Hypervalent Iodine Based Reversible Covalent Bond in Rotaxane Synthesis

Reversible covalent bonds play a significant role in achieving the high‐yielding synthesis of mechanically interlocked molecules. Still, only a handful of such bonds have been successfully employed in synthetic procedures. Herein, we introduce a novel approach for the fast and simple preparation of interlocked molecules, combining the dynamic bond character of bis(acyloxy)iodate(I) anions with macrocyclic bambusuril anion receptors. The proof of principle was demonstrated on rotaxane synthesis, with near‐quantitative yields observed in both the classical and “in situ” approach. The rotaxane formation was confirmed in the solid‐state and solution by the X‐ray and NMR studies. Our novel approach could be utilized in the fields of dynamic combinatorial chemistry, supramolecular polymers, or molecular machines, as well inspire further research on molecules that exhibit dynamic behavior, but owing to their high reactivity, have not been considered as constituents of more elaborate supramolecular structures.     

Dynamic Covalent Synthesis of Donor–Acceptor Interlocked Architectures in Solution and at the Solution:Surface Interface

Despite advances in the range of mechanically interlocked architectures that can be synthesized and operated as supramolecular machines, motors and sensors in solution, in many cases their synthesis is laborious and expensive requiring long multistep pathways with extensive purification at each stage. Dynamic covalent chemistry has been shown to overcome problems with traditional kinetically controlled synthetic approaches that often afford low yields of interlocked architectures due to irreversible formation of non‐interlocked by‐products. Herein, we describe the use of reversible disulfide exchange reactions as a means to assemble catenanes and rotaxanes in organic solutions. Moreover, the application of this thermodynamic approach to assemble interlocked architectures at the solution:surface interface, specifically polymer resins, is discussed.     

Cooperative self-assembly: producing synthetic polymers with precise and concise primary structures

The quest to construct mechanically interlocked polymers, which present precise monodisperse primary structures that are produced both consistently and with high efficiencies, has been a daunting goal for synthetic chemists for many years. Our ability to realise this goal has been limited, until recently, by the need to develop synthetic strategies that can direct the formation of the desired covalent bonds in a precise and concise fashion while avoiding the formation of unwanted kinetic by-products. The challenge, however, is a timely and welcome one, as a consequence of, primarily, the potential for mechanically interlocked polymers to act as dynamic (noncovalent) yet robust (covalent) new materials for a wide array of applications. One such strategy which has been employed widely in recent years to address this issue, known as Dynamic Covalent Chemistry (DCC), is a strategy in which reactions operate under equilibrium and so offer elements of "proof-reading" and "error-checking" to the bond forming and breaking processes such that the final product distribution always reflects the thermodynamically most favourable compound. By coupling DCC with template-directed protocols, which utilise multiple weak noncovalent interactions to pre-organise and self-assemble simpler small molecular precursors into their desired geometries prior to covalent bond formation, we are able to produce compounds with highly symmetric, robust and complex topologies that are otherwise simply unobtainable by more traditional methods. Harnessing these strategies in an iterative, step-wise fashion brings us ever so much closer towards perfecting the controlled synthesis of high order main-chain mechanically interlocked polymers. This tutorial review focuses (i) on the development of DCC-namely, the formation of dynamic imine bonds-used in conjunction with template-directed protocols to afford a variety of mechanically interlocked molecules (MIMs) and ultimately (ii) on the synthesis of highly ordered poly[n]rotaxanes with high conversion efficiencies.     

De Novo Construction of Catenanes with Dissymmetric Cages by Space‐Discriminative Post‐Assembly Modification

Considerable efforts have been made to increase the topological complexity of mechanically interlocked molecules over the years. Three‐dimensional catenated structures composed of two or several (usually symmetrical) cages are one representative example. However, owing to the lack of an efficient universal synthetic strategy, interlocked structures made up of dissymmetric cages are relatively rare. Since the space volume of the inner cavity of an interlocked structure is smaller than that outside it, we developed a novel synthetic approach with the voluminous reductant NaBH(OAc)₃ that discriminates this space difference, and therefore selectively reduces the outer surface of a catenated dimer composed of two symmetric cages, thus yielding the corresponding catenane with dissymmetric cages. Insight into the template effect that facilitates the catenation of cages was provided by computational and experimental techniques.     

Covalent Organic Frameworks: Chemical Approaches to Designer Structures and Built‐In Functions

A new approach has been developed to design organic polymers using topology diagrams. This strategy enables covalent integration of organic units into ordered topologies and creates a new polymer form, that is, covalent organic frameworks. This is a breakthrough in chemistry because it sets a molecular platform for synthesizing polymers with predesignable primary and high‐order structures, which has been a central aim for over a century but unattainable with traditional design principles. This new field has its own features that are distinct from conventional polymers. This Review summarizes the fundamentals as well as major progress by focusing on the chemistry used to design structures, including the principles, synthetic strategies, and control methods. We scrutinize built‐in functions that are specific to the structures by revealing various interplays and mechanisms involved in the expression of function. We propose major fundamental issues to be addressed in chemistry as well as future directions from physics, materials, and application perspectives.     

Synthesizing interlocked molecules dynamically

As the complexity of mechanically interlocked molecular architectures increases, it is important to understand the underlying principles, such as molecular recognition and self‐assembly processes, that govern the practice of template‐directed synthesis necessary to create these particular compounds. In this review, we explain the importance of dynamic processes in the synthesis of mechanically interlocked compounds. We show how many different dynamic covalent bonds have been used in the synthesis of rotaxanes, catenanes, and other higher‐order mechanically interlocked compounds, with the goal of revealing the state of the art in dynamic covalent chemistry. © 2009 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 9: 136–154; 2009: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.20173     

Selective Synthesis of Discrete Mono‐, Interlocked‐, and Borromean Ring Ensembles Based on a π‐Electron‐Deficient Ligand

Herein, we present a new synthetic approach to achieve selective supramolecular transformations and construct different interlocked metallacycles featuring a π‐electron‐deficient thiazolo[5,4‐d]thiazole‐derived ligand. We demonstrate that the formation of mono‐rings, interlocked rings ([2]catenanes) and Borromean rings can be controlled by adjusting the length of the binuclear half‐sandwich Rh^III and Ir^III building blocks. Furthermore, a concentration effect or D‐A stacking interaction between the pyrene guest and the thiazolo[5,4‐d]thiazole‐based ligand promotes a unique and reversible conversion between catenane structures and metalla‐rectangles. The synthetic results are supported by single‐crystal X‐ray diffraction analysis.     

De Novo Construction of Catenanes with Dissymmetric Cages by Space-Discriminative Post-Assembly Modification

Considerable efforts have been made to increase the topological complexity of mechanically interlocked molecules over the years. Three-dimensional catenated structures composed of two or several (usually symmetrical) cages are one representative example. However, owing to the lack of an efficient universal synthetic strategy, interlocked structures made up of dissymmetric cages are relatively rare. Since the space volume of the inner cavity of an interlocked structure is smaller than that outside it, we developed a novel synthetic approach with the voluminous reductant NaBH(OAc)₃ that discriminates this space difference, and therefore selectively reduces the outer surface of a catenated dimer composed of two symmetric cages, thus yielding the corresponding catenane with dissymmetric cages. Insight into the template effect that facilitates the catenation of cages was provided by computational and experimental techniques.     

One‐Step Formation of “Chain‐Armor”‐Stabilized DNA Nanostructures

DNA‐based self‐assembled nanostructures are widely used to position organic and inorganic objects with nanoscale precision. A particular promising application of DNA structures is their usage as programmable carrier systems for targeted drug delivery. To provide DNA‐based templates that are robust against degradation at elevated temperatures, low ion concentrations, adverse pH conditions, and DNases, we built 6‐helix DNA tile tubes consisting of 24 oligonucleotides carrying alkyne groups on their 3′‐ends and azides on their 5′‐ends. By a mild click reaction, the two ends of selected oligonucleotides were covalently connected to form rings and interlocked DNA single strands, so‐called DNA catenanes. Strikingly, the structures stayed topologically intact in pure water and even after precipitation from EtOH. The structures even withstood a temperature of 95 °C when all of the 24 strands were chemically interlocked.     

Fast Pirouetting Motion in a Pyridine Bisamine‐Containing Copper‐Complexed Rotaxane

The present work reports the introduction of pyridine bisamine terdentate ligands in the structure of a pirouetting copper rotaxane. Rotaxane 2 [PF₆] constitutes the first example of the incorporation of imine‐based dynamic covalent chemistry in the synthesis of switchable copper‐complexed interlocked systems. In this rotaxane, the substitution of the classical terpyridine terdentate unit by a pyridine bisamine moiety has led to a significant stabilization of the pentacoordinated site. That fact has been evidenced by EPR spectroscopy and cyclic voltammetry. Regarding the tetracoordinated site, the congestion around the coordination sphere has been reduced to accelerate the typically slow reorganization of the Cu^II. Ethynyl‐3,8‐substitution on the axis phenanthroline along with the 2,9‐diphenyl‐1,10‐phenanthroline (dpp) present in the macrocycle afforded a very stable coordination environment for Cu^I, which is at the same time labile upon oxidation. In summary, the incorporation of a pyridine bisamine unit as a terdentate ligand and the optimization of the bidentate ligand of the axle not only has led to a simplification of the synthetic procedures, but it has also given rise to a bistable systems with an enhanced energetic separation between states and an acceleration of the reorganization processes. Thus far, rotaxane 2 [PF₆] presents the fastest switching cycle reported to date in copper‐interlocked dynamic systems.     

Interpenetrated Cage Structures

This Review covers design strategies, synthetic challenges, host–guest chemistry, and functional properties of interlocked supramolecular cages. Some dynamic covalent organic structures are discussed, as are selected examples of interpenetration in metal–organic frameworks, but the main focus is on discrete coordination architectures, that is, metal‐mediated dimers. Factors leading to interpenetration, such as geometry, flexibility and chemical makeup of the ligands, coordination environment, solvent effects, and selection of suitable counter anions and guest molecules, are discussed. In particular, banana‐shaped bis‐pyridyl ligands together with square‐planar metal cations have proven to be suitable building blocks for the construction of interpenetrated double‐cages obeying the formula [M₄L₈]. The peculiar topology of these double‐cages results in a linear arrangement of three mechanically coupled pockets. This allows for the implementation of interesting guest encapsulation effects such as allosteric binding and template‐controlled selectivity. In stimuli‐responsive systems, anionic triggers can toggle the binding of neutral guests or even induce complete structural conversions. The increasing structural and functional complexity in this class of self‐assembled hosts promises the construction of intelligent receptors, novel catalytic systems, and functional materials.     

Front Cover: Dynamic Covalent Chemistry for Synthesis and Co-conformational Control of Mechanically Interlocked Molecules (Eur. J. Org. Chem. 8/2023)

Mechanically interlocked molecules have found extensive applications in areas all across the physical sciences, from materials to catalysis and sensing. However, introducing mechanical bonds and entanglements at the molecular level is still a significant challenge due to the inherent restriction in entropy needed to preorganize strands before interlocking. Over the last decade, dynamic covalent chemistry has emerged as one of the most efficient methods of forming rotaxanes, catenanes and molecular knots. By using reversible bonds such as imines, disulfides and boronate esters, one can use the inherent error-correction in these linkages to form interlocked architectures with high fidelity and often in excellent yields. This review reports on recent advances in the use of dynamic covalent chemistry to make mechanically interlocked molecules, systematically surveying clipping, capping and templating approaches with dynamic bonds. Furthermore, it is also discussed how dynamic bonds can be used to control motion, co-conformational expression and catalytic activity in mechanically interlocked molecular machinery.     

Dynamic covalent chemistry

Dynamic covalent chemistry relates to chemical reactions carried out reversibly under conditions of equilibrium control. The reversible nature of the reactions introduces the prospects of "error checking" and "proof-reading" into synthetic processes where dynamic covalent chemistry operates. Since the formation of products occurs under thermodynamic control, product distributions depend only on the relative stabilities of the final products. In kinetically controlled reactions, however, it is the free energy differences between the transition states leading to the products that determines their relative proportions. Supramolecular chemistry has had a huge impact on synthesis at two levels: one is noncovalent synthesis, or strict self-assembly, and the other is supramolecular assistance to molecular synthesis, also referred to as self-assembly followed by covalent modification. Noncovalent synthesis has given us access to finite supermolecules and infinite supramolecular arrays. Supramolecular assistance to covalent synthesis has been exploited in the construction of more-complex systems, such as interlocked molecular compounds (for example, catenanes and rotaxanes) as well as container molecules (molecular capsules). The appealing prospect of also synthesizing these types of compounds with complex molecular architectures using reversible covalent bond forming chemistry has led to the development of dynamic covalent chemistry. Historically, dynamic covalent chemistry has played a central role in the development of conformational analysis by opening up the possibility to be able to equilibrate configurational isomers, sometimes with base (for example, esters) and sometimes with acid (for example, acetals). These stereochemical "balancing acts" revealed another major advantage that dynamic covalent chemistry offers the chemist, which is not so easily accessible in the kinetically controlled regime: the ability to re-adjust the product distribution of a reaction, even once the initial products have been formed, by changing the reaction's environment (for example, concentration, temperature, presence or absence of a template). This highly transparent, yet tremendously subtle, characteristic of dynamic covalent chemistry has led to key discoveries in polymer chemistry. In this review, some recent examples where dynamic covalent chemistry has been demonstrated are shown to emphasise the basic concepts of this area of science.     

Strategies and tactics for the metal-directed synthesis of rotaxanes, knots, catenanes, and higher order links

More than a quarter of a century after the first metal template synthesis of a [2]catenane in Strasbourg, there now exists a plethora of strategies available for the construction of mechanically bonded and entwined molecular level structures. Catenanes, rotaxanes, knots and Borromean rings have all been successfully accessed by methods in which metal ions play a pivotal role. Originally metal ions were used solely for their coordination chemistry; acting either to gather and position the building blocks such that subsequent reactions generated the interlocked products or by being an integral part of the rings or "stoppers" of the interlocked assembly. Recently the role of the metal has evolved to encompass catalysis: the metal ions not only organize the building blocks in an entwined or threaded arrangement but also actively promote the reaction that covalently captures the interlocked structure. This Review outlines the diverse strategies that currently exist for forming mechanically bonded molecular structures with metal ions and details the tactics that the chemist can utilize for creating cross-over points, maximizing the yield of interlocked over non-interlocked products, and the reactions-of-choice for the covalent capture of threaded and entwined intermediates.     

Homodiselenacalix[4]arenes: Molecules with Unique Channelled Crystal Structures

A synthetic route towards homodiselenacalix[4]arene macrocycles is presented, based on the dynamic covalent chemistry of diselenides. The calixarene inner rim is decorated with either alkoxy or tert‐butyl ester groups. Single‐crystal X‐ray analysis of two THF solvates with methoxy and ethoxy substituents reveals the high similarity of their molecular structures and alterations on the supramolecular level. In both crystal structures, solvent channels are present and differ in both shape and capacity. Furthermore, the methoxy‐substituted macrocycle undergoes a single‐crystal‐to‐single‐crystal transformation during which the molecular structure changes its conformation from 1,3‐alternate (loaded with THF/water) to 1,2‐alternate (apohost form). Molecular modelling techniques were applied to explore the conformational and energetic behaviour of the macrocycles.     

Mechanically Interlocked Single‐Wall Carbon Nanotubes

Extensive research has been devoted to the chemical manipulation of carbon nanotubes. The attachment of molecular fragments through covalent‐bond formation produces kinetically stable products, but implies the saturation of some of the C? C double bonds of the nanotubes. Supramolecular modification maintains the structure of the SWNTs but yields labile species. Herein, we present a strategy for the synthesis of mechanically interlocked derivatives of SWNTs (MINTs). In the key rotaxane‐forming step, we employed macrocycle precursors equipped with two π‐extended tetrathiafulvalene SWNT recognition units and terminated with bisalkenes that were closed around the nanotubes through ring‐closing metathesis (RCM). The mechanically interlocked nature of the derivatives was probed by analytical, spectroscopic, and microscopic techniques, as well as by appropriate control experiments. Individual macrocycles were observed by HR STEM to circumscribe the nanotubes.     

Solvent-Controlled Quadruple Catenation of Giant Chiral [8+12] Salicylimine Cubes Driven by Weak Hydrogen Bonding

Mechanically interlocked structures are fascinating synthetic targets and the topological complexity achieved through catenation offers numerous possibilities for the construction of new molecules with exciting properties. In the structural space of catenated organic cage molecules, only few examples have been realized so far, and control over the catenation process in solution is still barely achieved. Herein, we describe the formation of a quadruply interlocked catenane of giant chiral [8+12] salicylimine cubes. The formation could be controlled by the choice of solvent used in the reaction. The interlocked structure was unambiguously characterized by single crystal X-ray diffraction and weak hydrogen bonding was identified as a central driving force for the catenation. Furthermore, scrambling experiments using partially deuterated cages were performed, revealing that the catenane formation occurs through mechanical interlocking of preformed single cages.     

Solution‐Phase Dynamic Assembly of Permanently Interlocked Aryleneethynylene Cages through Alkyne Metathesis

Highly stable permanently interlocked aryleneethynylene molecular cages were synthesized from simple triyne monomers using dynamic alkyne metathesis. The interlocked complexes are predominantly formed in the reaction solution in the absence of any recognition motif and were isolated in a pure form using column chromatography. This study is the first example of the thermodynamically controlled solution‐phase synthesis of interlocked organic cages with high stability.     

Pillararene‐Based Assemblies: Design Principle,Preparation and Applications

In this review, we highlight recent advancements on pillararene‐based assemblies. The driving forces for the formation of the pillararene‐based assemblies are discussed first. The host–guest interactions are deemed as not only general strategy for constructing assemblies but also essential components for preventing the assemblies from the dissociation. Solvent effect is also important in the assembling process, since it could influence the host–guest interactions and provide solvophobic effect on pillararenes for the assembly. Then, several pillararene‐based assembly architectures are introduced, including pillararene‐based interlocked structures, such as (poly)pseudorotaxanes, (poly)rotaxanes, and daisy chains, classified by their topological structures and synthetic strategy. The morphologies of the supramolecular assemblies are divided into several types, for example, nanospheres, nanotubes and supramolecular polymers. Furthermore, the functions and potential applications are summarized accompanied with related assembly structures. The review not only provides fundamental findings, but also foresights future research directions in the research area of pillararene‐based assemblies.     

Nucleic Acid/Organic Polymer Hybrid Materials: Synthesis,Superstructures, and Applications

Extensive efforts have been devoted to the development of hybrid structures consisting of biomacromolecules and organic polymers connected through covalent bonds. While the combination of proteins and peptides with synthetic macromolecules has been explored in depth, far fewer examples of nucleic acid/polymer hybrids are known. In this Review we give selected examples of this exciting class of materials which can be arranged as linear block copolymer architectures, as side‐chain polymers, or as cross‐linked networks. Emphasis is placed on the fabrication of these materials as well as on their potential applications in nanoscience, diagnostics, and biomedicine.