Antoine J Maryline

Fabien Julie Jacques

Julien F Christian

Pauline Srba

Maya Laurent

Les Autres…

Philippe Hélène

Caroline Yannis

Clarisse

Catherine Gilles

Alex Lara

Claudia Sandra

Nat Gajan

Jenny Xiao

Ms Cécile Roche

Keywords: rotaxane, porphyrin, macrocycle, phenanthroline, bipyridine, copper(I), zinc(II), organic synthesis, coordination chemistry, template effect, host-guest chemistry, molecular receptor. viii rotaxane, porphyrine, macrocycle, phénanthroline, bipyridine, cuivre(I), zinc(II), synthèse organique, chimie de coordination, effet template, système hôte/invité, récepteur moléculaire

I am very grateful to the members of the Crossley group, in particular Fargol, Derrick and Dianne, who gave me a very warm welcome in Sydney. Fargol, you are one of the kindest people I have ever met, thank you so much

J'ai beaucoup appris en travaillant avec vous pendant ces quelques années et je vous en suis très reconnaissante. I am very grateful to Max Crossley for his warm welcome in his group and for giving me the opportunity to have a very fulfilling research experience in Australia.

My thanks also go to all the people who have participated in parts of this research project.

These are David Amabilino, who initiated the synthesis of the porphyrin tetra-macrocycle as a postdoc a long time ago; Nathan Strutt, who started the work on the [6]rotaxane project here in Strasbourg and who is now taking over this part of the project as a PhD student with Prof. Fraser Stoddart at Northwestern University; Frédéric Niess, who spared me the tedious synthesis and purification of the mesityldipyrrylmethane; Bernhard Schäfer, who helped with the synthesis of the rod; and Derrick Roberts, who kindly gave me a sample of a porphyrin tetraone precursor.

Je remercie aussi les membres des laboratoires dans lesquels j'ai pu travailler pendant cette thèse. Merci à Jean-Paul Collin, toujours disponible et de bon conseil, et à Valérie Heitz pour son soutien et son hospitalité dans son nouveau laboratoire. Merci Yann, ton rail et tes conseils ont été très utiles! My thanks also go to Sasha Martynov for very helpful discussions about synthetic issues. Je remercie vivement tous les membres, anciens et actuels, du LCOM et du LSAMM à Strasbourg, grâce auxquels l'ambiance était toujours excellente. Merci Julien et Anh-Thu, compagnons de rédaction! Au cours de ces trois (et quelques) années de thèse vous êtes devenus de vrais amis et j'ai été très contente de partager les joies et les épreuves de la thèse avec vous, surtout la rédaction… Merci Julien pour toutes ces (magnifiques) chansons que tu nous as si gentiment fredonnées… encore… encore… et encore…… Le labo aurait été bien triste sans toi! Merci Steph, toujours partante pour un pot ou une petite séance de grimpe :-) Merci -P. Sauvage. The strategy involves the formation of a double helical complex of bis-phenanthroline ligands around two copper(I) centres, followed by ring closure and demetalation. The knotted structure of the Cu(I) complex was confirmed by X-ray crystallography. [START_REF] Forgan | Chemical Topology: Complex Molecular Knots, Links, and Entanglements[END_REF][START_REF] Dietrich-Buchecker | A Synthetic Molecular Trefoil Knot[END_REF][START_REF] Dietrich-Buchecker | Structure of a Synthetic Trefoil Knot Coordinated to Two Copper(I) Centers[END_REF][START_REF] Dietrich-Buchecker | Molecular Knots. Templates in Chemistry II[END_REF] A non-covalent catenane assembled via labile metal-ligand coordination bonds. The [2]catenane is in equilibrium with the corresponding non-interlocked macrocycles. The catenated form is largely predominant at high concentration. [START_REF] Fujita | Quantitative self-assembly of a [2]catenane from two preformed molecular rings[END_REF] [2]catenane); 36 b) Molecular Borromean rings (three interlocking, but non-catenated macrocycles); 37 c) A [3]rotacatenane (combination of [2]catenane and [2]rotaxane structures). [START_REF] Barin | A Multistate Switchable [3]Rotacatenane[END_REF] The first [2]rotaxane exclusively made of double-stranded DNA, assembled via base-pairing between the axle and the ring. [START_REF] Ackermann | A double-stranded DNA rotaxane[END_REF] [3]rotaxane. Instances of these geometries have been described in the literature: a) Two rings threaded on one axle; [START_REF] Coumans | Synthesis of porphyrin-containing [3]rotaxanes by olefin metathesis[END_REF][START_REF] Marois | 3]rotaxane-porphyrin conjugate as a novel supramolecular host for fullerenes[END_REF][START_REF] Collin | Rotaxanes and[END_REF][54] b) Two axles passing through the same ring; 55-57 c) and d) Two axles passing through the rings formed by a bis-macrocyclic component. [START_REF] Wittenberg | A clipped [3]rotaxane derived from bis-nor-seco-cucurbit[10]uril[END_REF][START_REF] Goldup | Two Axles Threaded Using a Single Template Site: Active Metal Template Macrobicyclic[END_REF] ........ 8

List of Figures

Summary in French

Figure I.11. An original rotaxane architecture: a hetero- [7]rotaxane incorporating two different macrocycles. [START_REF] Zhang | A Twin-Axial Hetero[7]rotaxane[END_REF] (i) an unfolded protein (red) is trapped at the entrance of the cavity (green/blue); (ii) fixation of ATP (T) triggers conformational changes and binding of the GroES lid (grey) and allows folding of the guest protein; (iii) hydrolysis of ATP to ADP (D) weakens the GroEL/GroES complex and induces release of the lid and folded protein. [START_REF] Bukau | The Hsp70 and Hsp60 chaperone machines[END_REF][START_REF] Yébenes | Chaperonins: two rings for folding[END_REF] A unidirectional molecular motor based on a [3]catenane structure (left). The sequential rotary motion of the two small rings around the larger ring is illustrated (right). Successive E to Z photoisomerisation of site A, followed by E to Z photoisomerisation of site B and then thermal reconversion of sites A and B to the E isomers promotes successive rotary motions of the small rings. The rotation direction is restricted by the presence of the second small ring. Conditions: (1) 350 nm, 5 min; (2) 254 nm, 20 min; (3) heat, 100 °C, 24h or catalytic Br 2 , 400-670 nm, -78 °C, 10 min. A fast-moving copper-complexed [2]rotaxane shuttle. The translational motion is controlled electrochemically: copper(I) binds preferentially to the sterically hindered bidentate chelate of the axle xv while copper(II) binds to the less hindered bidentate site that allows coordination of an additional ligand. 118 ....................................................................................................................................................... 16 Figure I.19. A molecular elevator based on a triply interlocked [2]rotaxane structure. The interactions of the rings on the axles depend on the pH: the rings bind on the ammonium units when these are protonated and switch to the bipyridinium sites upon deprotonation of the ammonium groups. The shuttling motion of the rings along the axles lifts the central platform up and down. 119 Discrimination between the syn and anti isomers of a bis-porphyrin using axial coordination with a "molecular ruler". The bifunctional ruler ligand forms a strong complex with the syn isomer but is too short to bind both Zn-porphryin sites on the anti isomer. 148,149 Pirouetting motion of a [2]rotaxane that contains three porphyrin units. A gold(III) porphyrin is incorporated in the macrocyclic component, and the axle bears two zinc(II) porphyrins as stoppers. 190 29 Figure I.33. A porphyrin-incorporating [6]pseudorotaxane structure reminiscent of the special pair of the photosynthetic reaction centre. Two central copper(II) porphyrins are held in a slipped cofacial arrangement by the surrounding interlocked scaffold. Parallel spin electron coupling between the Cu(II) centres results from the close proximity of the metalloporphyrins. 192 A tetra-interlocked [2]rotaxane with face-to-face Cu(II)-porphyrin and Cu(II)phthalocyanine units. The distance between the copper(II) centres is monitored by protonation/deprotonation of amine groups on the axles. Switchable spin-spin communication is achieved: the spins are isolated in the protonated state of the rotaxane whereas antiferromagnetic coupling is observed upon deprotonation. 193 (top) and copper-free (bottom) forms of a [3]rotaxane. The rotaxane is a good molecular receptor for ditopic pyridyl guests of various lengths. The copper(I)-complexed rotaxane forms stronger complexes with short guests, while the copper-free rotaxane has better affinity for long guests. 194,195 A [4]rotaxane with two face-to-face porphyrins. The copper(I)-complexed rotaxane forms guest inclusion complexes with short substrates. However, the rotaxane collapses upon demetalation of the copper(I) centres and does not show any host-guest properties after demetalation. 196,197 [4]rotaxane composed of two axles and two bis-macrocycles. Each bismacrocycle consists of two flexible rings attached to a central Zn porphyrin. The synthetic strategy is based on the ''gathering-and-threading'' approach using a copper(I) template, followed by stoppering. The porphyrin is represented as a square or a diamond, the bidentate chelates are indicated by green or xviii blue U-shaped symbols and the gathering metal centre (copper(I)) is a pink dot. The stoppers are depicted as large grey spheres. ................................................................................................................................... 59 Figure III.4. Two-step, one-pot synthesis of [4]rotaxane 19 4+ in 50% yield by (1) threading of bismacrocycle 8 and axle 16 into a [4]pseudorotaxane and ( 2 4+ . The main signal is magnified to show the isotope profile (top right); this profile fits well with the calculated spectrum (bottom). ......... 62 Figure III.6. Hypothetical threading and stoppering scheme leading to a [2]rotaxane. Mass spectrometry results indicated that this threading scheme is not favoured. The isotope profile is consistent with a [4] [4]rotaxane in very slow exchange with the major conformer. This minor conformer diffuses at the same rate as the major conformer. A good fit is obtained for the estimated size of the rotaxane using CPK models and the diffusion coefficient measured by DOSY NMR. The rotaxane approximates to a 48 Å sphere. . and the [3]rotaxane that will be described in Chapter V. Both rotaxanes comprise exactly the same dumbbell resulting from the click reaction of two stoppers 18 on the axle 16, and are complexed to four Cu(I) centres. However, only one porphyrin is incorporated in the [3]rotaxane while the [4] 196,197,217 The rigidity of the new system will be intermediate between the very flexible bis-macrocycle 8 and the very rigid bis-macrocycle studied by former members of the Sauvage group. .. 84

Chapter II. Rotaxane Building Blocks: A New Zinc Porphyrin Substituted with Two Coordinating Macrocycles, a Molecular Rod and a Stopper

Figure IV.2. The Crossley synthetic approach for the functionalisation of porphyrins at the β positions. The method involves the formation of porphyrin-dione (a) or tetraone (b) derivatives, followed by condensation with a (substituted) 1,2-phenylenediamine unit. It allows the formation of linear or "corner" planar multifunctional systems, whose functional groups are covalently linked to the porphyrin via an extended aromatic system (Ar = aryl group). 265 [3]rotaxane whose central fragment consists of a Zn-complexed porphyrin bearing four coordinating rings. The synthetic strategy is based on the "gathering-and-threading" approach followed by stoppering. The threading scheme that prevails in this case differs from that observed for the formation of the [4]

COSY

Correlation SpectroscopY

CPK

Corey-Pauling-Koltun

CuAAC

Copper(I)-catalysed Azide-Alkyne Cycloaddition Notre projet s'inspire du mode de fonctionnement des protéines chaperonnes. L'objectif n'est pas exactement de modeler une protéine mais de créer un système basé sur des mouvements plus simples, qui serait capable de piéger une molécule invitée, et qui pourrait par la suite changer la conformation du substrat piégé par compression. Le projet porte donc sur la synthèse et l'étude de multi-rotaxanes porphyriniques se comportant comme des récepteurs moléculaires xxx modulables et présentant un caractère de "presse moléculaire". Les porphyrines de zinc ont été choisies comme plaques de la presse pour leur capacité à se lier à divers substrats organiques. Le mouvement des porphyrines l'une par rapport à l'autre est permis grâce à la structure de type rotaxane. Le principe général du projet est schématisé ci-dessous (Figure 1). Comme indiqué sur le schéma, le mouvement est déclenché par un signal chimique, plus précisément par la présence ou l'absence de cuivre(I). Lorsque le [4]rotaxane est libre (en l'absence de cuivre(I)), les plaques porphyriniques peuvent se déplacer librement l'une par rapport à l'autre. Comme représenté en rouge sur le schéma, un substrat coordiné aux ions zinc, entre les deux porphyrines, peut alors adopter une conformation étendue, stable du point de vue thermodynamique. En revanche, en présence de cuivre(I), la position des anneaux sur les axes est fixée au niveau des complexes de Cu(I), ce qui devrait provoquer le rapprochement des plaques porphyriniques, et par conséquent la compression du substrat localisé entre ces deux plaques.

δ chemical shift DABCO 1,4-diazabicyclo[2,2,2]octane dap 2,9-dianisyl-1,10-phenanthroline dba dibenzylideneacetone N N N N NH 2 O OH OH O P O O P O -O -O -O N N N N NH 2 O OH OH O P O O P O O -O -O P O -O -O PPh 2 PPh 2 N N N N O O N N N N MeO OMe O xxiv DDQ 2
La réalisation de ce projet implique la synthèse de nouvelles porphyrines liées à des anneaux chélatants, la synthèse d'un axe (ou rail moléculaire) et d'un "bouchon" encombrant, ainsi que la construction de multi-rotaxanes à partir de ces composants et l'étude des propriétés de récepteur moléculaire des rotaxanes. Cette partie porte sur la synthèse d'un rotaxane à partir des composants décrits en II., ainsi que sur l'étude des propriétés de récepteur moléculaire du rotaxane. L'enfilage du bismacrocycle porphyrinique par le rail à deux chélates a mené à la formation d'un [4]pseudorotaxane, puis le [4]rotaxane cible a été obtenu par réaction "click" (Figure 4). Ce rotaxane a été caractérisé par spectrométrie de masse, par spectroscopie d'absorption UV-visible et par de nombreuses expériences de RMN dans différents solvants ( 1 H, Afin de tester ses propriétés de récepteur moléculaire, les constantes d'association du rotaxane avec diverses molécules invitées ont été mesurées. Les substrats choisis sont des ligands azotés ditopiques rigides de longueur croissante (Figure 5). La coordination des différentes molécules invitées avec le [4]rotaxane a été étudiée par spectroscopie d'absorption UV-visible. Après la synthèse du bis-macrocycle final, un rotaxane pourra être construit à partir du même rail que celui utilisé précédemment. Nous pourrions alors étudier les interactions entre le [4]rotaxane (forme libre et forme complexée avec du cuivre) et des substrats de diverses longueurs susceptibles d'être complexés à l'intérieur de l'espace disponible entre les deux porphyrines, afin de tester la capacité du récepteur à comprimer ces substrats. A partir de ce nouveau tétra-macrocycle porphyrinique, nous envisagions de construire un [6]rotaxane. Ce rotaxane serait constitué de deux porphyrines superposées, dont les anneaux seraient enfilés par quatre rails perpendiculaires au plan des porphyrines (Figure 10). Un tel système, comportant des porphyrines à quatre anneaux, pourrait permettre un contrôle géométrique de la presse encore plus strict que celui présenté dans l'introduction, qui était basé sur l'utilisation d'une porphyrine à deux anneaux.

N N O O N O O O O O N N O O O O O N N N N N O O O O O N N O O O O O N N N N N N N N N N O Zn Zn O N N N N N N N N N O O O N N N O 4+ 4PF 6 N Cu N Cu Cu Cu xxxiv
Figure 10. Représentation d'un [6]rotaxane composé de deux tétra-macrocycles porphyriniques et de quatre rails. A topologically interesting branch of chemistry deals with molecules displaying an interlaced structure, like catenanes, rotaxanes and knots. [1][2][3][4][5][6][START_REF] Amabilino | Topology in molecules inspired, seen and represented[END_REF][START_REF] Stoddart | The chemistry of the mechanical bond[END_REF][START_REF] Beves | Strategies and Tactics for the Metal-Directed Synthesis of Rotaxanes, Knots, Catenanes, and Higher Order Links[END_REF][START_REF] Forgan | Chemical Topology: Complex Molecular Knots, Links, and Entanglements[END_REF] In this introduction we do not intend to review this field of research exhaustively; we will give definitions and describe a selection of Tying knots on a string is very easy (and often happens involuntarily), and the discovery of complex knotted DNA architectures proved that it is possible even at the nanometric scale. [START_REF] Liu | Knotted single-stranded DNA rings: A novel topological isomer of circular single-stranded DNA formed by treatment with Escherichia coli ω protein[END_REF][START_REF] Liu | Type II DNA topoisomerases: Enzymes that can unknot a topologically knotted DNA molecule via a reversible double-strand break[END_REF][START_REF] Dean | Duplex DNA knots produced by Escherichia coli topoisomerase I. Structure and requirements for formation[END_REF] However, the construction of synthetic molecular knots turned out to be very challenging. The [START_REF] Dietrich-Buchecker | A Synthetic Molecular Trefoil Knot[END_REF] Careful design of the system allowed for the formation of trefoil knots in high yields using this strategy, as reported in subsequent papers. 15 Sauvage. The strategy involves the formation of a double helical complex of bisphenanthroline ligands around two copper(I) centres, followed by ring closure and demetalation. The knotted structure of the Cu(I) complex was confirmed by X-ray crystallography. [START_REF] Forgan | Chemical Topology: Complex Molecular Knots, Links, and Entanglements[END_REF][START_REF] Dietrich-Buchecker | A Synthetic Molecular Trefoil Knot[END_REF][START_REF] Dietrich-Buchecker | Structure of a Synthetic Trefoil Knot Coordinated to Two Copper(I) Centers[END_REF][START_REF] Dietrich-Buchecker | Molecular Knots. Templates in Chemistry II[END_REF] Some alternative strategies for the formation of molecular trefoil knots were reported later. The group of F. Vögtle described the first metal-free synthesis of a trefoil knot. The knot is formed in one step from short linear precursors assembled via hydrogen bonds. [START_REF] Safarowsky | A molecular knot with twelve amide groups -One-step synthesis, crystal structure, chirality[END_REF] C. A. Hunter and coworkers synthesised a trefoil knot by complexation of a linear tris-bipyridine ligand with Zn(II), [START_REF] Adams | Knot tied around an octahedral metal centre[END_REF] followed by ring-closing metathesis and demetalation. [START_REF] Guo | Synthesis of a molecular trefoil knot by folding and closing on an octahedral coordination template[END_REF] The group of J. S. Siegel prepared a trigonal ligand with six bipyridine chelates arranged around a 1,3,5-trisubstituted benzene core and preorganised by copper(I) coordination. [START_REF] Woods | Trinuclear Copper(I)-bipyridine Triskelion: Template/Bascule Control of Coordination Complex Stereochemistry in a Trefoil Knot Precursor[END_REF] A knotted structure was subsequently obtained by homocoupling between the terminal alkyne groups. 22 The class of the catenanes constitutes another type of topologically non-trivial molecules.

A catenane is composed of (at least) two mechanically interlocked macrocycles (Figure

I.3. a).
The mechanical link in a catenated structure makes it impossible to separate the rings without breaking a chemical bound and opening one of the macrocycles. In a similar manner to a molecular knot, a catenane has a topologically non-trivial structure: it cannot be drawn in two dimensions without any intersection. Historically, the formation of the first synthetic catenane was evidenced by E. Wasserman in 1960. [START_REF] Wasserman | The Preparation Of Interlocking Rings: A Catenane[END_REF] However, the statistical method employed gave rise to a very low yield of catenane, which could not be isolated from non-catenated macrocycles. In 1964, G. Schill and A. Lüttringhaus reported the directed synthesis of a catenane. [START_REF] Schill | The Preparation of Catena Compounds by Directed Synthesis[END_REF] The limitations of their elegant approach arise from the numerous synthetic steps required for the A non-covalent catenane assembled via labile metal-ligand coordination bonds. The [2]catenane is in equilibrium with the corresponding non-interlocked macrocycles. The catenated form is largely predominant at high concentration. [START_REF] Fujita | Quantitative self-assembly of a [2]catenane from two preformed molecular rings[END_REF] Since these pioneering works on the formation of [2]catenanes, the syntheses of numerous catenated compounds have been reported. Some of them consist of more than two interlocking rings. Notable reports of such molecules include catenanes composed of three to five interlocking rings, [START_REF] Dietrich-Buchecker | Multiring Catenanes with a Macrobicyclic Core[END_REF]31 a cyclic [3]catenane made of three interlocking bis-macrocyclic components, [START_REF] Hori | A circular tris[2]catenane from molecular 'figure-of-eight[END_REF] and a [5]catenane resembling the Olympic rings, named olympiadane. [START_REF] Amabilino | Olympiadane[END_REF] A class of interlocked molecules called rotaxanes is derived from an extension of the definition of catenanes. By elongating one of the rings of a [2]catenane infinitely the structure can be seen as equivalent to a ring threaded by an infinite axle. Chemists imagined the substitution of the infinite axle for a finite axle ending with bulky groups called stoppers, that are big enough to prevent unthreading of the ring. The definition of the simplest rotaxane emerged from this idea: a [2]rotaxane is a molecular species composed of a ring threaded on a stoppered axle, reminiscent of the shape of a dumbbell (

N N N Pd NH 2 H 2 N Pd NH 2 H 2 N 4+ 4(NO 3 -) 2 N N N Pd NH 2 H 2 N Pd NH 2 H 2 N N N N NH 2 H 2 N Pd NH 2 N H 2 N N 8+ 8(NO 3 -) Pd a) b)
After the theoretical mention of the [2]rotaxane structure by H. L. Frisch and E.

Wasserman, 1 the first rotaxane was synthesised using a statistical method in 1967. [START_REF] Harrison | Synthesis of a stable complex of a macrocycle and a threaded chain[END_REF] The authors, I. T. Harrison and S. Harrison, proposed the name hooplane for this type of structure, but the term rotaxane was later adopted, as suggested by G. Schill who described the first directed rotaxane synthesis in 1969. [START_REF] Schill | Rotaxan-Verbindungen, I[END_REF] His approach involved the use of covalent bonds as templates in the Besides the catenanes, rotaxanes and knots, a number of other interlocked structures have attracted the attention of chemists over the years. For instance, molecular Solomon links, Borromean rings, and rotacatenanes (combinations of rotaxane and catenane structures) have been described (Figure I.7). [START_REF] Forgan | Chemical Topology: Complex Molecular Knots, Links, and Entanglements[END_REF][START_REF] Dietrich-Buchecker | Lithium templated synthesis of catenanes: efficient synthesis of doubly interlocked [2]-catenanes[END_REF][START_REF] Chichak | Molecular Borromean rings[END_REF][START_REF] Amabilino | Molecular meccano, 52 -Template-directed synthesis of a rotacatenane[END_REF][START_REF] Barin | A Multistate Switchable [3]Rotacatenane[END_REF] The beauty of mechanically interlocked molecules has fascinated topological chemists for decades and their challenging syntheses keep inspiring them.

The elaboration of new interlocked architectures, and in particular rotaxane-type structures, forms part of the motivation for this PhD project. Copper(I) can be used as a templating agent as described for the synthesis of catenanes in the previous part. Since copper(I) preferentially forms tetrahedral complexes, coordination with two bidentate chelates affords complexes whose ligands are orthogonal to each other and therefore ideally preorganised for the formation of an interlocked species. Metal templating has been used in the synthesis of many rotaxanes (e.g. the rotaxane depicted in Figure I.8. a) [START_REF] Chambron | A Rotaxane with Two Rigidly Held Porphyrins as Stoppers[END_REF][START_REF] Diederich | A Copper(I)-Complexed Rotaxane with Two Fullerene Stoppers[END_REF][START_REF] Li | Convergent synthesis and photophysics of [60]fullerene/porphyrin-based rotaxanes[END_REF][START_REF] Durot | Synthesis of new copper(I)complexed rotaxanes via click chemistry[END_REF] and was chosen in the design of the rotaxanes described in this thesis.

Other assembling methods involving non-covalent interactions between the ring and dumbbell precursors have been widely exploited. For instance F. 42 Threading of cyclodextrins driven by hydrophobic interactions, [START_REF] Ogino | Relatively High-Yield Syntheses of Rotaxanes -Syntheses and Properties of Compounds Consisting of Cyclodextrins Threaded by α , ω -Diaminoalkanes Coordinated to Cobalt(III) Complexes[END_REF] and molecular recognition between crown ethers and cationic axles [START_REF] Hsu | Solvent-free synthesis of the smallest rotaxane prepared to date[END_REF] are other efficient methods for the assembly of rotaxanes.

In addition to these "passive" template methods, an "active" metal template strategy was developed and reported independently by the groups of D. A. Leigh and S. Saito in 2006. In this approach, the metal template plays a dual role: (i) it gathers the rotaxane precursors and preorganises them in an intertwined geometry; and (ii) it serves as a catalyst in the covalent bond formation between the dumbbell precursors that will lock the system into the threaded architecture. [START_REF] Aucagne | Catalytic "click" rotaxanes: A substoichiometric metal-template pathway to mechanically interlocked architectures[END_REF][START_REF] Saito | Synthesis of [2]rotaxanes by the catalytic reactions of a macrocyclic copper complex[END_REF] An original approach was taken recently by the group of M. Famulok who combined the fields of rotaxane synthesis and DNA nanotechnology. They reported the formation of the first [2]rotaxane whose dumbbell and macrocycle are both exclusively made of double-stranded DNA (Figure I.9). In this case the system is assembled by base-pairing interactions. [START_REF] Ackermann | A double-stranded DNA rotaxane[END_REF] Figure I.9. The first [2]rotaxane exclusively made of double-stranded DNA, assembled via base-pairing between the axle and the ring. 50

I. 1. c) [2]Rotaxanes and Multi-Rotaxanes

The architectures described above belong to the simplest form of rotaxanes: they consist in one ring and one dumbbell, i.e. two interlocked organic components that are not covalently linked together. This type of structure is denominated as a [2]rotaxane. More generally, a

[n]rotaxane is composed of several interlocked rings and threads, the number n designating the total number of independent organic components. According to this definition a single denomination can designate several types of rotaxane architectures. For example, two rings threaded on the one dumbbell form a [3] andd). In this last case, the rotaxane possesses two dumbbells threaded through two rings.

However, the structure corresponds to a [3]rotaxane, not a [4]rotaxane, because the rings are covalently linked together. [3]rotaxane. Instances of these geometries have been described in the literature: a) Two rings threaded on one axle; [START_REF] Coumans | Synthesis of porphyrin-containing [3]rotaxanes by olefin metathesis[END_REF][START_REF] Marois | 3]rotaxane-porphyrin conjugate as a novel supramolecular host for fullerenes[END_REF][START_REF] Collin | Rotaxanes and[END_REF][54] b) Two axles passing through the same ring; 55-57 c) and d) Two axles passing through the rings formed by a bis-macrocyclic component. [START_REF] Wittenberg | A clipped [3]rotaxane derived from bis-nor-seco-cucurbit[10]uril[END_REF][START_REF] Goldup | Two Axles Threaded Using a Single Template Site: Active Metal Template Macrobicyclic[END_REF] The geometries depicted above give an insight into the countless potential geometries of rotaxanes. The design of new rotaxane architectures is a fascinating research area that will probably keep chemists busy for many more years. Rotaxane structures can be finite or polymeric. [START_REF] Huang | Polypseudorotaxanes and polyrotaxanes[END_REF][START_REF] Gibson | Rotaxanes, Catenanes, Polyrotaxanes, Polycatenanes and Related Materials[END_REF] Various finite multi-rotaxanes have been described, including [3]-, [4]-, [5]-and [7]rotaxanes. [START_REF] Fuller | One template, multiple rings: Controlled iterative addition of macrocycles onto a single binding site rotaxane thread[END_REF][START_REF] Yin | Synthesis of [n]Rotaxanes by Template-Directed Clipping: The Role of the Dialkylammonium Recognition Sites[END_REF][START_REF] Wu | Efficient production of [n]rotaxanes by using template-directed clipping reactions[END_REF][START_REF] Zhang | A Twin-Axial Hetero[7]rotaxane[END_REF] At the boundary between oligo-and polyrotaxanes, a linear [11]rotaxane composed of ten rings threaded on one long axle has also been described. [START_REF] Wu | Efficient production of [n]rotaxanes by using template-directed clipping reactions[END_REF] A characteristic feature of the [7]rotaxane synthesised by Y. Liu and coworkers is the incorporation of two different macrocycles. The hetero- [7]rotaxane is composed of two dumbbells, each of them bearing two rings and connected to each other via threading through a fifth, large ring (Figure I.11). [START_REF] Zhang | A Twin-Axial Hetero[7]rotaxane[END_REF] These multi-rotaxanes pave the way towards the still challenging synthesis of more sophisticated higher-order rotaxanes.

I. 1. d) Applications of Rotaxanes

The interest of rotaxanes is not limited to their challenging syntheses; they find applications in various fields. [START_REF] Chambron | Functional rotaxanes: From controlled molecular motions to electron transfer between chemically nonconnected chromophores[END_REF][START_REF] Ma | Bright functional rotaxanes[END_REF] For instance, rotaxanes with appended chromophores have been used as light-harvesting antennae in the design of photosynthetic models. [START_REF] Schuster | Porphyrin-fullerene photosynthetic model systems with rotaxane and catenane architectures[END_REF][69][START_REF] Gallina | Light-Harvesting in Multichromophoric Rotaxanes[END_REF] Other rotaxane systems have been designed and shown properties in catalysis, [START_REF] Thordarson | Epoxidation of polybutadiene by a topologically linked catalyst[END_REF] anion sensing [START_REF] Evans | Beer: A redox-active [3]rotaxane capable of binding and electrochemically sensing chloride and sulfate anions[END_REF][START_REF] Brown | Porphyrin-functionalised rotaxanes for anion recognition[END_REF] and peptide delivery. [START_REF] Wang | Investigation of the intracellular delivery of fluoresceinated peptides by a host-[2]rotaxane[END_REF] Another, novel application was developed by B. D. Smith, who described squaraine rotaxane endoperoxides exhibiting remarkable chemiluminescent properties, paving the way towards new optical imaging agents. [START_REF] Baumes | Storable, thermally activated, near-infrared chemiluminescent dyes and dye-stained microparticles for optical imaging[END_REF] The system is a [2]rotaxane whose axle contains a central squaraine unit and whose ring incorporates an anthracene endoperoxide group (Figure I.12). The endoperoxide is stable at low temperature, but undergoes a cycloreversion reaction upon heating to body temperature. The energy released by the reaction is transferred to the squaraine chromophore, which emits near-infrared light that can pass through a living mouse. Another major field of applications of rotaxanes is the vast domain of molecular machines. This topic will be covered in the next part of this introduction.

I. 2. Molecular Machines: From Natural Systems to

Synthetic Devices

By definition, a molecular machine is a molecular system able to perform mechanical work. A molecular machine is generally composed of at least two components that can be set in motion in relation to each other. This motion must be triggered by an external stimulus, and be controlled and of relatively great amplitude, by opposition to the Brownian motion that animates all molecules. Typically, the stimulus can be chemical (variation of pH, exchange of ion or other chemical signal), photochemical or electrochemical. Moreover, the motion of a molecular machine is characterised by its reversibility: the system must be able to go back to its initial state and start over the cycle. Molecular machines were defined by analogy with macroscopic machines. In the macroscopic world, a machine is an apparatus that functions by applying a mechanical power, thereby inducing changes in the relative positions of the components. The relative motion of the constituents of a machine at the molecular level is reminiscent of a macroscopic machine at work. [START_REF] Balzani | Artificial molecular machines[END_REF][START_REF] Kinbara | Toward intelligent molecular machines: Directed motions of biological and artificial molecules and assemblies[END_REF][78][START_REF] Kay | Synthetic molecular motors and mechanical machines[END_REF] Molecular devices were defined using a similar analogy between the macroscopic and the nanometric worlds. The term "molecular device" refers to molecular systems that have a specific functionality, other than their intrinsic chemical reactivity; it is a broader concept than molecular machines. For example, molecular electronics and molecular sensors fall into the category of molecular devices. It would be impossible in this introduction to provide an exhaustive review on molecular machines and devices; we will describe only a short selection of some remarkable natural and synthetic systems.

I. 2. a) Natural Molecular Machines

Chemists may have defined molecular machines, but Nature invented them. Various (iii) hydrolysis of ATP to ADP (D) weakens the GroEL/GroES complex and induces release of the lid and folded protein. [START_REF] Bukau | The Hsp70 and Hsp60 chaperone machines[END_REF][START_REF] Yébenes | Chaperonins: two rings for folding[END_REF] The mechanism of action of the GroEL chaperonin involves several key steps. First, an unfolded protein binds to the hydrophobic sites at the entrance of the cavity of GroEL. Then, concerted fixation of seven molecules of ATP on GroEL triggers conformational changes that facilitate binding of the GroES lid. This results in an enlargement of the cavity that allows folding of the guest protein. Finally, hydrolysis of the bound ATP to ADP weakens the GroEL/GroES complex and induces release of the lid and folded protein. [START_REF] Kinbara | Toward intelligent molecular machines: Directed motions of biological and artificial molecules and assemblies[END_REF][START_REF] Yébenes | Chaperonins: two rings for folding[END_REF] The action of the chaperonin can be summarised in three consecutive steps: capture, folding and release of a guest protein.

I. 2. b) Artificial Molecular Machines

As shown by the above examples, Nature has developed extremely efficient tools to direct motion and perform tasks in living organisms. These natural molecular machines are an endless source of inspiration for synthetic chemists. Two approaches can be taken when attempting to reproduce the functions of natural systems or to create new molecular machines.

They consist in grafting synthetic units on natural machines, [START_REF] Van Den Heuvel | Motor proteins at work for nanotechnology[END_REF] or in designing entirely synthetic devices. [START_REF] Balzani | Artificial molecular machines[END_REF][START_REF] Kay | Synthetic molecular motors and mechanical machines[END_REF] Both approaches have been widely exploited, and a great variety of artificial molecular machine prototypes have been described.

Most of the synthetic molecular devices developed so far were studied in solution.

Although In the solid state isomerisation occurs near the surface upon irradiation with UV light from one side of the crystal. This results in a directly observable bending motion of a thin, 1-5 mm long, plate-shaped crystal. The process is reversible, and irradiation with visible light brings the system back to its initial shape. This device was successfully used as a cantilever that can lift metal balls in a stunning experiment. A rectangular plate crystal was fixed at the edge of a glass The molecular cantilever described above is a nice example of a molecular device based on a covalently bonded system. While a few other covalent structures have been used to make molecular rotors, [START_REF] Koumura | Lightdriven monodirectional molecular rotor[END_REF][START_REF] Van Delden | Unidirectional molecular motor on a gold surface[END_REF][START_REF] Karim | Symmetry and polar-pi effects on the dynamics of enshrouded aryl-alkyne molecular rotors[END_REF][START_REF] Ruangsupapichat | Reversing the direction in a light-driven rotary molecular motor[END_REF][START_REF] Lemouchi | Ultra-fast Rotors for Molecular Machines and Functional Materials via Halogen Bonding: Crystals of 1,4-Bis(iodoethynyl)bicyclo[2.2.2octane with Distinct Gigahertz Rotation at Two Sites[END_REF] wheelbarrows, [START_REF] Joachim | The design of a nanoscale molecular barrow[END_REF] scissors, 93 nanocars [START_REF] Shirai | Directional control in thermally driven single-molecule nanocars[END_REF][START_REF] Kudernac | Electrically driven directional motion of a four-wheeled molecule on a metal surface[END_REF] and spur gears, [START_REF] Frantz | Molecular Spur Gears Comprising Triptycene Rotators and Bibenzimidazole-Based Stators[END_REF] it is often advantageous to utilise the interlocked structure of mechanically bonded systems in the design of molecular machines. Catenanes and rotaxanes are composed of at least two components that are non-covalently but mechanically linked together. In the absence of interactions between the different constituents these will move freely in relation to each other. However, if the interactions between the components can be adjusted by external stimuli then the relative motions of the components can be monitored. Therefore, the intrinsic structure of catenanes and rotaxanes makes them excellent candidates for the construction of molecular machines, and they have indeed been extensively used in the design of various molecular devices. [START_REF] Sauvage | Transition metal-containing rotaxanes and catenanes in motion: Toward molecular machines and motors[END_REF][START_REF] Flood | Meccano on the nanoscale -A blueprint for making some of the world's tiniest machines[END_REF][START_REF] Coronado | Catenanes and threaded systems: from solution to surfaces[END_REF][100] For example the rotational motion of one ring with regard to the second one in a [2]catenane can be monitored using chemical, electrochemical or photochemical stimuli. [101][102][103][104][105][106][107] This motion can be seen as a pirouetting motion of one ring around the other or as a sliding motion of one ring along the other. In most cases the direction of the motion can not be monitored: the catenane can switch from one state to the other but no control is exerted on the direction of the rotation. The [3]catenane synthesised by D. A. Leigh and coworkers is an exception. The structure of this [3]catenane consists of two identical macrocycles, both threaded on a third, larger ring. Unidirectional rotary motion of the two small rings along the third one was achieved with this system (Figure I.17). 108 The large ring contains four binding sites (A, B, C, and D), which can interact with the small rings via hydrogen bonding. The affinity of the small macrocycles for sites A and B can be tuned by photoisomerisation of their central C=C

I. 2. c) Rotaxane-based Machines

The rotaxane structure is a very interesting framework for the construction of artificial molecular machines. [START_REF] Balzani | Artificial molecular machines[END_REF][START_REF] Kay | Synthetic molecular motors and mechanical machines[END_REF]109,110 The rotary motion of a catenane-based molecular motor can be translated in two different types of motion in a rotaxane: pirouetting of the ring around the axle;

or shuttling of the ring along the axle. Pirouetting rotaxanes [111][112][113][114] and shuttling rotaxanes 115,116 have both been described. Particular interest has been shown in shuttling devices for their potential use as transporters. 117 The translation motion achieved in a shuttling rotaxane brings up the possibility of transport and delivery of functional substrates.

For instance, a copper-complexed [2]rotaxane that acts as a fast-moving molecular shuttle was recently described by the group of J. Copper(I) preferentially forms tetrahedral complexes and is stabilised by hindered ligands, while copper(II) can be penta-coordinated. In this new [2]rotaxane shuttle the axle contains two bidentate chelating sites, and the motion is based solely on a difference in steric hindrance between the binding sites. The copper(I) complex is located on the hindered 2,9-diphenyl-1,10-phenanthroline site, but oxidation to copper(II) is followed by a fast translation motion resulting in complexation of the copper(II) centre on the less hindered 2,2'-bipyridine chelate. This process is reversible, and reduction of the metal centre to copper(I) brings the ring back to its initial position.

The shuttling motion of a ring along an axle has also been applied to multiply interlocked rotaxanes. J. F. Stoddart and coworkers used a rotaxane structure in the design of a molecular elevator whose platform goes up and down thanks to the shuttling motion of the rotaxane units.

The system is based on a triply interlocked [2] harvesting antennae and in the energy and electron transfer processes involved in photosynthesis. [120][121][122] Inspired by nature, chemists have designed many multi-porphyrin arrays as models of light-harvesting antennae and artificial photosynthetic systems. [123][124][125][126][127][128] The photophysical properties of porphyrin compounds also make them interesting as photosensitizers in photodynamic therapy and tumour imaging. 129,130 Figure I.20. Chemical structures of the porphyrin core and of two related heterocycles: the chlorin family and the bacteriochlorin family. One or two C=C double bonds are reduced in the chlorins and bacteriochlorins, respectively, compared to the porphyrin structure.

Porphyrins are excellent tetradentate chelating ligands. In its doubly deprotonated form a porphyrin can bind transition metals, which will lie either in the plane of the porphyrin or above this plane if the metal is too large to fit inside the central cavity. 131 In particular, zinc(II) ions are easily inserted in porphyrins and removed. Contrary to some other metal ions they form diamagnetic complexes with porphyrins, which facilitates their spectral characterisation by NMR. Another interesting feature of porphyrins resides in the number of sites available for functionalisation. Porphyrins can be substituted at part or all of their β and meso positions, which makes them versatile platforms for various applications, e.g. in the field of molecular electronics or materials. [132][133][134][135][136] Several synthetic strategies have been developed for the introduction of meso substituents; some of these strategies will be illustrated in Chapters II and V. Extension of the π system of a porphyrin by appropriate β,β'-functionalisation is also possible. The group of M. J. Crossley developed a synthetic strategy for the connection of aromatic moieties to porphyrin cores via pyrazine bridges; this strategy will be described in Chapter IV of this thesis.

I. 3. a) Axial ligation on metalloporphyrins

As mentioned above, an interesting feature of metalated porphyrins is their ability to bind axial ligands. This interaction considerably widens the range of applications available with metalloporphyrins. In addition to the introduction of β or meso substituents, further functionality can arise from binding of axial substrates. Axial coordination on metalloporphyrins has been notably exploited in catalysis, 137,138 in the assembly of various porphyrin-containing multicomponent structures 139,140 and in host-guest chemistry. This last topic will be detailed in part I. 3. b). Recently reported assemblies based on the coordination of axial ligands on metalloporphyrins include the formation of non-covalent [2]catenanes and the templated synthesis of a 12-porphyrin nano-ring, which are chosen as examples to illustrate this type of interaction in this introduction. A series of [2]catenanes assembled by coordination chemistry was described by the group of J.-P. Sauvage in the recent years. 141,142 Each catenane is composed of two different subcomponents: a 2,9-diphenyl-1,10-phenanthroline (dpp) chelate attached to two peripheral zinc porphyrins, and a ligand that contains two pyridyl units linked either by a phenanthroline or by a naphthalene spacer. A copper(I) template preorganises two bis-porphyrin components in an intertwined fashion by formation of a [Cu(dpp) 2 ] + -type complex. The macrocycles are then closed by axial coordination of the bifunctional pyridyl ligands on the Zn-porphyrins to form a [2]catenane (Figure I.22). The geometrical fit between the components was shown to be better in the catenane containing the bis-pyridyl substituted naphthalene than in the one containing the phenanthroline units. These new non-covalent catenanes pave the way towards more complex interlocked architectures. H. L. Anderson and coworkers recently reported the very elegant, novel synthesis of a 12porphyrin nano-ring, whose construction involved the Zn-porphyrin/pyridine axial coordination as a key interaction. 143 Their group has developed the synthesis of linear conjugated Znporphyrin oligomers and studied the formation of various assemblies by axial coordination of multifunctional templates to the Zn-porphyrin wires. For example, they described ladder-shaped assemblies obtained by coordination of DABCO with two porphyrin wires. 144,145 In their recent report they used a new strategy to preorganise the building blocks. They named this strategy Vernier templating by analogy to the Vernier scale system and Vernier complexes. 146,147 In this type of approach two buildings blocks containing complementary binding sites are assembled. If one of the building blocks contains n binding sites and the second building block contains m sites then a multi-component assembly will be formed, where the number of bound sites is the lowest common multiple of n and m. In the system described by Anderson a six-pyridyl template interacts with a four-porphyrin oligomer by axial coordination to form a twelve-site Vernier As mentioned before, axial coordination on metalloporphyrins has found applications in many fields of research. An original approach was taken by M. J. Crossley and P. Thordarson, who used this interaction as a tool in the characterisation of bis-porphyrins. 148 Their system is composed of two capped porphyrins covalently linked by a rigid aromatic spacer. The reaction leading to the bis-porphyrin yields two isomers, with syn and anti orientations of the capping groups, respectively (Figure I.24). The isomers could be separated, but assignment of the structures using conventional spectroscopic techniques proved difficult. Axial coordination of a "molecular ruler" was used to distinguish between both isomers. The ruler is the bifunctional ligand 1,12-diaminododecane, which can bind on the unprotected faces of the Zn-porphyrin units.

Covalent! coupling! Template! removal! Axial ! binding! 12-porphyrin! nano-ring! figure-of-eight! complex! Vernier complexes! linear! porphyrin! tetramer! template!
The ligand is just long enough to span the Zn-Zn distance in the syn isomer and to form a strong intramolecular complex, but it is too short to wind itself around the anti isomer and to form a complex involving both faces. The isomers were thus assigned according to their binding constants with the molecular ruler (Figure I.24).

Figure I.24.

Discrimination between the syn and anti isomers of a bis-porphyrin using axial coordination with a "molecular ruler". The bifunctional ruler ligand forms a strong complex with the syn isomer but is too short to bind both Zn-porphryin sites on the anti isomer. 148,149 In a different system, the groups of K. P. Ghiggino and M. J. Crossley used axial ligation on a Zn-porphyrin to tune the energy and charge transfer properties of multi-porphyrin arrays. 150 Photoinduced charge transfer was switched on upon axial coordination of a chloride anion on a Zn-porphyrin in a porphyrin triad.

These few examples give an insight of the various applications brought up by axial coordination on metalloporphyrins. This interaction also plays a major role in host-guest systems based on porphyrins, which we will illustrate in the next part.

H 2 N NH 2 NH 2 H 2 N + + NH 2 H 2 N N N N N Zn N N N N Zn N N O O O O O O O O O O O O O O O O O O O O O O N O O N N N N Zn N O O O O O O O O O O N O O O O O O N N N Zn O O O O O O O O N N N

I. 3. b) Host-guest chemistry with porphyrins

Since the introduction of the concept of host-guest chemistry, 151 a great variety of molecular containers have been designed, and their abilities to bind guest substrates have been studied. The host-guest recognition can be based on diverse types of interactions, e.g. H-bonding, metal-ligand interactions or Van der Waals interactions. In particular, metalloporphyrincontaining hosts can bind substrates thanks to the axial ligation interaction described above. The group of J. M. K. Sanders contributed significantly to this field of research and published pioneering work on the synthesis of cyclic porphyrin dimers that can host ditopic guests in their central cavity. 152,153 In these systems the porphyrins are covalently linked by chains of various length and flexibility. Two of these dimers are depicted in Figure I.25. Both systems contain zinc porphyrins and can accommodate the aliphatic diamine 1,4-diazabicyclo[2.2.2]octane (DABCO). The association constants of the bis-porphyrin dimers with DABCO in dichloromethane (~10 7 -10 8 M -1 ) are two to three orders of magnitude higher than the binding constants observed for the corresponding porphyrin monomers with DABCO in the same solvent (~10 5 M -1 ). This highlights the cooperative effect in the double binding process in the inner cavity and the stabilisation of the inclusion complex compared to 1:1 porphyrinmonomer/DABCO complexes. 153,154 The length and nature of the chains linking the porphyrins in the dimer can be varied so as to accommodate longer guests. 155 Host-guest complexes of covalently linked Zn-porphyrin dimers and ditopic nitrogen ligands (DABCO or 4,4'-bipyridine) synthesised and studied in the group of J. K. M. Sanders. 153,154 Other groups designed some tweezers-shaped bis-porphyrin hosts, in which a single bridge links the metalloporphyrins. M. J. Crossley and his group synthesised several molecular receptors constituted of two porphyrins linked by a Tröger's base bridge. The porphyrins can be

N N N N Zn N N N N Zn O O O O N N O O O O N N N N C 6 H
N N N N Zn N N R R R R N N N N Zn N N R R R R N N N N N N Zn N N R R R R N N N N Zn N N R R R R N N N N H 2 N H 2 N H 2 N H 2 N R = Favoured! conformation! N N N N Mg N N N N Mg O O O O Me H 2 N H N H O
Axial coordination on metalloporphyrins gives rise to a wide range of molecular recognition possibilities. However, the host-guest chemistry of porphyrin systems is not limited to complexes formed by this type of interaction. Some cyclic porphyrin hosts form complexes with fullerene guests. 161 Inclusion of fullerenes in these systems occurs by Van der Waals interactions and in some cases via π-electronic charge transfer from the porphyrin moiety to the fullerene. For example, the disulfide-bonded host illustrated in Molecular receptors and cages provide a specific confined environment for guest substrates that can be very different from the environment experienced by the guests in solution.

This can promote unusual reactivity and unique chemical phenomena in the cavity. [165][166][167][168] For instance folding of short peptides can be triggered by encapsulation in a porphyrin-faced cage, as reported by M.

I. 3. c) Porphyrins and Molecular Machines

As seen in the examples above, porphyrins are interesting for their interactions and binding properties with various substrates, which justifies their incorporation in molecular machines. To date porphyrin-containing molecular machines are not so common. The porphyrin moiety is sometimes used as a stopper or as part of the axle in rotaxane shuttling systems, where it can play a role in the trigger mechanism of the shuttling ring. 172,173 T. Aida and coworkers designed a different molecular device whose motion is reminiscent of a molecular pedal, and that utilises axial coordination on Zn-porphyrins as a key interaction in the machine mechanism. Oligopeptide inclusion and folding photoisomerisation of the azobenzene unit from trans to cis and back promotes a rotary motion of the cyclopentadienyl rings of the ferrocene pivot, which in turn leads to a pedal-like conformational change of the zinc porphyrin units. This photoinduced motion of the host is then transferred to the rotary guest molecule, which undergoes twisting in a clockwise or anticlockwise fashion. 174 A photoresponsive self-locking molecule based on an analogous system was later described. The new switchable device involves the rotary motion of a ferrocene pivot and axial coordination of a ditopic guest between two porphyrins as for the previous system. 175

I. 4. Porphyrin-containing Rotaxanes

In the previous parts of this introduction we presented the properties of the rotaxane architectures and of the porphyrin moiety, as well as their applications, in particular in the construction of molecular machines. Here we aim to show how porphyrins and rotaxane structures can be combined in the design of functional molecular assemblies and devices.

I. 4. a) Examples of Porphyrin-containing Rotaxanes

Porphyrin units can be incorporated in a rotaxane in several ways. Due to their large size they have been used as stoppers at the end of the axle component, and they can be linked to the axle either by axial coordination 181,182 or by covalent substitution on one of the meso positions. [START_REF] Chambron | A Rotaxane with Two Rigidly Held Porphyrins as Stoppers[END_REF][START_REF] Li | Convergent synthesis and photophysics of [60]fullerene/porphyrin-based rotaxanes[END_REF]183 In some cases the porphyrin is part of the axle 173 and can be used to compartmentalise the dumbbell component in the case of a multi-rotaxane. For example [3]-and [5]rotaxanes that are constituted of two and four rings (respectively) threaded on a dumbbell have been described. 184,185 In these rotaxanes the porphyrin units incorporated in the dumbbell segregate each ring to a specific section of the axle. Porphyrins can also be part of or covalently linked to the ring component of a rotaxane. C. A. Hunter and coworkers described a self-assembled [2]rotaxane whose ring is a zinc porphyrin dimer closed by axial coordination on the Zn-porphyrins. 186 Strapped and capped porphyrins form hollow cycles that can serve as the ring component of a rotaxane as well. 187,188 The spatial proximity between the porphyrin and the axle in such rotaxanes has been used in the catalysis of chemical transformations on the axle by the porphyrin. [START_REF] Thordarson | Epoxidation of polybutadiene by a topologically linked catalyst[END_REF] Another possibility is to attach porphyrins to the ring component of a rotaxane. Such porphyrin-appended rotaxanes have shown interesting properties in electron and energy transfer or in host-guest chemistry. [START_REF] Marois | 3]rotaxane-porphyrin conjugate as a novel supramolecular host for fullerenes[END_REF][START_REF] Brown | Porphyrin-functionalised rotaxanes for anion recognition[END_REF]189 The group of J.-P. Sauvage described a [2]rotaxane that contains three porphyrin units: a gold(III)-porphyrin is incorporated in the ring component and two zinc(II)-porphyrins act as stoppers at the extremities of the dumbbell component. 190 Pirouetting of the ring around the axle is observed upon complexation/decomplexation of copper(I) (Figure I.32). In the presence of copper(I) the orientation of the ring is imposed by the formation of a tetrahedral complex with the bidentate sites of the macrocycle and dumbbell components, and the gold porphyrin is located far away from the zinc porphyrin stoppers. After demetalation of the copper(I) centre the ring undergoes a half-turn rotation and the rotaxane adopts a conformation where the electronacceptor Au(III)-porphyrin is located between the electron-donor Zn(II)-porphyrins. This pirouetting rotaxane is a nice example of a molecular machine based on a porphyrin-containing rotaxane. [2]rotaxane that contains three porphyrin units. A gold(III) porphyrin is incorporated in the macrocyclic component, and the axle bears two zinc(II) porphyrins as stoppers. 190

N N N N Cu N N N N Zn O O O O R R R R N N N N Zn R R R R N N N N Au + N N N N N N Zn R R R R N N N N Zn R R R R N N O O N N N N Au + O O R = C 6 H 13 -Cu + + Cu +
The geometrical features of porphyrins make them useful in the design of multi-rotaxanes.

For example a porphyrin can be substituted with four thread-like chains at its four meso positions.

Subsequent threading of rings and stoppering of the axles can lead to the formation of a [5]rotaxane with a central porphyrin platform, as described by D. Tuncel et al. 191 If the rings are large enough to enclose two threads then a [6]rotaxane structure can be formed with two face-toface porphyrins surrounded by four doubly threaded rings. R. J. M. Nolte, J. F. Stoddart and coworkers reported the formation of this type of structure in 1997 (Figure I.33). 192 Their system can not strictly be called a rotaxane because the axles are not stoppered, but the interlaced structure of the [6]pseudorotaxane is maintained by the interactions between the ammonium groups of the axles and the crown-ether rings. The assembly features two slipped cofacial Cu(II) porphyrins maintained in close proximity, and parallel electron spin coupling is observed between the Cu(II) centres in the threaded assembly. The system resembles the special pair of the photosynthetic reaction centre of bacteria.

Figure I.33.

A porphyrin-incorporating [6]pseudorotaxane structure reminiscent of the special pair of the photosynthetic reaction centre. Two central copper(II) porphyrins are held in a slipped cofacial arrangement by the surrounding interlocked scaffold. Parallel spin electron coupling between the Cu(II) centres results from the close proximity of the metalloporphyrins. 192 A similar tetra-substituted porphyrin was used by the group of K. Tanaka in the design and synthesis of a tetra-interlocked [2]rotaxane. 193 The two components of this rotaxane are a copper(II) phthalocyanine tetra-substituted with four crown-ether rings and a copper(II) porphyrin with four thread-like substituents. The final [2] The association constants measured with these guest substrates were in the range 10 6 -10 7.5 M -1 . In the case of a long guest the association constant of the copper-free rotaxane was higher than that of the copper(I)-complexed rotaxane, in accordance with the expected adaptability of the copperfree host. 194,195 Figure I.35. Schematic views of the copper(I)-complexed (top) and copper-free (bottom) forms of a [3]rotaxane. The rotaxane is a good molecular receptor for ditopic pyridyl guests of various lengths. The copper(I)-complexed rotaxane forms stronger complexes with short guests, while the copper-free rotaxane has better affinity for long guests. 194,195 A [4]rotaxane designed in a similar way was later described. In this rotaxane the porphyrin moieties were substituted with peripheral macrocycles at two antipodal positions. The coordinating macrocycle and the spacer between the ring and the porphyrin were identical to those used in the synthesis of the [3] In the case of the copper(I)-complexed [4]rotaxane, short ditopic ligands formed guest inclusion complexes between the porphyrins, but longer guests did not fit in the central cavity. 196 Thus the copper(I)-complexed [4]rotaxane showed more selective host-guest properties than the corresponding [3]rotaxane. However, completely different behaviour was observed for the copper-free forms of the [3]-and [4]rotaxanes. While the demetalated [3]rotaxane was a good molecular receptor the [4]rotaxane collapsed upon demetalation of the copper(I) centres and did not have any affinity for guest molecules after demetalation. This was attributed to π-stacking between the aromatic systems of the two porphyrinic bis-macrocycles and to axial coordination of the triazole groups of the dumbbells on the Zn-porphyrins. 197 The [4]rotaxane described above contains a porphyrinic bis-macrocycle component whose central part is a rigid, very extended aromatic system, and whose synthesis is very lengthy and tedious. The host-guest properties of the rotaxane were limited by its rigidity and by the collapse of the system upon demetalation. This encouraged the design of a new [4]rotaxane based on a very different porphyrinic bis-macrocycle, which will be described in this thesis.

I. 4. c) Present Research Project: Design and Synthesis of Porphyrin-Based Multi-Rotaxanes as Adaptable Molecular Receptors

The main objective of this PhD research project is the design and synthesis of new adjustable molecular receptors. The theme of the project was initially inspired from the work performed by chaperone proteins. As described in part I. 2. a) of this introduction these natural molecular machines are molecular receptors for newly formed, unfolded proteins, and they assist folding of the guest proteins. Rather than trying to mimic the exact function of chaperonins (i.e.

protein folding) we took inspiration from their mechanism of action with its three consecutive steps: capture, conformational change and release of a guest substrate. We envisioned that it could be possible to achieve the capture, conformational change and release of small organic guests with a fully synthetic receptor, which would be structurally much simpler than chaperone proteins. In particular, we envisaged the design of a molecular receptor whose internal cavity could be reduced in size upon application of an external stimulus. This receptor would be able to change the conformation of a guest substrate by compression and can therefore be seen as a molecular press.

When we designed our new molecular receptor we decided to use two cofacially arranged metalloporphyrins and to exploit their axial coordination properties to bind ditopic guest substrates in the internal cavity formed between the porphyrins. By surrounding the metalloporphyrins with a rotaxane scaffold the face-to-face arrangement of the porphyrins would be maintained. Moreover, a shuttling motion of the rings along the axles could enable to monitor the inter-porphyrin distance. The target rotaxane is schematically depicted in The aromatic system of the porphyrinic bis-macrocycle component of the rotaxane will be significantly reduced in this new system by comparison with the [4]rotaxane described in part I. 4. b). In the new system the macrocycles will be linked to the porphyrins via single C-C bonds at the meso positions, which should bring more flexibility to the assembly and prevent the collapse of the system upon demetalation of the copper(I) centres. The number of synthetic steps will be significantly reduced. While functionalisation of the porphyrin with four coordinating rings was hardy achievable with the previous design, it will be possible with the present system.

The use of a porphyrinic tetra-macrocycle will open up the possibilities for the construction of architecturally interesting molecules. For example a porphyrin substituted with four coordinating macrocycles (instead of two) could give rise to a [6]rotaxane upon threading with adequate axles followed by stoppering. This rotaxane would be constituted of two face-to-face zinc porphyrins whose rings would be threaded by four dumbbells (Figure I.39). Thanks to the presence of two additional dumbbells a greater geometrical control over the inter-porphyrin distance could be achieved with this system compared to the system depicted in In addition to their potential as molecular receptors or presses, the rotaxanes studied in this thesis are interesting by virtue of their challenging syntheses and of the prospect of obtaining new, aesthetically attractive interlocked architectures. The project involves the syntheses of a molecular thread and stopper, as well as the syntheses of new porphyrin building blocks substituted with coordinating macrocycles, which will potentially find applications in the elaboration of other intertwined molecules in the future. The target bis-macrocyclic component is a new Zn-porphyrin substituted with two dppcontaining rings at antipodal meso positions. The molecular rod, or axle, has a central aromatic part that forms two rigidly held bidentate chelating sites derived from the 2,2'-bipyridine motif.

The porphyrinic bis-macrocycle and the axle are designed to form a [4]pseudorotaxane upon complexation with a copper(I) template, which will then be converted to the desired [4]rotaxane by introduction of stoppers at the ends of the axles. The stopper building block possesses a bulky tris(p-tert-butylphenyl)methane group. The axle and the stopper are functionalised with terminal acetylenic and azide groups, respectively, which makes them "clickable" via a Huisgen

Copper(I)-catalysed Azide-Alkyne Cycloaddition (CuAAC).

II. 1. b) Comparison of the Present Porphyrinic Bis-Macrocycle with the Previous System

As mentioned in part I. 4. c) of the introduction the present project is related to previous work performed in our laboratory. Former PhD students and postdoctoral researchers studied a In the previous system the linker between the porphyrin and the dpp chelates was very rigid since the porphyrin nucleus and the chelates were fused via pyrazine-benzene-pyrazine bridges at antipodal β positions of the porphyrin. In addition, the porphyrin was attached to the "back" of the 1,10-phenanthroline aromatic fragment, imposing an exo coordination mode of this chelate with respect to the porphyrin. The connection mode was such that the lateral ring was rigid and could not rotate much with respect to the porphyrin plane. In the present target compound the situation is dramatically different since (i) the porphyrin and the coordinating rings are linked via single C-C bonds between the porphyrin meso positions and the macrocycle, making the latter susceptible to rotate with respect to the plane of the porphyrin, and (ii) the coordinating axis of the dpp fragment is pointing towards the porphyrin. In other words, the dpp unit will be located far away from the porphyrin and it will be electronically decoupled from it, contrary to the first series of porphyrin-incorporating multi-rotaxanes made in our group. These differences will introduce a greater flexibility in the rotaxanes that will be built from the new target bis-macrocycle. Consequently, original host-guest properties will be expected with the new system. Another important difference between the previous and the present systems is the number of organic steps involved in the synthesis of the porphyrinic bis-macrocycle. The synthesis of the previously described free-base porphyrin was long and tedious. It consisted in fifteen independent organic steps 196 while this number is reduced to seven for the present target compound, as will be detailed in this chapter.

II. 2. A dpp-Containing Macrocyclic Precursor

II. 2. a) Target Structure and Retrosynthesis

The macrocycle whose structure is depicted in The synthetic approach chosen to form the macrocycle is a double Williamson reaction between 3,5-dihydroxybenzaldehyde and a dpp-derivative functionalised with two tosylateterminated chains.

II. 2. b) Synthesis of the dpp-Containing m-31 Macrocycle

The aldehyde-appended macrocycle 5 was synthesised in five steps from commercial

II. 2. c) Characterisation of the Macrocycle: X-Ray Crystal Structure

In addition to 1 H NMR spectroscopy and mass spectrometry, In the crystalline state the conformation of the macrocycle is surprisingly close to planarity, the benzaldehyde ring being nearly coplanar with the phenanthroline. The structure of 5 possesses no symmetry element, and the phenyl groups attached to the phenanthroline differ in their orientations. One of these phenyl rings is twisted by 22.45° in regard to the phenanthroline and stacks with the benzaldehyde ring of an upper molecule. Its orientation is typical of 2,9diphenyl-1,10-phenanthroline moieties. 201 The second phenyl ring shows bending rather than twisting in regard to the phenanthroline. The torsion angle is only 3.68° but the phenyl ring points out of the mean plane of the phenanthroline. The molecules are packed in such a way that the cavities of the macrocycles form narrow channels filled with solvent molecules. A molecule of dichloromethane is present in the macrocycles, with the Cl atoms pointing towards the phenanthroline moiety.

The aldehyde-appended macrocyclic precursor 5 will be used in the synthesis of a porphyrinic bis-macrocycle, as we will detail in part II. 3. The free-base porphyrin 7 was formed by MacDonald condensation of macrocycle 5 with 5-mesityldipyrrylmethane 6. The latter compound was chosen because it increases the solubility and prevents π-stacking of the corresponding porphyrin, and it reduces scrambling during the condensation reaction. 205 The dipyrrylmethane 6 was formed by condensation of mesitylaldehyde with pyrrole in the presence of a large excess of the latter reagent using ceric ammonium nitrate (CAN) as a catalyst. 207 We then followed the optimised condensation conditions described by Lindsey and coworkers for the synthesis of the porphyrin. 204 The dipyrrylmethane and the macrocyclic aldehyde (10 mM in CH 2 Cl 2 containing 18 mM TFA) were stirred at room temperature. The reaction turned out to be very slow. After 20 hours we obtained the desired porphyrin in poor yield (< 2%). We performed other condensation reactions with different

II. 3. A Zn

N N O O O O O O N N O O O O O O N NH N HN N N O O O O O O O H + NH HN 1) TFA 2) DDQ 3) Na 2 CO 3 N N O O O O O O N N O O O O O O N N N N Zn 1) Zn(OAc) 2 .2H 2 O 2) Na 4 EDTA Global yield: 19 % H O N H + 1) CAN 2) NaOH 25 % 5 6 7 8
concentrations of trifluoroacetic acid and observed that five equivalents of TFA were necessary to allow an efficient condensation. Chromatographic purification of the free-base porphyrin 7

proved difficult. The porphyrin could not be fully purified so the compound was treated with excess zinc acetate with the expectation that the product would be more easily isolated in its metalated form. In the course of this metalation reaction, the dpp chelates of the macrocycles formed complexes with Zn(II) as well as the porphyrin core. Purification of the product at this stage proceeded much more easily, and the porphyrinic bis-macrocycle complexed to three Bis-macrocycle 8 was designed to be a good candidate for threading. The "gathering-andthreading" effect of copper(I) was used in the synthesis of a prototypical [3]pseudorotaxane from compound 8, in order to test its ability to form threaded assemblies. " (nm)!

(τ 1 = 1.85 ± 0.20 ns). 210 The emission lifetime of the pseudorotaxane 9 2+ turns out to be much shorter (τ 2 = 0.15 ± 0.05 ns) than that of the copper-free compound 8. This observation is not especially surprising and is in line with previous work on related compounds containing zinc porphyrins and copper complexes of the Cu(dpp) 2 + family. 210 The singlet excited state of the Zn porphyrin is rapidly quenched by the copper(I) complex, due to the presence of a low lying triplet MLCT.

A prototypical [3]pseudorotaxane was successfully obtained by double threading reaction of the dap chelate in the rings of porphyrinic compound 8 in the presence of a copper(I) template.

This result encouraged us to continue our works towards the construction of more complex rotaxane structures.

II. 5. A Molecular

II. 5. b) Synthesis of a Two-Station Axle terminated with Acetylenic

Functions

The molecular rod represented in Figure II.12 has already been used in the synthesis of several pseudorotaxanes and rotaxanes. [START_REF] Collin | Rotaxanes and[END_REF]196,[217][218][219] The

R H N 3 R' N N N R R' Cu(I) + alkyne azide anti 1,2,3-triazole CuAAC N N N N H H O N 3
Molecular rod or axle Stopper

3,8-dibromo-4,7-phenanthroline precursor 12 is obtained in three steps from 4,7-phenanthroline following a procedure described by the group of Lehn. 220 The procedure described in this paper is then adapted to lead to the desired dibromo-functionalised compound 14. 221 In this chapter we described the syntheses of three important building blocks: a zinc porphyrin substituted with two coordinating macrocycles, a two-station rigid axle and a stopper that can be "clicked" at the ends of the axle. These building blocks were carefully designed to allow their assembly into rotaxane structures. In the next chapter we will put this concept in practice and investigate the formation of a rotaxane from the molecular bricks presented here.

A Distensible Molecular Receptor

After describing the syntheses of three building blocks we will now discuss the formation of a new rotaxane from these precursors. The rotaxane will be assembled via a "threadingfollowed-by-stoppering" strategy. Its synthesis, characterisation and molecular receptor properties will be described.

III. 1. Synthetic Approach for the Formation of a [4]rotaxane

III. 1. a) General Strategies for the Synthesis of Rotaxanes

Various synthetic approaches have been developed to assemble building blocks into rotaxane structures, in a way that makes it impossible to unthread the rings from the dumbbell components once the rotaxanes are formed. The main two strategies are the "threading-andstoppering" and the "clipping" methods. In the threading-and-stoppering approach, threading of a preformed ring on an axle is followed by introduction of two bulky stoppers at the ends of the axle. [START_REF] Diederich | A Copper(I)-Complexed Rotaxane with Two Fullerene Stoppers[END_REF][START_REF] Durot | Synthesis of new copper(I)complexed rotaxanes via click chemistry[END_REF]182,189,[225][226][227][228][229][230] A variant of this method resides in the use of an axle bearing one stopper in the threading step. In that case only one more stopper needs to be introduced in the second step. [START_REF] Chambron | A Rotaxane with Two Rigidly Held Porphyrins as Stoppers[END_REF] The clipping approach consists in the macrocyclisation of an open ring precursor around a preformed dumbbell. [START_REF] Wittenberg | A clipped [3]rotaxane derived from bis-nor-seco-cucurbit[10]uril[END_REF]231,232 A schematic view of these main two methods is depicted in Beside the "threading-and-stoppering" and "clipping" strategies, a few other methods have been reported for the formation of rotaxanes. Direct threading (or slippage) of the ring on a stoppered dumbbell can be induced at high temperature. The threaded species obtained is thermodynamically stable upon cooling to room temperature. 233,234 Another strategy was described by M. Asakawa and coworkers. They used a macrocycle incorporating a tetradentate salophen moiety. In the absence of metal the macrocycle is big enough to slip onto the dumbbell, however a square-planar complex is formed in the presence of Pd(II), which shrinks the size of the ring formed by the complexed macrocycle and locks the system in the threaded state. 235 S.-H. Chiu recently reported a metal-free variant to this "threading-and-shrinking" method where ring shrinking is achieved by photoextrusion of SO 2 from a sulfone-incorporating macrocycle. 236 The same group also took an alternative approach, which consists in making the stoppers swell instead of making the ring shrink. The end groups of the axle are cis-1,2- divinylcyclopropane units, that can be converted into bulkier cycloheptadiene rings by Cope rearrangement after threading of the ring. 237,238 A similar strategy to this "threading-andswelling" approach relies on the use of a stopper that can be reversibly switched between two states: an extended state that allows threading and unthreading of the ring, and a folded, bulkier state that prevents slippage. Examples of switchable stoppers include a methylstilbene unit whose extended E isomer is converted to the folded Z isomer upon photo-irradiation, 239 and an arylamide foldamer stopper. 240 This switchable-stoppering approach could find applications in the controlled release of active substances in the medicinal field.

In spite of the attractiveness of the new strategies described above we decided to opt for the more classical threading-and-stoppering approach when designing our new target rotaxanes. This method has the advantage of being well documented, versatile and efficient. A wide range of reactions for the introduction of stoppers is available, including Williamson ether synthesis, 225 C-C coupling, [START_REF] Diederich | A Copper(I)-Complexed Rotaxane with Two Fullerene Stoppers[END_REF] formation of a bulky metal complex, 226 formation of porphyrins, 40 axial ligation on porphyrins, 182 Diels-Alder reaction, 189 and Huisgen Copper(I)-Catalysed Azide-Alkyne Cycloaddition (CuAAC). [START_REF] Durot | Synthesis of new copper(I)complexed rotaxanes via click chemistry[END_REF][227][228][229][230] As mentioned in the previous chapter we selected the CuAAC as the stoppering reaction for our new multi-rotaxanes. This type of click reaction has been extensively used in the synthesis of rotaxanes in recent years; 241 its mild conditions make it compatible with various rotaxane precursors.

III. 1. b) Design of the System and [4]Rotaxane Formation Strategy

The chemical structure of the target copper(I)-complexed [4]rotaxane is represented in Figure III.2. As previously mentioned the [4]rotaxane will consist of two dumbbells and of two bis-macrocycles that incorporate a central Zn-porphyrin. Each dumbbell will be threaded through one of the rings of each porphyrin in a cyclic structure. The dumbbells are composed of the bisbidentate axle described in Chapter II, "clicked" to bulky stoppers stoppers at each end. The bismacrocycle component was presented in Chapter II as well, and we showed that it could be used to form threaded assemblies in quantitative yield. The "threading-followed-by-stoppering" approach will be taken for the formation of the [4]rotaxane (Figure III.3). In a first step the "gathering-and-threading" effect of copper(I) [START_REF] Dietrich-Buchecker | Une nouvelle famille de molecules : les metallo-catenanes[END_REF][START_REF] Chambron | A Rotaxane with Two Rigidly Held Porphyrins as Stoppers[END_REF][START_REF] Durot | Synthesis of new copper(I)complexed rotaxanes via click chemistry[END_REF] is utilised to form a [4]pseudorotaxane from the bis-macrocycle and axle building blocks. The stoppers are then introduced via a quadruple CuAAC click reaction 215 to give the [4]rotaxane. [4]rotaxane composed of two axles and two bismacrocycles. Each bis-macrocycle consists of two flexible rings attached to a central Zn porphyrin. The synthetic strategy is based on the ''gathering-and-threading'' approach using a copper(I) template, followed by stoppering. The porphyrin is represented as a square or a diamond, the bidentate chelates are indicated by green or blue U-shaped symbols and the gathering metal centre (copper(I)) is a pink dot. The stoppers are depicted as large grey spheres.

N N O O N O O O O O N N O O O O O N N N N N O O O O O N N O O O O O N N N N N N N N N N O Zn Zn O N N N N N N N N N O O O N N N O 4+ 4PF 6 N Cu N Cu Cu Cu Figure III.3. Preparation of a
The rotaxane incorporates two central face-to-face Zn-porphyrins, which will allow for complexation of linear ditopic guests via axial coordination between the metalated porphyrins.

The specificity of the present system is that the new bis-macrocyclic component will make the rotaxane assembly much more flexible than previously described [4]rotaxanes (see Part I. 4. b)). 196,197 Therefore, the new [4]rotaxane should be adaptable even in its coppercomplexed form, contrary to the previous system which was more rigid and which collapsed after demetalation. Due to a higher flexibility of the connectors between the porphyrinic plates and the axles, the receptor should be "inflatable", depending on the complexed substrate, in a manner reminiscent of the induced-fit in enzymes. [242][243][244][245][246][247] As shown in previous studies the 31membered ring can be distorted and a non-planar ring can be generated. 200,248 In this chapter we will see how this distortion ability influences the host-guest properties of the rotaxane. The gathering-and-threading effect of copper(I) was utilised in the first step (threading), which led to the formation of a cyclic [4]pseudorotaxane consisting of two porphyrin-bismacrocycles and two threads. First, an acetonitrile solution of [Cu(CH 3 CN) 4 ](PF 6 ) was added to a suspension of the poorly soluble porphyrin 8 in dichloromethane to give a deep red solution of bis-macrocycle 8 complexed to two copper(I) ions at the dpp chelating sites. This solution was then added to a suspension of acetylenic thread 16 (stoichiometric amount) in dichloromethane.

This resulted in the formation of the [4]pseudorotaxane with four tetrahedral copper(I) complexes linking the dpp sites of the macrocycles and the bipyridine-type sites of the threads.

In a second step, bulky azide-functionalised stopper precursors were introduced at each acetylenic end of the threads via a CuAAC click reaction. Stopper 18, catalytic [Cu(CH 3 CN) 4 ](PF 6 ) and base (Na 2 CO 3 ) were added to the reaction mixture containing the [4]pseudorotaxane. The resulting stoppered [4]rotaxane 19 4+ 4PF 6 was obtained as a deep purple solid after purification by consecutive alumina, size-exclusion and silica column chromatographies. The global yield over two steps (threading and quadruple stoppering) was 50%. The isotope profile confirms that the [4]rotaxane obtained has four positive charges and consists of two dumbbells and two bis-macrocycles (2:2 species), linked by Cu(I) cations. A different threading scheme could have been expected where a single axle would be threaded through both rings of the same bis-macrocycle. This would have led to a doubly charged [2]rotaxane consisting of one dumbbell and one bis-macrocycle (1:1 species) (Figure III.6). The 1:1 species would have had the same m/z value as the 2:2 species, but the isotope profile would have been different, with a larger gap between two signals, which was not observed experimentally. Therefore, the observed profile confirms that the isolated product is a [4]rotaxane, not a [2]rotaxane. Mass spectrometry results indicated that this threading scheme is not favoured. The isotope profile is consistent with a [4]rotaxane containing four copper(I) centres

III. 2. c) NMR Characterisation of the [4]Rotaxane

NMR characterisation of the [4]rotaxane was not as straightforward as mass spectrometry characterisation. 1 The 1 H NMR data confirm the interlocked structure of the rotaxane. This is evidenced by characteristic chemical shifts in the rotaxane compared to the free porphyrinic bis-macrocycle 8,

for example the upfield shift of the phenyl protons of the dpp units (protons o and m on Consequently, we tend to believe that the minor signals observed do not correspond to an impurity but to a different conformer of the [4]rotaxane. This conformer does not seem to exchange fast with the major conformer in CD 2 Cl 2 solution. Unfortunately, we were not able to identify what the structure of the minor conformation is. Using the Stokes-Einstein equation applied to a spherical model we deduce a diameter of 48 Å for the rotaxane. This is consistent with the formation of the [4]rotaxane 19 4+ whose size was estimated using CPK models. According to the CPK model the length of the porphyrinic bismacrocycle approximates to 43 Å and the length of the dumbbell component in fully extended conformation approximates to 54 Å. Given that the linker between the central part of the dumbbell and the stopper is flexible, we can assume that the conformation of the dumbbell is not fully extended in solution and that its length averages shorter values. In conclusion, the CPKestimated size fits well with an experimentally measured ball-shaped model of 48 Å.

III. 2. d) UV-visible Absorption Characterisation of the [4]rotaxane

Finally, the [4]rotaxane was characterised by UV-visible absorption spectroscopy. The Figure III.12. UV-visible absorption spectra (Soret band) of [4]rotaxane 19 4+ and its precursor, porphyrinic bis-macrocycle 8 in CH 2 Cl 2 with [porphyrin] = 1.9*10 -6 M. The blue shift and broadening of the Soret band of the rotaxane is attributed to exciton coupling between the two central porphyrins.

!"

!#$" !#%" !#&" !#'" (" %!)" %(!" %()" %$!" %$)" %*!" %*)" %%!"
+,-+./-01"2034567-,7/789 :%;-,<6=619"("

! (nm) A porphyrin bis-macrocycle 8! [4]rotaxane 19 4+!
The rotaxane has a slightly blue-shifted and significantly broadened Soret band compared to the free porphyrin. A half-band width of 13 nm is measured for the rotaxane, as opposed to 10 nm for porphyrin 8. These changes are typical of an excitonic coupling between two parallel porphyrins and suggest that the two porphyrins are in close proximity in the rotaxane. [252][253][254][255][256] Other potential causes for a shift of the absorption band might have been the impact of the nearby Cu(I) complexes and of the dumbbell. Nevertheless, these possibilities can be ruled out by comparison with the UV-visible absorption properties of similar (pseudo)rotaxanes built with either the same bis-macrocycle or the same dumbbell as rotaxane 19 4+ . The [3]pseudorotaxane 9 2+ (Chapter II)

was built with the same porphyrinic component 8 as the [4]rotaxane 19 4+ , and it incorporates tetrahedral Cu(I) complexes analogous to those of the [4]rotaxane. No shift or broadening of the Soret band was observed for the pseudorotaxane 9 2+ compared to compound 8. By analogy, we conclude that complexation with Cu(I) is not likely to be responsible for the variations observed in the present study. Influence of the dumbbell component can be estimated by comparison with another rotaxane built with the same axle as 19 4+ . In Chapter V, we will describe a [3]rotaxane whose porphyrinic component is substituted with four macrocycles instead of two. This Figure III.13. Scheme highlighting the similarities and differences between the present [4]rotaxane 19 4+ and the [3]rotaxane that will be described in Chapter V. Both rotaxanes comprise exactly the same dumbbell resulting from the click reaction of two stoppers 18 on the axle 16, and are complexed to four Cu(I) centres. However, only one porphyrin is incorporated in the [3]rotaxane while the [4]rotaxane contains two cofacial porphyrins. A 3 nm red shift was observed for the Soret band of the [3]rotaxane compared to its porphyrinic precursor. Although the same axle and stopper were used to form the [4]rotaxane, the Soret band was shifted in the opposite direction. This is clear evidence that other factors are prevailing in the case of the [4]rotaxane and are strong enough to counterbalance the influence of the dumbbells. A major difference between the [3]rotaxane described in Chapter IV and the present [4]rotaxane is the number of porphyrins: the [3]rotaxane contains only one porphyrin whereas the [4]rotaxane contains two cofacially arranged porphyrin units. This supports the idea that the variations in the absorption spectrum are the result of an exciton coupling between the porphyrins of the [4]rotaxane, as proposed above. Excitonic coupling between chromophores may lead to hypso-or bathochromic shifts depending on the relative orientation of the transition dipoles. [252][253][254][255][256] Thus, exciton coupling in a face-to-face bis-porphyrin leads to a hypsochromic shift of the Soret band (parallel transition dipoles), whereas a bathochromic shift is observed in the case of linear, head-to-tail bis-porphyrins (in-line transition dipoles). As for oblique bisporphyrin dimers, splitting of the Soret band is typically observed. The hypsochromic shift observed for the present bis-porphyrinic rotaxane is consistent with a face-to-face, parallel orientation of the porphyrins.

III. 2. e) Demetalation of the Copper(I)-Complexed [4]Rotaxane

Attempts to demetalate the copper(I)-complexed [4]rotaxane with potassium cyanide gave mixtures of products. A very small amount (∼ 1 mg) of copper-free rotaxane was isolated, yet its characterisation proved difficult. MALDI-TOF mass spectrometry gave a signal at m/z = 6788.327 (calculated for [M+H] + : m/z = 6788.198), but proton NMR showed broad signals that were difficult to interpret. Consequently, we did not proceed with further studies of the demetalated, copper-free rotaxane. All four guests are rigid, with a N-N distance varying from 2.6 to 15.8 Å according to crystallographic data. 257,258 They are known to form axial complexes with zinc porphyrins. 131,153,155,195,196,259,260 While DABCO G1 and 4,4'-bipyridine G2 are commercial compounds, the extended bipyridines G3 and G4 are not commercially available and were The 1,4-bis(4-pyridyl)benzene guest G3 was synthesised in 77% yield by Suzuki coupling of pyridine-4-boronic acid and p-dibromobenzene. The 4,4′-bis(4-pyridyl)biphenyl guest G4 was prepared from a 4,4'-dibromobiphenyl precursor following the same procedure.

III. 3. The

We performed host-guest titrations with the rigid substrates G1 -G4 of increasing length in order to measure their association constants with the host rotaxane 19 4+ . The Soret band of Znporphyrins has been shown to undergo a bathochromic shift upon axial coordination of nitrogen ligands. 131 This makes UV-visible titration an excellent method for assessing the host-guest interactions between the [4]rotaxane and substrates G1 -G4. In the titration experiment 0.1 equivalent aliquots of the guest were added to a 10 -6 M solution of the [4]rotaxane in toluene and the absorbance of the Soret band (400 to 450 nm) was recorded after stirring for 2 minutes.

Several coordination modes between the rotaxane host 19 4+

III. 3. b) Titration with the DABCO Guest G1

The data obtained in the case of the short DABCO guest G1 indicated the coexistence of several host-guest species. A bathochromic shift of the Soret band of the host was observed upon addition of the guest. Superimposition of the absorption spectra obtained upon addition of 0.0 to 0.7 equivalents of DABCO brought up an isosbestic point (Figure III.17). Mathematical treatment of the data with the Specfit/32 software corroborated a 1:1 host-guest stoichiometry with an association constant of log K a1 = 8.1 ± 0.5 (see Eq. 1). The binding constant is consistent with an internal coordination mode where the guest is complexed between the porphyrins, inside the cavity of the rotaxane. Indeed, DABCO typically binds simple zinc porphyrins with an association constant of 10 5 mol.L -1 in toluene. 131 The high affinity observed here reflects the cooperative effect of the coordination of the ditopic ligand between two zinc porphyrins. The association constant of the very short DABCO guest with rotaxane host 19 4+ is slightly higher than that observed with the more rigid [4] H + G HG Eq. 1

H + 2 G GHG Eq. 2 !" !#$" !#%" !#&" !#'" !#(" !#)" !#*" !#+" !#," $" '$!" '$(" '%!" '%(" '&!" '&(" ''!" ''(" !#!"-." !#%"-." !#'"-." !#)"-." !#+"-." $#!"-." $#%"-." $#'"-." $#)"-." $#+"-." %#!"-." Wavelength (nm) A ! K a 2 = G • H • G [ ] H [ ] * G [ ] 2 ! K a1 = H • G [ ] H [ ] * G [ ]
Both equilibria were considered simultaneously in the mathematical treatment with log K a1 = 8.1 ± 0.5 for the formation of the 1:1 host-guest complex. The data fitted with an association constant of log K a2 = 14.5 ± 0.2 for the formation of the 1:2 complex. We can conclude that the 1:1 guest inclusion complex is predominantly formed with a high association constant in the presence of substoichiometric amounts of DABCO whereas additional binding of ligand is observed in the presence of excess guest.

III. 3. c) Titration with the 4,4'-Bipy Guest G2

In the case of the 4,4'-bipyridine guest G2 a clear isosbestic point was observed (Figure III.18). This indicates that only one equilibrium is to be considered and that a single complex is formed. Mathematical treatment of the spectra fits with the formation of a 1:1 host : guest complex with an association constant of log K a1 = 6.2 ± 0.1. Other stoichiometries between host and guest (e.g. 1:2 or 2:1) were not corroborated by the mathematical treatment.

The high binding constant is consistent with an internal coordination mode where the guest is complexed between the porphyrins. Indeed, a pyridyl ligand typically binds a zinc porphyrin with a relatively low association constant of 10 3 mol.L -1 in toluene. Higher binding constants with bipyridine ligands usually reflect a cooperative effect of ligand binding between two cofacial metalloporphyrins. 131 The association constant observed here is one order of magnitude lower than that obtained with the related bis-porphyrin system previously studied in our group, with log K a1 = 7.3. In the present system, the porphyrin is a classical tetraaryl tetrapyrrolic compound whereas in the previous system investigated, electron withdrawing groups were attached on two pyrrole rings of the porphyrin. Lewis acidity of the zinc(II) centre is thus less pronounced in the present system than in the previous case reported by our group, 196 which could explain the lower binding constant observed.

III. 3. d) Titrations with Guests G3 and G4

Similar results were obtained with guests G3 and G4 upon addition of 0.1 to 2.0 equivalents of guest to the rotaxane solution. In both cases a bathochromic shift of the Soret band was observed as expected and superimposition of the spectra showed isosbestic points (Figures III. 20 and III.21). The data fit with the formation of 1:1 complexes with an association constant of log K a1 = 6.1 ± 0.1 and log K a1 = 5.6 ± 0.1 for G3 and G4, respectively. These values are two to three orders of magnitude higher than the expected binding constant for the monocomplexation of a bipyridine-type ligand on a single porphyrin, which evidences a cooperative effect and hence internal binding of the guest inside the cyclic rotaxane.

!"#$%&'()*+,-.,/#(+*, 01+-21&)3(,&*,456,)7,

!"#$ !"##$ !"%$ !"%#$ !"&$ !"&#$ !"'$ !"'#$ !"($ !"(#$ !$ !")$ !"*$ !"%$ !"'$ +$ +")$ +"*$ +"%$ +"'$ )$ G1! G2! Figure III.
!" !#$" !#%" !#&" !#'" !#(" !#)" !#*" !#+" '$!" '$(" '%!" '%(" '&!" '&(" ''!" ''("
!#!",-" !#%",-" !#'",-" !#)",-" !#+",-" $#!",-" $#%",-" $#'",-" $#)",-" $#+",-" %#!",-"

Wavelength (nm) A !" !#$" !#%" !#&" !#'" !#(" !#)" !#*" !#+" !#," '$!" '$(" '%!" '%(" '&!" '&(" ''!" ''(" !#!"-."" !#%"-." !#'"-." !#)"-." !#+"-." $#!"-." $#%"-." $#'"-." $#)"-." $#+"-." %#!"-."
Wavelength (nm) A

III. 3. e) Titration Results Analysis: A Distensible Molecular Host

Very close binding constants were obtained for guests G2 and G3; this attests for the flexibility of the rotaxane that can equally accommodate these two guests of increasing lengths (7.1 and 11.4 Å, respectively). The exceptional flexibility of the rotaxane is confirmed by the binding constant obtained for the extended guest G4. The constant is slightly lower -presumably due to steric constraints -yet consistent with guest inclusion into the central cavity of the rotaxane. The results are summarised in Table 1. *for the 1:1 host/guest complexes. In the case of DABCO (G1), 1:2 host/guest complexes were also formed with an association constant of log K a2 = 14.5 ± 0.2.

The titrations point out the remarkable adaptability of the rotaxane host, which "inflates"

or "deflates" depending on the guest substrate, as illustrated in Figure III.22. Rotaxane 19 4+ is one of very few reported bis-porphyrinic systems able to accommodate guests G3 and G4. 195,262 This adaptability differentiates the present rotaxane 19 4+ from the [4]rotaxane host previously reported in the Sauvage group. 196 In the previous system the guest G4 was too long to fit between the porphyrins. Only 1:2 host/guest species were observed where the guests were bound

externally. An intermediate situation was observed in the case of G3, which suggested that guest G3 had a critical size and that several complexes coexisted in solution. The previous rotaxane was unable to adjust its conformation to the size of the guest because of the rigidity of the porphyrinic bis-macrocycle component. Moreover, this rotaxane collapsed upon demetalation of the copper(I) centres and did not exhibit any host/guest recognition properties after demetalation. 197 On the contrary, the spacer between the porphyrin units and the copper(I)

anchoring points in rotaxane 19 4+ is very flexible, which allows for inclusion of a large range of guests in the rotaxane. An analogy can be drawn between rotaxane host 19 4+ and the induced fit of substrates in enzymes: both systems are flexible and can adjust their conformation to the size and the shape -for enzymes-of the substrate to be recognised. In conclusion, the now well-established "gathering-and-threading" principle based on copper(I) and bidentate ligand-containing cyclic and acyclic fragments turned out to be remarkably efficient for preparing a new [4]rotaxane that consists of two bis-macrocycles and two rigid axles. Each bis-ring fragment contains a central zinc porphyrin. Two flexible coordinating rings are attached via single C-C bonds on two antipodal meso carbon atoms of the porphyrin. The final rotaxane has been characterised by high-resolution electrospray mass spectrometry, 1 H and [START_REF] Dean | Duplex DNA knots produced by Escherichia coli topoisomerase I. Structure and requirements for formation[END_REF] C NMR and UV-visible absorption spectroscopy.

The new [4]rotaxane described in here incorporates two face-to-face zinc-complexed porphyrins, making it an interesting receptor for a variety of substrates. It shows structural similarities with previously described compounds 196,197 in the sense that it also belongs to the family of [4]rotaxanes consisting of two axles and two bis-macrocycles. However, the greater flexibility of the system, originating from the totally different connections between the threads and the rings, leads to very different host-guest properties. Interestingly, rod-like guests of extremely different lengths could be accommodated between the two porphyrins, affording complexes of similar stability constants, thus demonstrating that the present [4]rotaxane behaves as a distensible receptor, able to inflate or deflate at will to adjust to the guest size. This property is well illustrated by the fact that exotopic guests of the 4,4'-bipyridine family with overall lengths varying from 7.1 Å to 15.8 Å form complexes of comparable stability.

The photophysical porperties of the [4]rotaxane could be studied in the future. Its electronic properties should be very different from those of the previously reported [4]rotaxane since the two porphyrins incorporated in the present compound are "normal" porphyrins of the tetra-aryl series whereas they were π-extended porphyrins in the previous system.

Chapter IV. Towards A New Porphyrinic

Bis-Macrocycle:

Two Coordinating Rings Linked to a Central

Porphyrin via an Extended Aromatic System

IV. 1. Design of the New Porphyrinic Bis-Macrocycle and Retrosynthetic Strategies

IV. 1. a) Design of the System

The results described in the previous chapter prompted us to design a new, more rigid porphyrinic bis-macrocycle in order to improve our model of a molecular press. In particular, a key point in the new design is to rigidify the bridge between the porphyrin and the rings.

In Chapter III, we showed that the [4]rotaxane 19 4+ is a good molecular receptor for ditopic guests. However, no comparison between the host-guest properties of the copper-free rotaxane and of the copper(I)-complexed rotaxane could be drawn because of difficulties encountered with the demetalation of the copper-complexed rotaxane. Furthermore the [4]rotaxane proved to be very flexible in its metalated form. It can adjust its shape and the distance between the porphyrin sites to the size of the guest to be complexed. Complexation with flexible guests was not tested but the great adaptability of the rotaxane suggests that no significant constraint would be applied on the conformation of the guest molecule. Moreover the characterisation of a potential conformational change of the guest by NMR spectroscopy would be difficult because of the complexity of the 1 H NMR spectrum of the rotaxane. A more rigid bis-macrocyclic structure is likely to lead to a more symmetrical rotaxane in solution, as observed with other [4]pseudorotaxane and [4]rotaxane structures. 196,217,221 It should also limit the adaptability of the rotaxane in its copper(I)-complexed form, which will have a greater impact on the conformation of a flexible guest molecule. We conclude from these observations that a rotaxane based on a more rigid bis-macrocycle should be a better candidate as a molecular press. 196,197,217 The rigidity of the new system will be intermediate between the very flexible bis-macrocycle 8 and the very rigid bis-macrocycle studied by former members of the Sauvage group.

The new target building block is schematically depicted in

The main differences between the new target ( 196,197,217 the π system of the new target compound will be significantly reduced. The dpp units of the macrocycles will be electronically decoupled from the extended porphyrin core, while they were coupled in the previously studied system. This is to avoid the collapse of the corresponding rotaxane and the π-stacking interactions observed upon demetalation of the copper(I) centres in the case of the rotaxane studied before. The synthesis of the new target bis-macrocycle involves the functionalisation of the porphyrin core at its β positions. M. J. Crossley and his group developed a synthetic strategy that enables the attachment of various moieties to the β,β'-pyrrolic sites of a porphyrin via an extended π system (Figure IV.2). [263][264][265] Figure IV.2. The Crossley synthetic approach for the functionalisation of porphyrins at the β positions. The method involves the formation of porphyrin-dione (a) or tetraone (b) derivatives, followed by condensation with a (substituted) 1,2-phenylenediamine unit. It allows the formation of linear or "corner" planar multifunctional systems, whose functional groups are covalently linked to the porphyrin via an extended aromatic system (Ar = aryl group). 265 The approach consists in introducing two vicinal ketone groups on the β and β' positions of one or two of the pyrrole rings on the porphyrin core. Subsequent condensation with a 1,2phenylenediamine leads to a quinoxalino-or bis(quinoxalino)-porphyrin derivative by ring annulation at the β,β' pyrrolic sites (Figure IV.2). The condensation is compatible with the presence of a wide range of substituents on the 1,2-benzenediamine unit, allowing the construction of multi-functional systems. This approach has notably been used in the synthesis of covalently linked multi-porphyrin arrays. 124,[264][265][266][267][268] It was later extended to the stepwise annulation of three 269 or four 270 pyrrolic rings of a porphyrin. In the present study the target compound is a porphyrin substituted with two macrocycles at antipodal β,β'-pyrrolic sites; we will use the ring annulation on a linear porphyrin-tetraone for this synthesis.

IV. 1. c) Retrosynthetic Strategies

The chemical structure of the target porphyrinic bis-macrocycle is depicted in Strategies A and B toward the new porphyrinic bis-macrocycle were both tested. Both approaches involve an important intermediate: the linear porphyrin-tetraone derived from tetrakis (3,5-di-tert-butylphenyl)porphyrin. We will now describe the synthesis of this intermediate. Attempts to synthesise the target bis-macrocycle using strategies A and B will then be detailed in parts IV. 2. and IV. 3, respectively.

IV. 1. d) Synthesis of a Linear Porphyrin Tetraone

As explained above, the linear tetrakis (3,5-di-tert-butylphenyl)porphyrin-tetraone 25 is a key intermediate in both possible strategies towards the formation of our target bis-macrocycle.

This intermediate will then be further functionalised by ring annulation at the pyrrolic sites using appropriately functionalised 1,2-benzenediamine derivatives. The linear porphyrin-tetraone was synthesised following a literature procedure; 265 the synthetic scheme is represented in The linear porphyrin-tetraone 25 was obtained in six steps from 5,10,15,20-tetrakis(3,5di-tert-butylphenyl)porphyrin. This porphyrinic starting material can easily be synthesised by condensation of 3,5-di-tert-butylbenzaldehyde and pyrrole in Adler-Rothemund conditions. In a first step, the free-base porphyrin was quantitatively metalated using copper(II) acetate. Double Surprisingly, no reaction occurred upon treatment of the starting material with boron tribromide, even in the presence of a large excess of BBr 3 . Heating to 220 °C in pyridinium chloride 272 proved equally inefficient, and the unreacted starting material was recovered. Demethylation of the methyl ethers was then attempted by treatment with aluminium trichloride and ethanethiol. 273 These conditions have been successfully used in the synthesis of a dicatechol ligand where other deprotection conditions had only led to partial cleavage of the methyl ethers. 274 In our case disappearance of the starting material and formation of a very polar species was observed by TLC. However, attempts to characterise the product of the reaction were unsuccessful.

Extremely broad signals were observed by NMR spectroscopy, and mass spectrometry analyses gave no peak. The tetra-hydroxyl product might have formed coordination polymers with Al(III), which would not ionise very easily in electrospray or other mass spectrometry techniques. Even though compound 30 could not be fully characterised, the clean mass spectrum prompted us to proceed with the following macrocyclisation step. The multiple difficulties encountered incited us to follow another synthetic strategy towards the synthesis of the desired porphyrinic bis-macrocycle. Attempts to synthesise the target bis-macrocycle by means of Strategy B will be described in the next section of this chapter. The substituted catechol 31 was then reacted with ditosylate 4 in classical macrocyclisation conditions in DMF. However, TLC analysis showed that a mixture of products was obtained.

The products were isolated by column chromatography but the desired dinitro-substituted macrocycle could not be identified. This negative result could be explained by the presence of electron-withdrawing nitro substituents on compound 31, which significantly reduce the nucleophilicity of the phenolate groups in the macrocyclisation reaction.

IV. 3. b) Route B.2: Attempted Synthesis of a Boc-Protected Diamino-Macrocycle

A second synthetic route was considered in the light of the results obtained with Route B.1. We reasoned that reduction of the nitro groups to electron-donating amines prior to the macrocyclisation should favour the reaction. The phenolate groups of diaminocatechol 29 should be significantly more nucleophilic than the corresponding dinitrocatechol 31. Nonetheless, we decided to protect the amine groups of compound 29 in order to avoid any competition between the phenolate and the amine nucleophiles in the macrocyclisation reaction.

t-Butyloxycarbonyl (Boc) was chosen as a protective group for its ease of introduction and The protection reaction was achieved by neutralisation of diaminocatechol hydrobromide 29 with pyridine and immediate treatment with di-tert-butyl dicarbonate (Boc 2 O) in conditions described in the literature. 278 Carbamate formation at the amine sites occurred selectively, and the Boc-protected diaminocatechol 32 was obtained in 83% yield after recrystallisation.

Identification of the product was confirmed by mass spectrometry and NMR. Surprisingly, macrocyclisation attempts using ditosylate 4 and catechol derivative 32 did not yield the expected compound. The products of the reaction could not be clearly identified. The 1 H NMR spectra seemed to indicate the loss of the Boc groups. Consequently, we decided to use a different protecting group.

IV. 3. c) Route B.3: Protection of the Amine Groups using Anisaldehyde

After the unsuccessful macrocyclisation with the Boc-protected compound 32 an alternative protecting group was sought for the amine functions of the diaminocatechol 29. We decided to exploit the ability of primary amines to form imines reversibly by condensation with aldehydes. Aromatic aldehydes are the most widely used reagents for this type of protection. 277 Anisaldehyde was used in the present study; p-methoxyl groups were introduced to increase the electron-donating character of the protective group and the reactivity of the protected catechol derivative towards nucleophilic substitution in the subsequent macrocyclisation reaction.

c 1! CH 2! o 1! OH 1! Me 1! CH 2 Cl 2! OH 2! m 1! o 2! m 2! c 2! HO OH N N OMe OMe o 1 c 2 2 1 c 1 1 m 2 o 2 m 1 2 CH 2 Me 1!
Several reaction mechanisms have been proposed in the literature for the formation of 1benzyl-2-phenylbenzimidazoles from 1,2-phenylenediamine derivatives. 279,281,282 All of these mechanisms involve an inter-or intramolecular hydride transfer step. However, hydride shifts are high energy processes and are not very likely in the mild conditions used here (the reaction was run at room temperature in methanol/water as solvent). The mechanism depicted in Figure IV.16 seems more plausible. This mechanism involves the initial formation of the expected bisimine compound. Pyridinium bromide is present in solution as a result of the neutralisation of the hydrobromide salt 29 with pyridine; it provides a source of protons. Protonation at one of the nitrogen sites favours cyclisation to a five-membered ring. A tautomerism equilibrium can then take place, and the final deprotonation is driven by the rearomatisation of the system. We did not perform any additional experiment to validate the proposed mechanism. The outcome of the reaction presented here with the formation of a benzimidazole derivative as a major product differs from the results obtained by D. Coucouvanis and coworkers.

In their study, the diaminocatechol 29 is condensed with substituted salicylaldehyde derivatives, and the bis-Schiff bases are the major products. 275 The bis-imine adducts obtained from these aldehydes are stabilised by intramolecular hydrogen bonds between the ortho -OH groups of the salicylidene moieties and the N atoms of the imines. This could explain the different reactivity

Groups

Given the difficulties faced with the synthesis of a macrocycle that incorporates protected amine groups, we designed a fourth synthetic route towards the formation of the desired diamino-macrocycle. We considered that the macrocyclic structure could be formed first, and that the amine functions could be subsequently introduced. The synthetic route relies on the formation of a dibromo-functionalised macrocycle, whose bromo substituents will then be converted to amine functions via Hartwig-Buchwald amination. [284][285][286][287] The synthetic scheme leading to the formation of the dibromo-substituted macrocycle 36 is depicted in Macrocycle 36 was then coupled to an ammonia equivalent in order to form the desired C-N bonds. Benzophenone imine was chosen as the ammonia equivalent because it results in adducts that are stable to chromatographic purification after coupling. We followed a procedure developed by the group of S. L. Buchwald ). The expected bis-imine macrocycle 37 was formed in the reaction as evidenced by mass spectrometry. However, we faced purification problems and the product could not be isolated for the time being. Once the macrocycle is isolated the imines will be cleaved to give the desired diamino-macrocycle. Several methods are available for this cleavage reaction (transamination, hydrogenolysis or acidic hydrolysis). 289,290 The target porphyrinic bis-macrocycle presented at the start of this chapter should then be accessible by condensation of the diamino-macrocycle with the linear porphyrin-tetraone 25. In conclusion, numerous difficulties were met towards the formation of a new, rigid porphyrinic bis-macrocycle. The synthetic strategy had to be redesigned several times, and the target molecule has not been obtained yet. However, the last synthetic route presented here gave encouraging results. Overcoming the purification problems with precursor 37 should give access to the desired bis-macrocycle. This building block could then be tested in a threading-followedby-stoppering reaction with axle 16 and stopper 18. The formation of a cyclic [4]rotaxane with a structure similar to that of rotaxane 19 4+ is expected. The ability of the rotaxane to bind guest substrates and compress them upon complexation with copper(I) could be studied. The molecular press properties of the rotaxane would thus be tested.

Br Br N N O O O O O O 36 N N O O O O O O 37 + NH NaOtBu Pd 2 (dba) 3 rac-BINAP N N H 2 N NH 2 N N O O O O O O deprotection 2 toluene 110 °C Chapter V. A [3]Rotaxane of Novel

Architecture and its Precursor:

A New Zinc Porphyrin Substituted with Four

Coordinating Macrocycles

In the previous chapters we described the synthesis and attempted synthesis of porphyrins substituted with two macrocycles, and the formation and host-guest properties of a [4]rotaxane that incorporates one of these porphyrinic bis-macrocycles. In order to obtain more elaborate structures we then designed a new porphyrin substituted with four coordinating macrocycles. In this chapter we will describe the synthesis of a tetra-substituted porphyrin and investigate the formation of multi-rotaxanes from this new porphyrinic building block.

V. 1. A Zinc Porphyrin Substituted with Four

Coordinating Macrocycles

V. 1. a) Design of the system

After the study of our new [4]rotaxane based on a porphyrinic bis-macrocycle, we decided to further functionalise our building blocks in order to gain access to higher order rotaxanes. The new target is a porphyrin linked to four peripheral rings instead of two, which should widen the range of threading options. We envisioned that a [6]rotaxane could be obtained from this new tetra-macrocyclic building block (Figure V.1). A templated assembly with a twostation axle could lead to this [6]rotaxane following a threading scheme similar to that observed for the formation of the [4]rotaxane described in Chapter III. The final [6]rotaxane would be constituted of two face-to-face zinc porphyrins mechanically linked to four dumbbell components. This architecture is reminiscent of the [6]pseudorotaxane described by the groups of J. F. Stoddart and R. J. M. Nolte (see part I. 4. a)). However in this system the porphyrins were attached to the thread components of the pseudorotaxane while in the present system the porphyrins will be covalently linked to the ring components. The cofacial arrangement of the porphyrins in the [6]rotaxane should allow the complexation of various guest molecules between the two porphyrins. Figure V.1 shows a schematic view of the target [6]rotaxane and the retrosynthetic route for its formation, as well as the chemical structure of the target porphyrinic tetra-macrocycle building block. The structure consists of four coordinating rings attached to the meso positions of a central zinc porphyrin via single C-C bonds. The macrocycles are identical to those incorporated in the porphyrinic bis-macrocycle described in Chapter II; they are 31membered rings that contain 2,9-diphenyl-1,10-phenanthroline fragments located relatively far away from the porphyrin nucleus. The free rotation around the single carbon-carbon bond linking the rings and the porphyrin allows the rings to be tilted in relation to the plane of the porphyrin. It is also noteworthy that these rings are flexible enough to fold up and adopt a nonplanar geometry without imposing a significant strain onto the whole molecular system. After a few generalities on the synthesis of porphyrins, we will now describe the synthesis of the target tetra-macrocycle.

Figure V.1. Schematic view of the target [6]rotaxane constituted of two face-to-face porphyrins, each of them covalently linked to four coordinating macrocycles and mechanically linked to four dumbbells. The retrosynthetic route for the formation of this [6]rotaxane involves the use of a two-station axle, a stopper and a new porphyrinic tetra-macrocycle whose target chemical structure is depicted. 291 Symmetrical meso tetra-substituted porphyrins are accessible via this method, the meso substituent depending on the starting aldehyde used in the condensation. Mixtures of aldehydes afford unsymmetrical meso-substituted porphyrins; however the relative positions of the different substituents cannot be monitored and statistical mixtures are obtained. β-substituted porphyrins can also by synthesised with this method if the starting material is a substituted pyrrole. Two main sets of conditions are typically used in the condensation-followed-by-oxidation process. In the Adler-Rothemund method the aldehyde and pyrrole are condensed in refluxing propionic acid; and exposure of the reaction mixture to air allows in situ oxidation by molecular oxygen. 292,293 In the Lindsey procedure the condensation is catalysed by an acid, typically trifluoroacetic acid (TFA) or trifluoroborate-etherate (BF 3 OEt 2 ); and a chemical oxidant like 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or p-chloranil is used to obtain the aromatic ring (Figure V.2). 294,295 Condensation of an aldehyde with pyrrole never affords the desired porphyrin in quantitative yield because side products are formed in the reaction (e.g. open-chain oligomers). The porphyrin yield is typically around 20 to 25% and depends a lot on the -R substituent of the aldehyde and on the conditions of the reaction. Alternatives to the Adler-Rothemund and Lindsey conditions for the synthesis of symmetrical tetra-substituted porphyrins have been described and give good results in some cases. [296][297][298][299][300] Some of these alternatives will be discussed in this chapter. Porphyrins functionalised with polydentate nitrogen ligands (e.g. 1,10-phenanthroline or 2,2'-biypridine chelates) are useful building blocks for the construction of functional assemblies.

Two main routes can be considered for the synthesis of this type of porphyrins. The chelate can be introduced on the preformed porphyrin ring by appropriate coupling; or it can be attached to the aldehyde precursor used in the condensation, leading directly to the functionalised porphyrin.

This last route can reduce the number of synthetic steps. However, reports describing the formation of chelate-functionalised porphyrins following this direct strategy are rare, probably owing to synthetic difficulties. [301][302][303][304] Here we will present our optimisation of the reaction conditions in the case of an aldehyde attached to a dpp unit.

V. 1. c) Synthesis of the New Porphyrinic Tetra-Macrocycle

The strategy adopted for the synthesis of the new tetra-substituted porphyrin depicted in The aldehyde precursor used in the condensation reaction is the macrocycle and pyrrole under these conditions (Table V.1, Entries 4-5). This indicated that mild conditions were not adequate for the synthesis of porphyrin 38, presumably due to the presence of a 1,10phenanthroline moiety in the macrocycle. Our results incited us to try harsher conditions. We then tested reaction conditions derived from the Adler-Rothemund method (Table V.2). 292,293 Refluxing pyrrole and aldehyde 5 in propionic acid afforded porphyrin 38 in an encouraging yield of 9% (Table V.2, Entry 1). Based upon the observation by Newkome and coworkers that a microwave-enhanced synthesis led to an improved yield in the synthesis of a terpyridine-containing porphyrin, 304 we tested the microwave activation effect on our reaction.

Indeed, the reaction time went from 2 h to 30 min and the yield was increased to 12% when the reaction was run in a microwave reactor (Table V.2,Entry 2). Use of nitrobenzene as cosolvent and oxidising agent in this type of reaction has been reported to give rise to higher yields. 300 In our case it increased the solubility of the starting material in the reaction mixture and free-base porphyrin 38 was obtained in 15% yield after 10 minutes of microwave irradiation (Table V Metalation of the porphyrinic site was carried out by adding excess zinc acetate in methanol to a refluxing solution of 38 in chloroform. Further treatment with EDTA to remove zinc(II) from the phenanthroline chelates afforded zinc porphyrin 39 as a purple solid in quantitative yield (Figure V.4). By using the optimal experimental procedure based on the above-described study, it was possible to prepare batches of the tetra-substituted Znporphyrin 39 on the 100 mg scale. The condensation conditions and their optimisation presented here might lead to real advances in the synthesis of porphyrins incorporating polypyridine chelates or other polydentate ligands. These porphyrins are typically obtained in poor yields (5-12%) when they are formed by the direct condensation of pyrrole and chelate-appended aldehydes. [302][303][304] The reaction conditions developed here could afford better yields in the syntheses of this type of porphyrins. Once the zinc porphyrin 39 substituted with four coordinating rings was obtained, it was used as a building block in the templated assembly of a copper(I)-complexed multi-rotaxane. As explained at the start of this chapter, the formation of a [6]rotaxane was expected by threading of two-station axles through the rings of compound 39 followed by the introduction of stoppers. We used the alkyne-functionalised bis-bidentate ligand 16 and the azide-functionalised derivative 18

(both described in Chapter II) as the axle and the stopper, respectively, in the reaction of formation of the rotaxane. However, a different threading scheme is prevailing in this case, as evidenced by the formation of a [3]rotaxane instead of the expected [6] Although its formation was not expected, the [3]rotaxane is far from being devoid of interest. Its architecture is novel and is reminiscent of two "simple" [3]rotaxanes (consisting of a dumbbell and two threaded rings) whose rings are linked together by a central porphyrinic plate. 3]rotaxane whose central fragment consists of a Zncomplexed porphyrin bearing four coordinating rings. The synthetic strategy is based on the "gathering-and-threading" approach followed by stoppering. The threading scheme that prevails in this case differs from that observed for the formation of the [4]rotaxane in Chapter III. Free rotation of the rings in relation to the porphyrin allows threading of the axles through two adjacent rings of the porphyrin. was obtained as a dark red solid in 44% yield (threading and quadruple stoppering steps). However, the m/z value does not enable to distinguish between the expected [6]rotaxane and the obtained [3]rotaxane. Indeed, the [6]rotaxane would have had twice the molecular mass and twice as many positive charges as the [3]rotaxane, which would have resulted in the same m/z value. Observation of the isotope profile is needed to discriminate between both multi-rotaxanes. The gap between signals observed in the experimental isotope profile is characteristic of a species bearing four positive charges. This gap would have been twice as small for a [6] ! "

# 1 , # 2 $ 1 , $ 2
The interlocked structure of rotaxane of the [3]rotaxane is given by the signals of the pyrrolic protons of the porphyrin moiety. The pyrrolic protons were equivalent in compound 39 and appeared as a singlet at 8.92 ppm, whereas they are observed as two singlets at 9.20 and 9.12 ppm in the rotaxane. This splitting is consistent with the proposed chemical structure of rotaxane 40 4+ , where protons pyA and pyB experience different chemical environments.

Figure V.9. Aromatic region of the 1 H-1 H NOESY (600 MHz) spectrum of rotaxane 40 4+ . NOE correlations between the rod and the tetra-macrocycle in the aromatic region are highlighted.

V. 2. d) UV-visible Characterisation of the [3]Rotaxane

The UV-visible absorption spectrum of free-base porphyrin 38 measured in dichloromethane shows a porphyrin Soret band at 421 nm and four Q bands at 515, 550, 588, and 645 nm in the visible region. In the case of the zinc porphyrin 39 the Soret band is observed at 424 nm and two Q bands are observed at 550 and 590 nm. The threading induces a 3 to 5 nm red shift of the B and Q bands with the Soret band appearing at 427 nm for [3] rotaxane 40 4+ (Figure V.10). It is noteworthy that a bathochromic shift is observed upon threading of the axles in this case, while a hypsochromic shift occurred in the case of the [4]rotaxane 19 4+ (Chapter III).

The hypsochromic shift of 19 4+ was attributed to excitonic coupling between two face-to-face porphyrins, which can not occur in [3]rotaxane 40 4+ that contains a single porphyrin unit. The red shift observed here did not occur upon complexation of Cu(I) and threading of dap chelates through the rings of bis-macrocycle 8 to form the [3]pseudorotaxane 9 2+ (Chapter II). The absorption maxima were observed at 421, 548 and 585 nm for 9 2+ , with no shift compared to the copper-free porphyrin precursor 8. This seems to indicate that the MLCT absorbance of the Cu(I) complexes do not induce any shift of the absorption bands of the porphyrin. Consequently, the bathochromic shift observed in the present case is not likely to be due to the presence of the Cu(I) centres and might be the result of a distortion of the porphyrin in the [3]rotaxane. In conclusion we synthesised and fully characterised a [3]rotaxane that consists of a zinc porphyrin component substituted with four coordinating macrocycles and of two dumbbell components. Each dumbbell is threaded through two adjacent rings of the porphyrin in a novel architecture. We then modified the design of the system with the aim of forming a [6]rotaxane.

V. 3. Towards a [6]Rotaxane: Design of a New Axle

V. 3. a) Strategy for the Formation of a [6]Rotaxane

After the description of a novel [3]rotaxane structure obtained from our new porphyrinic tetra-macrocycle, we decided to pursue our efforts towards the formation of a [6]rotaxane as described at the beginning of this chapter. The [6]rotaxane structure would be novel as well, and could present interesting host-guest properties.

Our strategy towards the formation of a [6]rotaxane composed of two porphyrinic tetramacrocycles and four dumbbells is based on the use of porphyrin 39 as the tetra-macrocyclic component and of an axle that differs from axle 16 as the dumbbell precursor. We envisioned that the introduction of a longer spacer between the bidentate sites of the axle would force the system towards the formation of a [6]pseudorotaxane instead of a [3]pseudorotaxane in the threading step (Figure V.11). If the bidentate sites are far apart on the axle then the formation of tetrahedral copper(I) complexes with the phenanthroline sites of two adjacent rings of the porphyrin will not be possible. Consequently, the formation of a [3]pseudorotaxane will not be favoured because not all binding sites will be occupied. Other threaded assemblies allowing maximal occupancy of the binding sites will be thermodynamically favoured, and the [6]pseudorotaxane will most likely be the most stable interlocking species.

V. 3. b) Design of the Axle and First Results

As explained above, our strategy toward the construction of the desired [6] precursor substituted with two terminal methoxyl groups located in α position to the nitrogen atoms. This intermediate was used in a preliminary threading test with the porphyrinic tetramacrocycle. However, only the [3]pseudorotaxane was observed in mass spectrometry and no trace of [6]pseudorotaxane was detected.

Subsequently, molecular modelling studies were performed with the Avogadro software.

Structure minimisations using force-field calculations suggested that the porphyrinic tetramacrocycle is flexible enough for the [3]pseudorotaxane to form upon threading of a rod that contains up to three phenylene spacers between the bidentate sites. Therefore, a linear spacer with more than three aryl rings is probably needed in order to favour the formation of the molecular modelling shows that the formation of a [3]pseudorotaxane might still be possible with this rod but the system would be sterically constrained and the copper(I) complexes would most likely be distorted and destabilised. Rod e contains three aryl and four alkyne groups as a spacer. Threading of the rods and complexation with the Cu(I) template into a [3]pseudorotaxane structure would not be possible with this rod according to the molecular model. Consequently, these last two rods appear to be good candidates for the formation of a [6]rotaxane; they will be synthesised and tested in the near future.

In conclusion, we prepared a tetra-substituted porphyrin bearing macrocycles at its four meso positions. A large variety of experimental conditions were explored to prepare the freebase porphyrin, which gradually led to a remarkable improvement of the yield. Under the best experimental conditions, a 25% yield was obtained, affording the desired compound at the 0.1 g scale. More generally, the reaction conditions developed here could be useful for the synthesis of porphyrins incorporating polypyridine chelates or other polydentate ligands.

In a copper(I)-driven multi "gathering-and-threading" step followed by a stoppering reaction, a [3]rotaxane was obtained in good yield. The structure of this [3]rotaxane is novel: it consists of two dumbbell components, each of them threaded through two adjacent rings of a central porphyrinic tetra-macrocycle. The synthesis principle described in this chapter should be generalised in the future so as to afford related porphyrinic multi-rotaxanes displaying several possible geometries, in relation to molecular machines and receptors. The design and synthesis of a new axle for the elaboration of a [6]rotaxane is under way in a collaboration with Nathan Strutt and Fraser Stoddart. As well as a novel architecture, the target [6]rotaxane should display interesting properties as a molecular receptor. The formation of other types of interlocked structures can also be envisaged from our new porphyrinic tetra-macrocycle. For example, the extremities of the rods could be joined in the [3]pseudorotaxane formed by threading of axle 16

through the rings of porphyrin 39. This would result in the formation of a [2]catenane composed of one large ring threaded through all four rings of the porphyrinic tetra-macrocycle (Figure

V.13).

Figure V.13. Schematic view of a new topologically interesting [2]catenane. This type of structure could be obtained by junction of the axle ends of the [3]pseudorotaxane resulting from threading of rods 16 with tetra-macrocycle 39.

Zn

solution. Observation of an excitonic coupling confirmed the cofacial arrangement of the metalloporphyrins, which form an internal cavity suitable for complexation of guest substrates.

Indeed, host-guest studies with linear ditopic nitrogen ligands showed that the rotaxane is a good molecular receptor. Rigid guests substrates of various lengths were tested, and high association constants were observed in all cases. The complexation of 2.6 to 15.8 Å-long rod-like guests within the internal cavity attests the exceptional adaptability of the rotaxane, which can adjust its shape to the size of the guest substrate. The [4]rotaxane can be described as a distensible molecular receptor, which can adopt an "inflated" or a "deflated" conformation depending on the guest. Complexation with chiral diamines could be attempted in the future. Chirogenesis could be observed upon binding of a chiral guest, which would make the rotaxane host a good chiral sensor for this type of molecules. The photophysical properties of the [4]rotaxane could also be studied.

A new porphyrinic bis-macrocycle was then designed towards the formation of a more rigid [4]rotaxane host. An aromatic bridge will be introduced between the porphyrin moiety and the macrocycles to lock the rings in a coplanar orientation to the porphyrin core. The resulting [4]rotaxane would be less adaptable than that described above. The complexation of flexible guest molecules and the impact of the [4]rotaxane host on the conformation of the guest could be tested to check if the host acts as a molecular press. Several synthetic routes were envisaged for the formation of the new target bis-macrocycle. Difficulties were faced with some of the synthetic steps, and the synthesis of the target molecule is still in progress. However, the latest results are encouraging, and interesting macrocyclic intermediates could be obtained. Only two more steps should be required to obtain the desired extended porphyrin. In the future, the formation of the corresponding [4]rotaxane could be tested, and its receptor properties could be studied. Comparative host-guest studies between the copper-free rotaxane and the copper(I)- complexed rotaxane could be performed to assess the ability of the host to "compress" guest substrates upon complexation with Cu(I). We could then envisage to replace one of the zinc(II) centres with another metal, which would enable the axial coordination of oxygen ligands (e.g. tin(IV)). The rotaxane would then be a host for amino acids and small peptides. The ability of the rotaxane to change the conformation of a peptide guest would make it a new synthetic prototype of a chaperone protein.

Finally, a porphyrinic tetra-macrocycle was designed and synthesised from the aldehydefunctionalised macrocyclic precursor used in the first study. In this new structure the central porphyrin is linked to lateral dpp-containing rings at its four meso positions. While the classical porphyrin condensation conditions afforded the desired tetra-substituted porphyrin in very poor amounts, optimisation of the reaction conditions led to a significant increase of the yield. The optimised conditions are derived from the Adler-Rothemund method; we showed that the combined use of nitrobenzene as a cosolvent and of microwave activation favoured the formation of the porphyrin product. More generally, the condensation conditions developed here could prove useful for the synthesis of other porphyrins substituted with polydentate ligands. A multiply-interlocked, copper(I)-complexed [3]rotaxane was obtained by threading of bisbidentate axles through the rings of the porphyrinic tetra-macrocycle, followed by stoppering.

The structure of this rotaxane is novel: it contains two dumbbell components, each of them threaded through two adjacent rings of the central porphyrin unit. The formation of this [3]rotaxane attests the remarkable flexibility of the tetra-macrocyclic precursor, whose dpp chelates can rotate in relation to the plane of the porphyrin to allow the threading of axles through neighbouring rings. Future work could deal with the synthesis of a novel [2]catenane structure from the porphyrinic tetra-macrocycle. Instead of clicking stoppers to the [3]pseudorotaxane precursor, the ends of the axles could be joined via an appropriate spacer, forming a large ring threaded through all four rings of the porphyrinic tetra-macrocycle. The design and synthesis of longer axles is also under way in a collaboration with Nathan Strutt and Fraser Stoddart at Northwestern University. The formation of a [6]rotaxane is expected after threading with the tetra-macrocycle. This novel structure could exhibit interesting molecular receptor properties.

2,9-Dianisyl-1,10-phenanthroline (dap) 1 198,199 A solution of 4-bromoanisole (10 mL, 80 mmol) in dry THF (100 mL) was degassed with argon and cooled down to -78 °C. A 1.6 M solution of BuLi in hexanes (100 mL, 0.16 mol) was added dropwise. The reaction mixture was then stirred for 3 h at -78 °C under argon. It was allowed to warm up to -10 °C, then transferred by cannula to a solution of pre-dried 1,10phenanthroline (5.8 g, 32 mmol) in 150 mL of dry, degassed toluene at 0 °C. The reaction mixture was allowed to warm up to room temperature and stirred under argon for 20 hours. The solution was hydrolysed with 50 mL of water. After evaporation of the solvents the solid was dissolved in CH 2 Cl 2 (250 mL) and washed three times with water (250 mL). The organic layer was rearomatised by successive additions of MnO 2 under effective magnetic stirring The rearomatisation was followed by TLC and disappearance of the yellow colour, and was ended after addition of 60 g MnO 2 . The mixture was dried over MgSO 4 and filtered on Celite. The solvent was evaporated and the solid was recrystallised from hot toluene. Final purification was achieved by silica column chromatography using dichloromethane/methanol (100:1) as eluent to yield 6.7 g of dap 1 (53%) as a pale yellow solid. 2,9-Diphenol-1,10-phenanthroline (dpp) 2 198,199 Anhydrous pyridine (10.2 mL) was placed in a 50 mL three-necked round-bottomed flask fitted with a thermometer and a magnetic stirrer. With rapid stirring concentrated hydrochloric acid (11.2 mL) was added. The flask was equipped for distillation, and water was distilled from the mixture until its internal temperature rose to 210 °C. After cooling to 140 °C, dap 1 (4.00 g, 10.2 mmol) was added as a solid and the reaction flask was fitted with a reflux condenser connected to a source of argon. The yellow mixture was stirred and refluxed for three hours (200-220 °C). The reaction mixture was allowed to cool to 120 °C, diluted with 15 mL of warm water and slowly poured into 75 mL of warm water. The resulting bright yellow suspension was refrigerated overnight. After cooling, the precipitated solid was filtered by suction, and washed with cold water. Crude acidic diphenol 2 was suspended (it dissolves partially) in an ethanolwater mixture (75 mL/50 mL) and neutralised with a dilute NaOH solution to pH = 7. The solution was diluted with hot water (300 mL), and neutral 2 precipitated as a beige solid upon cooling. The precipitate was filtered off and dried overnight to yield 3.53 g of dpp 2 (95%) as a red solid, which could be used without further purification. The diol 3 (3.04 g, 5.62 mmol) was partly dissolved in dry dichloromethane (200 mL).

The solution was cooled to 0 °C in an ice-bath under argon. Triethylamine (4.7 mL, 34 mmol) and DMAP (4-dimethylaminopyridine) (56 mg, 0.46 mmol) were added to the cooled mixture.

Tosyl chloride (4.68 g, 24.6 mmol) was slowly added. The solution was stirred under argon at 0°C for 2 h, then at room temperature for 12 h. Additional 1.07 g of tosyl chloride were added to the reaction mixture and the solution was stirred at room temperature overnight. The solution was then poured onto a mixture of ice (200 g) and HCl (1% aq., 50 mL). The aqueous layer was neutralised to pH 7 with aqueous NaOH. The organic layer was separated and the aqueous layer was washed with dichloromethane (2 × 250 mL). The organic layers were combined, washed with water (200mL), and dried with Na 2 SO 4 . The solvent was removed in vacuo. The resulting yellow oil was subjected to silica gel chromatography using dichloromethane/methanol (100:1)

as an eluent to yield the ditosylate 4 (4.29 g, 90%) as a yellow solid. A solution of the ditosylate phenanthroline derivative 4 (4.18 g, 4.92 mmol) and 3,5dihydroxybenzaldehyde (0.680 g, 4.92 mmol) in DMF (400 mL) was degassed, transferred to an addition funnel, and added dropwise to a suspension of Cs 2 CO 3 (8.02 g, 24.6 mmol) in DMF (600 mL) over a period of 4 h. The mixture was then heated to 60 °C and stirred under argon for 16 h. The warm mixture was filtered and the solid residue was washed with DMF (100 mL).

After evaporation of the solvent, the remaining solid was dissolved in dichloromethane (300 mL), washed with water (3 × 300mL) and dried over Na 2 SO 4 . The organic layer was evaporated, and the crude product was purified by silica gel chromatography in dichloromethane/methanol (100:1) to yield the macrocycle 5 as a pale yellow solid (2.10 g, 67%). N 3.80; found C 65.38, H 5.05, N 3.56.

5-Mesityldipyrrylmethane 6 207

Pyrrole (10 mL, 0.14 mol) and mesitylaldehyde (0.85 mL, 5.7 mmol) were added to a dry round-bottomed flask and degassed with a stream of Ar for 5 min. Ceric ammonium nitrate (0.31 g, 0.57 mmol) was added, and the solution was stirred under Ar at room temperature for 25 min. Ethyl acetate (20 mL) was then added, and the reaction was quenched by neutralisation with 0.1 M NaOH. The organic phase was washed with water (2 × 25 mL) and dried with Na 2 SO 4 . The solvent was evaporated to yield a dark green oil. The crude product was purified by flash column chromatography (petroleum ether/ethyl acetate/triethylamine, 80 : 20 : 1). Removal of the solvent under vacuum gave a solid that was washed with cold cyclohexane to dissolve the green impurities. The product was dried overnight to give 5-mesityldipyrrylmethane 6 (0.41 g, 27%) as an off-white solid.

Free-base porphyrin bis-macrocycle 7

To a solution of the macrocyclic aldehyde 5 (313 mg, 0.487 mmol) in dry dichloromethane (50 mL) was added trifluoroacetic acid (181 μL, 2.44 mmol) and 5mesityldipyrrylmethane 6 (135 mg, 0.511 mmol). The flask was protected from light and the solution was stirred for 2 h under argon. DDQ (2,3-dichloro-5,6-dicyanobenzoquinone) (177 mg, 0.779 mmol) was added and the solution was stirred under argon for an additional hour. A solution of Na 2 CO 3 (1.0 g) in water (50 mL) was added and the solution was stirred vigorously for 30 min. The two phases were separated and the aqueous layer was washed twice with dichloromethane. The organic solvents were evaporated and the compound was purified by silica gel chromatography using dichloromethane/methanol (100:0.5) as eluent. Complete purification of the product at this stage was difficult, so the partially purified free-base porphyrin (109 mg) was directly metalated.

Zinc porphyrin bis-macrocycle 8

The partially purified free-base porphyrin 7 (109 mg) was dissolved in chloroform (95 mL) and a saturated solution of Zn(OAc) 2 .2H 2 O in methanol (5 mL) was added. The mixture was refluxed for 5 h. The solvent was evaporated and the resulting solid was purified by alumina column chromatography with dichloromethane as eluent. The product was dissolved in CH 2 Cl 2 (100 mL) and treated with an aqueous solution of Na 4 EDTA (0.02 M, 100 mL). The biphasic mixture was vigorously stirred for 24 hours at room temperature. The organic layer was separated, washed three times with water. After evaporation, compound 8 was obtained as a purple solid (84 mg, 19%). (10 mL), and the resulting deep red solution was stirred under argon for 30 min. A degassed solution of 2,9-dianisyl-1,10-phenanthroline 1 (5.42 mg, 13.8 μmol) in CH 2 Cl 2 (5 mL) was then added by cannula. After stirring for 3 h at room temperature, the solvent was evaporated. The solid was dissolved in acetonitrile and the solution was filtered. The solvent was then evaporated to dryness giving the pseudorotaxane 9 2+ .2PF 6 as a purple solid in quantitative yield (18.0 mg).

4,7-Phenanthroline derivative 10 220

A large excess of MeI (21 mL, 0.34 mol) was added to a solution of 4,7-phenanthroline (1.84 g, 10.2 mmol) in DMF (250 mL) and the resulting reaction mixture was stirred at room temperature for 48 h. The precipitate formed was collected by filtration and dried under vacuum.

More MeI (10 mL, 0.16 mol) was added to the filtrate and the reaction further stirred for 24 h.

The precipitate formed was again collected by filtration and dried under vacuum. Product 10 was isolated as an orange crystalline solid (4.83 g, 98%). 3,8-Dibromo-4,7-phenanthroline 12 220 Compound 11 (1.28 g, 5.34 mmol), POBr 3 (44 g, 0.15 mol) and PBr 3 (7.5 g, 22 mmol) were placed in a round bottom flask fitted with an air condenser under argon. The mixture was heated at 180 °C for 48 hours. After cooling to about 60 °C, the black residue formed was added to excess ice/water (600 mL) and was vigorously stirred until hydrolysis of the remaining phosphorous halides was complete. Further ice was added and the mixture adjusted to pH 13 by dropwise addition of 20 % aq. NaOH. The final mixture was stirred for 30 min and then cooled down in an ice bath. The precipitate formed was collected by filtration, and then washed with hot CHCl 3 (8 × 100 mL). The aqueous filtrate was extracted with CHCl 3 (4 × 250 mL). The combined organic layers were evaporated to afford 12 as a pale yellow solid (1.51 g, 84%). BuLi (9.2 mL of a 1.65 M solution in hexane, 15 mmol) was added dropwise to a solution of 5-bromo-2-iodopyridine (4.01 g, 14.1 mmol) in dry toluene (130 mL) at -20 °C. During the addition, the temperature was progressively lowered to -78 °C. After the end of the addition, the reaction mixture was further stirred for 2 h at -78 °C. A solution of trimethyltin chloride (3.41 g, 16.8 mmol) in dry toluene (40 mL) was added and the resulting yellow solution was stirred for 1 h at -78 °C. It was then allowed to warm up to room temperature. The solvent was evaporated and the resulting solid was taken up in CH 2 Cl 2 . Insoluble salts were filtered off and the filtrate was evaporated to dryness. The resulting yellow oil was submitted to column chromatography on alumina with pentane as an eluent to afford compound 13 as a yellow oil (3.82 g, 85%). Dibromo bis-bidentate ligand 14 221 3,8-Dibromo-4,7-phenanthroline 12 (2.20 g, 3.56 mmol) and 5-bromo-2-trimethyltin pyridine 13 (2.35 g, 7.30 mmol) were suspended in dry toluene (150 mL) and the mixture was degassed with argon. Pd(PPh 3 ) 4 (0.23 g, 0.24 mmol) was added. The resulting reaction mixture was again degassed, and then refluxed under argon for 18 h. More Pd(PPh 3 ) 4 (0.19 g) was added and the reaction stirred for another 48 h under reflux. The solvent was evaporated to afford the crude product as a grey solid that was washed with MeOH (100 mL) and Et 2 O (3 × 100 mL). The solid was placed in a soxhlet and extracted with chloroform for 10 days to afford compound 14 (1.52 g, 87%) as a yellow/grey solid. TIPS bis-bidentate axle 15 [START_REF] Collin | Rotaxanes and[END_REF] Compound 14 (787 mg, 1.60 mmol), triisopropylsilylacetylene (1.6 mL, 7.0 mmol), CuI (45 mg, 0.24 mmol) and PdCl 2 (PPh 3 ) 2 (0.12 mg, 0.18 mmol) were introduced in an oven-dried flask. A degassed mixture of anhydrous DMF (30 mL) and distilled NEt 3 (3 mL) was subsequently added. The reaction mixture was further degassed with argon, and was then stirred for 18 h at 100 °C under argon. The reaction mixture was cooled down to room temperature and 40 mg of PdCl 2 (PPh 3 ) 2 were added. The solution was stirred at 100 °C for 5 h, and then cooled down to room temperature. The solvents were evaporated and the crude product was purified by column chromatography on silica (eluent: dichloromethane) and then washed with pentane to afford 655 mg of compound 15 (59%) as a pale yellow solid. Alkyne bis-bidentate axle 16 [START_REF] Collin | Rotaxanes and[END_REF] TIPS derivative 15 (150 mg, 0.216 mmol) were suspended in THF (10 mL). A 1 M solution of TBAF (0.60 mL, 0.60 mmol) in THF was then added, and a fine precipitate immediately formed. The reaction mixture was stirred for 30 min at room temperature. The solvent was evaporated, and the residual brown precipitate was washed with water, diethylether and pentane, and filtered over a Millipore filter. Compound 16 (70 mg, 85%) was obtained as a light brown powder. Bromo stopper 17 223 Pre-dried 4-[tris(p-tert-butylphenyl)methyl]phenol (1.00 g, 1.98 mmol) and Cs 2 CO 3 (1.29 g, 3.96 mmol) were introduced in an oven dried round-bottom flask and 30 mL of degassed anhydrous DMF were added. The reaction mixture was heated to 60 °C under argon and 1,3dibromopropanol (2.0 mL, 20 mmol) was then added. The reaction mixture was stirred under argon at 60 °C for 24 h. The solvent was evaporated and the resulting solid was taken up with CH 2 Cl 2 (200 mL). The solution was washed with water (3 × 200 mL), then the organic layer was evaporated and the resulting solid was purified by silica column chromatography with CH 2 Cl 2 /pentane 1:1 as an eluent. Bromo stopper 17 (882 mg, 71%) was obtained as a white solid. Azide stopper 18 [START_REF] Collin | Rotaxanes and[END_REF] Bromo stopper 16 (882 mg, 1.41 mmol) was dissolved in 10 mL of CH 2 Cl 2 . A solution of sodium azide in water (3 mL) and DMF (10 mL) was added, and the reaction mixture was stirred at 100 °C for 24 h. The solvents were evaporated and the resulting solid was taken up in CH 2 Cl 2 (150 mL). The solution was washed with water (3 × 150 mL), then the organic layer was evaporated and the resulting solid was purified by silica column chromatography with CH 2 Cl 2 /pentane 1:1 as an eluent. Azide stopper 18 (638 mg, 77%) was obtained as a white solid. Guest G3 261 1,4-Dibromobenzene (235 mg, 1.00 mmol), pyridine 4-boronic acid (430 mg, 3.50 mmol), Pd(dppf) 2 Cl 2 (82 mg, 0.10 mmol), and Na 2 CO 3 (0.21 g, 2.0 mmol) were introduced in a 10 mL round-bottom flask, and a mixture of toluene/water 1:1 (5 mL) was added. The mixture was degassed for 10 min and allowed to reflux for 72 h under argon atmosphere. The solvent was evaporated, and the residue was extracted with ethyl acetate (50 mL). The solution was washed with water (3 × 50 mL). The organic layer was dried over anhydrous MgSO 4 and evaporated to afford a brown solid, which was purified by silica gel column chromatography in ethyl acetate/pentane/triethylamine 8:5:1 to afford pure 1,4-bis(4-pyridyl)benzene G3 as an off-white solid (180 mg, 77%). UV-visible absorption (CHCl 3 ): λ max (log ε) = 420 (5.69), 541 nm (4.30).

Dinitro copper(II) porphyrins 21 265

A solution of nitrogen dioxide in light petroleum (0.5 M, 10 mL) was added in small aliquots to a solution of copper(II) porphyrin 20 (2.20 g, 1.96 mmol) in dichloromethane (100 mL). The reaction was followed by TLC (dichloromethane/light petroleum 1:4). A new spot corresponding to the mono-nitrated adduct appeared on TLC, followed by appearance of other spots corresponding to dinitrated porphyrins. When conversion to the dinitrated species was complete according to TLC, the mixture was immediately passed through a plug of silica gel using dichloromethane as eluent. The solvent was evaporated to give a purple residue, which was further purified by column chromatography over silica using dichloromethane/light petroleum (1:4) as eluent. A mixture of dinitro copper(II) porphyrin isomers 21 was obtained as a redpurple solid (2.02 g, 85%). Identification of the product was confirmed by comparison of the TLC and UV-visible absorption spectrum with those of an authentic sample.

UV-visible absorption (CHCl 3 ): λ max (log ε) = 438 (5.19), 559 (4.08), 601 nm (4.03). Dinitro free-base porphyrins 22 265 Concentrated sulphuric acid (5 mL) was added dropwise to a solution of 21 (2.02 g, 1.67 mmol) in dichloromethane (60 mL). The reaction mixture was stirred at room temperature for 15 min and then poured into an ice-water mixture (100 mL). The organic layer was washed with water (100 mL), 10 % aqueous sodium carbonate (100 mL), water (100 mL), dried over Na 2 SO 4 , and filtered. The solvent was evaporated to give a purple solid, which was purified by column chromatography on silica gel using dichloromethane-light petroleum 1:4 as eluent.

Dinitro free-base porphyrin isomers 24 were obtained as a purple solid (1.92 g, quantitative). Diamino free-base porphyrins 23 265 Isomers 22 (1.92 g, 1.67 mmol) and tin(II) chloride dihydrate (4.52 g, 20.0 mmol) were dissolved in dichloromethane/diethylether 1:1 (40 mL) and the solution was cooled in an ice bath.

A solution of hydrochloric acid in diethylether (~2 M, 10 mL) was slowly added. The solution was allowed to warm up to room temperature and stirred for 2 h. It was washed with water (50 mL), 10 % aqueous NaHCO 3 (50 mL) and water (50 mL). The organic layer was evaporated to give the crude diamino free-base porphyrins 23 (1.77 g), which were immediately photooxidised. Corner amino free-base porphyrin-diones 24 and linear free-base porphyrintetraone 25 265 The crude diamino free-base porphyrins 23 (1.77 g) were dissolved in dichloromethane.

Photooxidation was achieved by irradiation with UV-light and bubbling of oxygen through the solution for 3.5 h. The solvent was evaporated to give a mixture of 7-and 8-aminoporphyrin diones 24 and linear porphyrin-tetraone 25, which were subjected to selective metalation.

Corner amino zinc porphyrin-diones 26 and linear free-base porphyrintetraone 25 265 The mixture of 27 and 28 was dissolved in dichloromethane (100 mL), and a solution of zinc acetate dihydrate (1.42 g, 6.46 mmol) 1,2-Dimethoxybenzene (veratrole) (20 mL, 0.16 mol) was added dropwise over 1 h to a vigorously stirred mixture of concentrated HNO 3 (50 mL) and H 2 O (5 mL) at 0 °C. The resulting yellow slurry was then warmed to 60 °C to liberate NO 2 as a brown gas. After gas evolution ceased (4 h), the solution was poured into 500 mL of ice water and the yellow solid was isolated by suction filtration. The solid was washed thoroughly with a saturated solution of NaHCO 3 followed by H 2 O. After drying, the product was recrystallised from hot ethanol. 4,5-Dinitroveratrole was isolated as a crystalline yellow solid (29 g, 81%). The colour of the reaction solution proceeded from orange through yellow to colourless within 2 h. The slurry was filtered through Celite and the filtrate was evaporated to yield 4,5diaminoveratrole 28 as an off-white solid (3.71 g, quantitative). producing a purple solution. The solvent was evaporated, and the methanol treatment was repeated twice. The final crude purple residue was recrystallised from MeOH/THF (1:9) to yield 4,5-diaminocatechol hydrobromide 29 as a purple crystalline solid (4.35 g, 89%).

1 H NMR (300 MHz, CD 3 OD): δ = 6.96 (s, 2H, H Ar ), 5.01 ppm (br s, 5H, NH 2 ).

Linear bis(dihydroxyquinoxalino)porphyrin 30

Linear porphyrin-tetraone 25 (50 mg, 45 μmol) and 4,5-diaminocatechol hydrobromide 29 (39 mg, 0.11 mmol) were dissolved in degassed distilled pyridine, and the reaction mixture was refluxed under argon for 20 h. The solvent was evaporated, and the resulting solid was dissolved in dichloromethane (50 mL) and washed with water (50 mL), 10 % aqueous NaHCO 3 (50 mL) and water (50 mL). The solvent was evaporated and the solid was recrystallised from dichloromethane/methanol to give compound 30 as a dark red solid (50 mg, 85%).

HRES-MS

4,5-Dinitrocatechol 31 276

4,5-Dinitroveratrole 27 (8.5 g, 37 mmol) and hydrobromic acid (48%, 50 mL) were heated to 90 °C for 48 h. A brown solid precipitated. It was filtered off, and the product was extracted from the filtrate with diethylether (3 × 100 mL). The organic layers were combined and the solvent was evaporated to give 4,5-dinitrocatechol 31 as an orange solid (3.0 g, 41%). The solvent was evaporated and the product was recrystallised in THF to give the Boc-protected compound 32 as a purple solid (548 mg, 83%). 82, 158.44, 150.90, 143.18, 142.63, 135.84, 129.99, 129.28, 128.97, 127.20, 122.98, 114.12, 114.07, 103.99, 96.40, 55.20, 55.01, 46.89

Benzimidazole macrocycle 34

A mixture of the ditosylate phenanthroline derivative 4 (100 mg, 118 μmol) and catechol derivative 33 (44.4 mg, 118 μmol) in DMF (20 mL) was degassed, transferred to an addition funnel, and added dropwise to a degassed suspension of Cs 2 CO 3 (231 mg, 708 μmol) in DMF (30 mL) over a period of 2 h. The mixture was then heated to 90°C and stirred under argon for 16 h. After evaporation of the solvent, the remaining solid was dissolved in dichloromethane (50 mL), washed with water (3 × 50 mL) and dried over Na 2 SO 4 . The organic layer was evaporated, and the crude product was purified by alumina column chromatography in dichloromethane/methanol (100:0.4) to yield macrocycle 34 as a pale yellow solid (62 mg, 60%). 7.10 (d, 2H, 3 J = 8.5 Hz, H mp1 ), 6.86 (d, 4H, 3 J = 8.5 Hz, H ob2 + H mb1 ), 6.78 (s, 1H, H c2 ), 6.75 (d, 2H, 3 J = 8.5 Hz, H mb2 ), 5.22 (s, 2H, CH 2 ), 4.37 (t, 2H, 3 J = 5.5 Hz, H α1 ), 4.35 (t, 2H, 3 J = 5.5 Hz, H α2 ), 4.32 (t, 2H, 3 J = 5.5 Hz, H δ1 ), 4.18 (t, 2H, 3 J = 5.5 Hz, H δ2 ), 4.00 (t, 2H, 3 J = 5.5 Hz, H γ1 ), 3.92 (t, 2H, 3 J = 5.5 Hz, H β1 ), 3.86 (t, 2H, 3 J = 5.5 Hz, H γ2 ), 3.81 (t, 2H, 3 J = 5.5 Hz, H β2 ), 3.80 (s, 3H, Me 1 ), 3.72 ppm (s, 3H, Me 2 ). 13 C NMR (125 MHz, CDCl 3 ): δ = 160. 77, 160.07, 159.15, 156.46, 156.37, 153.07, 146.92, 146.69, 146.12, 146.06, 137.34, 136.80, 136.71, 133.10, 132.72, 130.58, 130.34, 129.27, 129.13, 128.48, 127.52, 127.49, 127.32, 125.71, 125.63, 122.45, 119.31, 119.24, 116.08, 115.72, 114.49, 114.22, 105.19, 98.33, 70.25, 69.96, 69.93, 69.62, 69.49, 69.15, 68.03, 67.89, 55.49, 55.41, 48.08 ! 1

" 1 # 1 $ 1 ! 2 " 2 # 2 $ 2

4,5-Dibromocatechol 35 288

A solution of Br 2 (4.7 mL, 91 mmol) in CHCl 3 (6 mL) was added dropwise over 1 h to a suspension of catechol (5.00 g, 45.4 mmol) in CHCl 3 (50 mL) at 0 °C. The reaction mixture was then allowed to warm up to room temperature and was stirred for 20 h. The precipitate was isolated by filtration to give dibromocatechol 35 (6.47 g, 53%) as an off-white solid.

Dibromo macrocycle 36

A mixture of the ditosylate phenanthroline derivative 4 (750 mg, 0.883 mmol) and 4,5dibromocatechol 35 (237 mg, 0.883 mmol) in DMF (75 mL) was degassed, transferred to an addition funnel, and added dropwise to a degassed suspension of Cs 2 CO 3 (1.73 g, 5.30 mmol) in DMF (110 mL) over a period of 4 h. The mixture was then heated to 90°C and stirred under argon for 16 h. After evaporation of the solvent, the remaining solid was dissolved in dichloromethane (150 mL), washed with water (3 × 150 mL) and dried over Na 2 SO 4 . The organic layer was evaporated, and the crude product was purified by silica gel chromatography in dichloromethane/methanol (100:1) to yield the macrocycle 36 as a pale yellow solid (247 mg, 36%).

1 H NMR (400 MHz, CDCl 3 ): δ = 8. 40 (d,3 J = 8.8 Hz,4H,H o ),8.27 (d,3 J = 8.4 Hz,2H,H 3,[START_REF] Stoddart | The chemistry of the mechanical bond[END_REF]8.06 (d,3 J = 8.4 Hz,2H,H 4,[START_REF] Amabilino | Topology in molecules inspired, seen and represented[END_REF]7.75 (s,2H,H 5,6 ),7.20 (s,2H,H b ),7.17 (d,3 J = 8.8 Hz, 4H, H m ), 4.39 (t, 3 J = 5.6 Hz, 4H, CH 2 ), 4.20 (t, 3 J = 5.6 Hz, 4H, CH 2 ), 3.94 (t, 3 J = 5.6 Hz, 4H, CH 2 ), 3.89 ppm (t, 3 J = 5.6 Hz, 4H, CH 2 ). After evaporation of the solvent, the crude product was purified by silica gel chromatography (gradient of chloroform/methanol from 100:0 to 98:2) and size-exclusion chromatography (Biobeads S-X1 in ethanol-free chloroform) to give porphyrin 38 as a purple solid (0.11 g, 25%). 05, 157.93, 156.17, 145.94, 143.87, 136.69, 132.63, 129.04, 127.96, 127.40, 125.54, 119.75, 119.09, 115.51, 114.09, 102.48, 70.05, 69.56, 67.63 (CH 2 Cl 2 ): λ max (log ε) = 284 (5.36), 323 (5.10), 421 (5.65), 515 (4.30), 550 (3.78), 588 (3.76), 645 (3.51) nm.

Zinc porphyrin tetra-macrocycle 39

Free-base porphyrin 38 (44 mg, 16 µmol) was dissolved in CHCl 3 (25 mL), and a saturated solution of Zn(OAc) 2 •2H 2 O in methanol (5 mL) was added. The solution was heated to reflux and stirred for 5 h under argon. The solvents were evaporated and the solid was taken up with chloroform (25 mL) and washed with water (2 × 25 mL). An aqueous solution of Na 4 EDTA (0.1 M, 25 mL) was added to the organic layer and the biphasic mixture was vigorously stirred for further 24 hours at room temperature. The organic layer was separated, washed twice with water, dried with Na 2 SO 4 and evaporated under reduced pressure to give Znporphyrin 39 as a purple solid in quantitative yield (45 mg). 15, 158.01, 156.32, 146.05, 143.99, 136.85, 132.73, 129.17, 127.54, 125.69, 119.84, 119.27, 115.62, 114.16, 102.57, 70.18, 69.68, 67.78 (5.39), 322 (5.13), 424 (5.75), 550 (4.35), 590 (3.52) nm. added by cannula to a degassed solution of Zn-porphyrin 39 (30 mg, 11 µmol) in CHCl 3 (5 mL).

The mixture was stirred under argon for 30 min. This solution was then added to a degassed suspension of acetylenic thread 16 (8.1 mg, 21 µmol) in CHCl 3 (5 mL). The mixture was stirred for 24 h under argon. Azide stopper 18 (37 mg, 64 µmol), [Cu(CH 3 CN) 4 ](PF 6 ) (7.9 mg, 21 µmol), Na 2 CO 3 (0.9 mg, 8.5 µmol) and sodium ascorbate (1.7 mg, 8.5 µmol) were then added to the solution. The mixture was stirred under argon during 6 days. The solvents were then evaporated and the resulting deep red solid was purified by silica chromatography. Two consecutive columns using a gradient of eluent from CH 2 Cl 2 /MeOH 100:0 to 92:8 gave 32 mg of rotaxane 40 4+ •4PF 6 (44%) as a dark red solid.

First

  , I would like to thank my examiners, Prof. David Amabilino, Prof. Jay Siegel and Prof. Véronique Bulach for their interest in my research work. Je voudrais également remercier mes directeurs de thèse, français et australien. Un grand merci à Jean-Pierre Sauvage et Angélique Sour pour m'avoir accueillie à Strasbourg. Après un passage à Paris, j'ai été très heureuse de retrouver l'Alsace et d'intégrer une équipe aussi sympathique et dynamique. Vous avez encadré ma thèse avec énormément d'enthousiasme et de disponibilité, et vous avez su me soutenir dans les bons comme dans les moins bons moments.

Figure 1 .Figure 2 .Figure 3 .Figure 4 .Figure 5 .Figure 6 .Figure 7 .Figure 8 .Figure 9 .Figure 10 .Figure 11 .Figure I. 1 . 2 Figure I. 2 .

 1234567891011122 Figure 1. Principe du récepteur moléculaire modulable. .......................................................................... xxx Figure 2. Structures chimiques du précurseur macrocyclique et du [3]pseudorotaxane obtenu par complexation du nouveau bis-macrocycle porphyrinique et du ligand dap avec le cuivre(I). ................ xxxi Figure 3. Structures chimiques du rail et du bouchon. .......................................................................... xxxii Figure 4. Structure chimique du [4]rotaxane. ....................................................................................... xxxiii Figure 5. Molécules invitées testées avec le [4]rotaxane. ..................................................................... xxxiv Figure 6. Titration UV-visible (bande de Soret) pour la complexation entre la 4,4'-bipyridine G2 et le [4]rotaxane. ............................................................................................................................................ xxxiv Figure 7. Projet de nouveau bis-macrocycle porphyrinique rigide. ...................................................... xxxvi Figure 8. Schéma rétrosynthétique pour l'obtention du nouveau bis-macrocycle porphyrinique. ...... xxxvii Figure 9. Structure chimique du nouveau tétra-macrocycle porphyrinique. ...................................... xxxviii Figure 10. Représentation d'un [6]rotaxane composé de deux tétra-macrocycles porphyriniques et de quatre rails. .......................................................................................................................................... xxxviii Figure 11. Structure chimique du [3]rotaxane obtenu. ......................................................................... xxxix

2 Figure I. 3 . 3 Figure

 233 Figure I.2.First synthetic trefoil knot reported by C. O. Dietrich-Buchecker and J.-P. Sauvage. The strategy involves the formation of a double helical complex of bis-phenanthroline ligands around two copper(I) centres, followed by ring closure and demetalation. The knotted structure of the Cu(I) complex was confirmed by X-ray crystallography.[START_REF] Forgan | Chemical Topology: Complex Molecular Knots, Links, and Entanglements[END_REF][START_REF] Dietrich-Buchecker | A Synthetic Molecular Trefoil Knot[END_REF][START_REF] Dietrich-Buchecker | Structure of a Synthetic Trefoil Knot Coordinated to Two Copper(I) Centers[END_REF][START_REF] Dietrich-Buchecker | Molecular Knots. Templates in Chemistry II[END_REF] .......................................................................................... 2 Figure I.3. a) Schematic view of a [2]catenane. b) First copper(I)-templated catenane synthesised by C. O. Dietrich-Buchecker and J.-P. Sauvage. 25 ....................................................................................................... 3 Figure I.4. A non-covalent catenane assembled via labile metal-ligand coordination bonds. The [2]catenane is in equilibrium with the corresponding non-interlocked macrocycles. The catenated form is largely predominant at high concentration. 29 ................................................................................................. 4

4 Figure I. 5 . 4 Figure I. 6 . 5 Figure I. 7 .

 454657 Figure I.4.A non-covalent catenane assembled via labile metal-ligand coordination bonds. The[2]catenane is in equilibrium with the corresponding non-interlocked macrocycles. The catenated form is largely predominant at high concentration.[START_REF] Fujita | Quantitative self-assembly of a [2]catenane from two preformed molecular rings[END_REF] ................................................................................................. 4 Figure I.5. Schematic views of a) a [2]rotaxane composed of a ring threaded on an axle ending with bulky stoppers (to prevent unthreading); and b) a pseudorotaxane. .............................................................. 4 Figure I.6. Strategy used by G. Schill in the first directed rotaxane synthesis, involving the use of covalent bonds as templates. 35 ....................................................................................................................... 5

6 Figure I. 8 . 6 Figure

 686 Figure I.7. Examples of other interlocked structures. a) A molecular Solomon link (doubly interlocking[2]catenane); 36 b) Molecular Borromean rings (three interlocking, but non-catenated macrocycles); 37 c) A[3]rotacatenane (combination of[2]catenane and[2]rotaxane structures).[START_REF] Barin | A Multistate Switchable [3]Rotacatenane[END_REF] ................................................. 6 Figure I.8. Three examples of rotaxanes assembled via directed strategies. a) Use of the gathering effect of the copper(I) template; 40 b) Preorganisation of the system via hydrogen bonding between the ring component and the dumbbell component; 41 c) Interlocking favoured by π-donor/π-acceptor interactions between the axle and the macrocycle. 42 ......................................................................................................... 6 Figure I.9. The first [2]rotaxane exclusively made of double-stranded DNA, assembled via base-pairing between the axle and the ring. 50 ..................................................................................................................... 7

7 Figure I. 10 .

 710 Figure I.9. The first[2]rotaxane exclusively made of double-stranded DNA, assembled via base-pairing between the axle and the ring.[START_REF] Ackermann | A double-stranded DNA rotaxane[END_REF] ..................................................................................................................... 7 Figure I.10. Different possible geometries for a[3]rotaxane. Instances of these geometries have been described in the literature: a) Two rings threaded on one axle; 51-54 b) Two axles passing through the same ring; 55-57 c) and d) Two axles passing through the rings formed by a bis-macrocyclic component.[START_REF] Wittenberg | A clipped [3]rotaxane derived from bis-nor-seco-cucurbit[10]uril[END_REF][START_REF] Goldup | Two Axles Threaded Using a Single Template Site: Active Metal Template Macrobicyclic[END_REF] ........ 8

9 Figure I. 13 .

 913 Figure I.11. An original rotaxane architecture: a hetero-[7]rotaxane incorporating two different macrocycles. 65 ................................................................................................................................................ 9 Figure I.12. A thermally activated, near infrared chemiluminescent squaraine rotaxane for optical imaging. 75 ....................................................................................................................................................... 9 Figure I.13. The ATP synthase, a natural molecular machine. 80,81 ATP synthases are rotary motors: a flow of protons through the membrane causes rotation of the rotor component (γ, ε and c) in relation to the stator component (α 3 β 3 ). This motion triggers sequential conformational changes in the β subunits, which are responsible for the consecutive steps of the formation of ATP: binding of the substrates ADP and P i , chemical transformation and release of the newly formed ATP. ................................................................ 11 Figure I.14. a) Structure of the GroEL chaperonin and the GroEL/GroES complex (side view). b) Section of the internal cavities of the GroEL/GroES complex. c) Mechanism of action of the GroEL chaperonin: (i) an unfolded protein (red) is trapped at the entrance of the cavity (green/blue); (ii) fixation of ATP (T) triggers conformational changes and binding of the GroES lid (grey) and allows folding of the guest protein; (iii) hydrolysis of ATP to ADP (D) weakens the GroEL/GroES complex and induces release of the lid and folded protein. 83,84 ....................................................................................................................... 12

12 Figure I. 15 . 13 Figure I. 16 . 14 Figure

 1215131614 Figure I.14. a) Structure of the GroEL chaperonin and the GroEL/GroES complex (side view). b) Section of the internal cavities of the GroEL/GroES complex. c) Mechanism of action of the GroEL chaperonin: (i) an unfolded protein (red) is trapped at the entrance of the cavity (green/blue); (ii) fixation of ATP (T) triggers conformational changes and binding of the GroES lid (grey) and allows folding of the guest protein; (iii) hydrolysis of ATP to ADP (D) weakens the GroEL/GroES complex and induces release of the lid and folded protein. 83,84 ....................................................................................................................... 12 Figure I.15. Macroscopic bending motion of a cocrystal of a dithienylethene derivative and perfluoronaphthalene. The motion is due to the shape change of the dithienylethene units by photocyclisation upon irradiation with UV light. 86 ...................................................................................... 13 Figure I.16. A molecular crystal cantilever at work: a 0.17 mg photochromic crystal lifts a 47 mg lead ball upon irradiation with UV light. 86 .......................................................................................................... 14 Figure I.17. A unidirectional molecular motor based on a [3]catenane structure (left). The sequential

  Figure I.18.A fast-moving copper-complexed[2]rotaxane shuttle. The translational motion is controlled

  Figure I.19.A molecular elevator based on a triply interlocked[2]rotaxane structure. The interactions of the rings on the axles depend on the pH: the rings bind on the ammonium units when these are protonated and switch to the bipyridinium sites upon deprotonation of the ammonium groups. The shuttling motion of the rings along the axles lifts the central platform up and down. 119 ........................................................ 17

Figure I. 20 . 18 Figure I. 21 . 19 Figure I. 22 . 20 Figure I. 23 .

 20182119222023 Figure I.20. Chemical structures of the porphyrin core and of two related heterocycles: the chlorin family and the bacteriochlorin family. One or two C=C double bonds are reduced in the chlorins and bacteriochlorins, respectively, compared to the porphyrin structure. .......................................................... 18 Figure I.21. Structure of metalloporphyrins and coordination of axial ligands. ........................................ 19 Figure I.22. [2]catenanes obtained by axial coordination of bifunctional pyridyl ligands on Znporphyrins. 141,142 ........................................................................................................................................... 20 Figure I.23. A novel approach for the templated synthesis of large multi-porphyrin rings. A linear porphyrin tetramer and a cyclic six-site template with mismatched numbers of binding sites were assembled by axial porphyrin coordination to give Vernier complexes. Covalent coupling of the porphyrin oligomers followed by template removal afforded a 12-porphyrin nano-ring. 143 ....................... 21 Figure I.24. Discrimination between the syn and anti isomers of a bis-porphyrin using axial coordination

22 Figure I. 25 . 23 Figure I. 26 . 24 Figure I. 27 . 25 Figure I. 29 . 26 Figure I. 30 .

 22252326242725292630 Figure I.25. Host-guest complexes of covalently linked Zn-porphyrin dimers and ditopic nitrogen ligands (DABCO or 4,4'-bipyridine) synthesised and studied in the group of J. K. M. Sanders. 153,154 ................... 23 Figure I.26. Chemical structure (left) and molecular model (right) of a self-assembled capsule formed by axial coordination of a tetramine guest on the zinc(II) sites of two bis-porphyrin receptors. 159 ................. 24 Figure I.27. Determination of the absolute configuration of α-chiral carboxylic acids with a bisporphyrin host. Binding of the chiral guest induces a conformational change of the host with a preferred helicity, which is measured by circular dichroism. 160 .................................................................................. 24 Figure I.28. a) A porphyrin-faced cubic host for C 70 fullerene. 162 b) A supramolecular polymer formed through head-to-tail host-guest self-recognition of a hermaphroditic monomer. The host part of the monomer is an electron-rich bis-porphyrin unit, which is linked to an electron-deficient trinitrofluorenone guest moiety. 163 ............................................................................................................................................ 25 Figure I.29. A tris-porphyrin prism host that can encapsulate and fold short peptides in hybrid α-helix/βturn conformations. 171 .................................................................................................................................. 26 Figure I.30. A photoresponsive, porphyrin-containing molecular machine whose motion is reminiscent of a molecular pedal. Photoisomerisation of the azobenzene unit results in a rotary motion of the ferrocene pivot and of a pedal-like conformational change of the zinc porphyrin dimer. This motion is transferred to the biisoquinoline guest, which undergoes twisting around its central C-C bond. 174 .................................. 27 Figure I.31. A molecular gate composed of a Sn(IV)-porphyrin rotor linked to a handle stator by axial coordination. The gate is closed by coordination of silver(I) on the pyridyl sites of the handle and of the porphyrin. 176,177 ............................................................................................................................................. 28

30 Figure

 30 Figure I.33. A porphyrin-incorporating [6]pseudorotaxane structure reminiscent of the special pair of the photosynthetic reaction centre. Two central copper(II) porphyrins are held in a slipped cofacial arrangement by the surrounding interlocked scaffold. Parallel spin electron coupling between the Cu(II) centres results from the close proximity of the metalloporphyrins. 192 ......................................................... 30 Figure I.34. A tetra-interlocked [2]rotaxane with face-to-face Cu(II)-porphyrin and Cu(II)phthalocyanine units. The distance between the copper(II) centres is monitored by protonation/deprotonation of amine groups on the axles. Switchable spin-spin communication is achieved: the spins are isolated in the protonated state of the rotaxane whereas antiferromagnetic coupling is observed upon deprotonation. 193 .............................................................................................................. 31

Figure I. 35 .

 35 Figure I.34.A tetra-interlocked[2]rotaxane with face-to-face Cu(II)-porphyrin and Cu(II)phthalocyanine units. The distance between the copper(II) centres is monitored by protonation/deprotonation of amine groups on the axles. Switchable spin-spin communication is achieved: the spins are isolated in the protonated state of the rotaxane whereas antiferromagnetic coupling is observed upon deprotonation.193 .............................................................................................................. 31 Figure I.35. Schematic views of the copper(I)-complexed (top) and copper-free (bottom) forms of a [3]rotaxane. The rotaxane is a good molecular receptor for ditopic pyridyl guests of various lengths. The copper(I)-complexed rotaxane forms stronger complexes with short guests, while the copper-free rotaxane has better affinity for long guests. 194,195 ......................................................................................... 32

  Figure I.35. Schematic views of the copper(I)-complexed (top) and copper-free (bottom) forms of a [3]rotaxane. The rotaxane is a good molecular receptor for ditopic pyridyl guests of various lengths. The copper(I)-complexed rotaxane forms stronger complexes with short guests, while the copper-free rotaxane has better affinity for long guests. 194,195 ......................................................................................... 32 Figure I.36. A [4]rotaxane with two face-to-face porphyrins. The copper(I)-complexed rotaxane forms guest inclusion complexes with short substrates. However, the rotaxane collapses upon demetalation of the copper(I) centres and does not show any host-guest properties after demetalation.196,197 ...................... 33

33 Figure I. 37 . 35 Figure I. 38 . 35 Figure I. 39 .

 333735383539 Figure I.36.A[4]rotaxane with two face-to-face porphyrins. The copper(I)-complexed rotaxane forms guest inclusion complexes with short substrates. However, the rotaxane collapses upon demetalation of the copper(I) centres and does not show any host-guest properties after demetalation.196,197 ...................... 33 Figure I.37. Schematic view of the target [4]rotaxane. Zn-porphyrins are depicted as diamond-shaped symbols; phenanthroline and bipyridine binding sites are blue and green U-shaped symbols, respectively; copper(I) centres are pink dots and stoppers are large grey spheres. .......................................................... 35 Figure I.38. Proposed mechanism of action of a molecular press based on a [4]rotaxane. A flexible guest molecule bound in the central cavity of the rotaxane by axial coordination on the Zn-porphyrins is depicted in red. In the absence of copper(I) the guest can adopt an elongated conformation. In the presence of copper(I) the porphyrins are expected to be in closer proximity and induce conformational changes on the guest. ................................................................................................................................... 35 Figure I.39. Design of a [6]rotaxane composed of two porphyrinic tetra-macrocycles and of four dumbbells. .................................................................................................................................................... 36

Figure II. 1 . 37 Figure II. 2 .Figure II. 3 . 40 Figure II. 4 . 41 Figure II. 5 . 42 Figure II. 6 . 43 Figure II. 7 . 44 Figure II. 8 . 46 Figure II. 9 . 1 H 48 Figure II. 11 . 51 Figure II. 12 . 51 Figure II. 13 . 52 Figure II. 14 . 53 Figure II. 15 .Figure III. 1 . 56 Figure III. 2 . 58 Figure III. 3 .

 137234044154264374484691481151125113521453151562583 Figure II.1. Retrosynthetic scheme displaying the chemical structures of the target building blocks needed for the formation of a [4]rotaxane with two cofacial Zn-porphyrins. The pink spheres represent copper(I), the "gathering-and-threading" centre. ......................................................................................... 37 Figure II.2. Schematic view of the structural difference between two porphyrinic bis-macrocycles: (a) previously made in our group 196 and (b) described in this chapter. The main differences reside in (i) the nature of the bridge (highlighted in blue) between the central porphyrin (purple) and the macrocycles (rigid pyrazine-benzene-pyrazine motif vs. single C-C bond); (ii) the position of the bridge on the porphyrin (β-pyrrolic vs. meso substitution); (iii) the orientation of the coordinating dpp unit (yellow) (exo vs. endo coordination mode with respect to the porphyrin); and (iv) the electronic coupling between the dpp chelate and the porphyrin (electronically coupled vs. decoupled). ................................................. 38

61 Figure III. 5 .

 615 Figure III.4. Two-step, one-pot synthesis of [4]rotaxane 19 4+ in 50% yield by (1) threading of bismacrocycle 8 and axle 16 into a [4]pseudorotaxane and (2) quadruple CuAAC stoppering reaction with azide stopper 18. .......................................................................................................................................... 61 Figure III.5. High resolution electrospray mass spectrum of rotaxane 19 4+ . The main signal is magnified to show the isotope profile (top right); this profile fits well with the calculated spectrum (bottom). ......... 62

63 Figure III. 7 . 63 Figure III. 8 . 1 H 64 Figure III. 9 . 65 Figure III. 10 . 66 Figure III. 11 .

 637638164965106611 Figure III.6. Hypothetical threading and stoppering scheme leading to a[2]rotaxane. Mass spectrometry results indicated that this threading scheme is not favoured. The isotope profile is consistent with a[4]rotaxane containing four copper(I) centres ............................................................................................. 63 Figure III.7. Variable temperature 1 H NMR spectra of [4]rotaxane 19 4+ in CD 3 NO 2 . Signals in the aromatic region are displayed. ..................................................................................................................... 63 Figure III.8. 1 H NMR spectrum of rotaxane 19 4+ in CD 2 Cl 2 at room temperature. Signals in the aromatic region are displayed (top), as well as proton assignments on the bis-macrocycle and dumbbell components of the rotaxane (bottom). Split signals are annotated with "a" and "b" subscripts. Signals were assigned using COSY, NOESY, HSQC and HMBC data. ................................................................. 64 Figure III.9. Part of the NOESY spectrum of rotaxane 19 4+ displaying NOE interactions between the central part of the dumbbell (protons 1' -4') and the ethyleneglycol chains of the macrocycles. ............... 65 Figure III.10. Schematic view of the proposed geometry of rotaxane 19 4+ in solution deduced from the NMR data. .................................................................................................................................................... 66 Figure III.11. DOSY spectrum of rotaxane 19 4+ in CD 2 Cl 2 , displaying signals in the aromatic region. The DOSY data show the presence of a single chemical species in solution; arrows point at minor signals that belong to a second, minor conformer of the [4]rotaxane in very slow exchange with the major conformer. This minor conformer diffuses at the same rate as the major conformer. A good fit is obtained for the estimated size of the rotaxane using CPK models and the diffusion coefficient measured by DOSY NMR. The rotaxane approximates to a 48 Å sphere. .............................................................................................. 67

68 Figure III. 13 .

 6813 Figure III.11. DOSY spectrum of rotaxane 19 4+ in CD 2 Cl 2 , displaying signals in the aromatic region. The DOSY data show the presence of a single chemical species in solution; arrows point at minor signals that belong to a second, minor conformer of the [4]rotaxane in very slow exchange with the major conformer. This minor conformer diffuses at the same rate as the major conformer. A good fit is obtained for the estimated size of the rotaxane using CPK models and the diffusion coefficient measured by DOSY NMR. The rotaxane approximates to a 48 Å sphere. .............................................................................................. 67 Figure III.12. UV-visible absorption spectra (Soret band) of [4]rotaxane 19 4+ and its precursor, porphyrinic bis-macrocycle 8 in CH 2 Cl 2 with [porphyrin] = 1.9*10 -6 M. The blue shift and broadening of the Soret band of the rotaxane is attributed to exciton coupling between the two central porphyrins. ....... 68 Figure III.13. Scheme highlighting the similarities and differences between the present [4]rotaxane 19 4+and the[3]rotaxane that will be described in Chapter V. Both rotaxanes comprise exactly the same dumbbell resulting from the click reaction of two stoppers 18 on the axle 16, and are complexed to four Cu(I) centres. However, only one porphyrin is incorporated in the[3]rotaxane while the[4]rotaxane contains two cofacial porphyrins. ................................................................................................................ 69

Figure III. 14 . 71 Figure III. 15 . 72 Figure III. 16 . 73 Figure III. 17 . 74 Figure III. 18 . 76 Figure III. 19 . 77 Figure III. 20 . 78 Figure III. 21 .Figure IV. 1 .

 1471157216731774187619772078211 Figure III.13. Scheme highlighting the similarities and differences between the present[4]rotaxane 194+ and the[3]rotaxane that will be described in Chapter V. Both rotaxanes comprise exactly the same dumbbell resulting from the click reaction of two stoppers 18 on the axle 16, and are complexed to four Cu(I) centres. However, only one porphyrin is incorporated in the[3]rotaxane while the[4]rotaxane contains two cofacial porphyrins. ................................................................................................................ 69 Figure III.14. Chemical structures of guests G1 -G4. ............................................................................... 71 Figure III.15. Synthesis of guests G3 and G4. 261 ....................................................................................... 72 Figure III.16. Possible coordination modes of guests G1 -G4 with rotaxane host 19 4+ . a) 1:1 host-guest stoichiometry, internal complex (guest inclusion); b) 1:1 stoichiometry, external complex; c) 1:2 hostguest stoichiometry, internal complexes; d) 1:2 stoichiometry, external complexes, e) 1:2 stoichiometry with one internal and one external guest. .................................................................................................... 73

85 Figure IV. 3 . 86 Figure IV. 4 . 87 Figure IV. 5 . 88 Figure IV. 6 . 90 Figure IV. 7 . 91 Figure IV. 8 .Figure IV. 9 . 92 Figure IV. 10 . 93 Figure IV. 11 . 93 Figure IV. 12 . 94 Figure IV. 13 . 95 Figure IV. 14 . 96 Figure IV. 15 . 97 Figure IV. 16 . 98 Figure IV. 17 . 99 Figure IV. 18 .Figure V. 1 .Figure V. 2 .Figure V. 3 .Figure V. 4 .Figure V. 5 .

 853864875886907918992109311931294139514961597169817991812345 Figure IV.2. The Crossley synthetic approach for the functionalisation of porphyrins at the β positions. The method involves the formation of porphyrin-dione (a) or tetraone (b) derivatives, followed by condensation with a (substituted) 1,2-phenylenediamine unit. It allows the formation of linear or "corner" planar multifunctional systems, whose functional groups are covalently linked to the porphyrin via an extended aromatic system (Ar = aryl group).265 ........................................................................................... 85 Figure IV.3. Chemical structure of the target extended porphyrin substituted with two coordinating macrocycles. ................................................................................................................................................ 86 Figure IV.4. Two retrosynthetic strategies for the synthesis of the target porphyrinic bis-macrocycle. Strategy A: double macrocyclisation on a bis(dihydroxyquinoxalino)-porphyrin. Strategy B: condensation of a porphyrin-tetraone with a diamino-substituted macrocycle. .......................................... 87 Figure IV.5. Six-step synthesis of linear porphyrin-tetraone 25 via a literature procedure. 265 ................... 88 Figure IV.6. Two retrosynthetic routes for the formation of a linear bis(dihydroxyquinoxalino)-porphyrin derivative. .................................................................................................................................................... 90 Figure IV.7. Attempted deprotection of the methoxyl groups of a bis(dimethoxyquinoxalino)-porphyrin. ..................................................................................................................................................................... 91 Figure IV.8. Synthesis of 4,5-diaminocatechol hydrobromide 29. 275 ......................................................... 92

Figure V. 9 .Figure V. 11 .Figure V. 12 . 1 .

 911121 Figure V.5. Preparation of a[3]rotaxane whose central fragment consists of a Zn-complexed porphyrin bearing four coordinating rings. The synthetic strategy is based on the "gathering-and-threading" approach followed by stoppering. The threading scheme that prevails in this case differs from that observed for the formation of the[4]rotaxane in Chapter III. Free rotation of the rings in relation to the porphyrin allows threading of the axles through two adjacent rings of the porphyrin. ............................. 111 Figure V.6. Two-step, one-pot synthesis of rotaxane 40 4+ by (1) formation of a [3]pseudorotaxane and (2) quadruple CuAAC stoppering reaction. .................................................................................................... 112 Figure V.7. HRES-MS spectrum of [3]rotaxane 40 4+ and isotope profile evidencing the 1:2 porphyrin/rod stoichiometry. ............................................................................................................................................ 113

  in Chapters II, V, and III (respectively) has been described in the following publications: Cécile Roche, Angélique Sour, Frédéric Niess, Valérie Heitz, Jean-Pierre Sauvage, A Zinc Porphyrin Bearing Two Lateral dpp-Containing Rings and Its [3]Pseudorotaxane (dpp: 2,9diphenyl-1,10-phenanthroline), Eur. J. Org. Chem. 2009, 2795-2800. Cécile Roche, Jean-Pierre Sauvage, Angélique Sour, Nathan L. Strutt, A [3]Rotaxane Composed of a Zinc Porphyrin Tetra-substituted with Coordinating Macrocycles and of Two Rigid Axles, New J. Chem. 2011, 35, 2820-2825. Cécile Roche, Angélique Sour, Jean-Pierre Sauvage, A flexible copper(I)-complexed [4]rotaxane containing two face-to-face porphyrinic plates which behaves as a distensible receptor, Chem. Eur. J. 2012, 18, 8366-8376 (selected as Very Important Paper). Communications Cécile Roche, Angélique Sour, Jean-Pierre Sauvage, Rotaxanes porphyriniques: vers une presse moléculaire, Oral Presentation at the "Journée des Doctorants" (Postgraduate Symposium), Université de Strasbourg, November 2009. Cécile Roche, Angélique Sour, Jean-Pierre Sauvage, Multirotaxanes porphyriniques: vers une presse moléculaire, Poster presentation at GECOM-CONCOORD (International conference in coordination chemistry, organometallic chemistry and catalysis), Lyon, France, June 2010 (2 nd Poster Prize). Cécile Roche, Nathan L. Strutt, Angélique Sour, Jean-Pierre Sauvage, Maxwell J. Crossley, Porphyrinic Multirotaxanes: Towards a Molecular Press, Oral communication at the "RACI NSW Organic Symposium" of the Royal Australian Chemical Institute, The University of Wollongong, Australia, December 2010. Cécile Roche, Nathan L. Strutt, Angélique Sour, Jean-Pierre Sauvage, Maxwell J. Crossley, Porphyrinic Multirotaxanes: Towards a Molecular Press, Flash oral presentation and poster presentation at ISMSC 6 (International Symposium on Macrocyclic and Supramolecular Chemistry), Brighton, UK, July 2011 (Chem. Soc. Rev. Poster Prize).Les caténanes et rotaxanes sont très intéressants de par le défi synthétique que représente leur préparation, ainsi que dans le domaine des machines et moteurs moléculaires. Les applications des machines moléculaires sont variées, et les recherches dans ce domaine portent sur le transfert d'électron ou d'énergie, l'élaboration de dispositifs de stockage de l'information, ou encore l'imitation de systèmes naturels. La nature utilise de nombreuses machines moléculaires nanométriques afin d'assurer des fonctions essentielles chez les organismes vivants.Par exemple, l'ATP synthase est un moteur moléculaire dont la rotation permet de promouvoir successivement la fixation des réactifs, la transformation chimique et la libération de l'ATP formé. Un autre exemple de machine moléculaire naturelle est celui des protéines chaperonnes, qui ont pour fonction d'aider le repliement d'autres protéines. Elles possèdent une cavité centrale dans laquelle une protéine "invitée" peut être piégée. La protéine est alors manipulée par le chaperon, ce qui conduit à un changement de conformation important: elle est transformée en sa forme active d'un point de vue enzymatique, puis est éjectée de la cavité. Le développement de nano-machines artificielles reproduisant l'action de ces machines moléculaires naturelles reste un challenge pour le chimiste synthétique.

Figure 1 .

 1 Figure 1. Principe du récepteur moléculaire modulable.

  Anneaux, un Rail Moléculaire et un BouchonLa première partie de ce travail a porté sur la synthèse de trois composants organiquesun nouveau bis-macrocycle porphyrinique, un rail moléculaire et un bouchon -pouvant par la suite être assemblés en une structure de type rotaxane. Le premier composant, une porphyrine de zinc reliée à deux macrocycles, a été obtenu à partir d'un précurseur macrocyclique incorporant un chélate de la famille de la 1,10-phénanthroline (Figure2). Le précurseur macrocyclique a été synthétisé en cinq étapes à partir de produits commerciaux, la dernière étape consistant en une macrocyclisation dans des conditions de haute dilution. Le macrocycle, obtenu avec un rendement de 67 %, contient un fragment 2,9-diphényl-1,10-phénanthroline (dpp) et est fermé par un cycle benzaldéhyde substitué. La structure a été confirmée par diffraction aux rayons X.Le bis-macrocycle porphyrinique a été obtenu par condensation de MacDonald entre le macrocycle et le mésityldipyrrylméthane. La porphyrine a ensuite été métallée par de l'acétate de zinc, le rendement global pour ces deux dernières étapes étant de 18 %. Afin de tester la capacité de ce nouveau bis-macrocycle à former des structures entrelacées, une complexation par le cuivre(I) et la 2,9-dianisyl-1,10-phénanthroline (dap) a été effectuée. Un[3]pseudorotaxane a été obtenu quantitativement (Figure2), ce qui nous a encouragés à poursuivre la synthèse de rotaxanes plus élaborés.

Figure 2 .

 2 Figure 2. Structures chimiques du précurseur macrocyclique et du [3]pseudorotaxane obtenu par complexation du nouveau bis-macrocycle porphyrinique et du ligand dap avec le cuivre(I).

  construire des structures de type rotaxane, nous avons également synthétisé un axe à deux chélates et une molécule de type "bouchon" possédant des groupes terminaux volumineux (Figure3). La synthèse de ces deux molécules a été réalisée selon un mode opératoire récemment développé au laboratoire. L'axe à deux chélates et le bouchon sont fonctionnalisés respectivement par des groupements acétyléniques et azotures, afin de pouvoir par la suite greffer le bouchon sur l'axe par une réaction "click" de type CuAAC (Copper(I)catalysed Azide-Alkyne Cycloaddition).

Figure 3 .

 3 Figure 3. Structures chimiques du rail et du bouchon.

Figure 4 .

 4 Figure 4. Structure chimique du [4]rotaxane.

Figure 5 .

 5 Figure 5. Molécules invitées testées avec le [4]rotaxane.

Figure 6 .

 6 Figure 6. Titration UV-visible (bande de Soret) pour la complexation entre la 4,4'bipyridine G2 et le [4]rotaxane.

Figure 7 .

 7 Figure 7. Projet de nouveau bis-macrocycle porphyrinique rigide.

Figure 8 .V. Un [ 3 ]

 83 Figure 8. Schéma rétrosynthétique pour l'obtention du nouveau bis-macrocycle porphyrinique.

Figure 9 .

 9 Figure 9. Structure chimique du nouveau tétra-macrocycle porphyrinique.

  "d'assemblage et d'enfilage" (en anglais: "gathering and threading") du cuivre(I) a été exploité lors de la réaction d'enfilage des axes à deux chélates (présentés en II.) sur le tétramacrocycle. Après introduction des bouchons aux extrémités des axes, un[3]rotaxane a été obtenu (Figure11).

Figure 11 .

 11 Figure 11. Structure chimique du [3]rotaxane obtenu.

  historical and significant examples of interlocked compounds. A molecular knot has a topologically non-trivial structure: it cannot be drawn in two dimensions without any intersection. This feature distinguishes a knot from an eight-shaped molecule for example. A figure-of-eight can be distorted to a simple ring and drawn with no intersection; therefore, it has a trivial topology (Figure I.1).

Figure I. 1 .

 1 Figure I.1. Schematic views of a) a molecular trefoil knot, b) a molecular figure-of-eight and c) a molecular ring. A knot is topologically non-trivial, whereas the figure-of-eight and ring are trivial structures.

  first successful strategy for the synthesis of a molecular trefoil knot, reported in 1989 by C. O. Dietrich-Buchecker and J.-P. Sauvage, was based on the metal-templated formation of double-stranded helices. After ring closing and demetallation a macrocycle of the desired trefoilknotted topology was obtained (Figure I.2).

Figure I. 2 .

 2 Figure I.2. First synthetic trefoil knot reported by C. O. Dietrich-Buchecker and J.-P.Sauvage. The strategy involves the formation of a double helical complex of bisphenanthroline ligands around two copper(I) centres, followed by ring closure and demetalation. The knotted structure of the Cu(I) complex was confirmed by X-ray crystallography.[START_REF] Forgan | Chemical Topology: Complex Molecular Knots, Links, and Entanglements[END_REF][START_REF] Dietrich-Buchecker | A Synthetic Molecular Trefoil Knot[END_REF][START_REF] Dietrich-Buchecker | Structure of a Synthetic Trefoil Knot Coordinated to Two Copper(I) Centers[END_REF][START_REF] Dietrich-Buchecker | Molecular Knots. Templates in Chemistry II[END_REF]

Figure I. 3 .

 3 Figure I.3. a) Schematic view of a [2]catenane. b) First copper(I)-templated catenane synthesised by C. O. Dietrich-Buchecker and J.-P. Sauvage. 25

Figure I. 5 .

 5 a). According to the mathematical definition a rotaxane is a trivial object. Indeed, it is theoretically possible to dissociate the ring from the axle and consequently to draw the two components without crossing by simply enlarging the ring. In practice, if the stoppering groups are big enough then it is physically impossible to unthread the macrocycle from the axle, so rotaxanes are definitely part of the family of interlocked molecules. A pseudorotaxane can be an intermediate in the synthesis of a rotaxane; it is the non-stoppered equivalent of the rotaxane structure (Figure I.5. b).

Figure I. 5 .

 5 Figure I.5. Schematic views of a) a [2]rotaxane composed of a ring threaded on an axle ending with bulky stoppers (to prevent unthreading); and b) a pseudorotaxane.

N

  construction of the desired interlocked architecture (Figure I.6). He synthesised a bismacrocycle with two functionalised chains hanging out on either side of the plane of the bismacrocycle. Introduction of bulky end groups and cleavage of the orienting covalent bonds afforded the free [2]rotaxane.

Figure I. 6 .

 6 Figure I.6. Strategy used by G. Schill in the first directed rotaxane synthesis, involving the use of covalent bonds as templates.[START_REF] Schill | Rotaxan-Verbindungen, I[END_REF]

Figure I. 7 .

 7 Figure I.7. Examples of other interlocked structures. a) A molecular Solomon link (doubly interlocking[2]catenane); 36 b) Molecular Borromean rings (three interlocking, but noncatenated macrocycles); 37 c) A[3]rotacatenane (combination of[2]catenane and[2]rotaxane structures).[START_REF] Barin | A Multistate Switchable [3]Rotacatenane[END_REF]

Figure I. 8 .

 8 Figure I.8. Three examples of rotaxanes assembled via directed strategies. a) Use of the gathering effect of the copper(I) template; 40 b) Preorganisation of the system via hydrogen bonding between the ring component and the dumbbell component; 41 c) Interlocking favoured by π-donor/π-acceptor interactions between the axle and the macrocycle.42

  Vögtle and coworkers designed an amide-containing macrocycle and axle that interact via multiple hydrogen bonds (Figure I.8. b). 41 J. F. Stoddart's "blue box" macrocycle is a very versatile tool for the assembly of rotaxanes based on aromatic donor-acceptor interactions (Figure I.8. c).

  rotaxane (Figure I.10. a). Alternatively, a [3]rotaxane can be composed of two axles passing through the same macrocycle (Figure I.10. b), or of two axles, each of them passing through one of the rings formed by a bis-macrocycle (Figure I.10. c

Figure I. 10 .

 10 Figure I.10. Different possible geometries for a[3]rotaxane. Instances of these geometries have been described in the literature: a) Two rings threaded on one axle;[START_REF] Coumans | Synthesis of porphyrin-containing [3]rotaxanes by olefin metathesis[END_REF][START_REF] Marois | 3]rotaxane-porphyrin conjugate as a novel supramolecular host for fullerenes[END_REF][START_REF] Collin | Rotaxanes and[END_REF][54] b) Two axles passing through the same ring; 55-57 c) and d) Two axles passing through the rings formed by a bis-macrocyclic component.[START_REF] Wittenberg | A clipped [3]rotaxane derived from bis-nor-seco-cucurbit[10]uril[END_REF][START_REF] Goldup | Two Axles Threaded Using a Single Template Site: Active Metal Template Macrobicyclic[END_REF]

Figure I. 11 .

 11 Figure I.11.An original rotaxane architecture: a hetero-[7]rotaxane incorporating two different macrocycles.[START_REF] Zhang | A Twin-Axial Hetero[7]rotaxane[END_REF]

Figure I. 12 .

 12 Figure I.12. A thermally activated, near infrared chemiluminescent squaraine rotaxane for optical imaging.[START_REF] Baumes | Storable, thermally activated, near-infrared chemiluminescent dyes and dye-stained microparticles for optical imaging[END_REF]

  nanometric molecular machines are used in nature to carry out essential functions in living organisms. The ATP synthase is a beautiful example of a natural machine. ATP synthases are membrane protein complexes present in vegetal, animal and bacterial organisms. The role of the enzyme is to produce ATP (adenosine triphosphate) from ADP (adenosine diphosphate) and inorganic phosphate P i . It is subdivided in two major components: a central part composed of the protein subunits γ, ε and c often referred to as rotor, capped by a cylindrical headpiece (α 3 β 3 ) called stator (Figure I.13).[START_REF] Boyer | Molecular motors -What makes ATP synthase spin[END_REF][START_REF] Yoshida | ATP synthase -A marvellous rotary engine of the cell[END_REF] The action of the enzyme is triggered by a proton flow through the membrane. This proton flow causes the rotation of the rotor unit, and the motion of the rotor in relation to the stator induces conformational changes in the α and β subunits, which in turn promote the chemical reaction. Each β sub-protein has an active site that passes sequentially through three different states associated to the three steps of the reaction: fixation of the substrates ADP and P i , chemical transformation into ATP, and release of the product. Switching from one state to the other is promoted by the conformational changes triggered by rotation of the γ subunit. It is noteworthy that the motion of ATP synthase is reversible. The rotor component can rotate in the reverse direction to pump protons into the cell.[START_REF] Yoshida | ATP synthase -A marvellous rotary engine of the cell[END_REF] The complex mechanisms involved in the functioning of ATP synthase make it one of the most fascinating molecular rotors.

Figure I. 13 . 83 Figure I. 14 .

 138314 Figure I.13. The ATP synthase, a natural molecular machine. 80,81 ATP synthases are rotary motors: a flow of protons through the membrane causes rotation of the rotor component (γ, ε and c) in relation to the stator component (α 3 β 3 ). This motion triggers sequential conformational changes in the β subunits, which are responsible for the consecutive steps of the formation of ATP: binding of the substrates ADP and P i , chemical transformation and release of the newly formed ATP.

  rarer, molecular machines operating in the solid state open the way towards a translation of the molecular motion to the macroscopic level. If the molecules are organised anisotropically (e.g. in a crystal) then the controlled motion of individual molecules should result in macroscopic work observable to the unaided eye. M. Irie achieved this with a cocrystal of a dithienylethene derivative and perfluoronaphthalene that acts as a molecular cantilever. 86 The dithienylethene unit undergoes photoconversion to the closed-ring isomer upon irradiation with UV light, which causes a slight shape change (Figure I.15).

Figure I. 15 .

 15 Figure I.15. Macroscopic bending motion of a cocrystal of a dithienylethene derivative and perfluoronaphthalene. The motion is due to the shape change of the dithienylethene units by photocyclisation upon irradiation with UV light.[START_REF] Morimoto | A Diarylethene Cocrystal that Converts Light into Mechanical Work[END_REF]

plate and a 2 -

 2 mm lead ball was loaded onto the crystal. Even though the ball is 275 times heavier than the crystal, it was lifted by nearly 1 millimetre upon irradiation with UV light from below (Figure I.16). This experiment is a remarkable demonstration of the potential of molecular machines. A slight photoinduced motion at the molecular level generated a strong force at the macroscopic level.

Figure I. 16 .

 16 Figure I.16.A molecular crystal cantilever at work: a 0.17 mg photochromic crystal lifts a 47 mg lead ball upon irradiation with UV light.[START_REF] Morimoto | A Diarylethene Cocrystal that Converts Light into Mechanical Work[END_REF]

  double bond. The Z isomers are poor binding sites, therefore isomerisation favours binding of the small rings on sites C and D. As shown in Figure I.17, sequential E to Z photoisomerisation of site A, followed by E to Z photoisomerisation of site B and then thermal reconversion of sites A and B to the E isomers promotes successive rotary motions of the small rings. At each step the presence of the second small ring blocks rotation in one direction, forcing an overall unidirectional motion of the two small rings around the larger ring.

Figure I. 17 .

 17 Figure I.17. A unidirectional molecular motor based on a [3]catenane structure (left). The sequential rotary motion of the two small rings around the larger ring is illustrated (right). Successive E to Z photoisomerisation of site A, followed by E to Z photoisomerisation of site B and then thermal reconversion of sites A and B to the E isomers promotes successive rotary motions of the small rings. The rotation direction is restricted by the presence of the second small ring. Conditions: (1) 350 nm, 5 min; (2) 254 nm, 20 min; (3) heat, 100 °C, 24h or catalytic Br 2 , 400-670 nm, -78 °C, 10 min. 108

  -P. Sauvage (Figure I.18). 118 The translation of the ring along the axle is controlled electrochemically and is based on the different coordination behaviours of copper(I) and copper(II).

Figure I. 18 .

 18 Figure I.18.A fast-moving copper-complexed[2]rotaxane shuttle. The translational motion is controlled electrochemically: copper(I) binds preferentially to the sterically hindered bidentate chelate of the axle while copper(II) binds to the less hindered bidentate site that allows coordination of an additional ligand.118

  rotaxane structure (Figure I.19). One of the components consists in three crown-ether rings linked to a central platform unit. The second component is composed of three thread-like axles connected to each other by a trifurcated triphenylbenzene derivative at one end and stoppered by di-tert-butylphenyl groups at the other end. Each axle is threaded through one of the rings of the platform and contains two binding stations: an ammonium (up) and a bipyridinium moiety (down). The rings slide from the upper position to the lower position and back upon deprotonation or protonation of the ammonium units, respectively; and they lift the central platform up and down in this shuttling motion.

Figure I. 19 .

 19 Figure I.19.A molecular elevator based on a triply interlocked[2]rotaxane structure. The interactions of the rings on the axles depend on the pH: the rings bind on the ammonium units when these are protonated and switch to the bipyridinium sites upon deprotonation of the ammonium groups. The shuttling motion of the rings along the axles lifts the central platform up and down.119

For

  these reasons zinc(II) porphyrins are amongst the most commonly used synthetic metalloporphyrins. Axial coordination of one or two additional ligands on a metalloporphyrin is sometimes possible, depending on the metal (Figure I.21). In the case of zinc, coordination of ligand on the zinc(II) porphyrin is favoured. The ability of metalloporphyrins to bind axial ligands offers a myriad of possibilities to assemble multicomponent arrays, as will be developed later.

Figure I. 21 .

 21 Figure I.21. Structure of metalloporphyrins and coordination of axial ligands.

Figure I. 22 .

 22 Figure I.22.[2]catenanes obtained by axial coordination of bifunctional pyridyl ligands on Zn-porphyrins.141,142

  The novelty of the strategy resides in the use of a cyclic template, whereas previous Vernier complexes involved exclusively the use of linear components. The Vernier preorganisation leads to the formation of a figure-of-eight complex after covalent coupling of the linear porphyrin tetramers. Removal of the templates affords a twelve-porphyrin nano-ring. Thus, the new strategy allowed the formation of a large multi-porphyrin ring while avoiding the tedious synthesis of a twelve-site template. The method should be generalised in the future and give rise to the synthesis of functional nano-rings of a size not previously accessible.

Figure I. 23 .

 23 Figure I.23.A novel approach for the templated synthesis of large multi-porphyrin rings. A linear porphyrin tetramer and a cyclic six-site template with mismatched numbers of binding sites were assembled by axial porphyrin coordination to give Vernier complexes. Covalent coupling of the porphyrin oligomers followed by template removal afforded a 12-porphyrin nano-ring.143

  For example the dimer host closed via disulfide bonds (Figure I.25, right) has flexible chains and can bind the longer 4,4'bipyridine guest as well as DABCO.

Figure

  Figure I.25.Host-guest complexes of covalently linked Zn-porphyrin dimers and ditopic nitrogen ligands (DABCO or 4,4'-bipyridine) synthesised and studied in the group of J. K. M. Sanders.153,154

Figure I. 26 .

 26 Figure I.26. Chemical structure (left) and molecular model (right) of a self-assembled capsule formed by axial coordination of a tetramine guest on the zinc(II) sites of two bis-porphyrin receptors. 159

  Figure I.25 is a good receptor for C 60 . 154 J. R. Nitschke and coworkers recently described a self-assembled cubic cage whose faces incorporate nickel(II) porphyrins (Figure I.28. a). The cage can host large aromatic molecules like coronene and fullerenes, and shows hierarchical binding preference for the larger fullerenes (e.g. C 70 ) over C 60 . 162 Another system based on aromatic donor-acceptor interactions was designed by T. Haino. His group reported the formation of a supramolecular polymer assembled by self-recognition of a hermaphroditic component (Figure I.28. b). The monomer is functionalised by a trinitrofluorenone moiety at one end and by a cofacially arranged bisporphyrin unit at the other end. Host-guest recognition between the electron-acceptor trinitrofluorenone and the electron-rich bis-porphyrin leads to the formation of the supramolecular polymer. 163 Complexes of electron-donor bis-porphyrin hosts with electrondeficient guests sometimes exhibit interesting photophysical properties. S. Yagi and coworkers reported the efficient photoinduced electron transfer from a bis(Zn-porphyrin) tweezers host to a hexyl viologen guest substrate. The electron transfer can be switched off by substrate exchange of the viologen guest with DABCO. 164

Figure I. 28

 28 Figure I.28. a) A porphyrin-faced cubic host for C 70 fullerene. 162 b) A supramolecular polymer formed through head-to-tail host-guest self-recognition of a hermaphroditic monomer. The host part of the monomer is an electron-rich bis-porphyrin unit, which is linked to an electron-deficient trinitrofluorenone guest moiety. 163

  Figure I.29. A tris-porphyrin prism host that can encapsulate and fold short peptides in hybrid α-helix/β-turn conformations. 171

  The system is composed of a central ferrocene pivot substituted on one side with an azobenzene unit and on the opposite side with two cofacial zinc porphyrins arranged in a tweezers-like fashion (Figure I.30). The bis-porphyrin tweezers can host a ditopic nitrogen ligand like the 4,4'-biisoquinoline used in the study. The

Figure I. 30 .

 30 Figure I.30. A photoresponsive, porphyrin-containing molecular machine whose motion is reminiscent of a molecular pedal. Photoisomerisation of the azobenzene unit results in a rotary motion of the ferrocene pivot and of a pedal-like conformational change of the zinc porphyrin dimer. This motion is transferred to the biisoquinoline guest, which undergoes twisting around its central C-C bond. 174

Figure I. 32 .

 32 Figure I.32.Pirouetting motion of a[2]rotaxane that contains three porphyrin units. A gold(III) porphyrin is incorporated in the macrocyclic component, and the axle bears two zinc(II) porphyrins as stoppers.190

  rotaxane consists of a metalloporphyrin and a metallophthalocyanine arranged in a face-to-face way, each axle of the porphyrin being threaded through one of the peripheral rings of the phthalocyanine(Figure I.34). The structure of this rotaxane is reminiscent of the molecular elevator reported by J. F. Stoddart and described in part I. 2. c) of this introduction. Both systems consist of rotaxane-like structures arranged platforms, but the present system has four interlocked units instead of three. The position of the crown-ether rings along the threads can be monitored by protonation/deprotonation of an amine group incorporated in the axle. In the protonated state the interactions of the rings with the ammonium groups keep the Cu(II)-phthalocyanine and the Cu(II)-porphyrin relatively far from each other. As a consequence the spins of the copper(II) centres are isolated and no exchange interaction is observed. However, in the deprotonated state the phthalocyanine component is free to slide along the axles and adopt a conformation where the Cu(II)-phthalocyanine and the Cu(II)-porphyrin are in close proximity. Spin exchange between the two copper(II) centres is indeed observed in the form of an antiferromagnetic coupling. Thus, switchable spin-spin communication was achieved with this new system, which is a nice example of a functional porphyrin-incorporating rotaxane.

Figure I. 34 .

 34 Figure I.34.A tetra-interlocked[2]rotaxane with face-to-face Cu(II)-porphyrin and Cu(II)phthalocyanine units. The distance between the copper(II) centres is monitored by protonation/deprotonation of amine groups on the axles. Switchable spin-spin communication is achieved: the spins are isolated in the protonated state of the rotaxane whereas antiferromagnetic coupling is observed upon deprotonation.193

  rotaxane depicted in Figure I.35, except that two of these rings were attached to the porphyrin. Similar dumbbells with two bidentate sites were used to form the desired [4]rotaxane, as shown in Figure I.36.

Figure I. 36 .

 36 Figure I.36.A[4]rotaxane with two face-to-face porphyrins. The copper(I)-complexed rotaxane forms guest inclusion complexes with short substrates. However, the rotaxane collapses upon demetalation of the copper(I) centres and does not show any host-guest properties after demetalation.196,197

  Figure I.37. It is composed of two dumbbells and of two bis-macrocycles linked by a central zinc porphyrin. Each axle contains two bidentate binding sites derived from the 2,2'-bipyridine motif. The porphyrinic component is a tetra-aryl zinc porphyrin substituted with 1,10-phenanthroline-incorporating macrocycles at two antipodal meso positions. The rotaxane is assembled via a copper(I) template that forms complexes with the bipyridine and phenanthroline chelates of the axles and of the rings.

Figure I. 37 .

 37 Figure I.37. Schematic view of the target[4]rotaxane. Zn-porphyrins are depicted as diamond-shaped symbols; phenanthroline and bipyridine binding sites are blue and green U-shaped symbols, respectively; copper(I) centres are pink dots and stoppers are large grey spheres.

Figure I. 38 .

 38 Figure I.38. Proposed mechanism of action of a molecular press based on a [4]rotaxane. A flexible guest molecule bound in the central cavity of the rotaxane by axial coordination on the Zn-porphyrins is depicted in red. In the absence of copper(I) the guest can adopt an elongated conformation. In the presence of copper(I) the porphyrins are expected to be in closer proximity and induce conformational changes on the guest.

  Figure I.38.

Figure I. 39 .

 39 Figure I.39. Design of a [6]rotaxane composed of two porphyrinic tetra-macrocycles and of four dumbbells.

  scheme showing the chemical structures of the target building blocks is depicted in Figure II.1.

Figure II. 1 .

 1 Figure II.1. Retrosynthetic scheme displaying the chemical structures of the target building blocks needed for the formation of a[4]rotaxane with two cofacial Zn-porphyrins. The pink spheres represent copper(I), the "gathering-and-threading" centre.

[ 4 ]

 4 rotaxane with a cyclic structure similar to that of our new target rotaxane.196 The bismacrocyclic component of the previously described rotaxane was a Zn-porphyrin rigidly linked to two phenanthroline-containing macrocycles. Several main differences, highlighted in Figure II.2, distinguish the present target bis-macrocycle from the previous system.

Figure II. 2 .

 2 Figure II.2. Schematic view of the structural difference between two porphyrinic bismacrocycles: (a) previously made in our group 196 and (b) described in this chapter. The main differences reside in (i) the nature of the bridge (highlighted in blue) between the central porphyrin (purple) and the macrocycles (rigid pyrazine-benzene-pyrazine motif vs. single C-C bond); (ii) the position of the bridge on the porphyrin (β-pyrrolic vs. meso substitution); (iii) the orientation of the coordinating dpp unit (yellow) (exo vs. endo coordination mode with respect to the porphyrin); and (iv) the electronic coupling between the dpp chelate and the porphyrin (electronically coupled vs. decoupled).

Figure II. 3

 3 is an important intermediate in the synthesis of the new porphyrinic building block. The macrocycle can be denominated as "m-31" according to the nomenclature traditionally used in our group because its cycle is constituted of 31 atoms. It incorporates a 2,9-diphenyl-1,10-phenanthroline (dpp) chelate and is closed by a 3,5-disubstituted benzaldehyde ring. The aldehyde function was introduced to allow the subsequent formation of a porphyrin by condensation with a pyrrolic derivative.

Figure II. 3 .

 3 Figure II.3. Chemical structure of the macrocyclic precursor and retrosynthetic route.

4 . 2

 42 compounds. The synthetic route is represented in Figure II.In a first step, 1,10-phenanthroline was functionalised with anisyl groups at positions 2 and 9. (4-methoxyphenyl)lithium was generated in situ by treatment of p-bromoanisole with butyl lithium. It was reacted with 1,10phenanthroline, and the obtained intermediate was hydrolysed and oxidised with MnO 2 to afford 2,9-dianisyl-1,10-phenanthroline (dap) 1 in 53% yield. The phenol functions were then deprotected by treatment of dap with pyridinium chloride at 210 °C. 2,9-diphenol-1,10-was obtained in 95% yield.198,199 The dpp chelate was further functionalised with diethyleneglycol chains by Williamson reaction with 2-(2chloroethoxy)ethanol. Tosylation of the terminal hydroxyl groups of 3 was achieved by treatment of the compound with p-toluenesulfonyl (tosyl) chloride.200 Macrocycle 5 was prepared by the cyclisation reaction of ditosylate 4 with 3,5-dihydroxybenzaldehyde in the presence of cesium carbonate in high dilution conditions. After purification, the compound was obtained as a white powder in a very satisfactory 67% yield.

Figure II. 4 .

 4 Figure II.4. Synthesis of the dpp-incorporating aldehyde-appended macrocycle 5.

Figure II. 5 .

 5 Figure II.5. X-Ray structure of the 31-membered ring 5. A dichloromethane molecule resides in the structure (Carbon atoms are represented in grey, nitrogen atoms in blue, oxygen atoms in red, chlorine atoms in green; hydrogen atoms are omitted for clarity). (i) Top view; (ii) side view.

2 Porphyrins

 2 Figure II.6. [2+2] MacDonald condensation of a dipyrrylmethane and an aldehyde for the formation of trans-A 2 B 2 porphyrins.

Figure II. 7 .

 7 Figure II.7. Synthesis of compound 8, a Zn-porphyrin substituted with two dpp-containing macrocycles at antipodal meso positions.

  zinc(II) centres was obtained as an intermediate. Subsequent treatment with an EDTA solution to remove the zinc ions from the 1,10-phenanthroline chelates afforded the desired disubstituted Zn-porphyrin 8. The global yield over the porphyrin condensation and metalation steps was 19%.Compound 8 was fully characterized by 1 H NMR, ES-MS and UV-visible absorption spectroscopy. The 1 H NMR spectrum in CD 2 Cl 2 shows two doublets for the pyrrolic protons, which is in accordance with a trans meso-substituted porphyrin. Despite the introduction of mesityl substituents, porphyrin 8 is very poorly soluble in common organic solvents like dichloromethane or chloroform. The poor solubility may be due to intermolecular π-stacking between the phenanthroline units and the porphyrin core.

Figure II. 8 .The [ 3 ]

 83 Figure II.8. Threading reaction of bis-macrocycle 8 with dap chelate 1 via copper(I) templating to afford the [3]pseudorotaxane 9 2+ .

Figure II. 9 . 1 H

 91 Figure II.9. 1 H NMR of the porphyrinic bis-macrocycle 8 and [3]pseudorotaxane 9 2+ (signals in the aromatic region are displayed). The chemical shifts observed for 9 2+ are typical of this type of threaded species. In particular, protons 3, 8 and m undergo strong upfield shifts upon threading of dap (blue arrows).

Figure II. 10 .

 10 Figure II.10. UV-visible absorption and normalised emission spectra of porphyrinic bismacrocycle 8 and [3]pseudorotaxane 9 2+ in CH 2 Cl 2 . Both compounds have a Soret band at 421 nm and Q bands at 548 and 585 nm. Emission spectra were recorded upon excitation at 548 nm. In both cases emission maxima are observed at 595 and 646 nm.

  of the Axle and StopperThe construction of our target[4]rotaxane requires the synthesis of two more building blocks in addition to the porphyrinic bis-macrocycle presented above. These building blocks are a rigid axle, or molecular rod, with two chelating sites and a stopper possessing a bulky terminal group that will prevent unthreading in the final interlocked compound. The axle and stopper need to be appropriately functionalised to allow the attachment of the stoppers on the preformed pseudorotaxane in high yield. Ideally the stoppering reaction should proceed quantitatively and in mild conditions compatible with the presence of copper(I) complexes in the pseudorotaxane. The reactions falling into the category of click chemistry, as defined by K. B. Sharpless and co-authors in 2001, are excellent options for this type of reaction. 211Click chemistry was introduced as a new synthetic concept to generate functional molecules by joining building blocks in an easily practicable way. The reactions belonging to the family of click chemistry must meet a list of criteria, including "be modular, wide in scope, high yielding, create only inoffensive by-products (that can be removed without chromatography), be stereospecific and simple to perform".211 Click reactions comprise nucleophilic ring-opening reactions, non-aldol carbonyl chemistry, additions to carbon-carbon multiple bonds (especially thiol-ene reactions and Michael additions), and cycloadditions (e.g. Diels-Alder reactions and 1,3-dipolar cycloadditions). Although click chemistry was introduced as a new tool for drug discovery, it has found applications in many other fields including polymer and materials science, 212 and in the construction of supramolecular and interlocked architectures.213 In particular the Huisgen Copper(I)-catalysed Azide-Alkyne Cycloaddition (CuAAC) 214,215 is a standard of click chemistry and is widely used in various fields.216 The azide and alkyne precursors for this reaction are usually relatively easy to prepare, and in the presence of a copper(I) catalyst the cycloaddition proceeds with almost complete conversion and selectivity for the anti1,2,3-triazole (Figure II.11).

Figure II. 11 .

 11 Figure II.11. The Huisgen Copper(I)-catalysed Azide-Alkyne Cycloaddition (CuAAC) reaction.With Cu(I) as a catalyst the reaction usually proceeds in high yields and the anti 1,2,3triazole is formed selectively.

Figure II. 12 .

 12 Figure II.12. Target chemical structures of the dumbbell building blocks. The molecular rod, or axle, is functionalised with two terminal alkyne groups and contains two coplanar 2,2'-bipyridine chelates facing towards the same side of the axle (left). The stopper comprises a hindering group at one end and an azide group at the other end (right).

  Yann Trolez, a former PhD student in Strasbourg, developed the synthetic scheme for this molecule. The alkyne-terminated bisbidentate axle is obtained in seven steps from commercial compounds. The first five steps consist in the formation of the central brominated bis-bidentate fragment 14 (Figure II.13).

Figure II. 13 .

 13 Figure II.13. Synthesis of the dibromo bis-bidentate fragment 14.

Figure II. 14 .Figure II. 15 .

 1415 Figure II.14. Synthesis of the two-station axle 16 functionalised with acetylenic groups.

Figure III. 1 ,

 1 Figure III.1, along with three auxiliary strategies.

Figure III. 1 .

 1 Figure III.1. Different strategies used in the assembly of rotaxanes.

Figure III. 2 .

 2 Figure III.2. Chemical structure of the target copper(I)-complexed [4]rotaxane.

  The synthetic approach was to form[4]rotaxane 19 4+ 4PF 6 from bis-macrocycle 8, thread 16 and stopper 18 in a two-step, one-pot experiment involving both the threading and stoppering reactions (Figure III.4). The building blocks (porphyrin-bis-macrocycle 8, acetylenic thread 16 and azide stopper 18) were synthesised as described in Chapter II.

Figure III. 4 .

 4 Figure III.4. Two-step, one-pot synthesis of[4]rotaxane 19 4+ in 50% yield by(1) threading of bis-macrocycle 8 and axle 16 into a[4]pseudorotaxane and (2) quadruple CuAAC stoppering reaction with azide stopper 18.

Figure III. 5 .

 5 Figure III.5. High resolution electrospray mass spectrum of rotaxane 19 4+ . The main signal is magnified to show the isotope profile (top right); this profile fits well with the calculated spectrum (bottom).

Figure III. 6 .

 6 Figure III.6. Hypothetical threading and stoppering scheme leading to a[2]rotaxane. Mass spectrometry results indicated that this threading scheme is not favoured. The isotope profile is consistent with a[4]rotaxane containing four copper(I) centres

  H NMR spectra were recorded in a series of deuterated solvents (CDCl 3 , CD 2 Cl 2 , C 2 D 2 Cl 4 , CD 3 CN, CD 3 NO 2 , C 6 D 6 and DMSO-d 6 ). In most of these solvents very broad signals were observed at room temperature. However, the signals sharpened and shifted upon heating to higher temperatures, as observed in particular with nitromethane as solvent (Figure III.7).

Figure III. 7 .

 7 Figure III.7.Variable temperature 1 H NMR spectra of[4]rotaxane 19 4+ in CD 3 NO 2 . Signals in the aromatic region are displayed.

Figure III. 8 . 1 H

 81 Figure III.8.1 H NMR spectrum of rotaxane 19 4+ in CD 2 Cl 2 at room temperature. Signals in the aromatic region are displayed (top), as well as proton assignments on the bismacrocycle and dumbbell components of the rotaxane (bottom). Split signals are annotated with "a" and "b" subscripts. Signals were assigned using COSY, NOESY, HSQC and HMBC data.

Figure III. 8 ).

 8 Figure III.8). In addition, many NOE interactions are observed between the ethyleneglycol chains of the macrocycles and the central bis-3,8-(o-pyridyl)-4,7-phenanthroline moiety of the axle on the NOESY spectrum (Figure III.9).

Figure III. 9 .

 9 Figure III.9. Part of the NOESY spectrum of rotaxane 19 4+ displaying NOE interactions between the central part of the dumbbell (protons 1' -4') and the ethyleneglycol chains of the macrocycles.

Figure III. 10 .

 10 Figure III.10. Schematic view of the proposed geometry of rotaxane 19 4+ in solution deduced from the NMR data.

Figure III. 11 .

 11 Figure III.11. DOSY spectrum of rotaxane 19 4+ in CD 2 Cl 2 , displaying signals in the aromatic region. The DOSY data show the presence of a single chemical species in solution; arrows point at minor signals that belong to a second, minor conformer of the[4]rotaxane in very slow exchange with the major conformer. This minor conformer diffuses at the same rate as the major conformer. A good fit is obtained for the estimated size of the rotaxane using CPK models and the diffusion coefficient measured by DOSY NMR. The rotaxane approximates to a 48 Å sphere.

spectrum of 19 4+

 19 shows a Soret band at 420 nm and Q bands at 551 and 591 nm in dichloromethane. The absorption spectra of rotaxane 19 4+ and its precursor, porphyrin 8 were recorded in CH 2 Cl 2 solutions at the same concentration in porphyrin units ([19 4+ ] = 0.95*10 -6 M and [8] = 1.9*10 -6 M) for comparison (Figure III.12).

[ 3 ]

 3 rotaxane contains the same Cu(I) complexes and the same dumbbell (resulting from click reaction of two stoppers 18 on the axle 16) as rotaxane 19 4+ , but it incorporates only one porphyrin as opposed to two cofacial porphyrins in the case of 19 4+ (Figure III.13).

  and Synthesis of the Guest Molecules The coordination mode and association constant of rotaxane 19 4+ with four guest substrates were investigated by UV-visible absorption titration in toluene. The guests are depicted in Figure III.14. Guest G1 is the aliphatic diamine 1,4-diazabicyclo[2.2.2]octane (DABCO) whereas guests G2 -G4 are bifunctional pyridine-type ligands with phenylene spacers between the pyridyl units (0, 1 and 2 phenylene spacers, respectively).

Figure III. 14 .

 14 Figure III.14. Chemical structures of guests G1 -G4.

Figure III. 15 .

 15 Figure III.15. Synthesis of guests G3 and G4. 261

  rotaxane described previously in theSauvage group, 196 explained by the greater adaptability of the present host compared to the previous system. Due to the flexible anchoring points between the porphyrinic component and the axles of the rotaxane, the two porphyrins can come to relatively close proximity so as to adjust the Zn…Zn distance to the small DABCO guest.

Figure III. 17 .

 17 Figure III.17. UV-visible titration spectra in toluene (Soret band) of rotaxane 19 4+ (0.92 x 10 -6 M) with DABCO guest G1 (2.8 x 10 -5 M) from 0.0 to 2.0 equiv. Arrows show changes in the host spectrum with increasing guest concentration; a 6 nm red shift from 423 to 429 nm is observed.

Figure III. 18 .Figure III. 19 .

 1819 Figure III.18. UV-visible titration spectra in toluene (Soret band) of rotaxane 19 4+(0.92 x 10 -6 M) with 4,4'-bipyridine guest G2 (2.8 x 10 -5 M) from 0.0 to 2.0 equiv. Arrows show changes in the host spectrum with increasing guest concentration; a 5 nm red shift from 423 to 428 nm is observed.

Figure III. 22 .

 22 Figure III.22. a) "inflated" and b) "deflated" conformations of the host 194+ . The rotaxane can adjust its geometry to accommodate either extended guests (e.g. G4) or very short guests (e.g. DABCO).

Figure

Figure IV. 1 .

 1 Figure IV.1. Schematic view of the structural differences between three porphyrinic bismacrocycles: (a) compound 8 described in Chapters II and III of this thesis; (b) new target compound; (c) compound used in previous studies.196,197,217 The rigidity of the new system will be intermediate between the very flexible bis-macrocycle 8 and the very rigid bis-macrocycle studied by former members of the Sauvage group.

  Figure IV.1.b) and the porphyrinic bismacrocycle 8 (Figure IV.1.a) reside in the nature and the position of the bridges between the porphyrin moiety and the macrocycles. In the previous system single C-C bonds were linking the rings to the porphyrin core at the meso positions. The single-bonded bridge allowed free rotation of the macrocycles in relation to the plane of the porphyrin. In the new system a quinoxaline spacer will link the macrocycles to the β positions of the porphyrin. This aromatic bridge will restrict the rotational freedom of the rings. The macrocycles will be m-30 rings composed of the same dpp chelates and diethyleneglycol chains as in the case of compound 8. By comparison with the porphyrinic bis-macrocycle previously studied in the Sauvage group (Figure V.1.c, Part I. 4. b)),

  197

Figure IV. 3 .

 3 Figure IV.3. As mentioned above the central part of the molecule is an extended porphyrin. The dpp-containing macrocycles are linked to the porphyrin core via rigid quinoxaline spacers.

Figure IV. 3 .Figure IV. 4 .

 34 Figure IV.3. Chemical structure of the target extended porphyrin substituted with two coordinating macrocycles.

Figure

  Figure IV.5.

Figure IV. 5 .

 5 Figure IV.5. Six-step synthesis of linear porphyrin-tetraone 25 via a literature procedure. 265

22 4 ,

 224 Photooxidation

Figure

  Figure IV.6. Two retrosynthetic routes for the formation of a linear bis(dihydroxyquinoxalino)-porphyrin derivative.

1

 1 was tested on a sample of the tetramethoxyl-substituted precursor available in the laboratory. This compound was synthesised by Linda J. Govenlock, a former PhD student in the Crossley group. It was obtained in high yield by reaction of 4,5-diaminoveratrole (4,5dimethoxybenzene-1,2-diamine) with the porphyrin-tetraone 25. 271 Several sets of conditions were tested for the cleavage of the methyl ether groups of the extended porphyrin (Figure IV.7).

Figure

  Figure IV.7. Attempted deprotection of the methoxyl groups of a bis(dimethoxyquinoxalino)-porphyrin.

Figure IV. 8 .

 8 Figure IV.8. Synthesis of 4,5-diaminocatechol hydrobromide 29. 275

Figure IV. 9 .

 9 Figure IV.9. Synthesis of the linear bis(dihydroxyquinoxalino)-porphyrin 30.

Figure IV. 10 .

 10 Figure IV.10. Tautomerisation of the dihydroxyquinoxaline moieties of compound 30.

Figure IV. 11 .

 11 Figure IV.11. Attempted synthesis of the target porphyrinic bis-macrocycle.

Figure IV. 4 .

 4 Figure IV.4.In this approach the final synthetic step consists in the condensation of two macrocycles on the linear porphyrin-tetraone 25. A macrocyclic precursor functionalised with two vicinal aromatic amines is needed for this condensation. Here we will describe attempts to synthesise this diamino-substituted macrocycle using several routes.

Figure IV. 12 .

 12 Figure IV.12. Route B.1: Attempted synthesis of a dinitro-substituted macrocycle.

  Figure IV.13. Route B.2: Attempted synthesis of a Boc-protected diamino-macrocycle.BocHNNHBoc

Figure IV. 14 .

 14 Figure IV.14. Condensation reaction of 4,5-diaminocatechol 29 with anisaldehyde. The 1benzyl-2-phenylbenzimidazole derivative 33 was obtained instead of the expected bis(Nanisylidenamine) species.

  diaminocatechol hydrobromide 29 was neutralised with pyridine and condensed with two equivalents of anisaldehyde at room temperature in conditions similar to those reported by the group of D. Coucouvanis for the formation of salphen ligands from compound 29 and salicylaldehyde derivatives (Figure IV.14). 275 An off-white solid precipitated out of the reaction mixture, and was filtered off and recrystallised from hot ethanol. Analysis of a sample by electrospray mass spectrometry gave a signal at m/z = 376.80 as expected for the desired bis(Nanisylidenamine) derivative (calculated value for M + H + : m/z = 377.15). However, the 1 H NMR spectrum indicated the formation of an asymmetrical species (Figure IV.15). We performed further NMR analyses in order to identify the product of the reaction. The DEPT-135 spectrum indicated the presence of a secondary carbon atom in the molecule, which is not consistent with the expected structure. A literature search revealed that the formation of 1-benzyl-2phenylbenzimidazole derivatives has been observed from the reaction of o-phenylenediamine with aldehydes in some cases. 279-281 This type of structure would be consistent with the observation of a -CH 2 -signal in the DEPT spectrum. Consequently, we propose the substituted benzimidazole structure 33 for the product isolated here (Figure IV.14). Compound 33 is an isomer of the expected bis-imine product, which explains that the expected mass was found by ES-MS. Complete assignment of the 1 H and 13 C NMR spectra using COSY, ROESY, HSQC and HMBC data supports the proposed structure (Figure IV.15). The molecule contains two nonequivalent anisyl groups with two distinct sets of protons. The chemical shift of the CH 2 signal at 5.31 ppm is typical of benzylic protons in this type of structure. 281-283 The asymmetry of the structure results in splitting of the signals of the catechol protons (c 1 , c 2 , OH 1 and OH 2 ).

Figure IV. 15 .

 15 Figure IV.15. Proton NMR spectrum of the 1-benzyl-2-phenylbenzimidazole derivative 33 in DMSO-d 6 (500 MHz). Signals were assigned using COSY, ROESY, HSQC and HMBC data.ppm! 9.0! 8.5! 8.0! 7.5! 7.0! 6.5! 6.0! 5.5! 5.0! 4.5! 4.0! 3.5!

Figure IV. 16 .

 16 Figure IV.16. Possible mechanism for the formation of 33 in the presence of catalytic acid.

  aldehydes compared to aldehydes that do not incorporate hydrogen bond donors in ortho position, e.g. anisaldehyde.The formation of the benzimidazole derivative 33 is unfortunate because it impairs the subsequent deprotection of the amine groups. The macrocyclisation reaction was nevertheless tested with compound 33 (The reaction was run before the structure of 33 was completely elucidated). Williamson reaction of the catechol derivative 33 with the ditosylate 4 in high dilution conditions afforded the expected macrocycle 34 in 60% yield (Figure IV.17). The product was characterised by ES-MS and 1 H and[START_REF] Dean | Duplex DNA knots produced by Escherichia coli topoisomerase I. Structure and requirements for formation[END_REF] C NMR. The NMR spectra were fully assigned thanks to 2D 1 H-1 H and 1 H-[START_REF] Dean | Duplex DNA knots produced by Escherichia coli topoisomerase I. Structure and requirements for formation[END_REF] C correlation experiments. The asymmetry of the 1benzyl-2-phenylbenzimidazole moiety is conveyed to the macrocyclic part of the molecule.Splitting of almost all signals was observed in the proton NMR spectrum compared to a symmetrical macrocycle like compound 5; only the 5,6 protons of the phenanthroline unit came out as a single signal.Cleavage of the aromatic benzimidazole moiety is supposedly very difficult. Yet we estimated that it might be possible to convert it to the corresponding phenylenediamine by palladium-catalysed reduction under high pressure of hydrogen. All attempts were unsuccessful.Treatment of macrocycle 34 with catalytic palladium on charcoal under hydrogen pressure of up to 40 bars yielded mixtures of products; the desired diamino-macrocycle could not be isolated from these mixtures.

Figure IV. 17 .

 17 Figure IV.17. Synthesis of macrocycle 34 and attempted deprotection of the amine groups.

  Figure IV.18. First, catechol is converted to 4,5-dibromocatechol 35 in 53% yield by treatment with bromine in chloroform, following a published procedure. 288 Double Williamson reaction between the dibromocatechol 35 and the ditosylate 4 in high dilution was successful and gave the expected macrocycle 36 in 36% yield. The structure of compound 36 was confirmed by ES-MS and NMR.

Figure IV. 18 .

 18 Figure IV.18. Synthesis of the dibromo-substituted macrocycle 36.

  289 and later used by D. Jiang and coworkers for the six-fold amination of a hexabromo-triphenylene derivative.290 Dibromo-macrocycle 36 was refluxed with benzophenone imine, sodium tert-butoxide and catalytic amounts of Pd 2 (dba) 3 and racemic BINAP in toluene(Figure IV.19

Figure IV. 19 .

 19 Figure IV.19. Synthesis of bis-imine macrocycle 37 by Buchwald-Hartwig reaction with benzophenone imine. 289

  Approaches for the Formation of PorphyrinsWith the growing interest for porphyrin derivatives several synthetic strategies have been developed for their formation. The present target molecule is a symmetrical tetra-aryl porphyrin.The most straightforward strategy for the synthesis of this type of porphyrin consists in condensing pyrrole with an aldehyde, and oxidising the intermediate porphyrinogen to the aromatic porphyrin ring (Figure V.2).

Figure V. 2 .

 2 Figure V.2. Porphyrin synthesis by condensation of an aldehyde and pyrrole to a porphyrinogen intermediate, followed by oxidation to form the aromatic porphyrin ring. The conditions for the Adler-Rothemund and the Lindsey procedures are given.

Figure V. 1 Figure V. 3 ,

 13 Figure V.1 involves condensation of a macrocyclic aldehyde with pyrrole, as shown in Figure V.3, followed by metalation with zinc acetate.

Figure V. 3 .

 3 Figure V.3. Synthesis of tetra-substituted free-base porphyrin 38. Optimised conditions for the condensation: 5 (1 eq., 200 mM), pyrrole (1 eq., 200 mM), propionic acid/nitrobenzene 7:3, microwaves, 141°C, 10 min (25%).

Figure V. 4 .

 4 Figure V.4. Synthesis of tetra-substituted zinc(II) porphyrin 39 (quantitative yield).

  Figure V.5. Although its formation was not expected, the[3]rotaxane is far from being devoid of

Figure V. 5 .

 5 Figure V.5. Preparation of a[3]rotaxane whose central fragment consists of a Zncomplexed porphyrin bearing four coordinating rings. The synthetic strategy is based on the "gathering-and-threading" approach followed by stoppering. The threading scheme that prevails in this case differs from that observed for the formation of the[4]rotaxane in Chapter III. Free rotation of the rings in relation to the porphyrin allows threading of the axles through two adjacent rings of the porphyrin.

Figure V. 6

 6 Figure V.6 shows the reaction conditions leading to the formation of the new[3]rotaxane 40 4+ •4PF 6 . The rotaxane was obtained via a two-step, one-pot synthesis consisting of (i) formation of a[3]pseudorotaxane and (ii) stoppering reaction. In a first step, the[3]pseudorotaxane was formed by mixing tetra-macrocycle 39 and [Cu(CH 3 CN) 4 ](PF 6 ) in chloroform/acetonitrile, and then transferring the resulting solution to a suspension of acetylenic thread 16 in chloroform and stirring under argon for 24 h. The classical threading procedure adopted here involves complexation of Cu(I) with the dpp units of the macrocycle and then addition of the rod, threading through the macrocycles and formation of tetrahedral complexes with Cu(I) to give a[3]pseudorotaxane as an intermediate. In a second step, azide stopper precursor 18 and catalytic [Cu(CH 3 CN) 4 ](PF 6 ) and Na 2 CO 3 were added to the reaction mixture, which was subsequently stirred under argon for six days. In this step the stoppers were introduced by formation of triazoles at the end of the threads via a Huisgen copper-catalysed azide-alkyne cycloaddition (CuAAC). After chromatographic purification, the[3]rotaxane 404+

Figure V. 6 .

 6 Figure V.6. Two-step, one-pot synthesis of rotaxane 40 4+ by (1) formation of a [3]pseudorotaxane and (2) quadruple CuAAC stoppering reaction.

  rotaxane 40 4+ •4PF 6 was characterised by high resolution electrospray ionisation mass spectrometry (HRES-MS), 1 H NMR (1D, COSY, NOESY), 13 C NMR and UV-visible absorption spectroscopy. The mass spectrum gave the first proof of the formation of a [3]rotaxane. A largely major peak was observed at m/z = 1548.606 in high resolution ES-MS, in accordance with the calculated value for the [3]rotaxane complexed to four copper(I) centres at m/z = 1548.615 (Figure V.7).

  rotaxane with eight Cu(I) centres. In a whole the experimental isotopic profile fits perfectly with the simulation (Figure V.7). Two minor peaks are also observed at m/z = 2043.501 and m/z = 2112.134 in the mass spectrum. Both peaks correspond to triply charged species according to their isotope profiles. Simulations showed that the peak at m/z = 2112.134 corresponds to [3]rotaxane 40 4+ with one PF 6 -counterion while the peak at m/z = 2043.501 corresponds to [3]rotaxane 40 4+ with one missing Cu(I) centre. Decomplexation of a copper ion probably occurred during the electrospray ionisation process. These ES-MS results are in agreement with the formation and isolation of the [3]rotaxane structure 40 4+ .

Figure V. 7 .

 7 Figure V.7. HRES-MS spectrum of [3]rotaxane 40 4+ and isotope profile evidencing the 1:2 porphyrin/rod stoichiometry.m/z 1000 2000 3000 4000 5000 6000

Figure V. 8 . 1 H

 81 Figure V.8. 1 H NMR spectra of rotaxane 40 4+ , Zn-porphyrin 39 and rod 15; signals in the aromatic region are displayed (top). NMR assignments of the [3]rotaxane 40 4+ (bottom).

  404+ was confirmed by the characteristic upfield chemical shift of the aromatic o and m protons of the porphyrinic component 39 and of protons 6' of the rod component 16. Downfield chemical shifts of protons 1' and 4' in rod 15 were also observed upon copper(I) complexation and threading. Furthermore, NOESY NMR showed NOE interactions between H 2' and H 3' from the rod and H p" belonging to the macrocycle. It also showed strong NOE interactions between H 1' from the rod and H pyB belonging to the porphyrin (Figure V.9). These observations are clear evidence that the two axles are threaded through the macrocycles of the porphyrin. The peak integrations corresponding to the zinc porphyrin and the rod in compound 40 4+ support a 1:2 porphyrin/rod stoichiometry. Another characteristic feature

Figure V. 10 .

 10 Figure V.10. UV-visible absorption spectra of free-base porphyrin 38, Zn-porphyrin 39 and rotaxane 40 4+ in CH 2 Cl 2 .

Figure V. 11 .

 11 Figure V.11. Introduction of a longer spacer between the bidentate sites of the axle to avoid the formation of a[3]rotaxane and consequently favour the formation of a[6]rotaxane.

  The chemical structures of rod 16 used in the previous studies and of the new target axles are depicted in Figure V.12. Rod 16 was very short with a single chemical bond between the bidentate sites. Several new rods with spacers of various lengths were then designed. The first target structure is composed of two 3,8-disubstituted-1,10-phenanthroline units separated by two phenylene rings (Figure V.12.b). The syntheses of the non-symmetrical phenanthroline precursors needed as intermediates for this rod proved difficult and low yielding. Therefore the synthesis of this rod was abandoned and new rods were designed.

Figure V. 12 .

 12 Figure V.12. Chemical structures of bis-bidentate molecular rods. a) Rod 16 used in the previous studies, with a very short spacer between the coordination sites. b) Design of a rod with two phenylene spacers, abandoned due to synthetic problems. c) New rod with one phenylene spacer. A threading test with a precursor of this rod gave the[3]pseudorotaxane. d) and e) Target structures of rods with very long spacers between the bidentate sites.

[ 6 ]

 6 pseudorotaxane. Two new rods were then designed; their target chemical structures are depicted in Figure V.12.d and e. Rod d contains three aryl and two alkyne groups as a spacer;

1 H

 1 NMR (300 MHz, CDCl 3 ): δ = 8.44 (d, 3 J = 8.7 Hz, 4H, H o ), 8.26 (d, 3 J = 8.4 Hz, 2H, H 3,8 ), 8.09 (d, 3 J = 8.4 Hz, 2H, H 4,7 ), 7.74 (s, 2H, H 5,6 ), 7.12 (d, 3 J = 8.7 Hz, 4H, H m ), 3.93 ppm (s, 6H, OMe).

[ 3 ]

 3 Pseudorotaxane 9 2+A degassed solution of [Cu(MeCN) 4 ](PF 6 )(5.15 mg, 13.8 μmol) in CH 3 CN (3 mL) was added by cannula to a degassed suspension of zinc porphyrin 8(12.2 mg, 6.65 μmol) in CH 2 Cl 2

1 HCompound 10 ( 4 .

 1104 NMR (300 MHz, D 2 O): δ = 10.07 (dd, 3 J = 8.4 Hz, 4 J = 0.6 Hz, 2H, H α ), 9.49 (dd, 3 J = 6.0 Hz, 4 J = 0.6 Hz, 2H, H 1 ), 9.04 (s, 2H, H 6 ), 8.43 (dd, 3 J = 8.4 Hz, 3 J = 6.0 Hz, 2H, H 2 82 g, 10.4 mmol) was dissolved in distilled water (200 mL). 5 drops of aqueous NaOH (1 M) were added. An aqueous solution of K 3 Fe(CN) 6 (405 mM, 128 mL) was then added to the stirred solution dropwise over a period of 1 h. The pH was adjusted to pH 8 by addition of 1 M NaOH. 72 mL of the aq. K 3 Fe(CN) 6 were added dropwise and the solution was stirred for 4 h. The solution was concentrated and extracted with CH 2 Cl 2(5 × 250 mL). The organic layers were combined and the solvent was evaporated to give 2.01 g (81%) of 11 as a brown solid.

1 H

 1 NMR (300 MHz, CDCl 3 ): δ = 8.80 (d, 4 J = 2.1 Hz, 1H, H 5 ), 7.65 (dd, 3 J = 8.1 Hz, J = 2.4 Hz, 1H, H 4 ), 7.33 (d, 3 J = 8.1 Hz, 1H, H 3 ), 0.34 ppm (s with Sn satellites, 9H, Me).

1 H

 1 NMR (300 MHz, CDCl 3 ): δ = 9.05 (d, 3 J = 8.7 Hz, 2H, H 1 ), 8.80 (d, 4 J = 1.8 Hz, 2H, H 5 ), 8.74 (d, 3 J = 8.7 Hz, 2H, H 2 ), 8.64 (d, 3 J = 8.7 Hz, 2H, H 3 ), 8.31 (s, 2H, H 6 ), 8.03 ppm (dd, 3 J = 8.7 Hz, 4 J = 1.8 Hz, 2H, H 4 ).

1 H

 1 -NMR (300 MHz, CDCl 3 ): δ = 9.07 (d, 3 J = 8.7 Hz, 2H, H 1 ), 8.85 (dd, 4 J = 2.1 Hz, 5 J = 0.6 Hz, 2H, H 5 ), 8.78 (d, 3 J = 8.7 Hz, 2H, H 2 ), 8.72 (dd, 3 J = 8.1 Hz, 5 J = 0.6, 2H, H 3 ), 8.33 (s, 2H, H 6 ), 7.99 (dd, 3 J = 8.1 Hz, 4 J = 2.1 Hz, 2H, H 4 ), 3.34 ppm (s, 2H, H 7 ).

1 H

 1 -NMR (300 MHz, CDCl 3 ): δ = 7.23 (d, 3 J = 8.7 Hz, 6H, H 13 ), 7.09 (d, 3 J = 9.0 Hz, 2H, H 12 ), 7.08 (d, 3 J = 8.7 Hz, 6H, H 14 ), 6.77 (d, 3 J = 9.0 Hz, 2H, H 11 ), 4.08 (t, 3 J = 5.7 Hz, 2H, H 8 ), 3.60 (t, 3 J = 6.3 Hz, 2H, H 10 ), 2.31 (q, 3 J = 6.0 Hz, 2H, H 9 ), 1.30 ppm (s, 27H, H 15 ).

1 H

 1 -NMR (300 MHz, CDCl 3 ): δ = 7.23 (d, 3 J = 8.7 Hz, 6H, H 13 ), 7.09 (d, 3 J = 9.0 Hz, 2H, H 12 ), 7.08 (d, 3 J = 8.7 Hz, 6H, H 14 ), 6.76 (d, 3 J = 9.0 Hz, 2H, H 11 ), 4.02 (t, 3 J = 5.7 Hz, 2H, H 8 ), 3.51 (t, 3 J = 6.6 Hz, 2H, H 10 ), 2.04 (q, 3 J = 6.3 Hz, 2H, H 9 ), 1.30 ppm (s, 27H, H 15 ).

  of [Cu(CH 3 CN) 4 ](PF 6 ) (10 mg, 28 µmol) in CH 3 CN (3 mL) was added by cannula to a degassed suspension of Zn-porphyrin 8(25 mg, 14 µmol) in CH 2 Cl 2(3 mL). The mixture was stirred under argon for 30 min, resulting in a dark red solution. This solution was then added to a degassed suspension of acetylenic thread 16 (5.2 mg, 14 µmol) in CH 2 Cl 2 (3 mL). The mixture was stirred for 24 h under argon. Azide stopper 18 (24 mg, 41 µmol), [Cu(CH 3 CN) 4 ](PF 6 ) (5.1 mg, 14 µmol), Na 2 CO 3 (0.6 mg, 5.4 µmol) and sodium ascorbate (1.1 mg, 5.4 µmol) were then added to the solution. The mixture was stirred under argon during 5 days. The solvents were then evaporated and the resulting deep red solid was purified by column chromatography. Consecutive alumina chromatography (using a gradient of elution from CH 2 Cl 2 /MeOH 100:0 to 92:8), size-exclusion Biobeads S-X1 chromatography in distilled THF and silica chromatography (using a gradient of elution from CH 2 Cl 2 /MeOH 98:2 to 94:6) gave 26 mg of rotaxane 19 4+ •4PF 6 (50%) as a dark red solid.

1 H

 1 -NMR (400 MHz, CDCl 3 ): δ = 8.72 (br d, 4H), 7.78 (s, 4H), 7.57 ppm (br d, 4H).

  product was confirmed by comparison of the TLC and UV-visible absorption spectrum with those of an authentic sample.

5 -

 5 Dinitroveratrole 27(5.05 g, 22.1 mmol) and 10% Pd/C (0.20 g) were placed under argon and degassed absolute ethanol (115 mL) was added. Hydrazine monohydrate (11 mL, 0.23 mol) was added slowly and the reaction was stirred at room temperature under argon. A vigorous exothermic reaction occurred within the first 30 min. The reaction was then set to reflux.

5 -

 5 Diaminoveratrole 28(3.71 g, 22.1 mmol) was dissolved in degassed CH 2 Cl 2(50 mL) and the solution was cooled to 0 °C. BBr 3 (50 mL of a 1.0 M CH 2 Cl 2 solution, 50 mmol) was added slowly via cannula to the stirred solution. The resulting grey slurry was allowed to warm to room temperature and was stirred for 16 h under argon. Methanol (100 mL) was added slowly,

1 H

 1 NMR (300 MHz, DMSO-d 6 ): δ = 11.18 (br s, 2H, OH), 7.42 ppm (s, 2H, H Ar ).

5 -

 5 Diaminocatechol hydrobromide 29 (430 mg, 1.94 mmol) was dissolved in degassed absolute ethanol(5 mL). Pyridine (0.32 mL, 3.9 mmol) and di-tert-butyl dicarbonate (Boc 2 O)(1.70 g, 7.8 mmol) were added. The reaction mixture was stirred at 30 °C under argon for 20 h.

1 H

 1 NMR (500 MHz, CDCl 3 ): δ = 8.41 (d, 2H, 3 J = 8.5 Hz, H op2 ), 8.34 (d, 2H, 3 J = 8.5 Hz, H op1 ), 8.24 (d, 1H, 3 J = 8.5 Hz, H 7 ), 8.21 (d, 1H, 3 J = 8.5 Hz, H 4 ), 8.04 (d, 1H, 3 J = 8.5 Hz, H 8 ), 8.00 (d, 1H, 3 J = 8.5 Hz, H 3 ), 7.72 (s, 2H, H 5,6 ), 7.48 (d, 2H, 3 J = 8.5 Hz, H ob1 ), 7.42 (s, 1H, H c1 ), 7.21 (d, 2H, 3 J = 8.5 Hz, H mp2 ),

1 H

 1 NMR (500 MHz, CDCl 3 ): δ = 7.38 (s, 2H, H Ar ), 5.46 ppm (br s, 2H, OH).

37 AMacrocycle 5

 375 toluene solution (10 mL) of tris(dibenzylideneacetone)dipalladium(0) (4.7 mg, 5.2 μmol) and rac-BINAP (6.4 mg, 10 μmol) was degassed with argon, and stirred at 110 °C for 30 min under argon. After cooling to room temperature, benzophenone imine (23 μL, 0.14 mmol), dibromo macrocycle 36(40 mg, 52 μmol), and sodium tert-butoxide (13 mg, 0.13 mmol) were added to the solution, and the reaction mixture was stirred at 110 °C under argon for 48 h. The mixture was cooled to room temperature, diluted with CH 2 Cl 2 (10 mL), filtered through a pad of Celite, and evaporated to dryness. The residue was subjected to column chromatography on silica gel with CH 2 Cl 2 /methanol (100:3) as eluent. The desired bis-imine macrocycle 37 could not be completely purified but was detected by mass spectrometry.ES-MS: calcd for C 64 H 53 N 4 O 6 + (37 + H + ) m/z = 973.39; found 973.40. (0.40 g, 0.62 mmol) was dissolved in a 7:3 mixture of propionic acid and nitrobenzene (3 mL) in a 10 mL reaction vessel. Pyrrole (43 µL, 0.62 mmol) was added by syringe. The reaction vessel was sealed and subjected to microwave irradiation (maximum power 300 W) for 10 minutes at a controlled temperature of 140 °C. The resulting black solution was diluted with chloroform (100 mL), washed with water (3 × 100 mL) and dried with Na 2 SO 4 .

1 H

 1 NMR (300 MHz, CDCl 3 ): δ = 8.92 (s, 8H, H py ), 8.39 (d, 3 J = 8.7 Hz, 16H, H o ), 8.14 (d, 3 J = 8.4 Hz, 8H, H 3,8 ), 7.96 (d, 3 J = 8.4 Hz, 8H, H 4,7 ), 7.62 (s, 8H, H 5,6 ), 7.30 (d, 4 J = 2.4 Hz, 8H, H o" ), 7.11 (d, 3 J = 8.7 Hz, 16H, H m ), 6.92 (t, 4 J = 2.1 Hz, 4H, H p" ), 4.18 (t, 3 J = 5.1 Hz, 16H, CH 2 ), 4.12-4.10 (m, 16H, CH 2 ), 3.73-3.76 (m, 32H, CH 2 ), ppm. 13 C NMR (125 MHz, CDCl 3 ): δ = 160.

  of [Cu(CH 3 CN) 4 ](PF 6 ) (16 mg, 43 µmol) in CH 3 CN (5 mL) was

1 H

 1 NMR (300 MHz, CD 2 Cl 2 ): δ = 9.38 (d, 3 J = 9.0 Hz, 4H, H 1' ), 9.20 (s, 4H, H pyA ), 9.12 (s, 4H, H pyB ), 8.91 (d, 4 J = 1.5 Hz, 4H, H 5' ), 8.79 (dd, 3 J = 8.4 Hz, 4 J = 1.8 Hz, 4H, H 4' ), 8.69 (d, 3 J = 8.4 Hz, 8H, H 4,7 ), 8.62 (d, 3 J = 8.7 Hz, 4H, H 2' ),8.60 (d, 3 J = 8.4 Hz, 4H, H 3' ), 8.37 (s, 4H, H 7' ),8.22 (s, 8H, H 5,6 ), 8.00 (d, 3 J = 8.4 Hz, 8H, H 3,8 ), 7.69 (d, 4 J = 2.1 Hz, 8H, H o" ),7.27 (d,

Table V . 1 .

 V1 Synthesis of free-base porphyrin 38 in classical Lindsey conditions or mild conditions. ...... 107

Table V . 2 .

 V2 Synthesis of free-base porphyrin 38 in conditions derived from the Adler-Rothemund method.

	List of Abbreviations
	ADP	Adenosine DiPhosphate
	ATP	Adenosine TriPhosphate
	a.u.	arbitrary unit
	BINAP	2,2'-bis(diphenylphosphino)-1,1'-binaphtyl
	bipy	2,2'-bipyridine	or 4,4'-bipyridine
	Boc	t-Butyl carbamate
	CAN	Ceric Ammonium Nitrate (NH 4 ) 2 Ce(NO 3 ) 6

................................................................................................................................................................... 108 xxii xxiii

  [START_REF] Dean | Duplex DNA knots produced by Escherichia coli topoisomerase I. Structure and requirements for formation[END_REF]

  , permettant une rotation des sites chélatants par rapport au plan du noyau porphyrinique. La RMN du rotaxane montre également que plusieurs conformations différentes sont en équilibre en solution, et cet équilibre est dépendant du solvant. L'une des conformations est largement majoritaire dans le dichlorométhane, cependant les différentes conformations s'échangent à l'échelle de temps de la RMN dans les autres solvants testés, comme l'attestent les signaux larges observés à température ambiante. La caractérisation par absorption UV-visible a mis en évidence un couplage excitonique entre les deux porphyrines du rotaxane, témoignant ainsi de la proximité spatiale des porphyrines.

	porphyrine aux macrocycles
						N 3
	H	N	N	N	N	H	O
	Rail moléculaire (ou "axe") à deux chélates	Bouchon
						xxxiii

C, COSY, NOESY, HSQC, HMBC, DOSY, températures variables). La RMN montre une perte de symétrie dans l'assemblage final par rapport à ses constituants libres. Nous proposons une conformation torsadée pour le rotaxane en solution, avec des rails non parallèles entre eux. Une telle conformation serait favorisée par la flexibilité du bis-macrocycle porphyrinique. En effet, ce composé possède des connecteurs flexibles entre les différents groupements fonctionnels: des chaînes éthylène-glycol sont incorporées dans le macrocycle, et une liaison C-C simple relie la

Molécules invitées log K* Distance N-N en Å (d'après des données cristallographiques)

  Les valeurs obtenues pour les substrats G2 et G3 sont très proches, ce qui atteste de la flexibilité du rotaxane. La molécule G3, longue de 11.4 Å, peut se loger entre les deux porphyrines du rotaxane tout aussi bien que G2 qui mesure 7.1 Å. La molécule invitée

	G4 a une constante d'association plus faible avec le rotaxane, probablement du fait de contraintes
	stériques. Cependant, le fait que cette molécule forme un complexe hôte/invité avec le rotaxane
	montre que ce dernier peut adopter des formes très variables et se "gonfler" de manière
	exceptionnelle lors de l'insertion d'une molécule invitée très longue (15.8 Å).
	Tableau 1. Constantes d'association des molécules invitées G1 à G4 avec le [4]rotaxane.
	*pour les complexes hôte/invité de stoechiométrie 1:1. Dans le cas du DABCO (G1), des
	complexes 1:2 sont également formés avec une constante d'association de
	log K 2 = 14.5 ± 0.2.
	G1	8.1 ± 0.5	2.6
	G2	6.2 ± 0.1	7.1
	G3	6.1 ± 0.1	11.4
	G4	5.6 ± 0.1	15.8
	Ainsi, nous avons conçu, synthétisé et entièrement caractérisé un nouveau [4]rotaxane.
	Les études hôte/invité ont montré que le rotaxane présente des propriétés très intéressantes,
	1.2 eq 1.4 eq puisqu'il s'agit d'un excellent récepteur moléculaire pour des substrats de longueurs variables. La
	1.6 eq distance entre les plaques porphyriniques du rotaxane peut s'adapter à la taille de la molécule
	1.8 eq invitée, d'une manière analogue à l'ajustement induit du site actif de certaines enzymes par la
	complexation du substrat.		2.0 eq

xxxv Les constantes d'association mesurées pour les différentes molécules invitées sont résumées dans le Tableau 1. xxxvi IV.

Vers un nouveau Bis-Macrocycle Porphyrinique Rigide

	Afin d'obtenir un rotaxane pouvant changer la conformation d'une molécule invitée par
	compression, nous avons conçu une nouvelle porphyrine liée à deux anneaux, plus rigide que la
	celle décrite en II. et III. La synthèse de ce nouveau bis-macrocycle implique l'utilisation de
	méthodes développées par le groupe du Professeur Crossley, qui a réalisé de nombreuses études
	sur des porphyrines possédant un système aromatique étendu. Cette synthèse a donc été
	entreprise dans le cadre de ma cotutelle de thèse avec l'Université de Sydney.

1. Rotaxanes: Topology, Synthetic Strategies and Applications I. 1. a) Interlocked Structures: Catenanes, Rotaxanes and Knots

	Conclusion Chapter I. General Introduction
	Ces travaux de recherche ont été réalisés dans le cadre d'une Cotutelle de thèse entre
	l'Université de Strasbourg et l'Université de Sydney. Deux nouvelles porphyrines portant deux et
	quatre macrocycles coordinants (respectivement) ont été synthétisées. Un [4]rotaxane basé sur le The ultimate aim of our research project is to create a chemical system able to trap a
	bis-macrocycle porphyrinique a été synthétisé et entièrement caractérisé, et les études d'insertion guest molecule and to change its conformation by compression. This model is a new type of
	de quatre substrats de longueurs différentes ont montré que le [4]rotaxane se comporte comme molecular machine that we named a "Molecular Press". In this thesis we will describe our work
	un récepteur moléculaire adaptable et gonflable. Un [3]rotaxane possédant une architecture and results towards a molecular press. This work was fulfilled as part of a Cotutelle PhD, in a
	originale a été obtenu à partir du tétra-macrocycle porphyrinique. Nous avons préparé des collaboration between the group of Jean-Pierre Sauvage at the University of Strasbourg and the
	précurseurs d'un nouveau bis-macrocycle porphyrinique, plus rigide, qui pourra être utilisé dans group of Maxwell J. Crossley at The University of Sydney. Chapters II, III and V of this thesis
	la construction d'un nouveau [4]rotaxane et pourrait ouvrir la voie vers un modèle de presse relate to the work performed in Strasbourg. We will discuss the design of new rotaxanes that
	moléculaire amélioré. incorporate porphyrins, and describe their syntheses and properties as molecular receptors.
	Chapter IV deals with the work accomplished in Sydney. The chemistry of extended porphyrins
	De futurs travaux pourraient porter sur l'étude de rotaxanes comportant différents métaux developed by the group of M. J. Crossley will be exploited in the design of a new porphyrinic
	au niveau des centres porphyriniques. Par exemple, à l'aide d'un [4]rotaxane comportant une building block. As an introduction to this thesis we will give an insight into the fields of
	porphyrine de zinc et une porphyrine d'étain, il devrait être possible de piéger des acides aminés rotaxanes, molecular machines, and porphyrins, and explain how we intend to combine the use
	ou de courts peptides. La compression d'oligopeptides par la presse moléculaire et l'étude de leur of rotaxanes and porphyrins in the construction of molecular press prototypes.
	changement de conformation au sein de la presse constituerait un nouveau pas vers un modèle de
	protéine chaperonne. D'autres recherches futures pourraient porter sur la construction d'espèces
	intéressantes d'un point de vue topologique à partir du tétra-macrocycle porphyrinique. Par une
	stratégie de synthèse analogue à celle employée pour la synthèse du [3]rotaxane, nous pourrions
	former un caténane d'architecture nouvelle, constitué d'un grand anneau enfilé sur les quatre
	macrocycles de la porphyrine.

I.

  2,9-dianisyl-1,10phenanthroline (dap) 1 is known to thread rapidly and to form stable four-coordinate Cu(I) complexes. This chelate was thus selected as threading element. Compound 8 and Cu(CH 3 CN) 4 PF 6(2 equiv.) were first mixed in dichloromethane/acetonitrile under argon and the dap thread 1 (2 equiv.) was subsequently added, which led to the desired pseudorotaxane 9

2+ •2PF 6 in quantitative yield after work-up (Figure II.8).

]Rotaxane Composed of Two Dumbbells and Two Bis-Macrocycles:

	Chapter III. A Cyclic [4
	Br		Br		Br	NaN 3	N 3
	OH	Cs 2 CO 3	O	CH 2 Cl 2 /DMF/	O
	DMF, 60	°C		H 2 O, 100 °C
		71%		17		77%	18

  Coordinationof two axial ligands on the same Zn(II) porphyrin was excluded because zinc porphyrins are preferentially penta-coordinated with only one axial ligand. In each titration experiment the host/guest stoichiometry was determined by mathematical treatment of the titration data with the

				Br
		Br			N
	N
		Br	N	Br
		Pd(dppf) 2 Cl 2, Na 2 CO 3	B(OH) 2	Pd(dppf) 2 Cl 2, Na 2 CO 3
	N	Toluene/H 2 O reflux		Toluene/H 2 O reflux
	G3	77%		58%	N
					G4
	Specfit/32 software. Guest inclusion complexes were distinguished from external complexes by
	comparison of the association constant with values reported in the literature for similar
	host/guest systems.

and the ditopic guests can potentially be considered with internal and/or external binding of the guest(s) (Figure III.16).

Figure III.16. Possible coordination modes of guests G1 -G4 with rotaxane host 19 4+ . a) 1:1 host-guest stoichiometry, internal complex (guest inclusion); b) 1:1 stoichiometry, external complex; c) 1:2 host-guest stoichiometry, internal complexes; d) 1:2 stoichiometry, external complexes, e) 1:2 stoichiometry with one internal and one external guest.

Table III . 1 .

 III1 Association constants of guests G1 -G4 with rotaxane host 194+ and lengths of the ligands.

	Guest	log K a1 *	N-N distance in Å
			(from crystallographic data) 257,258
	G1	8.1 ± 0.5	2.6
	G2	6.2 ± 0.1	7.1
	G3	6.1 ± 0.1	11.4
	G4	5.6 ± 0.1	15.8

  5, which was prepared in gram amounts as described in Chapter II. The chemical structure of the target freebase porphyrin 38 is depicted in Figure V.3 as well as the optimised conditions leading to its preparation. A series of different reaction conditions were tested in order to improve the porphyrin yield, which was initially very low. First, equimolar amounts of pyrrole and aldehyde 5 were condensed in classical Lindsey conditions using boron trifluoride etherate as a catalyst, followed by oxidation with DDQ.294 Porphyrin 38 was obtained in a very low yield of 3%. Use of trifluoroacetic acid (TFA) instead of boron trifluoride etherate gave similar results (TableV.1, Entries 1-2). In an attempt to increase the yield of this challenging synthesis, various alternative methods were then tested. Crossley et al. developed a procedure for the synthesis of porphyrins using p-toluenesulfonic acid as a catalyst with azeotropic removal of water.296 Low yields (2-4%) of porphyrin 38 were obtained with this method, possibly due to poor solubility of macrocycle 5 in toluene in the presence of p-toluenesulfonic acid (TableV.1, Entry 3). Use of equimolar amounts of CF 3 SO 2 Cl or catalytic amounts of iodine were reported to yield 25-64% of various meso-tetraarylporphyrins297,298 but absolutely no reaction occurred between aldehyde 5

Table V . 1 .

 V1 Synthesis of free-base porphyrin 38 in classical Lindsey conditions or mild conditions.

	Entry	Catalyst	Solvent	Temperature	Reaction time	Yield	Ref.
	1	BF 3 •OEt 2 (0.1 eq.)	CHCl 3	RT	1 h	3%	294
	2	TFA (0.1 eq.)	CH 2 Cl 2	RT	1 h	4%	294
	3	pTsOH (0.2 eq.)	Toluene	Reflux (Dean-Stark)	40 h	4%	296
	4	Iodine (0.2 eq.)	CH 2 Cl 2	Reflux (Microwaves)	30 min	0%	297
	5	CF 3 SO 2 Cl (1 eq.)	CHCl 3	RT	4 h	0%

. 2 ,

 2 Entry 3). Temperature and concentration also proved to be critical parameters in this reaction(Table V.2,Entries 4-6). Temperatures below 140 °C led to incomplete conversion and longer reaction times while increasing the temperature to 190°C led to partial decomposition of the product. Increasing the concentration of the starting materials from 50 to 200 mM improved the yield of the reaction considerably, and target porphyrin 38 was obtained in 25% yield. Thus, reacting 200 mM aldehyde and pyrrole at 141 °C for 10 minutes in a 7:3 mixture of propionic acid and nitrobenzene under microwave irradiation were found to be the best conditions for the synthesis of porphyrin 38. Purification by sequential silica and size-exclusion chromatographies gave pure free-base porphyrin 38 as a purple solid in 25% yield using these conditions.

Table V . 2 .

 V2 Synthesis of free-base porphyrin 38 in conditions derived from the Adler-Rothemund method.

	Entry	Solvent	Microwaves	Temperature	Reaction time	Concentration (mM)	Yield
	1	Propionic acid	No	141 °C	2 h	50	9%
	2	Propionic acid	Yes	141 °C	30 min	50	12%
	3	Propionic acid / nitrobenzene 7:3	Yes	141 °C	10 min	50	15%
	4	Propionic acid / nitrobenzene 7:3	Yes	190 °C	10 min	50	9%
	5	Propionic acid / nitrobenzene 7:3	Yes	141 °C	10 min	200	25%
	6	Propionic acid / nitrobenzene 7:3	Yes	100 °C	40 min	200	20%

  rotaxane structure relies on the synthesis of a new axle building block that incorporates a longer spacer between the bidentate chelates. This project forms part of a collaboration with Nathan L. Strutt, who was previously a student in the Sauvage group in Strasbourg and who is now a PhD candidate with J. F. Stoddart at Northwestern University. Nathan is carrying out the syntheses of the new axles and corresponding rotaxanes.

  NMR (300 MHz, CDCl 3 ): δ = 9.84 (s, 1H, aldehyde H), 8.41 (d, 3 J = 9.0 Hz, 4H, H o ), 8.26 (d, Elemental analysis: C 39 H 34 N 2 O 7 •0.5H 2 O•CH 2 Cl 2 (736.64): calcd. C 65.22, H 5.07,

	3 J = 8.4 Hz, 2H, H 3,8 ), 8.07 (d, 3 J = 8.4 Hz, 2H, H 4,7 ), 7.75 (s, 2H, H 5,6 ), 7.14 (d, 3 J = 9.0 Hz, 4H,
	H m ), 7.03 (d, 4 J = 2.4 Hz, 2H, H o" ), 6.91 (t, 4 J = 2.3 Hz, 1H, H p" ), 4.32-4.36 (m, 4H, CH 2 ), 4.20-
	4.23 (m, 4H, CH 2 ), 3.93-3.97 ppm (m, 8H, CH 2 ). ES-MS: calcd for C 39 H 35 N 2 O 7 [5+H] + 643.24;
	found 643.25.

1 H

  NMR (300 MHz, CD 2 Cl 2 ): δ = 8.92 (d, 3 J = 4.7 Hz, 4H, H pyA ), 8.67 (d, 3 J = 4.6 Hz, 4H, H pyB ), 8.45 (d, 3 J = 8.8 Hz, 8H, H o ), 8.28 (d, 3 J = 8.4 Hz, 4H, H 3,8 ), 8.08 (d, 3 J = 8.4 Hz, 4H, H 4,7 ), 7.77

	(s, 4H, H 5,6 ), 7.42 (d, 4 J = 2.4 Hz, 4H, H o" ), 7.20 (d, 3 J = 8.8 Hz, 8H, H m ), 7.19 (s, 4H, H m" ), 7.04
	(t, 4 J = 2.4 Hz, 2H, H p" ), 4.31 (m, 16H, OCH 2 ), 3.91 (m, 16H, OCH 2 ), 2.58 (s, 6H, CH 3p ), 1.75 (s,
	12H, CH 3o ) ppm. ES-MS: calcd for C 114 H 97 N 8 O 12 Zn (8 + H + ) 1833.65; found 1833.51. UV-
	visible absorption (CH 2 Cl 2 ) : λ max (logε) = 421 (5.76), 549 (4.37), 585 (3.63) nm.

1 H

  Hz, 8H, H m' ), 6.05 (d, 3 J = 8.6 Hz, 8H, H m ), 4.43 (m, 8H, OCH 2 ), 3.97 (m, 8H, OCH 2 ), 3.72 (m, 8H, OCH 2 ), 3.67 (m, 8H, OCH 2 ), 3.52 (s, 12H, OMe), 2.35 (s, 6H, CH 3p ), 1.68 (s, 12H, CH 3o ) ppm. ES-MS: calcd for C 166 H 136 Cu 2 N 12 O 16 Zn 2+ (9 2+ /2) 1371.41; found 1371.37. UV-visible absorption (CH 2 Cl 2 ) : λ max (logε) = 421 (5.84), 548 (4.51), 585 (3.79) nm.

	1 H NMR (300 MHz, CD 2 Cl 2 ): δ = 8.90 (d, 3 J = 4.8 Hz, 4H, H pyA ), 8.64 (d, 3 J = 8.4 Hz, 4H, H 4',7' ),
	8.58 (d, 3 J = 4.6 Hz, 4H, H pyB ), 8.50 (d, 3 J = 8.2 Hz, 4H, H 4,7 ), 8.25 (s, 4H, H 5',6' ), 8.04 (s, 4H,
	H 5,6 ), 7.92 (d, 3 J = 8.3 Hz, 4H, H 3',8' ), 7.89 (d, 3 J = 8.0 Hz, 4H, H 3,8 ), 7.53 (s, 4H, H o" ), 7.52 (d,
	3 J = 8.6 Hz, 8H, H o' ), 7.32 (d, 8.4 Hz, 8H, H o ), 7.29 (m, 2H, H p" ), 7.09 (s, 4H, H m" ), 6.12 (d,
	3 J = 8.6

  NMR (300 MHz, CDCl 3 ): δ = 9.05 (d, 3 J = 8.7 Hz, 2H, H 1 ), 8.82 (dd, 4 J = 2.1 Hz, 5 J = 0.6 Hz, 2H, H 5 ), 8.78 (d, 3 J = 8.7 Hz, 2H, H 2 ), 8.69 (dd, 3 J = 8.1 Hz, 5 J = 0.6, 2H, H 3 ), 8.32 (s, 2H, H 6 ), 7.95 (dd, 3 J = 8.1 Hz, 4 J = 2.1 Hz, 2H, H 4 ), 1.18 ppm (s, 42H, H TIPS ).

1 H-

  NMR (300 MHz, CDCl 3 ,): δ = 8.77-9.11 (m, 6H, H py ), 8.00-8.14 (m, 8H, H o ), 7.80-7.88 (m, 4H, H p ), 1.50-1.56 (72H, H tBu ), -2.09 to -2.18 and -2.40 to -2.48 ppm (6H, NH). UV-visible absorption (CHCl 3 ): λ max (log ε) = 442(5.32), 539 (4.13), 583 (3.96), 618 (3.76), 683 nm (4.04).

1 H

  in methanol (15 mL) was added. The reaction mixture was refluxed for 2 h, and the solvents were then evaporated. The resulting solid was subjected to silica column chromatography in dichloromethane/hexane 1:1 to isolate the linear free-base porphyrin-tetraone 25 (453 mg, 21% from dinitro isomers 22) and the corner zinc(II)

aminoporphyrin-diones 26

(1.26

g, 54% from dinitro isomers 22). 25: 1 H NMR (400 MHz, CDCl 3 ): δ = 8.50 (s, 4H, H py ), 7.74 (t, 4 J = 1.7 Hz, 4H, H p ), 7.65 (t, 4 J = 1.7 Hz, 8H, H o ), 1.44 (s, 72H, H tBu ), -1.32 ppm (br s, 2H, NH).

  NMR (300 MHz, CDCl 3 ): δ = 7.33 (s, 2H, H Ar ), 4.01 ppm (s, 6H, H Me ).

1 H

  NMR (200 MHz, CDCl 3 ): δ = 6.38 (s, 2H, H Ar ), 3.79 (s, 6H, Me), 2.20 ppm (br s, 4H, NH 2 ).

1 H

  : calcd for C 88 H 99 N 8 O 4 + (30 + H + ) m/z = 1331.78; found 1331.93; calcd for C 88 H 97 N 8 O 4 -(30 -H + ) m/z = 1329.77; found 1329.93. 1 H NMR (300 MHz, CDCl 3 ): broad signals.

phenylbenzimidazole derivative 33 4

  NMR (200 MHz, DMSO-d 6 ): δ = 8.86 (br s, 2H, NH), 8.10 (br s, 2H, OH), 6.81 (s, 2H, H Ar ), 1.43 ppm (s, 18H, H tBu ). ES-MS: calcd for C 16 H 24 N 2 NaO 6 + (32 + Na + ) m/z = 383.15; found 362.67. ,5-Diaminocatechol hydrobromide (2.15 g, 9.71 mmol) was dissolved in a carefully degassed mixture of ethanol and water 1:2 (90 mL) to produce a dark purple solution. Pyridine (3.6 mL, 44 mmol) was added to neutralise the hydrobromic acid, and the solution turned red. Anisaldehyde (2.7 mL, 22 mmol) was added, and the solution was stirred at room temperature under argon for 4 h. A pale pink solid precipitated, it was filtered off and washed with diethylether. After recrystallisation from hot ethanol, compound 33 was obtained as an off-white solid (2.85 g, 78%). NMR (500 MHz, DMSO-d 6 ): δ = 8.78 (br s, 1H, OH 2 ), 8.74 (br s, 1H, OH 1 ), 7.58 (d, 2H, 3 J = 9.0 Hz, H o1 ), 7.04 (d, 2H, 3 J = 9.0 Hz, H m1 ), 7.01 (s, 1H, H c1 ), 6.94 (d, 2H, 3 J = 8.5 Hz, H o2 ), 6.86 (d, 2H, 3 J = 8.5 Hz, H m2 ), 6.67 (s, 1H, H c2 ), 5.31 (s, 2H, CH 2 ), 3.80 (s, 3H, Me 1 ), 3.70 ppm (s, 3H, Me 2 ). 13 C NMR (125 MHz, DMSO-d 6 ): δ = 159.

1 H 1-Benzyl-2-1 H

  ppm. ES-MS: calcd for C 22 H 21 N 2 O 4 + (33 + H + ) m/z = 377.15; found 376.80.

  ppm. ES-MS: calcd for C 54 H 49 N 4 O 8 + (34 + H + ) m/z = 881.36; found 881.33.

  NMR (300 MHz, CDCl 3 ): δ = 8.81 (s, 8H, H py ), 8.46 (d, 3 J = 8.7 Hz, 16H, H o ), 8.24 (d, 3 J = 8.4 Hz, 8H, H 3,8 ), 8.06 (d, 3 J = 8.4 Hz, 8H, H 4,7 ), 7.72 (s, 8H, H 5,6 ), 7.33 (d, 4 J = 2.4 Hz, 8H, H o" ), 7.22 (d, 3 J = 8.7 Hz, 16H, H m ), 7.02 (t, 4 J = 2.1 Hz, 4H, H p" ), 4.36 (t, 3 J = 5.1 Hz, 16H, CH 2 ), 4.27-4.24 (m, 16H, CH 2 ), 3.97-3.93 (m, 32H, CH 2 ), -2.98 (br s, 2H, NH) ppm. 13 C NMR (75.48 MHz, CDCl 3 ): δ = 160.

1 H

  . ES-MS: calcd for C 172 H 143 N 12 O 24 + [38 + H + ] m/z = 2,760.03; found 2,760.10. UV-visible absorption

  . ES-MS: calcd for C 172 H 141 N 12 O 24 Zn + (39 + H + ) m/z = 2,824.95; found 2,824.95. UV-visible absorption (CH 2 Cl 2 ): λ max (log ε) = 284

Remerciements

a bénéficié des aides spécifiques du CDE et a suivi un during the preparation of her PhD, from 2008 to 2012, class name Jane Goodall. She has benefited from specific financial supports offered by the College and, along with her mainstream research, has followed a special course on topics of general European interests presented by international experts. This PhD research project has been led

Conclusion

The work presented in this thesis focuses on the design of multiply interlocking assemblies and molecular receptors. The features and properties of the porphyrin core and of the rotaxane structure were exploited and combined in the elaboration of novel porphyrin-based multi-rotaxanes, whose syntheses constitute interesting challenges. New porphyrinic multimacrocycles and the corresponding [3]-and [4]rotaxanes were obtained and fully characterised, and the host-guest properties of the [4]rotaxane were studied. The synthesis of a new bismacrocyclic system is under way. This last system was designed to be a better molecular press model, which should be able to change the conformation of a guest substrate by compression.

The design of the systems presented here involved the incorporation of bidentate ligands in the building blocks and the use of the "gathering-and-threading" effect of copper(I) to interlace the components into rotaxane structures. The syntheses of three rotaxane building blocks were described first. A bis-bidentate molecular thread (or axle), a stopper and a new zinc(II) porphyrin linked to two dpp-containing rings were prepared. The molecular thread and stopper were needed as precursors of the "dumbbell" part of the rotaxanes. The new porphyrinic bis-macrocycle contains two rings linked to antipodal meso positions of a Zn-porphyrin via single C-C bonds. It was obtained in good yield by [2+2] MacDonald condensation of mesityldipyrrylmethane with a new aldehyde-functionalised macrocyclic precursor. This precursor, whose structure was confirmed by X-ray diffraction crystallography, was later used in the synthesis of a porphyrin substituted with four lateral rings. The ability of the porphyrinic bismacrocycle to form threaded assemblies was tested via the formation of a prototypical [3]pseudorotaxane. Complexation with copper(I) and two dap chelates led to the quantitative formation of a doubly threaded species as expected.

A new copper(I)-complexed [4]rotaxane was obtained in good yield from the porphyrinic bis-macrocycle, molecular axle and stopper described above. The building blocks were assembled in a two-step, one-pot reaction involving (i) Cu(I)-templated formation of a [4]pseudorotaxane and (ii) quadruple CuAAC stoppering reaction. The [4] NMR spectra for 1 H were acquired on Bruker AVANCE 600, 500, 400 or 300 MHz or on Bruker AC-200 (200 MHz) spectrometers. The spectra were referenced to residual protonsolvent references (CD 2 Cl 2 at 5.32 ppm ( 1 H) and 53.84 ppm ( 13 C); CDCl 3 at 7.26 ppm ( 1 H ) and 77.16 ppm ( 13 C); DMSO-d 6 at 2.50 ppm ( 1 H) and 39.52 ppm ( 13 C)). In the assignments, the chemical shift (in ppm) is given first, followed, in brackets, by the multiplicity of the signal (s, singlet; d, doublet; t, triplet; ; q, quintuplet; dd, doublet of doublets; m, multiplet; br, broad signal), the value of the coupling constants in Hz if applicable, the number of protons implied and finally the assignment. Mass spectra (ES-MS) were recorded on a Bruker MicroTOF spectrometer by the Service de Spectrométrie de Masse (Université de Strasbourg). UV-visible absorption spectra were recorded with a Kontron Instruments UVIKON 860 spectrometer at 21°C with a 1 cm path cell. Titration spectra were measured in 0.92 x 10 -6 M toluene solutions of rotaxane 19 4+ . Guest solutions (2.8 x 10 -5 M) were added to the rotaxane sample in 10 µL (0.1 equivalent) aliquots using a 100 µL Hamilton syringe. UV-visible spectrophotometric titrations were analyzed by fitting the series of spectra at 1 nm intervals by using the SPECFIT/32 3.0 software (Spectrum Software Associates), which takes into account the changes in volume during the titration. 306 Emission spectra were recorded using a Fluorolog FL3-22 de HORIBA Jobin Yvon spectrophotometer. Lifetime measurements were detected by a TCSPC (timecorrelated single-photon counting) technique with a NanoLED-370 electroluminescent diode as the excitation source. X-ray diffraction studies were performed by Dr. Lydia Brelot, Service de Radiocristallographie (Université de Strasbourg). CCDC-823860 contains the supplementary crystallographic data for macrocycle 5. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

Guest G4 261

4,4'-Dibromobiphenylene (312 mg, 1.00 mmol), pyridine 4-boronic acid (430 mg, 3.50 mmol), Pd(dppf) 2 Cl 2 (82 mg, 0.10 mmol), and Na 2 CO 3 (0.21 g, 2.0 mmol) were introduced in a 10 mL round-bottom flask, and a mixture of toluene/water 1:1 (5 mL) was added. The mixture was degassed for 10 min and allowed to reflux for 72 h under argon atmosphere. The solvent was evaporated, and the residue was extracted with ethyl acetate (50 mL). The solution was washed with water (3 × 50 mL). The organic layer was dried over anhydrous MgSO 4 and evaporated to afford a brown solid, which was purified by silica gel column chromatography in ethyl acetate/pentane/triethylamine 8:5:1 to afford pure 1,4-bis(4-pyridyl)benzene G3 as an offwhite solid (179 mg, 58%).

Copper(II) porphyrin 20 265

A solution of copper(II) acetate monohydrate (0.78 g, 3.9 mmol) in methanol (30 mL) was added to a solution of free-base 5,10,15,20-tetrakis(3,5-di-tert-butylphenyl)porphyrin (2.08 g, 1.96 mmol) in dichloromethane (100 mL). The reaction mixture was allowed to reflux for 1.5 h. After cooling, the solvent was evaporated. The residue was passed through a plug of silica using dichloromethane as eluent. The main fraction was collected and the solvent was evaporated to give copper(II) porphyrin 20 (2.20 g, quantitative) as a red-purple solid.

Porphyrin-based [3]-and [4]Rotaxanes

Towards an Adaptable Molecular Receptor

Résumé

La synthèse et l'étude de rotaxanes et de porphyrines sont deux domaines particulièrement actifs de la recherche en chimie. Cependant, les composés combinant les propriétés intéressantes de ces deux types de structures sont plus rares. De nouveaux multi-rotaxanes à base de porphyrines, dont la préparation représente un défi synthétique, sont décrits dans cette thèse.

Des porphyrines liées à deux ou quatre anneaux coordinants ont été synthétisées. Des rails moléculaires à deux chélates ont été enfilés dans les anneaux grâce à l'effet template du cuivre(I); l'introduction de bouchons a mené à la formation de rotaxanes. Dans le cas du bis-macrocycle porphyrinique, un [4]rotaxane a été obtenu. Des études de complexation hôte/invité avec des ligands azotés rigides ont montré que ce rotaxane est un récepteur moléculaire qui peut s'adapter à la taille du substrat invité en se "gonflant" ou en se "dégonflant". Dans le cas du tétra-macrocycle porphyrinique, la formation d'un [3]rotaxane d'architecture originale a été observée.

La synthèse d'un nouveau bis-macrocycle plus rigide est en cours. Ce composé sera utilisé pour la construction d'un [4]rotaxane, qui pourrait montrer un caractère de presse moléculaire capable de modifier la conformation d'un substrat invité en le comprimant.

Mots-clés: rotaxane, porphyrine, macrocycle, phénanthroline, bipyridine, cuivre(I), zinc(II), synthèse organique, chimie de coordination, effet template, système hôte/invité, récepteur moléculaire.

Résumé en anglais

Rotaxanes and porphyrins are two particularly active fields of research in chemistry. However, molecules that combine the interesting properties of these types of structures are not so common. In this thesis we describe new porphyrin-based multi-rotaxanes, whose syntheses constitute interesting challenges.

Porphyrins linked to two or four coordinating macrocycles were synthesised. The "gathering-andthreading" effect of copper(I) was used to thread molecular rods through the rings; the subsequent introduction of stoppers led to the formation of rotaxanes. In the case of the porphyrinic bis-macrocycle a [4]rotaxane was obtained. Host/guest complexation studies with rigid nitrogen ligands showed that the rotaxane behaves as a distensible molecular receptor that can adopt an "inflated" or "deflated" conformation and adjust its shape to the size of the guest. In the case of the porphyrinic tetra-macrocycle the formation of a [3]rotaxane of novel architecture was observed.

The synthesis of a new, more rigid bis-macrocycle is in progress. This compound will be used for the construction of a [4]rotaxane that could act as a molecular press able to change the conformation of a guest substrate by compression.

Keywords: rotaxane, porphyrin, macrocycle, phenanthroline, bipyridine, copper(I), zinc(II), organic synthesis, coordination chemistry, template effect, host-guest chemistry, molecular receptor.