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This thesis summarises attempts towards polyyne [n]rotaxanes and cyclocarbon [n]catenanes. Carbon allotropes built purely from sp carbon atoms have long fascinated chemists but have yet to be isolated or characterised due to their high reactivity. This thesis documents work towards isolating both linear and cyclic sp carbon chains. Chapter 1 reviews the history of carbon allotropes, focussing on cyclic and linear forms of sp carbon. Synthetic strategies towards preparing acetylene-rich molecules, rotaxanes and catenanes are discussed. Chapter 2 discusses development of a novel masked alkyne equivalent (MAE) with intrinsic metal binding abilities. A simple masked triyne can be synthesised in only three steps, but photochemical unmasking of this group could not be realised due to a competing dimerisation process. Chapter 3 details new strategies for synthesising polyyne [3]rotaxanes with two macrocycles on the same polyyne thread. An active metal template route using dicobalt-masked precursors was developed to prepare two polyyne [3]rotaxanes. The thermal stabilities of the two rotaxanes were evaluated relative to the naked polyyne dumbbell and were found to be significantly more stable in decalin at 80 °C. Chapter 4 presents a novel approach to cyclocarbon [n]catenanes and polyyne [n]rotaxanes. The coupling of a [2]rotaxane bearing two temporary bulky MAE stoppers provides access to precursors of cyclocarbon [n]catenanes and polyyne [n]rotaxanes. Early unmasking experiments have successfully afforded a polyyne bearing 24 contiguous acetylene units and indicate that larger polyynes should be viable using this route. Chapter 5 summarises

Mechanically interlocked molecules (MIMs) have gained attention in the field of catalysis due to their unique molecular properties. Central to MIMs, rotaxanes are highly promising and attractive supramolecular catalysts due to their unique three‐dimensional structures and the flexibility of their subcomponents. This Minireview discusses the use of rotaxanes in organocatalysis and transition‐metal catalysis., Rotaxanes are highly promising and attractive supramolecular catalysts. They offer conceptually novel possibilities in catalysis, such as switchability, the generation of highly congested reaction spaces or the development of bifunctional catalyst systems. This Minireview describes recent advances in the use of rotaxanes in organo‐ and transition‐metal catalysis, classified by the role of the macrocycle in each catalyst system.

Crown ethers are common building blocks in supramolecular chemistry and are frequently applied as cation sensors or as subunits in synthetic molecular machines. Developing switchable and specifically designed crown ethers enables the implementation of function into molecular assemblies. Seven tailor-made redox-active crown ethers incorporating tetrathiafulvalene (TTF) or naphthalene diimide (NDI) as redox-switchable building blocks are described with regard to their potential to form redox-switchable rotaxanes. A combination of isothermal titration calorimetry and voltammetric techniques reveals correlations between the binding energies and redox-switching properties of the corresponding pseudorotaxanes with secondary ammonium ions. For two different weakly coordinating anions, a surprising relation between the enthalpic and entropic binding contributions of the pseudorotaxanes was discovered. These findings were applied to the synthesis of an NDI-[2]rotaxane, which retains similar spectroelectrochemical properties compared to the corresponding free macrocycle. The detailed understanding of the thermodynamic and electrochemical properties of the tailor-made crown ethers lays the foundation for the construction of new types of molecular redox switches with emergent properties.

Advances in supramolecular chemistry are often underpinned by the development of fundamental building blocks and methods enabling their interconversion. In this work, we report the use of an underexplored dynamic covalent reaction for the synthesis of stimuli-responsive [2]rotaxanes. The formamidinium moiety lies at the heart of these mechanically interlocked architectures, because it enables both dynamic covalent exchange and the binding of simple crown ethers. We demonstrated that the rotaxane self-assembly follows a unique reaction pathway and that the complex interplay between crown ether and thread can be controlled in a transient fashion by addition of base and fuel acid. Dynamic combinatorial libraries, when exposed to diverse nucleophiles, revealed a profound stabilizing effect of the mechanical bond as well as intriguing reactivity differences between seemingly similar [2]rotaxanes.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES Rotaxanes are widely studied for their ability to move one component relative to another. Intercomponent interactions are widely studied in solution and have been gaining more field in the crystalline solid state. Intermolecular interactions in rotaxanes are still a field to be explored. This emphasizes the importance of studying intercomponent and intermolecular interactions to understand the behavior of these molecules in the crystalline solid state. Therefore, this thesis uses rotaxanes as models to understand the formation of different crystalline phases and evaluate the influence of intercomponent and intermolecular interactions in the crystallization process. For a series of rotaxanes containing Leigh-type macrocycle, self-assembly, solvates, and the formation of different polymorphic phases were evaluated. A new series of [2]- and [3]rotaxanes with two stations was synthesized and evaluated regarding intercomponent and intermolecular interactions. The studied rotaxanes showed similar general stages of crystallization, in which in the first stage there is the formation of one-dimensional nuclei and, in less cases, dimers. A wide molecular complementarity was observed, with a high contact area and a large number of interaction paths in the formed nuclei, which prevent the occurrence of specific interactions capable of directing the formation of crystals. This behavior can be explained by the intrinsic molecular topology of rotaxane molecules. The participation of the solvent during crystallization was evaluated and showed that the solvent can be easily trapped between the one-dimensional and dimeric nuclei during the last stages of crystallization. In one example, it was observed that its topology favored the entrapment of water molecules between the rotaxanes that form the one-dimensional nucleus in the first crystallization stage, and not because of the nuclei approximation. Initial insights into the contribution of solvents to the stabilization energy of solvates have been provided. Different polymorphic forms, with the solvent and temperature conditions to obtain each phase, were reported. The key to understand the existence of polymorphs at room temperature lies in the first crystallization nuclei to be formed, as both have similar stabilization energies at this point. The two-station thread allowed to obtain molecules of [2]- and [3]rotaxanes as a function of small modification in the stoppers groups. New parameters and approaches at the intercomponent and intermolecular level, to guide the interpretation of self-assembly, solvates, and polymorphs of rotaxane molecules, have been provided. Os rotaxanos são amplamente estudados devido sua capacidade de um componente mover-se em relação ao outro. As interações intercomponentes são amplamente estudadas em solução e vem ganhando mais campo no estado sólido cristalino. Já as interações intermoleculares em rotaxanos permanecem ainda como um campo a ser explorado. Com isso, ressalta-se a importância de estudar as interações intercomponentes e intermoleculares como forma de entender o comportamento destas moléculas no estado sólido cristalino. Sendo assim, esta tese utiliza rotaxanos como modelos para compreender a formação de diferentes fases cristalinas e avaliar a influência das interações intercomponentes e intermoleculares no processo de cristalização. Para uma série de rotaxanos, contendo macrociclo do tipo Leigh, foram avaliadas a autoassociação, a formação de solvatos, a formação de diferentes fases polimórficas. Uma nova série de [2]- e [3]rotaxanos com duas estações foi sintetizada e avaliada as interações intercomponentes e intermoleculares. Os rotaxanos estudados apresentaram estágios gerais de cristalização semelhantes, em que no primeiro estágio ocorre a formação de núcleos unidimensionais e, em menos casos, de dímeros. Foi observado uma grande complementaridade molecular, com alta área de contato e grande número de caminhos de interação nos núcleos formados, o que dificulta a ocorrência de interações específicas capazes de direcionar a formação de cristais. Este comportamento pode ser explicado pela topologia molecular intrínseca das moléculas de rotaxano. A participação do solvente na cristalização foi avaliada e mostrou que o solvente pode ser facilmente preso entre os núcleos unidimensionais e diméricos durante as últimas etapas de cristalização. Em um exemplo, foi observado que a topologia favoreceu o aprisionamento de moléculas de água entre as moléculas de rotaxanos que formam o núcleo unidimensional no primeiro estágio de cristalização e não por consequência da aproximação dos núcleos. Percepções iniciais da contribuição de solventes na estabilização energética de solvatos foram fornecidas. Diferentes formas polimórficas, juntamente com as condições de solvente e temperatura para obter cada fase, foram reportadas. A chave para entender a existência dos polimorfos à temperatura ambiente está no primeiro núcleo de cristalização a ser formado, já que ambos têm energias de estabilização semelhantes neste ponto. O modelo de eixo molecular de duas estações permitiu a obtenção de moléculas de [2]- e [3]rotaxanos em função de pequena modificação no grupo volumoso terminal. Novos parâmetros e abordagens no nível intercomponente e intermolecular, para guiar a interpretação da autoassociação e da formação de solvatos e polimorfos de moléculas de rotaxanos, foram fornecidos.

Electrochemically controllable rotaxanes are prime examples of supramolecular switches and promising prototypes for artificial molecular machines. This perspective discusses recent progress and applications beyond classical molecular shuttles., Are they still electrifying? Electrochemically switchable rotaxanes are well known for their ability to efficiently undergo changes of (co-)conformation and properties under redox-control. Thus, these mechanically interlocked assemblies represent an auspicious liaison between the fields of molecular switches and molecular electronics. Since the first reported example of a redox-switchable molecular shuttle in 1994, improved tools of organic and supramolecular synthesis have enabled sophisticated new architectures, which provide precise control over properties and function. This perspective covers recent advances in the area of electrochemically active rotaxanes including novel molecular switches and machines, metal-containing rotaxanes, non-equilibrium systems and potential applications.

Rotaxanes are currently one of the most promising objects of study in the field of artificial molecular machines. A rotaxane molecule is composed by two or more molecular components that are connected by a mechanical bond. 51 years ago, the first synthesis of this type of molecules was performed, since then, there has been a great effort in obtaining new models to study its molecular movements and application as molecular machines. Here, we present an overview of intercomponent interactions in rotaxanes and how these interactions affect the major movements presented by this class of molecules. For this, different approaches to assess these interactions are discussed, both in solution and solid state.

Functional molecules such as proteins and enzymes are the basis for a plethora of complex biochemical functions and thus a central aim for research in biology, chemistry and physics. Nature uses these molecular switches, motors and pumps to convert energy into work or information. Following their natural models, artificial molecular machines (AMMs) are comparably small functional molecules or assemblies with the goal to convert energy into harnessable work. In fact, many of the recent examples for switches, motors and pumps are mechanically interlocked molecules (MIMs) such as rotaxanes and catenanes. Taming these sophisticated molecules promises compelling applications in catalysts and stimuli-responsive materials. Nethertheless, to achieve the complexity and functionality of natural nanomachines three main challenges need to be resolved: Introducing directionality to steer and utilize movement; gaining control over the kinetics of movement and controlling the assembly of complex molecules. This work focuses on the synthesis and characterization of electrochemically switchable (pseudo)rotaxanes and the analysis with regard to their use as molecular switches and functional molecules. These challenges were adressed in three projects using crown/ammonium rotaxanes. The MIMs are equipped with either a reversibly oxidizable tetrathiafulvalene (TTF), a naphthalene diimide (NDI) or both. In the first project, a new directional reversibly redox-switchable crown ether bound on a directional axle gave a new chiroptical switch, which is able reverse the electronic circular dichroism (ECD) spectrum upon oxidation. This observation could be rationalized to the change of electronic structure using quantumchemical calculations. In the second project, kinetic control over co-conformational changes of the macrocycle upon deprotonation or oxidation was investigated. Thereby, considerable differences between pseudorotaxanes and rotaxanes were determined. While deprotonation led to instantaneous dethreading or shuttling, only in case of the pseudorotaxanes oxidation of the macrocycle led to expulsion of the binding site. Finally, the third project was concerned with investigation of new redox-switchable crown ethers with different cavity sizes. Afterwards, a procedure to synthesize different self-sorted hetero[3]rotaxanes was established. Notably, only the redox properties of NDI-moieties were found to be sequence-specific. In conclusion, the results of this thesis broaden the versatility of chiral and non-chiral redox-switchable rotaxanes and describe a blueprint for the controlled synthesis of functional sequence-specific molecules. The three mentioned challenges directionality, controlled kinetics and assembly were addressed successfully., Proteine und Enzyme sind nat��rliche molekulare Maschinen und die Basis einer Vielzahl von komplexen biochemischen Funktionen. Als molekulare Schalter, Motoren und Pumpen wandeln sie Energie in Arbeit oder Information um. Um ihre Eigenschaften zu imitieren und f��r neue Prozesse zug��nglich zu machen, stehen sie im Fokus biologischer, chemischer und physikalischer Forschungsbereiche. Entsprechend ihrer nat��rlichen Vorbilder haben k��nstliche molekulare Maschinen das Ziel, Energie in nutzbare Arbeit umzuwandeln. Besonders vielversprechende Kandidaten f��r die Erreichung dieses Ziels sind mechanisch verzahnte Molek��le wie Rotaxane und Catenane. Aktuelle Beispiele in der Literatur zeigen bereits ihre vielversprechende Verwendbarkeit als Schalter, Motoren und Pumpen. Diese anspruchsvollen Molek��le zu perfektionieren, wird zu ungeahnten Anwendungen unter anderem in der Katalyse und in stimuli-responsiven Materialien f��hren. Um die Komplexit��t und Funktionalit��t der nat��rlichen Nanomaschinen zu erreichen, m��ssen noch mindestens drei Herausforderungen gemeistert werden: Die Einbindung von Direktionalit��t, um gerichtete Bewegung zu nutzen, die Erlangung der Kontrolle ��ber die Kinetik der Bewegung und die kontrollierte Assemblierung der komplexen Molek��le. Die vorliegende Promotionsarbeit befasst sich mit der Herstellung und Charakterisierung von elektrochemisch schaltbaren (Pseudo)rotaxanen und ihrer Verwendbarkeit als molekulare Schalter und Maschinen. Mittels Krone-Ammonium-Rotaxanen wurden die genannten Herausforderungen in drei Projekten angegangen und L��sungsans��tze pr��sentiert. Daf��r wurden mechanisch verzahnten Molek��le entweder mit einem reversibel oxidierbarem Tetrathiafulvalen (TTF), einem reversibel reduzierbarem Naphthalendiimid (NDI) oder mit beiden Bausteinen funktionalisiert. Im ersten Projekt konnte ein neuer chiroptischer Schalter durch die Auff��delung eines neuen direktionalen und reversibel oxidierbaren Kronenethers auf einer direktionalen Achse realisiert werden. Er ist in der Lage das Vorzeichen des elektronischen Zirkulardichroismus (ECD) durch Oxidation umzukehren. Mittels quantenchemischer Berechnungen konnte diese Beobachtung im ECD-Spektrum ��nderungen der elektronischen Struktur im Molek��l zugeschrieben werden. Im zweiten Projekt wurde der Einfluss der Kinetik auf co-konformationelle ��nderungen des Makrozyklus durch Deprotonierung oder Oxidation untersucht. Es konnten dabei erhebliche Unterschiede zwischen Rotaxanen und Pseudorotaxanen festgestellt werden. W��hrend Deprotonierung in allen untersuchten Beispielen zum sofortigen Abf��deln beziehungsweise Pendeln f��hrte, wurde der Makrozyklus durch Oxidation nur im Fall des Pseudorotaxans von der Bindungsstelle abgesto��en. Schlie��lich wurden im dritten Projekt neue redox-schaltbare Kronenether mit unterschiedlichen Ringgr����en untersucht. Anschlie��end wurde eine Vorschrift zur Herstellung verschiedener selbst-sortierter Hetero[3]rotaxane formuliert. Dabei ergab sich eine ��nderung der Redoxeigenschaften der NDI-Bausteine in Abh��ngigkeit von der Sequenz der beiden Reife auf der Achse des Rotaxans. Die Ergebnisse dieser Arbeit tragen zum allgemeinen Verst��ndnis der Synthese und Verwendbarkeit von chiralen und nicht-chiralen Rotaxanen bei und liefern zus��tzlich Ans��tze zur kontrollierten Herstellung von redoxschaltbaren, sequenzspezifischen Molek��len. Dabei wurden die genannten Herausforderungen ��� Direktionalit��t, kontrollierte Kinetik und Assemblierung ��� erfolgreich angegangen.

Rotaxane building blocks bearing 3,5‐bis(trifluoromethyl) benzenesulfonate (BTBS) stoppers have been efficiently prepared from a pillar[5]arene derivative, 3,5‐bis(trifluoromethyl) benzenesulfonyl chloride (BTBSCl) and different diols, namely 1,10‐decanediol and 1,12‐dodecanediol. The BTBS moieties of these compounds are good leaving groups and stopper exchange reactions could be achieved by treatment with different nucleophiles thus affording rotaxanes with ester, thioether or ether stoppers., Rotaxanes, just pop the stoppers: Rotaxane building blocks bearing 3,5‐bis(trifluoromethyl) benzenesulfonate (BTBS) stoppers have been efficiently prepared. The BTBS moieties of these compounds are good leaving groups allowing to perform stopper exchange by treatment with different nucleophiles to afford rotaxanes with ester, ether or thioether stoppers.

Heterobifunctional rotaxanes serve as efficient catalysts for the addition of malonates to Michael acceptors. We report a series of four different heterobifunctional rotaxanes, featuring an amine‐based thread and a chiral 1,1′‐binaphthyl‐phosphoric‐acid‐based macrocycle. High‐level DFT calculations provided mechanistic insights and enabled rational catalyst improvements, leading to interlocked catalysts that surpass their non‐interlocked counterparts in terms of reaction rates and stereoselectivities., Heterobifunctional rotaxanes, featuring an amine‐based thread and a macrocyclic chiral 1,1′‐binaphthyl‐phosphoric acid, serve as efficient organocatalysts for the stereoselective addition of malonates to Michael acceptors. High‐level DFT calculations provided mechanistic insights and enabled rational catalyst improvements, leading to interlocked catalysts that surpass their non‐interlocked counterparts in terms of reaction rates and stereoselectivities.

The interlocking of ring and axle molecular components in rotaxanes provides a way to combine chromophoric, electron-donor and electron-acceptor moieties in the same molecular entity, in order to reproduce the features of photosynthetic reaction centers. To this aim, the photoinduced electron transfer processes involving a 1,8-naphthalimide chromophore, embedded in several rotaxane-based dyads, were investigated by steady-state and time-resolved absorption and luminescence spectroscopic experiments in the 300 fs-10 ns time window. Different rotaxanes built around the dialkylammonium/ dibenzo[24]crown-8 ether supramolecular motif were designed and synthesized to decipher the relevance of key structural factors, such as the chemical deactivation of the ammonium-crown ether recognition, the presence of a secondary site for the ring along the axle, and the covalent functionalization of the macrocycle with a phenothiazine electron donor. Indeed, the conformational freedom of these compounds gives rise to a rich dynamic behavior induced by light and may provide opportunities for investigating and understanding phenomena that take place in complex (bio)molecular architectures.

The synthesis of a pair of switchable interlocked prolinamides and their use as organocatalysts in three different enamine-activated processes are reported. A diacylaminopyridine moiety was incorporated into the thread for directing [2]rotaxane formation further allowing the association of complementary small molecules. The rotaxane-based systems were tested as organocatalysts in asymmetric enamine-mediated processes, revealing a significantly improved catalytic ability if compared with the non-interlocked thread. The presence of an electron-withdrawing nitro group at the macrocycle helps to achieve high conversions and enantioselectivities. These systems are able to interact with N-hexylthymine as a cofactor to form supramolecular catalysts displaying a divergent catalytic behaviour. The presence or absence of the cofactor controls the chemoselectivity in competitive reactions., The mechanical bonding and the cofactor assembly in interlocked prolinamide-based organocatalysts upgrade enamine-type transformations by increasing their yields and enantio- and chemo-selectivities.

Chiral interlocked molecules in which the mechanical bond provides the sole stereogenic unit are typically produced with no control over the mechanical stereochemistry. Here we report a stereoselective approach to mechanically planar chiral rotaxanes in up to 98:2 d.r. using a readily available α‐amino acid‐derived azide. Symmetrization of the covalent stereocenter yields a rotaxane in which the mechanical bond provides the only stereogenic element.

In this proof‐of‐concept study, an active‐template coupling is used to demonstrate a novel kinetic self‐sorting process. This process iteratively increases the yield of the target heterocircuit [3]rotaxane product at the expense of other threaded species.

Facile synthesis of diverse rotaxanes was successfully realized through a simple and efficient supramolecular transformation strategy. Starting from an organometallic [3]rotaxane with a platinum-acetylide moiety as the bridge moiety and transformation site, employing a simple phosphine ligand exchange and sequential reductive elimination reactions resulted in the successful preparation of various rotaxanes with diverse structures and properties.

Stable pillar[5]arene-containing [2]rotaxane building blocks with pentafluorophenyl ester stoppers have been efficiently prepared on a multi-gram scale. Reaction of these building blocks with various nucleophiles gave access to a wide range of [2]rotaxanes with amide, ester or thioester stoppers in good to excellent yields. The rotaxane structure is fully preserved during these chemical transformations. Actually, the addition-elimination mechanism at work during these transformations totally prevents the unthreading of the axle moiety of the mechanically interlocked system. The stopper exchange reactions were optimized both in solution and under mechanochemical solvent-free conditions. While amide formation is more efficient in solution, the solvent-free conditions are more powerful for the transesterification reactions. Starting from a fullerene-functionalized pillar[5]arene derivative, this new strategy gave easy access to a photoactive [2]rotaxane incorporating a C60 moiety and two Bodipy stoppers. Despite the absence of covalent connectivity between the Bodipy and the fullerene moieties in this photoactive molecular device, efficient through-space excited state interactions have been evidenced in this rotaxane.

Molecular chirality provides a key challenge in host–guest recognition and other related chemical applications such as asymmetric catalysis. For a molecule to act as an efficient enantioselective receptor, it requires multi‐point interactions between host and chiral guest, which may be achieved by an appropriate chiral 3D scaffold. As a consequence of their interlocked structure, catenanes and rotaxanes may present such a 3D scaffold, and can be chiral by inclusion of a classical chiral element and/or as a consequence of the mechanical bond. This Minireview presents illustrative examples of chiral [2]catenanes and [2]rotaxanes, and discusses where these molecules have been used in chemical applications such as chiral host–guest recognition and asymmetric catalysis.

The anion-templated synthesis of three novel halogen-bonding 5-halo-1,2,3-triazolium axle containing [2]rotaxanes is described, and the effects of altering the nature of the halogen-bond donor atom together with the degree of inter-component preorganisation on the anion-recognition properties of the interlocked host investigated. The ability of the bromotriazolium motif to direct the halide-anion-templated assembly of interpenetrated [2]pseudorotaxanes was studied initially; bromide was found to be the most effective template. As a consequence, bromide anion templation was used to synthesise the first bromotriazolium axle containing [2]rotaxane, the anion-binding properties of which, determined by (1) H NMR spectroscopic titration experiments, revealed enhanced bromide and iodide recognition relative to a hydrogen-bonding protic triazolium rotaxane analogue. Two halogen-bonding [2]rotaxanes with bromo- and iodotriazolium motifs integrated into shortened axles designed to increase inter-component preorganisation were also synthesised. Anion (1) H NMR spectroscopic titration experiments demonstrated that these rotaxanes were able to bind halide anions even more strongly, with the iodotriazolium axle integrated rotaxane capable of recognising halides in aqueous solvent media. Importantly, these observations suggest that a halogen-bonding interlocked host binding domain, in combination with increased inter-component preorganisation, are requisite design features for a potent anion receptor.

[2] and [3] hybrid rotaxanes are reported based on {Ti7M} rings (M is a trivalent metal such as FeIII or GaIII). NMR studies show that [2]rotaxanes can act as molecular shuttles, while EPR studies of [3]rotaxanes show weak interactions between the paramagnetic components of the supramolecular assemblies.

Summary The mechanical bond has opened a new world for structural and dynamic stereochemistry, which is still largely underexplored and whose significance for various applications is becoming increasingly evident. We demonstrate that designed rearrangements involving both covalent and mechanical bonds can be integrated in [2]rotaxanes, leading to interesting consequences in terms of E/Z isomerization mechanisms. Two entirely distinct and concomitant stereomutations, pertaining to the same stereogenic element but involving different kinds of linkages within the molecule, are observed and are thoroughly characterized. The rate of the two processes is affected in opposite ways upon changing solvent polarity; such a phenomenon can be used to selectively modify the rate of each motion and adjust the relative contribution of the two mechanisms to the isomerization. Although the movements are not synchronized, an analysis of the intriguing fundamental implications for transition state theory, reaction pathway bifurcation, and microscopic reversibility was triggered by our experimental observations.

A [2]rotaxane was produced through the assembly of a picolinaldehyde, an amine, and a bipyridine macrocycle around a Cu(I) template by imine bond formation in close-to-quantitative yield. An analogous [3]rotaxane is obtained in excellent yield by replacing the amine with a diamine, thus showing the suitability of the system for the construction of higher order interlocked structures. The rotaxanes are formed within a few minutes simply through mixing the components in solution at room temperature and they can be isolated through removal of the solvent or precipitation.

The mechanical interlocking of molecular components can lead to the appearance of novel and unconventional properties and processes, with potential relevance for applications in nanoscience, sensing, catalysis, and materials science. We describe a [3]rotaxane in which the number of recognition sites available on the axle component can be changed by acid–base inputs, encompassing cases in which this number is larger, equal to, or smaller than the number of interlocked macrocycles. These species exhibit very different properties and give rise to a unique network of acid–base reactions that leads to a fine pKa tuning of chemically equivalent acidic sites. The rotaxane where only one station is available for two rings exhibits a rich coconformational dynamics, unveiled by an integrated experimental and computational approach. In this compound, the two crown ethers compete for the sole recognition site, but can also come together to share it, driven by the need to minimize free energy without evident inter-ring interactions.

Selective monofunctionalization of substrates with distant, yet equally-reactive functional groups is difficult to achieve, as it requires the second functional group to selectively modulate its reactivity once the first functional group has reacted. We now show that mechanically-interlocked catalytic rings can effectively regulate the reactivity of stoppering groups in rotaxanes over a distance of ~2 nm. Our mechanism of communication is enabled by a unique interlocked design, which effectively removes the catalytic rings from the substrates via fast dethreading, as soon as the first reaction has taken place. Our method not only led to a rare example of selective monofunctionalization, but also to a “molecular if function”. Overall, the results reported in this research article present a way to get distant functional groups to communicate with each other in a reaction-history-dependent manner to create linkers that can ultimately perform logical operations at the molecular level.

We report the stepwise assembly of supramolecular daisy chain rotaxanes (DCR) made of double‐stranded DNA: Small dsDNA macrocycles bearing an axle assemble into a pseudo‐DCR precursor that was connected to rigid DNA stoppers to form DCR with the macrocycles hybridized to the axles. In presence of release oligodeoxynucleotides (rODNs), the macrocycles are released from their respective hybridization sites on the axles, leading to stable mechanically interlocked DCRs. Besides the expected threaded DCRs, certain amounts of externally hybridized structures were observed, which dissociate into dumbbell structures in presence of rODNs. We show that the genuine DCRs have significantly higher degrees of freedom in their movement along the thread axle than the hybridized DCR precursors. Interlocking of DNA in DCRs might serve as a versatile principle for constructing functional DNA nanostructures where the movement of the subunits is restricted within precisely confined tolerance ranges.

The work herein describes the synthesis and characterization of rotaxane molecules, the incorporation of a selection of these molecules into metal-organic frameworks (MOFs), and the study of how these rotaxanes respond to external stimuli such as changes in temperature and chemical environment, both in solution and when immobilized inside a MOF. Chapter 1 introduces the concepts utilized during this work and presents a general overview of the state of the field. Chapter 2 describes the fabrication of the first porphyrin-based MOFs incorporating a rotaxane linker, UWDM-7 and -8. Their structures were analyzed by single-crystal X-ray diffraction (SC-XRD), powder X-ray diffraction (PXRD), and the rotational dynamics of the crown ether rings were studied with variable temperature (VT) 2H solid-state nuclear magnetic resonance spectroscopy (SSNMR). It was found that the rotation of these rings could be controlled by modifying the rigidity of the framework and by adding/removing guest solvent molecules within the pores of the materials. Chapter 3 presents an initial approach to the use of reticular chemistry applied to MOFs containing mechanically interlocked molecules and porphyrins. The synthesis of two porphyrin linkers is described. Another example of a mixed-linker MOF, UWDM-9, is presented and its structural features are described. The topological analysis of UWDM-9 resulted in the report of the first occurrence of the tui topology. Preliminary VT 2H SSNMR studies are presented, and they a show lower activation energy for the partial rotation of the crown ether macrocycles compared to other UWDM MOFs. Chapter 4 describes a new method for the synthesis of rotaxanes with high compositional complexity. [5]Rotaxanes were synthesized using a capping method in a one-pot reaction that also creates a porphyrin core. This new synthetic route allows for the incorporation of various substituent groups on these molecules, different crown ether molecules, as well as recognition sites. Six [5]rotaxanes are presented and characterized using XRD, NMR spectroscopy, and mass spectrometry. In Chapter 5, some of these [5]rotaxanes are tested as linkers in the synthesis of MOFs. The process to decide the conditions to test and which structures to target is described, along with simulations supporting some of the findings. Finally, Chapter 6 puts the findings of this work in retrospect and analyzes potential future work derived from this dissertation and contemplates the directions the broader field might take.

Bistable [ c2]daisy chain rotaxanes represent a particularly intriguing class of interlocked molecules that can produce internal sliding movements with a net contraction or extension at the single-molecule level. These nanometric motions show some analogies with the sliding motions of actin and myosin filaments in sarcomeres, and this is why [ c2]daisy chain rotaxanes have been also named as “molecular muscles,” as their first synthesis in 2000. In this minireview, the authors discuss the recent history of these molecules, their modular chemical structures, and the various synthetic pathways described in the literature to access them. The authors also detail how their internal motions can be controlled and characterized by a number of chemical and physical tools. The authors finally show that their integration within polymers and materials can give access to synchronized motions and amplifications up to the macroscopic scale. Overall, the numerous examples that have been described in the literature to date demonstrate that this family of molecules has already strongly influenced the entire field of research on artificial molecular machines, and has the potential to be implemented as actuators working at all scales, from nanometric-switchable devices to mechanically active soft matter materials.

We report a family of hybrid [2]rotaxanes based on inorganic [Cr7NiF8(O2C t Bu)16]- ("{Cr7Ni}") rings templated about organic threads that are terminated at one end with pyridyl groups. These rotaxanes can be coordinated to [Cu(hfac)2] (where Hhfac = 1,1,1,5,5,5-hexafluoroacetylacetone), to give 1:1 or 1:2 Cu:{Cr7Ni} adducts: {[Cu(hfac)2](py-CH2NH2CH2CH2Ph)[Cr7NiF8(O2C t Bu)16]}, {[Cu(hfac)2][py-CH2NH2CH2CH3][Cr7NiF8(O2C t Bu)16]}, {[Cu(hfac)2]([py-CH2CH2NH2CH2C6H4SCH3][Cr7NiF8(O2C t Bu)16])2}, {[Cu(hfac)2]([py-C6H4-CH2NH2(CH2)4Ph][Cr7NiF8(O2C t Bu)16])2}, and {[Cu(hfac)2]([3-py-CH2CH2NH2(CH2)3SCH3][Cr7NiF8(O2C t Bu)16])2}, the structures of which have been determined by X-ray diffraction. The {Cr7Ni} rings and CuII ions both have electronic spin S = 1/2, but with very different g-values. Continuous-wave EPR spectroscopy reveals the exchange interactions between these dissimilar spins, and hence the communication between the different molecular components that comprise these supramolecular systems. The interactions are weak such that we observe AX or AX2 type spectra. The connectivity between the {Cr7Ni} ring and thread terminus is varied such that the magnitude of the exchange interaction J can be tuned. The coupling is shown to be dominated by through-bond rather than through-space mechanisms.

Threading a molecular needle: An α-hemolysin transmembrane pore can be threaded in a desired orientation by DNA-poly(ethylene glycol) (DNA-PEG) hybrid strands to yield functional rotaxanes (see figure). The single-molecule rotaxanes are stable and have a reversible two-state switching capacity that depends on the applied potential, orientation, and method of threading and capture used.

Electron-deficient heavy chalcogen atoms contain Lewis acidic σ-holes which are able to form attractive supramolecular interactions, known as chalcogen bonding (ChB), with Lewis bases. However, their potential in solution-phase anion binding applications is only just beginning to be realized in simple acyclic systems. Herein, we explore the 5-(methylchalcogeno)-1,2,3-triazole (chalcogen = Se, Te) motif as a novel ChB donor for anion binding. Other than being chemically robust enough to be incorporated into macrocyclic structures, thereby significantly expanding the scope and complexity of ChB host systems, we also demonstrate, by 1H NMR and DFT calculations, that the chalcogen atoms oriented within the macrocycle cavity are able to chelate copper(I) endotopically. Exploiting this property, the first examples of mechanically interlocked [2]rotaxanes containing ChB-donor groups are prepared via an active metal template strategy. Solution-phase 1H NMR and molecular modeling studies provide compelling evidence for the dominant influence of ChB in anion binding by these interlocked host systems. In addition, unprecedented charge-assisted ChB-mediated anion binding was also studied in aqueous solvent mixtures, which revealed considerable differences in anion recognition behavior in comparison with chalcogen-free host analogues. Moreover, DFT calculations and molecular dynamics simulations in aqueous solvent mixtures indicate that the selectivity is determined by the different hydrophilic characters of the anions allied to the hydration of the binding units in the presence of the anions. Exploiting the NMR-active nuclei of the ChB-donor chalcogen atoms, heteronuclear 77Se and 125Te NMR were used to directly study how anion recognition influences the local electronic environment of the chalcogen atoms in the mechanically bonded rotaxane binding sites in organic and aqueous solvent mixtures.

Proteins adopt complex folds in nature that typically avoid conformations that are knotted or “threaded” through closed loops. Is this the result of fundamental barriers to folding, or have proteins simply evolved to avoid threaded conformations? Organic synthesis has been used in supramolecular chemistry to install topological links in small molecules. By following these principles, we now show that it is possible to assemble a topologically linked protein complex by threading a linear protein through a cyclic protein to form a [2]pseudo-rotaxane. Subsequent ring closure using native chemical ligation cyclizes the linear protein, forming a [2]heterocatenane. Although the kinetics of protein threading are slower than the folding kinetics of the native protein, threading appears to be a highly efficient process.

Mechanically interlocked supramolecular assemblies are appealing building blocks for creating functional nanodevices. Herein, we describe the multistep assembly of large DNA origami rotaxanes that are capable of programmable structural switching. We validated the topology and structural integrity of these rotaxanes by analyzing the intermediate and final products of various assembly routes by electrophoresis and electron microscopy. We further analyzed two structure-switching behaviors of our rotaxanes, which are both mediated by DNA hybridization. In the first mechanism, the translational motion of the macrocycle can be triggered or halted at either terminus. In the second mechanism, the macrocycle can be elongated after completion of the rotaxane assembly, giving rise to a unique structure that is otherwise difficult to access.