 .

 21 Figure 21. Illustrative structure of the Shinkai group's molecular spring 14 in the open and closed form.[START_REF] Ikeda | A Preliminary Step toward Molecular Spring Driven by Cooperative Guest Binding[END_REF]

Figure 24 .

 24 Figure 24. Structure of the Álvarez group's free-base (17-2H) and zinc metalated (17-Zn(II))

Figure 25 .

 25 Figure 25. Structure and mechanism of action of the Schmittel group's self-locking allosteric photocatalyst 18.[START_REF] Schmittel | A Reversible Nanoswitch as an ON-OFF Photocatalyst[END_REF]

Figure 27 .

 27 Figure 27. Structure of the cavitand (19a) and tweezer (19b) synthesised by Lehn et al., and the range of binding constants of 19a (in black) and 19b (in blue) using different linkers with different guests.[START_REF] Claude | Binding of Nucleosides, Nucleotides and Anionic Planar Substrates by Bis-Intercaland Receptor Molecules[END_REF]

Figure 29 .

 29 Figure 29. Structure of the bisacridinium macrocycle 21 and the complexes it forms in

Figure 31 .

 31 Figure 31. The Fukuzumi group's porphyrin-acridinium fluorescence sensor 24 before and after addition of KO2. 100

Figure 32 .

 32 Figure 32. 3D illustration of the tweezer and cage receptor, and the allosteric mechanisms envisioned.

  Chapter three details the synthesis of the first receptor: a tweezer, with emphasis on finding efficient means of covalently linking the two faces of the receptors. The results from host-guest properties and effects of different stimuli on the tweezer are thereafter discussed.

Figure 2 .

 2 Figure 2. General synthesis of a porphyrin via the Lindsey methodology condensation ofpyrrole and aldehyde in the presence of acid and oxidant.7,8

Figure 3 .

 3 Figure 3. General synthesis of an N-substituted acridinium via stepwise functionalisation of 1H-acrid-9-one.

Figure 4 .

 4 Figure 4. Synthesis of the Fukuzumi groups' porphyrin-acridinium triad 24 via porphyrin condensation using a 9-(3,5-dimethylbenzaldehyde-4-yl)-10-methylacridinium 25,

Figure 5 .

 5 Figure 5. Retrosynthesis for an AB3 monoacridinium porphyrin conjugate via metal-halogen exchange.

Figure 6 .

 6 Figure 6. The proposed reaction scheme for synthesis of an AB3 mono(N-methyl)acridinium porphyrin conjugate via Br-Li exchange using the bromo-aryl functionalised porphyrin 26-2H (synthesised according to published work) 15 .

Figure 8 .

 8 Figure 8. Synthesis of 30•PF6 via palladium cross coupling of an acridane boronic ester (29) and a bromo aryl porphyrin (26-Zn).

Figure 9 .

 9 Figure 9. a) 1 H NMR (500 MHz, CD2Cl2, 298 K) spectrum and b) 13 C NMR (125 MHz, CD2Cl2, 298 K) spectrum of 30•PF6. Acridinium chemical shifts are given in blue and the porphyrin chemical shifts in purple.

Figure 10 .

 10 Figure 10. UV-Vis (CH2Cl2, l = 0.5 cm, 298 K,) spectrum of 30•PF6 (c = 4.75 M). The values for the peak wavelengths (in bold) and the corresponding extinction coefficients are given.

Figure 11 .

 11 Figure 11. Retrosynthesis of compounds 33•PF6 and 35•2PF6 via porphyrin condensation using a common formyl phenyl acridinium reactant 32•PF6.

Figure 12 .

 12 Figure 12. Synthesis of 32•PF6 from the synthon 4-bromo benzaldehyde and the corresponding 1 H NMR (500 MHz, CD3CN, 298 K) spectrum.

Figure 13 .

 13 Figure 13. Synthesis of the conjugate 33•PF6 from 32•PF6 via Lindsey-type porphyrin condensation.

Figure 14 .

 14 Figure 14. a) Stacked 1 H NMR (500 MHz, CD2Cl2, 298 K) spectra of a) i-30•PF6 and b) ii-33•PF6. b) Stacked 13 C NMR (125 MHz, CD2Cl2, 298 K) spectra of i-30•PF6 and ii-33•PF6. The downfield and upfield shifts are highlighted in blue for the acridinium, in purple for the pyrrolic peaks and in grey for the phenyl protons.

  M] + at m/z = 1204.1680 corresponding to a molecular formula of C82H86N5Zn + )

Figure 15 . 4 . 3 .

 1543 Figure 15. UV-Visible (CH2Cl2, l = 0.5 cm, 298 K) spectrum of 33•PF6 (c = 4.95 M).

Figure 16 .

 16 Figure 16. Synthesis of the A2B2 bisacridinium-porphyrin conjugate 35•2PF6 via porphyrin condensation from the formyl phenyl acridinium 32•PF6 and 2,2'-dipyrromethane 34.

35 •

 35 2PF6 was observed to have much reduced solubility in non-polar solvents compared to and 33•PF6. However, good solubility was seen for more polar solvents, leading to characterisation via NMR and UV-Vis spectroscopy in acetonitrile. In line with the increased symmetry of the molecule (D2h, compared to C2v for 30•PF6 & 33•PF6), only two pyrrolic peaks could be seen in the1 H NMR spectrum (doublets at 9.65 and 9.4 ppm, 3 J = 4.4 Hz), with a peak at 10.49 ppm characteristic of the porphyrin meso-protons (Figure17a). The acridinium peaks in contrast remained unchanged and preserved. The13 C NMR spectrum also supported formation of the bisacridinium conjugate (Figure17b), with a peak at 107.2 ppm, consistent with the unsubstituted meso-carbons.

Figure 17 .

 17 Figure 17. a) 1 H NMR (500 MHz, CD3CN, 298 K) and b) 13 C NMR (125 MHz, CD3CN, 298 K) spectra of 35•2PF6.

Figure 18 .

 18 Figure 18. UV-Vis (CH3CN, l = 0.1 cm, 298 K) spectrum of 35•2PF6 (c = 34.0 M).

  computational (caried out by Dr. Christophe Gourlaouen at the Institut de Chimie de Strasbourg, Université de Strasbourg), photophysical (carried out by Dr. Barbara Ventura and Daniel Sanchez-Resa at ISOF-Bologna) and electrochemical studies were conducted. The synthesis and results of the studies have recently been published.20 5.1. Computational studiesIn order to probe the nature and localization of the frontier orbitals of 35•2PF6, DFT calculations were performed. Via symmetry-less optimization of 35•2PF6, a structure was obtained featuring the porphyrin and acridinium units lying within the same horizontal plane, and the phenyl rings orthogonal to the motifs at a dihedral angle of 88°. Analysis of the structure revealed degeneracy in both the HOMOs and LUMOs (Figure19). The HOMOs were 0 localised on the porphyrin as a near degenerate set of orbitals at energy levels of -5.74 and -5.65 eV.

Figure 19 .

 19 Figure 19. Calculated molecular orbitals diagram for the conjugate 35•2PF6.

Figure 20 .

 20 Figure 20. Theoretical absorption spectrum of 35•2PF6 in CH3CN and the character of the singlet states generating the absorption bands in the absorption spectra of 35•2PF6.

Figure 22 .

 22 Figure 22. Cyclic voltammograms (DMF, WE: Pt, CE: Pt, RE: Hg/Hg2Cl2/KCl sat., 100 mV s -1 ) of a solution of 35•2PF6 (c = 1.00 mM) in the presence of TBAPF6 as supporting electrolyte (c = 0.1 mol L -1 ).

Figure 23 .

 23 Figure 23. Uncorrected emission spectra of the CH3CN solutions of 35•2PF6 (blue) and models 32•PF6 (black) and Zn-bP (red), isoabsorbing at 262 nm (A262 = 0.1), with λexc=262 nm. The blue spectrum has been multiplied by a factor of 100.

Figure 24 .

 24 Figure 24. Energy level diagram and kinetics of the photoinduced processes occurring in the conjugate 35•2PF6 in CH3CN, with "P" denoting the porphyrin unit, and "Ac" denoting the acridinium unit.

Figure 25 .

 25 Figure 25. 1 H NMR (500 MHz, CD3CN, 5.00 mM, 298 K) Spectra stack of a) 35•2PF6 upon addition of b) 0.5 equivalents of DABCO. Upfield shifts are highlighted in purple for the pyrrolic protons and in blue for the acridinium protons.

Figure 26 .

 26 Figure 26. Stacked 1 H NMR (500 MHz, CD3CN, 2.50 mM, 298 K) spectra of a) DABCO@35•2PF6 upon addition of b) one equivalent of pyrene. An NMR spectrum of c) pyrene is included for comparison.

Figure 27 .

 27 Figure 27. 1 H NMR (400 MHz, CD3CN, 5.00 mM, 298 K) Spectra stack of a) 35•2PF6 upon addition of b) one equivalent of pyrene. A 1 H NMR spectrum of c) pyrene is included for comparison.

Figure 1 .

 1 Figure 1. Illustration of the proposed design for the porphyrin-acridinium tweezer.

Figure 3 .

 3 Figure 3. Retrosynthesis of a porphyrin-acridinium tweezer.

Figure 4 .

 4 Figure 4. Synthesis of the formylphenyl N-(decenyl)acridinium 37•PF6 from the Ndecenylacridone 36.

Figure 5 .

 5 Figure 5. 1 H NMR (500 MHz, CD2Cl2, 298 K) spectrum of 37•PF6.

Figure 6 .

 6 Figure 6. Illustrative schematic showing the synthesis of the mono(N-decenyl)acridinium porphyrin conjugate 38•PF6 from 37•PF6.

Figure 7 .

 7 Figure 7. a) 1 H NMR (500 MHz, CD2Cl2, 298 K) spectrum of i-the mono(N-methyl)acridinium porphyrin conjugate 33•PF6 and ii-the mono(N-decenyl)acridinium porphyrin conjugate 38•PF6. b)13 C NMR (125 MHz, CD2Cl2, 298 K) spectrum of the conjugate 38•PF6.

Figure 8 .Figure 9 .

 89 Figure 8. High resolution mass (ESI-TOF) spectrum of 38•PF6, with a zoom-insert of the major mass ion peak 38 + , showing the measured and simulated isotopic pattern.

Figure 10 .

 10 Figure 10. Synthesis of 39•2PF6 from 38•PF6, via olefin metathesis using the Grubbs (I) catalyst.The tweezer 39•2PF6 was characterised via NMR spectroscopy, with disappearance of the three vinylic protons seen in the 1 H NMR spectrum (Figure11a), replaced with a multiplet at 5.5 ppm, in agreement with formation of a symmetrised di-substituted alkene bond via alkene metathesis. A small shoulder peak was also seen at 5.45 ppm, overlapping the NCH2 protons,

Figure 11 .Figure 12 .

 1112 Figure 11. Stacked a) 1 H NMR (500 MHz, CD2Cl2, 298 K) and b) 13 C NMR (125 MHz, CD2Cl2, 298 K) spectra of i-38•PF6 and ii-39•2PF6.

Figure 13 . 4 .(Figure 14 .

 13414 Figure 13. UV-Vis (CH2Cl2, l = 1 cm, 298 K) spectrum of the tweezer 39•2PF6 (c = 1.00 M).

Table 1 .Figure 15 . 1 H

 1151 Figure 15. 1 H DOSY NMR (600 MHz, CD2Cl2, 1.00 mM, 298 K) spectrum of DABCO@39•2PF6 and the energy minimised (Spartan'20) model of the complex, within a superimposed sphere (radius = 1.11 nm).

Addition of up to 4

 4 equivalents of DABCO to a micromolar solution of 39•2PF6 in CH2Cl2, gave rise to a bathochromic shift of the Soret band by 2 nm (from 426 nm to 428 nm), with an isosbestic point at 427 nm. Additionally, a narrowing of the Soret band width was observed, in agreement with formation of the less flexible 1:1 macrocyclic complex DABCO@39•2PF6 from the comparatively more flexible 39•2PF6.Further addition of up to 320 equivalents (Figure16), gave rise to a second process with further bathochromic shifts (and a broadening) of the Soret band, and a second local isosbestic point (at 431 nm). These results indicated binding of a second DABCO ligand at // D = 4.5 × 10 -6 cm 2 s -1 R h = 11.1 Å breaking the macrocyclic receptor to form an acyclic host:(guest)2 species.Fitting to a 1:2 binding model gave averaged binding constants of K11 = 2.0 (±0.3) × 10 6 and K12 = 6.0 (±0.6) × 10 3 M -1 for the 1:1 and 1:2 complexes. The 1:1 value was similar to values found for another reported porphyrin tweezer with a flexible/semi-flexible linker in the same solvent.24

Figure 16 .

 16 Figure 16. UV-Vis (CH2Cl2, l = 1 cm, 298 K) titration of 39•2PF6 (c = 1.00 M) with up to 320 equivalents of DABCO. The non-linear regression fit of the data and the calculated speciation diagram are provided.

  model gave a binding constant of 1.06 (±0.03) × 10 5 M -1 , 20 times smaller than seen for 39•2PF6 (Table2), further supporting a ditopic binding of biPy by 39•2PF6.

Figure 17 .

 17 Figure 17. UV-Vis (CH2Cl2, l = 1 cm, 298 K) titration of 33•PF6 (c = 2.00 M) with up to 50 equivalents of DABCO, and the non-linear regression fit, along with the accompanying calculated speciation diagram.

Figure 18 .

 18 Figure 18. Stacked 1 H NMR (400 MHz, CD2Cl2, 1.00 mM, 298 K) spectra of a) the macrocyclic complex and b) upon addition of 1 eq. of perylene. A 1 H NMR spectrum of c) perylene is provided for comparison.

Figure 19 .

 19 Figure 19. Stacked 1 H NMR (500 MHz, CD2Cl2, 1.00 mM, 298 K) spectra of a) DABCO@39•2PF6 upon addition of b) two equivalents of pyrene. A spectrum of c) pyrene is included for comparison.

Figure 21 .

 21 Figure 21. Stacked 1 H NMR (500 MHz, CD2Cl2, 2.00 mM, 298 K) spectra, showing a) 39•2PF6 before and b) after addition of one equivalent of pyrene. A spectrum of c) pyrene is provided for comparison.

Figure 22 . 4 . 2 .

 2242 Figure 22. Energy-minimised (Spartan'20) structures of the two ditopic ligands biPy and DABCO, with their respective N-N lengths.

Figure 23 .

 23 Figure 23. Stacked 1 H NMR (500 MHz, CD2Cl2, 1.90 mM, 298 K) spectra of a) 39•2PF6, b) biPy@39•2PF6 and c) biPy.

Table 3 .Figure 24 . 1 H

 3241 Figure 24. 1 H DOSY NMR (600 MHz, CD2Cl2, 1.90 mM, 298 K) spectrum and the energyminimised structure of biPy@39•2PF6, within a superimposed sphere (radius = 1.32 nm).

Figure 25 .

 25 Figure 25. UV-Vis (CH2Cl2, l = 0.1 cm, 298 K) titration of 39•2PF6 (c = 5.28 M) with up to 188 equivalents of biPy with the non-linear regression fit and calculated speciation diagram.

Figure 26 .

 26 Figure 26. UV-Vis (CH2Cl2, l = 0.5 cm, 298 K) titration of 33•PF6 (c = 4.95 M) with up to 2000 equivalents of biPy, and the non-linear regression fit with the accompanying calculated speciation diagram.

Figure 27 .

 27 Figure 27. Stacked 1 H NMR (500 MHz, CD2Cl2, 1.90 mM, 298 K) spectra of a) biPy@39•2PF6, b)

Figure 28 .

 28 Figure 28. The obtained curve of the NMR titration and the non-linear regression fit for an instantaneous 1:2 model, with the calculated speciation diagram.

Figure 29 .Figure 30 .

 2930 Figure 29. Stacked a) 1 H NMR (500 MHz, CD2Cl2, 1.00 mM, 298 K) and b)13 C NMR (125 MHz, CD2Cl2, 1.00 mM, 298 K) spectra of i-39•2PF6 and ii-40 formed after addition of TBAOH.

Figure 31 .

 31 Figure 31. Overlayed UV-Vis spectra (CH2Cl2, 0.1 mM, l = 0.1 cm, 298 K) of 39•2PF6 showing the effect of addition of 2.2 equivalents of TBAOH, followed by 2.2 equivalents of TFA on the acridinium's -* band.

Figure 32 .h

 32 Figure 32. Illustrative schematic of the photo-induced electron transfer process that takes place upon excitation of the porphyrin units of 39•2PF6.

Figure 33 .

 33 Figure 33. Overlayed fluorescence spectra (CH2Cl2, 298 K) showing the intensity of fluorescence of 39•2PF6 and 40 (c = 5.00 M) upon excitation of the Zn(II)-porphyrin Q band (ex = 553 nm).

  the porphyrin protons, most significantly for the pyrrolic protons (Hpy = -0.25 ppm). Interestingly, in contrast to the acridinium protons of 39•2PF6, the acridanol peaks were not observed to be upfield shifted, likely due to the loss of planarity and increased flexibility upon dearomatisation.

Figure 34 .

 34 Figure 34. Stacked 1 H NMR (500 MHz, CD2Cl2, 2.03 mM, 298 K) spectra of a) 40 upon addition of b) one equivalent of biPy forming biPy@40. A 1 H NMR spectrum of c) 4,4'-bipyridine is included for comparison.

5 .

 5 Data from the DOSY NMR experiments recorded for 39•2PF6 and biPy@39•2PF6.

Figure 35 .

 35 Figure 35. 1 H DOSY NMR (600 MHz, CD2Cl2, 2.03 mM, 298 K) spectrum of biPy@40 (diffusion coefficient and hydrodynamic radius are displayed), and the energy minimised (Spartan'20) structure of the complex within a sphere of radius = Rh.

1: 1 6 .Figure 36 .

 1636 Figure 36. UV-Vis (CH2Cl2, l = 0.1 cm, 298 K) titration of 40 (c = 5.74 M) with up to 488 equivalents of biPy, with the non-linear regression fit of the obtained curves, and the calculated speciation diagram.

Figure 37 .

 37 Figure 37. Stacked cyclic voltammograms (C2H4Cl2, 1.00 mM, 0.1 M TBAPF6, 100 mV/s, WE: Pt, CE: Pt, Ref: Hg/Hg2Cl2/KCl sat., 298 K) comparing the Eox and Ered of a) 39•2PF6, b) biPy@39•2PF6, c) 40, and d) biPy@40.

Figure 38 .

 38 Figure 38. Square scheme for the oxidation of the porphyrin tweezer, showing the thermodynamic cycle which allows calculation of the binding constant for the oxidised tweezers.

Figure 39 .

 39 Figure 39. Cubic graphical diagram illustrating the eight distinct states which can be accessed from 39•2PF6.

Figure 3 .Figure 4 .

 34 Figure3. a)1 H NMR (500 MHz, 298 K) in i-CD2Cl2 and ii-CD3CN and b)13 C NMR (125 MHz, CD2Cl2, 298 K) spectra of the cage precursor 41•4PF6.

Figure 5 .

 5 Figure 5. XRD crystal structure of the cage precursor 41•4PF6 from two points of view, showing the structure and coplanarity of the active units. For clarity, solvent, counter anions and disorder in the two alkenyl chains has been removed.

Figure 6 .

 6 Figure 6. Stacked 1 H (500 MHz, CD2Cl2, 298 K) spectra showing the cage precursor 41•4PF6 a) before and b) after addition of 0.5 equivalents of biPy.

  Initial trials in the synthesis (conducted at room temperature in CH2Cl2 at sub millimolar concentrations) revealed that although total consumption of 41•4PF6 could be had with one a

Figure 7 .

 7 Figure 7. Stacked 1 H NMR (500 MHz, CD2Cl2, 298 K) spectra of a) 41•4PF6 and b) the cage 42•8PF6. The pyrrolic protons and CH2 protons are highlighted in purple and grey respectively.

Figure 8 .

 8 Figure 8. Overlayed UV-Vis (l = 1 cm, 298 K) spectra of the cage 42•8PF6 (displayed in black) and 41•4PF6 at two times intensity (displayed in red) in a) CH2Cl2 (c = 1.00 M) and in b) CH3CN (c = 1.00 M). The absorbance maxima and corresponding extinction coefficients for 42•8PF6 are given above the associated band.

Figure 9 .Figure 10 . 1 H

 9101 Figure 9. High resolution mass (ESI-TOF) spectrum of 42•8PF6 with zoom-insert of the major mass ion peak 42 7+ /7.

Figure 11 . 1 H

 111 Figure 11. 1 H DOSY NMR (600 MHz, CD2Cl2/CD3CN (9:1), 1.00 mM, 298 K) spectrum of the biPy@42•8PF6 complex, and the energy-minimised (Spartan'20) structure within a sphere of radius = Rh.

D = 2 .Figure 12 .

 212 Figure 12. UV-Vis (CH2Cl2 (0.1% CH3CN), l = 1 cm, 298 K) titration of 42•8PF6 (c = 1.00 M) with up to 10 equivalents of biPy, and the non-linear regression fit of the obtained curve with the speciation diagram.

  -4.6 ppm, significantly upfield shifted from free DABCO, indicating internal ditopic binding of DABCO. Interestingly, only a subtle distinction was seen between the inward-facing and outward-facing meta and ortho protons of the phenyl spacers.

Figure 13 . 1 H

 131 Figure 13. 1 H NMR (500 MHz, CD3CN, 1.00 mM, 298 K) spectrum of DABCO@42•8PF6.

Figure 14 .

 14 Figure 14. a) 2D NOESY NMR (500 MHz, CD3CN, 1.00 mM, 298 K) spectrum of the DABCO@42•8PF6 complex. The distinct correlation between the DABCO and pyrrolic protons is highlighted with dashed lines. b) 1 H DOSY NMR (600 MHz, CD3CN, 1.00 mM, 298 K) spectrum of the DABCO@42•8PF6 complex, and the energy-minimised (Spartan'20) structure within a superimposed sphere with radius = Rh.

Figure 15 .

 15 Figure 15. UV-Vis (CH3CN, l = 1 cm, 298 K) titration of 42•8PF6 (c = 1.00 M) with up to 200 equivalents of DABCO, and the non-linear regression fit of the obtained curve with the accompanying speciation diagram.

Figure 16 .

 16 Figure 16. Stacked 1 H NMR (500 MHz, CD3CN, 0.5 mM, 298 K) spectra of a) the complex DABCO@42•8PF6 and b) DABCO@42•8PF6 plus pyrene (5 equivalents). A spectrum of c) pyrene is provided for comparison.

Figure 18 .

 18 Figure 18. Stacked 1 H NMR (500 MHz, CD2Cl2, 298 K) spetra of a) the cage precursor 41•4BArF and b) the cage 42•8BArF.

Figure 19 . 1 PyFigure 20 .

 19120 Figure 19. 1 H DOSY (600 MHz, CD2Cl2, 1.00 mM, 298 K) NMR spectra, of 42•8BArF and the energy-minimised (Spartan'20) structure of 42 8+ within a superimposed sphere of radius = Rh.

Figure 21 .

 21 Figure 21. Stacked 1 H (500 MHz, CD2Cl2, 1.00 mM, 298 K) NMR spectra of a) 42•8BArF and b)

Figure 22 . 1 Py

 221 Figure22.1 H DOSY (600 MHz, CD2Cl2, 1.00 mM, 298 K) NMR spectrum of the biPy@42•8BArF complex, and the energy-minimised (Spartan'20) structure of biPy@428+ within a superimposed sphere with radius = Rh.

Figure 23 .

 23 Figure 23. UV-Vis (CH2Cl2, l = 1 cm, 298 K) titration of 42•8BArF (c = 0.75 M) with biPy (up to 10 equivalents), and the non-linear regression fit of the obtained titration curve, with the calculated speciation diagram.

Figure 24 .

 24 Figure 24. Stacked 1 H (500 MHz, CD2Cl2, 1.00 mM, 298 K) NMR spectra, showing a) 42•8BArF and b) DABCO@42•8BArF.

Figure 25 .

 25 Figure 25. 2D-NOESY NMR (500 MHz, CD2Cl2, 1.00 mM, 298 K) spectrum for DABCO@42•8BArF.

Figure 26 .

 26 Figure 26. 1 H DOSY (600 MHz, CD2Cl2, 1.00 mM, 298 K) NMR spectrum for DABCO@42•8BArF, and the energy-minimised (Spartan'20) structure of DABCO@42 8+ within a superimposed sphere (of radius = Rh).

Figure 27 .

 27 Figure 27. UV-Vis (CH2Cl2, l = 1 cm, 298 K) titration of 42•8BArF (c = 0.325 M) with up to 5 equivalents of DABCO, and the non-linear regression fit of the titration curve with the accompanying calculated speciation diagram.

  acridinium protons throughout the titration, indicating host-guest exchange between all the 0

Figure 28 .

 28 Figure 28. Stacked 1 H NMR (400 MHz, CD2Cl2, 0.5 mM, 298 K) spectra, showing the changes in the spectra for DABCO@42•8BArF upon addition of up to 250 equivalents of pyrene.

Figure 30 .

 30 Figure 30. Stacked 1 H NMR (500 MHz, CD2Cl2, 298 K) spectra of a) the cage BArF (c = 0.5 mM), b) 42•8BArF + 30 equiv. pyrene. A 1 H NMR spectrum of c) pyrene is also included for comparison.

Figure 31 .

 31 Figure 31. a) 1 H NMR (400 MHz, CD2Cl2, 298 K) and b) 13 C NMR (125 MHz, CD2Cl2, 1.00 mM, 298 K) spectra for the acridane porphyrin cage 43 (after step 1: R = OH, after step 2: R = OMe).

Figure 32 .

 32 Figure 32. Mass spectrum (ESI-TOF) obtained for 43, with zoom insert of the regions m/z = 625 -645 and 750 -770.

1 .

 1 NMR study of the complexation of biPy

Figure 34 .

 34 Figure 34. Stacked 1 H NMR (400 MHz, 298 K) spectra of a) the complex biPy@42•8PF6 (CD2Cl2/CD3CN (9:1), 1.00 mM), b) biPy@43, (CD2Cl2, 1.00 mM) and c) 43. (CD2Cl2, 1.00 mM).

Figure 35 .

 35 Figure 35. UV-Vis (CH2Cl2, l = 1 cm, 298 K) titration of 43 (c = 0.475 M) with up to 100 equivalents of biPy, and the non-linear regression fit of the titration curve with the calculated speciation diagram.

  stimulated echo pulse sequence with bipolar z gradients. The limited Eddy current delay was fixed to 5 ms. For the tweezer receptors, and their respective bipyridine complexes: diffusion time () = 0.0999 s, and gradient pulse duration () = 2.2 ms. For the complex DABCO@39•2PF6:  = 0.1199 s, and  = 1.8 ms. For the cage receptors and their complexes:  = 0.1199 s, and  = 2.2 ms. A recycling delay (≥ 5 seconds) was also employed between scans. H2O and CH3CN were used as reference standards to calibrate the gradient. Sample measurements were recorded in either CD2Cl2 (η = 4.353 × 10 -4 Pa s) or CD3CN (η = 3.57 × 10 -4 Pa s). The spectra were then generated using the Dynamics centre module of the Bruker Topspin software package. The Stokes-Einstein equation was used to calculate the hydrodynamic radius (Rh):

1 H

 1 NMR (300 MHz, CDCl3, 298 K) δ (ppm) = 8.53 (ddd, 3 J = 8. 0 Hz, 4 J = 1.8 Hz, 5 J = 0.5 Hz, 2H, H1/8), 7.73 (ddd, 3 J = 8.7 & 7.0 Hz, 4 J = 1.8 Hz, 2H, H3/6), 7.54 (d, 3 J = 8.7 Hz, 2H, H4/5), 7.30 (ddd, 3 J = 8.0 & 7.0 Hz, 4 J = 1.0 Hz, 2H, H2/7), 3.91 (s, 3H, NCH3).

1 H

 1 NMR (500 MHz, CD3CN, 298 K) δ (ppm) = 8.61 (dt, 3 J = 9.3 Hz, 4,5 J = 0.8 Hz, 2H, H4/5), 8.39 (ddd, 3 J = 9.3 & 6.7 Hz, 4 J = 1.6 Hz, 2H, H3/6), 8.03 (ddd, 3 J = 8.8 Hz, 4 J = 1.6 Hz, 5 J = 0.6 Hz, 2H, H1/8), 7.93 (d, 3 J = 8.6 Hz, 2H, Haa'), 7.87 (ddd, 3 J = 8.8 & 6.7 Hz, 4 J = 0.9 Hz, 2H, H2/7) 7.45 (d, 3 J = 8.6 Hz, 2H, Hbb'), 4.84 (s, 3H, NCH3).

13 C{ 1

 1 H} NMR (125 MHz, CD3CN, 298 K) δ (ppm) = 160.9 (C9), 142.2 (CC4/5), 139.4 (C3/6), 132.9 (CCaa'), 132.6 (Cbb'), 132.4 (C1/8), 130.6 (Caa'), 128.5 (C2/7), 126.6 (CC1/8), 124.8 (CBr), 119.1 (C4/5), 39.4 (NCH3). HRMS (ESI-TOF): m/z cald. for C20H15 79 BrN + 348.0382, found 348.0392 ([M-PF6] + , 100%). 10-methyl-9-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-9,10dihydroacridine (29)

1 H

 1 NMR (300 MHz, CDCl3, 298 K) δ (ppm) = 7.72 -7.62 (m, 2H, Haa'), 7.22 (ddd, 3 J = 8.5 & 7.2 Hz, 4 J = 1.6 Hz, 2H, H3/6), 7.16 -7.11 (m, 4H, Hbb' & 1/8), 6.93 -6.87 (m, 4H, H4/5 & 2/7), 5.19 (s, 1H, H9), 3.40 (s, 3H, NCH3), 1.29 (s, 12H, C(CH3)2).

1 H

 1 NMR (500 MHz, CD2Cl2, 298 K) δ (ppm) = 9.08 (d, 3 J = 4.6 Hz, 2H, Hpy1), 9.06 (d, 3 J = 4.6 Hz, 2H, Hpy2), 9.02 (s, 4H, Hpy3-4), 8.59 (d, 3 J = 9.2 Hz, 2H, H4/5), 8.48 -8.42 (m, 4H, H3/6 & o1), 8.32 (d, 3 J = 8.2 Hz, 2H, Hbb'), 8.31 (dd, 3 J = 8.6 Hz, 4 J = 1.2 Hz, 3H, H1/8), 8.20 (d, 3 J = 8.1 Hz, 2H, Hm1), 8.13 (d, 4 J = 1.8 Hz, 4H, Ho2), 8.11 (d, 4 J = 1.8 Hz, 2H, Ho3), 7.95 (ddd, 3 J = 8.6 & 6.6 Hz, 4 J = 0.6 Hz, 2H, H2/7), 7.85 -7.84 (m, 3H, Hp2&3), 7.74 (d, 3 J = 8.2 Hz, 2H, Haa'), 4.95 (s, 3H, NCH3), 1.55 (s, 36H, tBu), 1.54 (s, 18H, tBu).

1 H

 1 NMR (500 MHz, CDCl3, 298 K) δ (ppm) = 7.49 (d, 3 J = 8.5 Hz, 2H, Haa'), 7.36 (d, 3 J = 8.5 Hz, 2H, Hbb'), 5.93 (s, 1H, O2CH), 1.31 (s, 6H, CH3), 1.24 (s, 6H, CH3).

13 C{ 1

 1 H} NMR (125 MHz, CDCl3, 298 K) δ (ppm) = 139.1 (CCbb'), 131.5 (Caa'), 128.1 (Cbb'), 122.7 (CCaa'), 99.3 (O2CH), 83.0 ((CH3)2C), 24.4 (CH3), 22.3 (CH3).

1 H

 1 NMR (500 MHz, CD3CN, 298 K) δ (ppm) = 10.25 (s, 1H, CHO), 8.63 (d, 3 J = 9.3 Hz, 2H, H4/5), 8.40 (ddd, 3 J = 9.3 & 6.7 Hz, 4 J = 1.5 Hz, 2H, H3/6), 8.28 -8.22 (m, 2H, Hbb'), 7.97 (dd, 3 J = 8.7 Hz, 4 J = 1.5 Hz, 2H, H1/8), 7.86 (ddd, 3 J = 8.7 & 6.7 Hz, 4 J = 1.0 Hz, 2H, H2/7), 7.76 -7.70 (m, 2H, Haa'), 4.86 (s, 3H, NCH3).

1 H

 1 NMR (300 MHz, CDCl3, 298 K) δ (ppm) = 7.89 (br.s, 2H, NH), 6.71-6.63 (m, Hpy1), 6.15 (dd, 3 J = 5.8 Hz, 4 J = 2.7 Hz, 2H, Hpy3), 6.09 -5.99 (m, Hpy2), 3.99 (s, 2H, CH2). 5,15-bis(10-methyl-9-phenylacridin-10-ium)porphyrin-Zn(II) hexafluorophosphate (35•2PF6)

1 H

 1 NMR (500 MHz, CDCl3, 298 K) δ (ppm) = 8.60 (dd, 3 J = 8.0 Hz, 4 J = 1.8 Hz, 2H, H1/8), 7.74 (ddd, 3 J = 8.7 & 7.0 Hz, 4 J = 1.8 Hz, 2H, H3/6), 7.51 (d, 3 J = 8.7 Hz, 2H, H4/5), 7.30 (ddd, 3 J = 8.0 & 7.0 Hz, 4 J = 0.9 Hz, 2H, H2/7), 5.82 (ddt, 3 J = 17.0, 10.2 & 6.7 Hz, 1H, HC=), 5.01 (dq, 3 J = 17.0, 2,4 J = 2.2 Hz, 1H, =CHHtrans), 4.95 (ddt, 3 J = 10.2 Hz, 2 J = 2.2 Hz, 4 J = 1.3 Hz, 1H, =CHcisH), 4.38 -4.31 (m, 2H, NCH2), 2.06 (q, 3 J = 6.7 Hz, 2H, g-CH2), 2.00 -1.90 (m, 2H, a-CH2), 1.58 -1.52 (m, 2H, b-CH2), 1.50 -1.42 (m, 2H, c-CH2), 1.41 -1.30 (m, 4H, (df)-CH2).

13 C{ 1 4 (

 14 H} NMR (125 MHz, CDCl3, 298 K) δ (ppm) = 178.2 (CO), 141.9 (CC4/5), 139.2 (=CH), 134.0 (C3/6), 128.2 (C1/8), 122.6 (CC1/8), 121.4 (C2/7), 114.7 (C4/5), 114.4 (H2C=), 46.NCH2), 33.9 (g-CH2), 29.6 (c-CH2), 29.5 (d/e/f-CH2), 29.2 (d/e/f-CH2), 29.0 (d/e/f-CH2), 27.3 (a-CH2), 27.1 (b-CH2).

1 H

 1 NMR (500 MHz, CD2Cl2, 298 K) δ (ppm) = 10.25 (s, 1H, CHO), 8.48 (d, 3 J = 9.3 Hz, 2H, H4/5), 8.43 (ddd, 3 J = 9.3 & 6.6 Hz, 4 J = 1.5 Hz, 2H, H3/6), 8.24 (d, 3 J = 8.2 Hz, 2H, Hbb'), 7.98 (dd, 3 J = 8.8 Hz, 4 J = 1.5 Hz, 2H, H1/8), 7.87 (ddd, 3 J = 8.8 & 6.6 Hz, 4 J = 1.1 Hz, 2H, H2/7), 7.70 (d, 3 J = 8.2 Hz, 2H, Haa'), 5.84 (ddt, 3 J = 17.0, 10.2 & 6.7 Hz, 1H, HC=), 5.38 -5.31 (m, 2H, NCH2), 5.01 (dq, 3 J = 17.0 Hz, 2,4 J = 1.7 Hz, 1H, =CHHtrans), 4.94 (ddt, 3 J = 10.2 Hz, 2 J = 2.4 Hz, 4 J = 1.2 Hz, 1H, =CHcisH), 2.33 -2.22 (m, 2H, a-CH2), 2.14 -2.03 (m, 2H, g-CH2), 1.78 (p, 3 J = 7.6 Hz, 2H, b-CH2), 1.57 -1.49 (m, 2H, c-CH2), 1.46 -1.37 (m, 6H, (d -f)-CH2).

13 C{ 1

 1 H} NMR (125 MHz, CD2Cl2, 298 K) δ (ppm) = 191.7 (CHO), 160.7 (C9), 141.0 (CC4/5), 140.0 (C3/6), 139.6 (CCaa'), 138.9 (=CH), 138.1 (CCHO), 131.0 (Cbb'), 130.8 (C1/8), 130.4 (Caa'), 128.7 (C2/7), 126.4 (CC1/8), 118.2 (C4/5), 114.4 (H2C=), 52.0 (NCH2), 34.1 (g-CH2), 29.7 (c-CH2), 29.6 (d/e/f-CH2), 29.4 (d/e/f-CH2), 29.3 (d/e/f-CH2), 29.2 (a-CH2), 27.3 (b-CH2).

19 F{ 1

 1 H} NMR (282 MHz, CD2Cl2, 298 K) δ (ppm) = -73.58 (d, 1 JP-F = 711 Hz).

31 P{ 1

 1 H} NMR (121 MHz, CD2Cl2, 298 K) δ (ppm) = -144.78 (hept, 1 JP-F = 711 Hz).HRMS (ESI-TOF):m/z cald. for C30H32NO + 422.2499, found 422.2478 ([M-PF6] + , 100%).5-((10-dec-9-en-1-yl)-9-phenylacridin-10-ium)-10,15,20-tris(3,5-di-tertbutylphenyl)porphyrin-Zn(II) hexafluorophosphate (38•PF6)

1 H

 1 NMR (500 MHz, CD2Cl2, 298 K) δ (ppm) = 9.15 (d, 3 J = 4.7 Hz, 2H, Hpy1), 9.13 (d, 3 J = 4.7 Hz, 2H, Hpy2), 9.05 (d, 3 J = 4.6 Hz, 2H, Hpy3/4), 9.03 (d, 3 J = 4.6 Hz, 2H, Hpy3/4), 8.64 (d, 3 J = 8.1 Hz, 2H, Ho1), 8.61 (dd, 3 J = 8.5 Hz, 4 J = 1.4 Hz, 2H, H1/8), 8.57 (d, 3 J = 9.1 Hz, 2H, H4/5), 8.54 (ddd, 3 J = 9.1 & 6.2 Hz, 4 J = 1.4 Hz, 2H, H3/6), 8.14 (d, 4 J = 1.8 Hz, 4H, Ho2), 8.11 (d, 4 J = 1.8 Hz, 2H, Ho3), 8.10 (ddd, 3 J = 8.5 & 6.2 Hz, 4 J = 0.9 Hz, 2H, H2/7), 7.93 (d, 3 J = 8.1 Hz, 2H, Hm1), 7.87 (t, 4 J = 1.9 Hz, 2H, Hp2), 7.86 (t, 4 J = 1.9 Hz, 1H, Hp3), 5.87 (ddt, 3 J = 17.0, 10.2 & 6.6 Hz, 1H, HC=), 5.45 -5.38 (m, 2H, NCH2), 5.03 (dq, 3 J = 17.0 Hz, 2,4 J = 1.7 Hz,Porphyrin-acridinium tweezer (39•2PF6)To a solution of 38•PF6 (60 mg, 40.6 mol) in anhydrous degassed CH2Cl2 (10 mL), was added Grubbs (I) Catalyst (3.72 mg, 4.52 mol, 10 mol%). The resultant solution was stirred in the dark for 16 hrs, before washing with brine (1 × 10 mL), and H2O (3 × 10 mL). Following removal of the solvent, the resultant solid was purified via column chromatography (SiO2, CH2Cl2/CH3CN, 99:1 to 97:3, Rf = 0.26), to give 39•2PF6 as a purple crystalline solid (45.8 mg, 77%).

1 H

 1 NMR (500 MHz, CD2Cl2, 298 K) δ (ppm) = 9.16 (d, 3 J = 4.6 Hz, 4H, Hpy1), 9.12 (d, 3 J = 4.6 Hz, 4H, Hpy2), 9.03 (s, 8H, Hpy3-4), 8.66 (d, 3 J = 8.0 Hz, 4H, Ho1), 8.61 -8.57 (m, 12H, H1/8, 4/5 & o1), 8.54 (ddd, 3 J = 9.2 & 6.4 Hz, 4 J = 1.5 Hz, 4H, H3/6), 8.13 (d, 4 J = 1.8 Hz, 8H, Ho2), 8.12 -8.06 (m, 8H, H2/7 & o3), 7.92 (d, 3 J = 8.0 Hz, 4H, Hm1), 7.87 (t, 4 J = 1.9 Hz, 4H, Hp2), 7.86 (d, 4 J = 1.8 Hz, 1H, Hp3), 5.53 -5.47 (m, 2H, =CH), 5.46 -5.39 (m, 4H, NCH2), 2.44 -2.31 (m, 4H, a-CH2), 2.11 -2.05 (m, 4H, g-CH2), 1.86 (p, 3 J = 8.2 Hz, 4H, b-CH2), 1.62 (p, 3 J = 7.0 Hz, 4H, c-CH2), 1.56-1.54 (m, 108H, tBu), 1.48 -1.41 (m, 12H, (d-f)-CH2 ).

13 C{ 1 8 ( 4 (

 184 H} NMR (125 MHz, CD2Cl2, 298 K) δ (ppm) = 162.7 (C9), 151.0 (CCpy), 150.9 (CCpy), 150.8 (CCpy), 149.9 (CCpy), 149.2 (CCp2-3), 146.1 (CCo1), 142.03 (CCo2-3), 141.2 (CC4/5), 140.0 (C3/6), 135.1 (Co1), 133.0 (Cpy), 132.8 (Cpy), 132.7 (Cpy), 132.3 (Cpy), 131.6 (C1/8), 130.HC=), 130.3 (Co2), 130.2 (Co3), 130.0 (CCm1), 128.8 (C2/7), 128.7 (Cm1),126.9 (CC1/8), 123.Cmeso), 123.1 (Cmeso), 121.5 (Cp2-3), 118.9 (Cmeso) 118.2 (C4/5), 51.7 (NCH2), 35.33 (C(CH3)3), 35.31 (C(CH3)3), 32.9 (g-CH2), 31.8 (CH3), 30.0 (c-CH2), 29.8 (d/e/f-CH2), 29.7 (d/e/f-CH2), 29.3 (a-CH2), 27.2 (b-CH2).

13 C{ 1 9 (

 19 H} NMR (125 MHz, CD2Cl2, 298 K) δ (ppm) = 150.5 (CCpy), 150.3 (CCpy), 150.2 (CCpy), 149.3 (CCpy), 148.9 (CCp2-3), 145.9 (CCo1), 142.3 (CC4/5), 142.11 (CCo2-3), 142.05 (CCo2-3), 141.1 (C3/6), 133.8 (Cbb'), 132.3 (Cpy), 132.24 (Cpy), 132.16 (Cpy), 131.5 (C1/8), 131.0 (CCm1), 130.8 (C=C), 130.5 (Co2-3), 128.1 (C2/7), 128.0 (Cm1), 127.2 (CC1/8), 122.1 (Cmeso),121.2 (Cp2), 121.2 (Cp3), 120.8 (Cmeso), 117.8 (C4/5), 51.4 (NCH2), 34.8 (C(CH3)3), 32.6 (g-CH2), 31.CH3), 29.9 (c-CH2), 29.6 (d/e/f-CH2), 29.3 (d/e/f-CH2), 29.2 (d/e/f-CH2), 28.8 (a-CH2), 27.5 (b-CH2).

19 F{ 1

 1 H} NMR (470 MHz, CD2Cl2, 298 K) δ (ppm) = -73.88 (d, 1 JP-F = 711.7 Hz). 31 P{ 1 H} NMR (202 MHz, CD2Cl2, 298 K) δ (ppm) = -144.92 (hept, 1 JP-F = 711.6 Hz).

1 H

 1 NMR (500 MHz, CD2Cl2, 298 K) δ (ppm) = 8.90 (d, 3 J = 4.5 Hz, 4H, Hpy1), 8.87 (d, 3 J = 4.5 Hz, 4H, Hpy2), 8.83 -8.78 (m, 8H, Hpy3-4), 8.48 -8.41 (m, 12H H1/8, 4/5 & 3/6), 8.39 (s, 4H, Ho1), 8.00 -7.93 (m, 4H, H2/7), 7.92 (d, 4 J = 1.9 Hz, 12H, Ho2-3), 7.78 -7.74 (m,10H, Hp2-3 & m1), 5.51 -5.43 (m, 2H, =CH), 5.32 -5.26 (m, 4H, NCH2), 4.94 (d, 3 J = 6.3 Hz, 4H, Hbipy-), 2.35 -2.30 (m, 8H, Hbipy- & a-CH2), 2.09 -2.05 (m, 4H, g-CH2), 1.87 -1.77 (m, 4H, b-CH2), 1.66 -1.58 (m, 4H, c-CH2), 1.49 -1.42 (m, 120H, tBu & (d-f)-CH2).

13 C{ 1 2 (

 12 H} NMR (125 MHz, CD2Cl2, 298 K) δ (ppm) = 150.7 (CCpy), 150.5 (CCpy), 150.4(CCpy), 149.5 (CCpy), 148.8 (CCp2-3), 146.3 (CCo1), 143.7 (Cbipy-), 142.4 (CCo2-3), 141.1 (CC4/5), 139.7 (C3/6), 132.5 (Cpy), 132.4 (Cpy), 132.3 (Cpy), 131.6 (C1/8), 131.2 (CCm1), 130.7 (C=C), 130.1 (Co2-3), 129.9 (C2/7), 128.4 (Cm1), 126.9 (CC1/8), 122.5 (Cmeso), 121.1 (Cp2-3), 120.Cbipy-), 118.3 (Cmeso), 117.9 (C4/5), 51.7 (NCH2), 35.2 (C(CH3)3), 32.9 (g-CH2), 31.8 (CH3), 30.1 (c-CH2), 29.7 (d/e/f-CH2), 29.6 (d/e/f-CH2), 29.4 (d/e/f-CH2), 29.0 (a-CH2), 27.5 (b-CH2).

1 H

 1 NMR (500 MHz, CD2Cl2, 298 K) δ (ppm) = 8.95 -8.89 (m, 8H, Hpy3-4), 8.89 (d, 3 J = 4.7 Hz, 4H, Hpy1/2), 8.85 (d, 3 J = 4.7 Hz, 4H, Hpy1/2), 8.10 -8.05 (m, 16H, Ho1-3), 7.82 (s, 6H, Hp2-(Porphyrin-acridanol tweezer)@4,4-bipyridine complex (biPy@40) To a solution of 40 (3.24 mg, 1.22 mol) in CD2Cl2 (0.55 mL) was added a solution of 4,4'bipyridine (0.19 mg, 1.22 mol) in CD2Cl2 (50 L). The mixture was manually stirred, and formation of the biPy@40 complex assessed via 1 H NMR spectroscopy.

1 H

 1 NMR (500 MHz, CD2Cl2, 298 K) δ (ppm) = 8.76 (s, 8H, Hpy3-4), 8.73 (d, 3 J = 4.5 Hz, 4H, Hpy1/2), 8.72 (d, 3 J = 4.5 Hz, 4H, Hpy1/2), 7.94 -7.86 (m, 16H, Ho1-3), 7.73 (s, 6H, Hp2-3), 7.64 -7.53 (m, 8H, Hm1 & 1/8), 7.38 (t, 3 J = 7.8 Hz, 4H, H3/6), 7.17 (d, 3 J = 8.3 Hz, 4H, H4/5), 7.03 (t, 3 J = 7.3 Hz, 4H, H2/7), 5.43 -5.38 (m, 2H, HC=), 4.86 (d, 3 J = 6.0 Hz, 4H, Hbipy-), 4.10 -4.02 (m, 4H, NCH2), 2.34 (s, 4H, Hbipy-), 2.10 -1.92 (m, 8H, (a&g)-CH2), 1.50 (m, 8H, (b&c)-CH2), 1.43 (s, 108H, CH3), 1.41 -1.35 (m, 12H, (d-f)-CH2).

13 C{ 1 8 ( 4 (

 184 H} NMR (125 MHz CD2Cl2, 298 K) δ (ppm) = 150.3 (CCPy), 150.1 (CCPy), 148.7 (CCp2-3), 144.0 (CCo1), 143.8(Cbipy-), 142.5(CCo2-3), 140.6(CC4/5), 134.3(Co1), 132.0 (CPy), 131.CPy), 130.8(C=C), 130.6 (C1/8), 130.1 (Co2-3), 129.9 (CCm1), 129.0 (C3/6), 124.3 (CC1/8 & Cm), 122.1 (Cmeso), 120.9 (Cp2-3), 120.5 (C2/7), 120.1 (CbiPy-), 112.7 (C4/5), 78.8 (COH), 46.NCH2), 35.2 (C(CH3)3), 32.8 (g-CH2), 31.8 (CH2), 31.7 (CH3), 29.8 (c/d/e/f-CH2), 29.7 (c/d/e/f-CH2), 29.6 (c/d/e/f-CH2), 29.0 (c/d/e/f-CH2), 27.1 (a-CH2), 26.4 (b-CH2).

3 Hz, 4 J

 34 -1 and E1/2 = -57 mVFor biPy@40: Ka-Red = 1.4 ×10 5 L mol -1 and E1/2 = -19 mV n = 2; F = 96485 C mol -1 ; R = 8.3144621 J mol -1 K -1 ; T = 293 K Tetrakis(10-decenyl-9-phenylacridin-10-ium)porphyrin-Zn(II) hexafluorophosphate(41•4PF6)To a solution of 37•PF6 (454 mg, 0.8 mmol) and pyrrole (55.5 L, 0.8 mmol, 1 eq.) in degassed CH2Cl2 (50 mL) was added TFA (95.7 L, 1.25 mmol, 1.2 eq.). The mixture was stirred in the dark for four hours before addition of DDQ (136 mg, 0.6 mmol, 0.75 eq.), then left to stir for an additional hour. The solution was then neutralised with Et3N (1 mL), and the resultant mixture filtered through a short plug of SiO2 (CH2Cl2/CH3OH, 95:5). After removal of the solvent, purification was carried out via column chromatography (SiO2, CH2Cl2/CH3OH, 96:4, Rf = 0.39), followed by recrystallisation from CH3CN/CHCl3 (1:10 v/v) giving a purple precipitate. The precipitate was isolated then dissolved in CH2Cl2 (50 mL), and a solution of Zn(OAc)2•2H2O (17.6 mg, 0.08 mmol, 0.1 eq.) in CH3OH (5 mL) added. The resultant mixture was heated to reflux for one hour, then extracted with H2O (3×50 mL). The retained organic layer was evaporated and the resultant solid triturated with CHCl3, then further purified via column chromatography (SiO2, CH2Cl2/0.02 M methanolic KPF6 soln./CH3CN 80:5:15, Rf = 0.81). The relevant fractions were combined and extracted with H2O (3 × 100 mL), retaining the organic fraction and evaporating the solvent to give 41•4PF6 as a purple solid (171 mg, 34%).Tetrakis(10-decenyl-9-phenylacridin-10-ium)porphyrin-Zn(II) tetrakis[3,5bis(trifluoromethyl)phenyl]borate (41•4BArF)To a solution 41•4PF6 (40.0 mg, 15.8 mol) of in CH2Cl2 was added NaBArF (56.0 mg, 63.3 mol, 4 eq.), and the mixture left to stir overnight. The resultant solution was washed with H2O (3 × 100 mL), with the organic fraction retained and dried, giving the product as a purple solid (85.3 mg, quant.) 1 H NMR (500 MHz, CD2Cl2, 298 K) δ (ppm) = 9.35 (s, 8H, HPy), 8.70 (d, 3 J = 7.6 Hz, 8H, Ho), 8.61 (dd, 3 J = 8.7, 4 J = 1.5 Hz, 8H, H1/8), 8.49 (d, 3 J = 9.2 Hz, 8H, H4/5), 8.43 (ddd, 3 J = 9.2 & 6.4 Hz, 4 J = 1.5 Hz, 8H, H3/6), 8.01 -7.88 (m, 16H, H2/7 & m), 7.69 -7.65 (m, 32H, HBArF-o), 7.48 (s, 16H, HBArF-p), 5.87 (ddt, 3 J = 16.9, 10.2 & 6.8 Hz, 4H, HC=), 5.40 -5.34 (m, 8H, NCH2), 5.04 (dq, 3 J = 17.1 Hz, 2,4 J = 1.7 Hz, 4H, =CHHtrans), 4.96 (ddt, 3 J = 10.1 Hz, 2 J = 2.= 1.2 Hz, 4H, =CHcisH), 2.37 (p, 3 J = 8.3 Hz, 8H, a-CH2), 2.11 (q, 3 J = 6.8 Hz, 8H, g-CH2), 1.85 (p, 3 J = 7.7 Hz, 8H, b-CH2), 1.61 (p, 3 J = 7.0 Hz, 8H, c-CH2), 1.51 -1.38 (m, 24H, (d-f)-CH2).13 C{ 1 H} NMR (125 MHz, CD2Cl2, 298 K) δ (ppm) = 163.0 (C9), 162.1 (q, 1 Jc-B = 49.9 Hz, CBBArF), 150.8 (CCpy), 145.9 (CCo), 141.1 (CC4/5), 140.2 (C3/6), 139.5 (HC=), 135.4 (Co), 135.

31 P{ 1

 1 H} NMR (121 MHz, CD3CN, 298 K) δ (ppm) = -144.69 (hept,1 JP-F = 707.3 Hz).For the UV-Vis titration two solutions were prepared: Host Solution: 42•8PF6 (99.0 g, 20.1 nmol) in CH3CN (20 mL) Guest Solution: DABCO (0.113 mg, 1.00 mol) in CH3CN (5 mL) Small aliquots of the guest solution were added to the host solution, and UV-Vis spectra recorded after each addition. The absorption values (at wavelengths 420 -440 nm) for each recorded spectrum were compiled in an excel file, corrected for dilution and the data analysed using the BindFit titration program (http://supramolecular.org). Fitting to a 1:1 binding model was observed to be most accurate, with an averaged value of Ka = 4.5 (± 0.2) × 10 5 L mol -1 obtained.

1 H

 1 NMR (500 MHz, CD2Cl2/CD3CN (9:1), 298 K) δ (ppm) = 9.10 (s, 16H, Hpy), 8.62 -8.54 (m, 8H, Ho-out), 8.49 -8.39 (m, 48H, H1/8, 3/6 & 4/5), 8.34 -8.25 (m, 8H, Ho-in), 7.98 (dd, 3 J = 8.5 & 5.7 Hz, 16H, H2/7), 7.89 -7.81 (m, 8H, Hm-out), 7.78 -7.68 (m, 8H, Hm-in), 5.48 -5.41

13 C{ 1

 1 H} NMR (125 MHz, CD2Cl2, 298 K) δ (ppm) = 163.0 (C9), 162.1 (q, 1 JC-B = 49.9 Hz, CB-BArF),150.4 (CCPy), 143.7 (Cbipy-), 140.9 (CC4/5), 140.0 (C3/6), 135.4 (Co-out), 135.3 (Co-in), 135.0 (CBArF-o), 132.2 (Cpy), 132.0 (CCm), 131.5 (C1/8), 130.6 (C=C), 129.1 (q, 2 JC-F = 31.7 Hz, CBArF-m), 128.4 (Cm-in&out), 128.2 (C2/7), 126.7 (CC1/8), 124.8 (q, 1 JC-F = 272.2 Hz, CF3-BArF),UV-Vis (CH2Cl2, 298 K) max (nm) = 294 ( Lmol -1 cm -1 180 000), 427 (804 000), 557(38 900), 600 (18 500).MS (ESI-TOF):m/z cald. for C264H249N16Zn2 6+ 628.48, found 628.47 ([M • -8OMe+H] 6+ , 100%).

1 H 26 - 7 .

 1267 NMR (500 MHz, CD2Cl2, 298 K) δ (ppm) = 8.63 (s, 16H, Hpy), 8.11 -7.93 (m, 8H, Ho-out), 7.70 -7.59 (m, 8H, Ho-in), 7.50 (d, 3 J = 7.8 Hz, 16H, H1/8), 7.43 -7.31 (m, 16H, H3/6), 7.10 (m, 24H, H4/5& m-out), 7.09 -6.88 (m, 24H, H2/7 & m-in), 5.49 -5.38 (m, 8H, HC=), 4.16 -3.92 (m, 16H, NCH2), 3.00 (s, 24H, OMe), 2.16 -1.82 (m, 52H,HbiPy- & (a, b & g)-CH2), 1.61 -1.47 (m, 64H, (c-f)-CH2).

  la lumière ont été utilisées par le groupe d'Aida pour contrôler le mouvement d'une pince moléculaire (2) incorporant deux unités porphyriniques reliées par un espaceur azobenzène. 1 Dans cet exemple, un ligand ditopique joue le rôle d'invité. Le changement de conformation de l'hôte porphyrinique induit un changement des propriétés chiroptiques de l'invité. Un second exemple reporté par le groupe de Nolte a démontré la possibilité de photo-contrôler l'association entre un invité viologène et un hôte porphyrinique comportant des rotors de type Feringa (3).2

Figure 1 .

 1 Figure 1. Structures des deux hôtes photosensibles : du groupe d'Aida (2) 1 et du groupe de Nolte (3).2

Figure 2 .

 2 Figure 2. Structures des hôtes rédox commutables avec leurs invités respectifs : du groupe de Bucher (4),3 du groupe de Weiss (5)4 et du groupe de Lipke (6).5

  d'interagir avec un large éventail d'invités. En raison de leur robustesse, les porphyrines ont été bien utilisées en association à différents motifs de reconnaissance orthogonaux.Ces systèmes ont été exploités pour créer des effets allostériques de grande amplitude (Figure4). Par exemple, une forte augmentation de l'affinité d'un hôte porphyrine 10 pour un invité tritopique a été observée par Shinkai et son groupe. Lors de l'interaction d'ions Na + avec les calixarènes du récepteur 9, l'association avec le ligand tritopique a été augmentée de trois ordres de grandeur.8 De manière analogue, la cage autoassemblée 10 du groupe Ballester 9 n'est capable de se former et d'encapsuler un invité polyaromatique qu'après coordination de trois ligand DABCO.

Figure 4 .

 4 Figure 4. Représentation des structures hôte-invité formées par les deux récepteurs du groupe Shinkai (9) 8 et Ballester(10).9

Figure 5 .

 5 Figure 5. Représentations des structures hôte-invité formées par les deux récepteurs biindole-porphyrine (11) et(12) du groupe Jang.10,11

Figure 7 .

 7 Figure 7. Représentations de la réponse aux stimuli des récepteurs allostériques catalytiques du macrocycle 16 du groupe Mirkin 16 et 18 du groupe Schmittel 17 sous leurs formes activées.

Figure 8 .

 8 Figure 8. Structures des récepteurs macrocycliques acridinium du groupe de Lehn (19),18

  porphyrine n'ont pas été utilisées en tant qu'unités de reconnaissance orthogonales en chimie supramoléculaire. Ceci implique un attachement covalent de ces deux fragments.Cette fonctionnalisation se limite aux travaux du groupe de Fukuzumi sur une triade composée d'un conjugué acridinium-porphyrine (24) mais ce système n'a été utilisé que comme détecteur de fluorescence du superoxyde et non pour la reconnaissance supramoléculaire.23

Figure 9 .

 9 Figure 9.Structures des systèmes porphyrine/acridinium publiés.[21][22][23]

Figure 10 .Figure 11 .

 1011 Figure 10. Illustration 3D du mécanisme par lequel un contrôle allostérique positif de la liaison de l'invité polyaromatique est assuré.

Figure 12 .

 12 Figure 12. Synthèse de 30•PF 6 via un couplage catalysé au palladium en utilisant l'ester boronique d'acridane 29 et la bromo-aryl porphyrine-Zn(II) 26-Zn.

Figure 13 .

 13 Figure 13. Synthèse du formyle phényl acridinium (32•PF6) par réaction d'un échange bromo lithium d'un bromo benzaldéhyde protégé(31).

Figure 14 .

 14 Figure 14. Synthèse du conjugué monoacridinium porphyrine (33•PF6), par condensation de porphyrine à partir de 32•PF6.

Figure 15 .

 15 Figure 15. Synthèse du conjugué bisacridinium porphyrine 35•2PF6 par condensation de porphyrine à partir de 32•PF 6 et de 2,2'-dipyrrométhane.

Figure 16 .

 16 Figure 16. Complexes formés lors de l'addition de DABCO (0,5 équivalent), suivi de pyrène (1 équivalent) à une solution de 35•2PF 6 dans CD3CN.

Figure 17 .

 17 Figure 17. Synthèse de la pince moléculaire 39•2PF6 à partir du synthon acridinium benzaldéhyde 37•PF6.

Figure 18 .

 18 Figure 18. Complexes formés entre la pince 39•2PF6 en présence d'un équivalent de DABCO (DABCO@39•2PF6) ou biPy (biPy@39•2PF6).

Figure 19 .

 19 Figure 19. Structure du complexe DABCO@39•2PF6 montrant le décalage des deux faces du récepteur.

Figure 20 .

 20 Figure 20. Complexes formés par 39•2PF 6 dans CD2Cl2 lors de l'ajout de biPy (biPy@39•2PF6) et celui attendu suite à l'ajout de deux équivalents de pyrène (biPy@39•2PF 6 + pyrène).

Figure 21 . 2 =

 212 Figure 21. Structure chimique de la pince moléculaire acridanol-porphyrine 40.

Figure 22 .

 22 Figure 22. Schéma cubique représentant les huit états de la pince moléculaire.

Figure 23 .

 23 Figure 23. Synthèse du précurseur de cage 41.4PF6.

Figure 24 .

 24 Figure 24. Synthèse du récepteur cage 42•8PF6 à partir du complexe biPy@(41•4PF6)2 par métathèse d'oléfine.

Figure 27 .

 27 Figure 27. Complexe formé par 42•8PF6 dans CD3CN lors de l'ajout de DABCO (DABCO@42•8PF6) suivi de pyrène (DABCO@42•8PF6 + pyrène).

Figure 28 .

 28 Figure 28. Structures des deux composés 41•4BArF et 42•8BArF.

Figure 29 .

 29 Figure 29. Structures des complexes biPy@42•8BArF et DABCO@42•8BArF.

Figure 30 .

 30 Figure 30. Structure du complexe formé lors de l'addition d'un équivalent de pyrène à une solution de DABCO@42•8BArF.

Figure 31 .

 31 Figure 31. Structure de la cage 43 formée lors de l'addition de KOH à une solution de 42.8PF6.

  [START_REF] Zanetti-Polzi | Allosteric Control of Naphthalene Diimide Encapsulation and Electron Transfer in Porphyrin Containers: Photophysical Studies and Molecular Dynamics Simulation[END_REF]

Table 1 a

 1 Emission maxima were obtained from corrected spectra. b Fluorescence quantum yields were measured with reference to meso-tetraphenylporphyrin (TPP) in aerated toluene as a standard for the porphyrin units and with reference to Coumarin 153 in ethanol for the acridinium units. c Fluorescence lifetimes are given in nanoseconds, with excitation at 465 nm

	for Zn-bP and at 368 nm for 32•PF6. d Selective excitation of the Zn(II)-porphyrin unit at 543
	nm gives a yield below the minimum value measurable with steady-state experiments (i.e. 1
	 10 -4 ).

Table 2 .

 2 Binding constants obtained via UV-Vis titrations of the two species 33

	eq.	40 eq.	50 eq.

•PF6 and 39•2PF6, with

  the guest DABCO.

	Species	Guest	Solvent	Ka (L mol -1 )
	33•PF6	DABCO	CH2Cl2	1 × 10 5
	39•2PF6	DABCO	CH2Cl2	K11 = 2 × 10 6 K12 = 6 × 10 3

Table 4 .

 4 Binding constants obtained for the monoacridinium porphyrin conjugate 33•PF6 and the tweezer 39•2PF6 when titrated with biPy in CH2Cl2.

	Species	Guest	Solvent	Ka (L mol -1 )
	33•PF6	biPy	CH2Cl2	3.8 × 10 3
	39•2PF6	biPy	CH2Cl2	K11 = 1.8 × 10 5 K12 =799

Table 7 .

 7 showing the associated binding constants for the tweezers, and the effect of oxidation

	on these value
		39 2+ + biPy ⇄	39 4+ + biPy ⇄	40+ biPy ⇄	40 2+ + biPy ⇄
		biPy@39 2+	biPy@39 4+	biPy@40	biPy@40 2+
	Ka (L mol -1 )	1.8 × 10 5	2.1 × 10 3	1.4 × 10 5	3.1 × 10 4

Table 1 .

 1 Diffusion coefficients and hydrodynamic radii of biPy

@42•8PF6 and biPy@39•2PF6.

	Species	Solvent	D (× 10 6 cm 2 s -1 )	Rh (Å)
	biPy@42•8PF6	CD2Cl2/CD3CN (9:1)	2.80 (± 0.13)	17.9
	biPy@39•2PF6	CD2Cl2	3.80 (± 0.15)	13.2

Table 3 .

 3 Diffusion coefficients and hydrodynamic radii of the salts 42•8BArF, 41•4BArF and NaBArF, obtained via DOSY NMR experiments.

	Species	Solvent	D (× 10 6 cm 2 s -1 )	Rh (Å)
	42•8BArF	42 8+ BArF	CD2Cl2 CD2Cl2	2.92 (± 0.14) 3.77 (± 0.01)	17.2 -
	41•4BArF	41 4+ BArF	CD2Cl2 CD2Cl2	3.55 (± 0.05) 4.95 (± 0.01)	14.1 -
	NaBArF	BArF	CD2Cl2	8.38 (± 0.05)	5.98

Table 4 .

 4 Diffusion coefficients and hydrodynamic radii of the biPy@

42•8PF6 and biPy@42•8BArF complexes.

	Species	Solvent	D (× 10 6 cm 2 s -1 )	Rh (Å)
	bipy@42•8BArF	bipy@42 8+ BArF	CD2Cl2 CD2Cl2	2.85 (± 0.13) 3.71	17.6 -
	biPy@42•8PF6		CD2Cl2/CD3CN (9:1)	2.80 (± 0.13)	17.9

Table 6 .

 6 Binding constants obtained via UV-Vis titrations of the cages (42•8PF6,

42•8BArF and 43) with

  biPy.

	Species	Guest	Solvent	Ka (L mol -1 )
	42•8PF6	biPy	CH2Cl2 (0.1% CH3CN)	4.2 × 10 6
	42•8BArF	biPy	CH2Cl2	1.3 × 10 7
	43	biPy	CH2Cl2	1 × 10 6

  (m, 8H, =CH), 5.30 -5.22 (m, 16H, NCH2), 4.95 (d, 3 J = 7.0 Hz, 4H, HbiPy-), 2.32 -2.23 (m, 16H, a-CH2), 2.08 -2.01 (m, 20H, HbiPy- & g-CH2), 1.83 -1.78 (m, 16H, b-CH2), 1.59 -1.54 (m, 16H, c-CH2), 1.47 -1.39 (m, 48H, (d-f)-CH2).

	13 C{ 1 H} NMR (125 MHz, CD2Cl2/CD3CN (9:1), 298 K) δ (ppm) = 162.5 (C9), 150.2 (CCpy),
	145.6 (CCo), 143.3 (Cbipy-), 141.0 (CC4/5), 139.7 (C3/6), 135.2 (Co-in), 134.5 (Co-out), 132.4
	(Cpy), 132.2 (CCm), 131.4 (C1/8), 130.6 (=CH), 128.6 (Cm-in), 128.4 (C2/7), 128.3 (Cm-out),
	126.7 (CC1/8), 120.1 (Cmeso), 119.9 (Cbipy-), 117.9 (C4/5), 51.6 (NCH2), 32.8 (g-CH2), 29.9 (c-
	CH2), 29.5 (d/e/f-CH2), 29.3 (d/e/f-CH2), 29.0 (a-CH2), 27.2 (b-CH2).

19 F{ 1 H} NMR (282 MHz, CD2Cl2/CD3CN (9:1), 298 K) δ (ppm) = -73.31 (d, 1 JP-F = 711.2 Hz). 31 P{ 1 H} NMR (121 MHz, CD2Cl2/CD3CN (9:1), 298 K) δ (ppm) = -144.71 (hept, 1 JP-F = 711.2 Hz).

  6 L mol -1 obtained.Les porphyrines sont des unités de reconnaissance intéressantes en chimie hôte-invité en vertu de leur capacité à former des interactions - ou métal-ligand, de leur possible fonctionnalisation en positions  ou méso, de leurs propriétés optiques ainsi que de leur réponse à des stimuli. Ainsi, les unités porphyrines ont été incorporées dans des hôtes supramoléculaires. Le développement de la chimie hôte-invité a conduit à l'élaboration de systèmes ayant des applications dans des domaines liés à la détection, à la catalyse commutable et à la vectorisation de médicaments. Cependant, une méthode de contrôle est nécessaire afin de réaliser des systèmes pour de telles applications. Ceci peut se faire par l'intermédiaire d'un stimulus lumineux, chimique ou rédox.

		Calculated Résumé de Thèse	Reported
	Volume	3332.3(2) Å	3332.3(2) Å
	Space group	P 1 ̅	P 1 ̅
	Hall group	-P 1	-P 1
		C136 H132 N8 Zn, 4(F6 P),
	Moiety formula	3(C2 H3 N) C136 H132 N8
		Zn, 4(F6 P), 3(C2 H3 N)
	Sum formula	C142 H141 F24 N11 P4 Zn C142 H141 F24 N11 P4 Zn
	Mr	2646.93	2646.90
	cald (g cm -3 )	1.319	1.319
	Z	1	1
	Mu (mm -1 )	1.456	1.456
	F000	1376.0	1376.0
	F000'	1380.09
	h, k, lmax	12, 21, 22	12, 21, 22
	Nref	11998	11834
	Tmin, Tmax	0.840, 0.865	0.589, 0.753
	Tmin'	0.747
	Correction method	T Limits: Tmin=0.589 Tmax=0.753
	AbsCorr	= MULTI-SCAN
	Data completeness =	0.986
	Theta(max)	= 67.455
	R(reflections) =	0.1356(7423)
	wR2(reflections) =	0.4169(11834)
	S =	1.530
	Npar =	798
	:

  Des exemples de systèmes allostériques synthétiques ont été décrits à la fin des années 1970 par le groupe de J. Rebek Jr. et ses collègues.7 Depuis, des récepteurs allostériques artificiels ont été synthétisés et exploitent différents motifs de reconnaissance afin

	Figure 3. Structure de l'hôte 7 du groupe Shionoya sous ses deux formes 7-bowl et 7-
	capsule lors de l'addition d'invités. 6
	La seconde utilisation d'un stimulus chimique peut être observée chez des hôtes

Sous sa forme bol (7-bowl), le récepteur 7 peut être converti réversiblement en sa forme 7-capsule par addition d'aryl sulfonamide ou d'adamantane. Pour chacun des invités, l'hôte 7 prend la géométrie la plus adaptée pour maximiser les interactions. multivalents, c'est-à-dire composés de plusieurs sites de reconnaissance. Dans ce cas, une coopérativité entre les sites d'interaction est nécessaire selon un mécanisme de contrôle allostérique. Il s'agit d'un processus de contrôle commun observé dans la nature (plus particulièrement dans l'action des enzymes et des protéines). Il est décrit par les changements conformationnels et/ou électroniques d'une macromolécule par une première molécule invitée effectrice. Ce changement a un impact sur l'activité biologique par modification des interactions de la macromolécule avec un ou plusieurs invités secondaires sur un site séparé et distinct. Lorsque l'interaction avec l'invité secondaire est inhibée en raison de la liaison de l'effecteur, le contrôle allostérique est dit négatif. Inversement lorsque l'invité voit son affinité pour la macromolécule augmentée, l'allostérie est qualifiée de positive. De plus, le processus de régulation allostérique est hétérotrope quand l'effecteur et l'invité ne sont pas la même espèce chimique ou homotrope quand l'effecteur et l'invité sont la même espèce.

C{ 1 H} NMR (125 MHz, CD3CN, 298 K) δ (ppm) = 193.3 (CHO), 160.9 (C9),

142.5 (CC4/5),

F{ 1 H} NMR (470 MHz, CD2Cl2, 298 K) δ (ppm) = -73.65 (d, 1 JP-F = 711.3 Hz).

P{ 1 H} NMR (202 MHz, CD2Cl2, 298 K) δ (ppm) = -144.67 (hept, 1 JP-F = 711.3 Hz).

Acknowledgements

List of Abbreviations [O]

Oxidant

[R]

The cage was shown to be able to ditopically bind both DABCO and biPy to form 1:1 hostguest species. In addition, within the context of allosteric control, the DABCO bound cage complex was shown via 1 H NMR spectroscopy to be able to bind aromatic guests.

Interestingly, where a strong interaction between the aromatic guest and the cage@DABCO complex was seen, interaction with the cage alone was not indicated. Thus, an allosteric system was successfully developed, with complexation of DABCO by the Zn(II)-porphyrin preorganising for binding of aromatic guests within the acridinium binding sites.

The effects of chemical stimulus in the form of nucleophiles were examined via NMR and UV-Vis spectroscopy, with switching to the neutral octaacridane porphyrin cage achieved via addition of KOH. The process was found to be reversible via addition of TFA, and the obtaned fatigue cycle showed the switching could be had without major loss of conversion for 10 cycles, representing a robust molecule. Finally, the addition of nucleophiles was found to drastically alter the binding affinity of the cage for biPy, with a lower binding constant compared to both the PF6 and BArF salt, indicating that addition of nucleophiles could be used as a remote-control for binding of biPy. In totality, the various studies allowed the characterisation of a highly complex, stimuli responsive receptor, showing control of binding affinity at the porphyrin via the acridinium/acridanol, as well as control of the binding affinity at the acridinium site via the porphyrin.

List of molecules

Syntheses and Characterisations

UV-Vis Titrations:

For the UV-Vis titration with biPy, two solutions were prepared:

Host Solution: 33•PF6 (0.1338 mg, 99.0 nmol) in CH2Cl2 (20 mL)

Guest Solution: biPy (193.2 mg, 1.24 mmol) in CH2Cl2 (5 mL)

Porphyrin acridane cage (43)

To a solution of the 42•8PF6 (3.95 mg, 0.8 mol) in CH2Cl2/CH3CN (2 mL, 95:5 v/v) was added a methanolic (0.2 mL) solution of KOH (0.404 mg, 7.2 mol, 9 eq.). The resultant solution was stirred for one minute, and conversion assessed via UV-Vis spectroscopy.

The solution was then diluted with CH2Cl2 (20 mL) and an extraction carried out using H2O (3 × 20 mL), retaining the organic fraction, which was then evaporated to dryness.

The solid was then dissolved in CH2Cl2 (1 mL), and CH3OH (2 mL) added, then the left to sit overnight, giving the product 43 as a purple precipitate (2.90 mg, 90%.) (dans CH2Cl2, 0,1% CH3CN) a pu être déterminée par dosage. Amy EDO-OSAGIE

Conception, synthèse et propriétés de récepteurs incorporant des unités acridiniums et porphyrines

Résumé

Les travaux de cette thèse portent sur la conception, la synthèse et l'étude de nouveaux récepteurs incorporant des conjugués acridinium-porphyrines. Les effets du couplage des deux motifs sur les propriétés électrochimiques et photochimiques des molécules et sur leur comportement de reconnaissance ont été explorés.

Deux voies de synthèse pour coupler les motifs acridinium et porphyrine ont été mises au point et ont conduit à différentes porphyrines méso-substituées par des acridiniums. Elles ont permis d'entreprendre la synthèse de récepteurs moléculaires, en utilisant la métathèse d'oléfines pour lier de manière covalente plusieurs conjugués acridinium-porphyrine. Grâce à cette réaction, une pince moléculaire et une cage acridinium-porphyrine ont été synthétisées avec succès. Les propriétés de reconnaissance de ces deux récepteurs ont été étudiées vis à vis de ligands ditopiques (DABCO et 4,4'-bipyridine) et d'hydrocarbures polyaromatiques. De plus, la présence/absence de coopérativité entre les sites de reconnaissance porphyrine et acridinium a été étudiée. Enfin, la réponse multiple suite à différents stimuli (chimiques et/ou redox) a été mise en évidence ainsi que le contrôle à distance de l'affinité de ces récepteurs pour les ligands ditopiques.

Mots-clés : pince moléculaire, cage moléculaire, récepteur à réponse multiple, reconnaissance moléculaire, acridinium, porphyrine.

Résumé en anglais

The work of this thesis has focused on the design, synthesis and study of new receptors incorporating acridinium-porphyrin conjugates. The effects of pairing the two motifs on the electroand photo-chemical properties of the molecules and on their recognition behaviour were explored.

Two synthetic methodologies for coupling acridinium and porphyrin motifs were found allowing the synthesis of different meso-substituted acridinium-porphyrins. This was then extended into the synthesis of molecular receptors, using olefin metathesis as a means of covalently linking acridiniumporphyrin conjugates. Via this method, both a porphyrin-acridinium tweezer and cage were successfully synthesised. The binding abilities of the two receptors were investigated with respect to ditopic ligands (DABCO and 4,4'-bipyridine) and polyaromatic hydrocarbons. Furthermore, the presence/absence of cooperativity between the porphyrin and acridinium binding sites was investigated. Finally, the multi-switching behaviour based on different stimuli (chemical and/or redox) was studied and the remote-controlled tuning of the binding affinity for ditopic ligands evidenced.