Cyclodextrin‐Based Size‐Complementary [3]Rotaxanes: Selective Synthesis and Specific Dissociation

α‐Cyclodextrin (CD)‐based size‐complementary [3]rotaxanes with alkylene axles were prepared in one‐pot by end‐capping reactions with aryl isocyanates in water. The selective formation of [3]rotaxane with a head‐to‐head regularity was indicated by the X‐ray structural analyses. Thermal degradation of the [3]rotaxanes bearing appropriate end groups proceeded by stepwise dissociation to yield not only the original components but also [2]rotaxanes. From the kinetic profiles of the deslippage, it turned out that the maximum yield of [2]rotaxane was estimated to be 94 %. Thermodynamic studies and NOESY analyses of such rotaxanes revealed that [2]rotaxanes are specially stabilized, and that the dissociation capability of the [3]rotaxanes to the components can be adjusted by controlling the structure of the end groups, direction of the CD groups, and length of the alkylene axle.     

Structural Analysis and Inclusion Mechanism of Native and Permethylated α‐Cyclodextrin‐Based Rotaxanes Containing Alkylene Axles

Native α‐cyclodextrin‐ (α‐CD) and permethylated α‐CD (PMeCD)‐based rotaxanes with various short alkylene chains as axles can be synthesized through a urea end‐capping method. Native α‐CD tends to form [3]‐ or [5]pseudorotaxanes and not [2]‐ or [4]pseudorotaxanes, which indicates that the coupled CDs act as a single fragment. End‐capping reactions of the pseudorotaxanes with C18 and C24 axle lengths do not occur because the axle termini are covered by the densely stacked CDs. The number of PMeCDs on the pseudorotaxane is flexible and mainly depends on the axle length. Peracetylated α‐CD (PAcCD)‐based rotaxanes are synthesized through O‐acetylation of the α‐CD‐based rotaxanes without any decomposition of the rotaxanated structures. The structures of PMeCD‐based [3]‐ and [4]rotaxanes, and the molecular dynamics calculations on [3]pseudorotaxanes, indicate that the tail face of PMeCDs is regularly directed toward the axle termini. On the basis of the results obtained, it can be concluded that the directions and numbers of CDs in rotaxanes containing short alkylene chains depend on 1) the interactions between CDs, 2) the length of the alkylene axle, and 3) the interactions between the axle end and tail face of the CD.     

Light‐Switchable Janus [2]Rotaxanes Based on α‐Cyclodextrin Derivatives Bearing Two Recognition Sites Linked with Oligo(ethylene glycol)

Two Janus [2]rotaxanes, 5a and 5b , with α‐cyclodextrin (α‐CD) derivatives substituted on the 6‐position with two recognition sites (azobenzene and heptamethylene (C7)) that were linked with linkers of different lengths (oligo(ethylene glycol) with a degree of polymerization equal to 2 or approximately 21) were synthesized and characterized. 2D ROESY NMR spectroscopy and circular dichroism (cd) spectra demonstrated that the recognition site of the α‐CD moiety was switched by photoisomerization of the azobenzene moiety in 5a and 5b . The different size changes of 5a and 5b in hydrodynamic radius (R_H) owing to the different length of linker between two recognition sites were observed by pulse‐field‐gradient spin‐echo NMR spectroscopy. The kinetic results indicated that the different length of linker had no or a weak effect for the photoisomerization process of 5a and 5b .     

Discriminating Influence of α‐ and Methylated β‐Cyclodextrins on Complexation and Polymerization of Diacrylate and Dimethacrylate Monomers

Summary: Host‐guest complexes of α‐cyclodextrin (α‐CD) and methylated β‐cyclodextrin (Me‐β‐CD) with diacrylates and dimethacrylates of butan‐1,4‐diol and hexan‐1,6‐diol at varying stoichiometries were studied. The complexes were analyzed by means of ¹H NMR, two‐dimensional ROESY spectroscopy and Job's curves, which clearly revealed the discriminating influence of the two hosts towards complex formation. The corresponding polymers were obtained using a redox initiator system in water. Thermal analysis and IR measurements of the polymers provided evidence for the existence of a polyrotaxane architecture.

Proposed structure of the cross‐linked polymers obtained by the redox polymerization of the Me‐β‐CD complexed monomers.     

Synthesis of α‐Cyclodextrin‐Conjugated Poly(ε‐lysine)s and Their Inclusion Complexation Behavior

Novel functional polymers utilizing specific host/guest interactions were designed by introducing α‐CD host molecules into poly(ε‐lysine) chains as side groups. An interesting phase separation was observed as a result of the inclusion complexation between the polymeric host and 3‐(trimethylsilyl)propionic acid as a model guest in aqueous media. This water‐soluble polymeric host would be useful for various applications, particularly drug delivery, due to its biodegradability, low toxicity, and unique functionality represented as a complexation‐induced phase separation.     

Logic Gating by Macrocycle Displacement Using a Double‐Stranded DNA [3]Rotaxane Shuttle

Molecular interlocked systems with mechanically trapped components can serve as versatile building blocks for dynamic nanostructures. Here we report the synthesis of unprecedented double‐stranded (ds) DNA [2]‐ and [3]rotaxanes with two distinct stations for the hybridization of the macrocycles on the axle. In the [3]rotaxane, the release and migration of the “shuttle ring” mobilizes a second macrocycle in a highly controlled fashion. Different oligodeoxynucleotides (ODNs) employed as inputs induce structural changes in the system that can be detected as diverse logically gated output signals. We also designed nonsymmetrical [2]rotaxanes which allow unambiguous localization of the position of the macrocycle by use of atomic force microscopy (AFM). Either light irradiation or the use of fuel ODNs can drive the threaded macrocycle to the desired station in these shuttle systems. The DNA nanostructures introduced here constitute promising prototypes for logically gated cargo delivery and release shuttles.     

Synthesis of a pH‐Sensitive Hetero[4]Rotaxane Molecular Machine that Combines [c2]Daisy and [2]Rotaxane Arrangements

The synthesis of a novel pH‐sensitive hetero[4]rotaxane molecular machine through a self‐sorting strategy is reported. The original tetra‐interlocked molecular architecture combines a [c2]daisy chain scaffold linked to two [2]rotaxane units. Actuation of the system through pH variation is possible thanks to the specific interactions of the dibenzo‐24‐crown‐8 (DB24C8) macrocycles for ammonium, anilinium, and triazolium molecular stations. Selective deprotonation of the anilinium moieties triggers shuttling of the unsubstituted DB24C8 along the [2]rotaxane units.     

β‐Substituted Terthiophene [2]Rotaxanes

Towards polythiophene polyrotaxanes : The β‐substituted terthiophene [2]rotaxanes have been synthesized (see figure). Basic optical and electrochemical properties of the synthesized [2]rotaxanes are also reported.

     

Face-selective [2]- and [3]rotaxanes: kinetic control of the threading direction of cyclodextrins

New [2]- and [3]pseudorotaxanes containing alpha-cyclodextrin (alpha-CDs) molecules as rotors and alkyl pyridinium derivatives as axles were prepared by a slipping process. The inclusion behavior of these rotaxanes was investigated by using one- and two-dimensional NMR spectroscopy. The methyl group at the 2-position of the pyridinium moiety at the end of each axle molecule was found to control the rates of threading of the alpha-CD onto the axle molecules. alpha-CD can approach axle molecules from a particular direction to form inclusion complexes. Axle molecules that contain a 2-methylpyridinium moiety at one end and a bulky stopper at the other end can regulate the direction of approach to give a [2]pseudorotaxane such as 2 b-alpha-CD. A [3]pseudorotaxane in which two alpha-CD molecules are arranged facing in the same direction at two stations of the tetracationic axle molecule was also obtained. These face-selective behaviors are dominated by kinetic processes rather than thermodynamic processes.     

A Dual‐Response [2]Rotaxane Based on a 1,2,3‐Triazole Ring as a Novel Recognition Station

Two novel multilevel switchable [2]rotaxanes containing an ammonium and a triazole station have been constructed by a Cu^I‐catalyzed azide–alkyne cycloaddition reaction. The macrocycle of [2]rotaxane containing a C6‐chain bridge between the two hydrogen bonding stations exhibits high selectivity for the ammonium cation in the protonated form. Interestingly, the macrocycle is able to interact with the two recognition stations when the bridge between them is shortened. Upon deprotonation of both [2]rotaxanes, the macrocycle moves towards the triazole recognition site due to the hydrogen‐bond interaction between the triazole nitrogen atoms and the amide groups in the macrocycle. Upon addition of chloride anion, the conformation of [2]rotaxane is changed because of the cooperative recognition of the chloride anion by a favorable hydrogen‐bond donor from both the macrocycle isophthalamide and thread triazole CH proton.     

Cover Feature: O-Acylative Vinylation of Cyclodextrin-Based [3]Rotaxane Towards Rotaxane Crosslinkers (Eur. J. Org. Chem. 12/2023)

The acylation of a cyclodextrin-based [3]rotaxane was implemented with anhydride reagents following a facile procedure. Methacrylic anhydride facilitated the introduction of a vinyl-group into the rotaxane structure toward achieving a crosslinker. Interestingly, only a few methacrylic units were attached to the cyclodextrin at reaction temperatures of up to 60 °C even with an excess amount of the reagent, probably due to steric hindrance. Therefore, the number of vinyl groups on the [3]rotaxane framework was easily controlled to be approximately two units via a simple random acylation, which worked effectively as a facile synthesis route for the rotaxane crosslinker. The acylation behavior was investigated in detail by NMR and MALDI-TOF-MS analyses. Such a proposed approach will help overcome the trade-off between convenience and utility associated with the mono-modification of cyclodextrins.     

Hydrogels Composed of Organic Amphiphiles and α‐Cyclodextrin: Supramolecular Networks of Their Pseudorotaxanes in Aqueous Media

Mixtures of N‐alkyl pyridinium compounds [py‐N‐(CH₂)_nOC₆H₃‐3,5‐(OMe)₂]⁺(X^?) ( 1b Cl: n=10, X=Cl; 1c Br: n=12, X=Br) and α‐cyclodextrin (α‐CD) form supramolecular hydrogels in aqueous media. The concentrations of the two components influences the sol–gel transition temperature, which ranges from 7 to 67 °C. Washing the hydrogel with acetone or evaporation of water left the xerogel, and ¹³C CP/MAS NMR measurements, powder X‐ray diffraction (XRD), and scanning electron microscopy (SEM) revealed that the xerogel of 1b Cl (or 1c Br) and α‐CD was composed of pseudorotaxanes with high crystallinity. ¹³C{¹H} and ¹H NMR spectra of the gel revealed the detailed composition of the components. The gel from 1b Cl and α‐CD contains the corresponding [2]‐ and [3]pseudorotaxanes, [ 1b? (α‐CD)]Br and [ 1b? (α‐CD)₂]Br, while that from 1c Br and α‐CD consists mainly of [3]pseudorotaxane [ 1c? (α‐CD)₂]Br. 2D ROESY ¹H NMR measurements suggested intermolecular contact of 3,5‐dimethoxyphenyl and pyridyl end groups of the axle component. The presence of the [3]pseudorotaxane is indispensable for gel formation. Thus, intermolecular interaction between the end groups of the axle component and that between α‐CDs of the [3]pseudorotaxane contribute to formation of the network. The supramolecular gels were transformed into sols by adding denaturing agents such as urea, C₆H₃‐1,3,5‐(OH)₃, and [py‐N‐nBu]⁺(Cl^?).     

Sulfate‐Selective Binding and Sensing of a Fluorescent [3]Rotaxane Host System

The chloride‐templated synthesis of a novel [3]rotaxane, capable of binding anionic guests, and incorporating a naphthalene group for fluorescence sensing is reported. Extensive ¹H NMR titration studies were used to probe the anion binding selectivity of the system. The rotaxane selectively recognises sulfate, undergoing an induced conformational change upon sulfate binding to form a 1:1 stoichiometric sandwich‐type complex, concomitant with significant quenching of the fluorescence. Binding of mono‐anionic guests results in the formation of a 2:1 stoichiometric guest–host complex, and a modest enhancement of the emission. Addition of an excess of sulfate in non‐competitive solvent also results in a 2:1 emissive complex.     

A pH‐Dependent,Mechanically Interlocked Switch: Organometallic [2]Rotaxane vs. Organic [3]Rotaxane

We present the first [2]rotaxane featuring a functional organometallic host. In contrast to the known organic scaffolds, this assembly shows a high post‐synthetic modifiability. The reactivity of the Ag₈ pillarplex host is fully retained, as is exemplified by the first transmetalation in a rotaxane framework to provide the respective Au₈ analogue. Additionally, a transformation under acidic conditions to give a purely organic [3]rotaxane is demonstrated which is reversible upon addition of a suitable base, rendering the assembly a pH‐dependent switch. Hereby, it is shown that the mechanically interlocked nature of the system enhances the kinetic stability of the NHC host complex by a factor of >1000 and corresponds to the first observation of a stabilizing “rotaxand effect”.     

A Strategy Utilizing a Recyclable Macrocycle Transporter for the Efficient Synthesis of a Triazolium‐Based [2]Rotaxane

A general synthesis of triazolium‐containing [2]rotaxanes, which could not be accessed by other methods, is reported. It is based on a sequential strategy starting from a well‐designed macrocycle transporter which contains a template for dibenzo‐24‐crown‐8 and a N‐hydroxysuccinimide (NHS) moiety. The sequence is: 1) synthesis by slippage of a [2]rotaxane building‐block; 2) its elongation at its NHS end; 3) the delivery of the macrocycle to the elongated part of the axle by an induced translational motion; 4) the contraction process to yield the targeted [2]rotaxane and recycle the initial transporter.     

A Doubly Alkynylpyrene‐Threaded [4]Rotaxane That Exhibits Strong Circularly Polarized Luminescence from the Spatially Restricted Excimer

The Sonogashira coupling of γ‐CD‐encapsulated alkynylpyrenes with terphenyl‐type stopper molecules gave a doubly alkynylpyrene‐threaded [4]rotaxane. The rotaxane showed only excimer emission, with a high fluorescence quantum yield of Φ_f=0.37, arising from the spatially restricted excimer within the cavity of the γ‐CD. The excimer emission suffered little from self‐quenching up to a concentration of 1.5×10^?5 M and was circularly polarized with a high g_lum value of ?1.5×10^?2. The strong circularly polarized luminescence may result from the two stacked pyrenes existing in the rotaxane in an asymmetrically twisted manner.     

Effect of Component Mobility on the Properties of Macromolecular [2]Rotaxanes

Macromolecular [2]rotaxanes comprising a polymer axle and crown ether wheel were synthesized to evaluate the effect of component mobility on the properties of the axle polymer, especially its crystallinity. Living ring‐opening polymerization of δ‐valerolactone with a pseudorotaxane initiator with a hydroxy group at the axle terminus was followed by end‐capping with a bulky isocyanate. This yielded macromolecular [2]rotaxanes (M2Rs) possessing polyester axles of varying molecular weights. The crystallinity of the axle polymers of two series of M2Rs, with either fixed and movable components, was evaluated by differential scanning calorimetry. The results revealed that the effect of component mobility was significant in the fixed and movable M2Rs with a certain axle length, thus suggesting that the properties of the axle polymer depend on the mobility of the polyrotaxane components.     

Acid‐Base Switchable [2]‐ and [3]Rotaxane Molecular Shuttles with Benzimidazolium and Bis(pyridinium) Recognition Sites

For the purpose of developing higher level mechanically interlocked molecules (MIMs), such as molecular switches and machines, a new rotaxane system was designed in which both the 1,2‐bis(pyridinium)ethane and benzimidazolium recognition templating motifs were combined. These two very different recognition sites were successfully incorporated into [2]rotaxane and [3]rotaxane molecular shuttles which were fully characterized by ¹H NMR, 2D EXSY, single‐crystal X‐ray diffraction and VT NMR analysis. By utilizing benzimidazolium as both a recognition site and stoppering group it was possible to create not only an acid/base switchable [2]rotaxane molecular shuttle (energy barrier 20.9 kcal?mol^?1) but also a [3]rotaxane molecular shuttle that displays unique dynamic behavior involving the simultaneous motion of two macrocyclic wheels on a single dumbbell. This study provides new insights into the design of switchable molecular shuttles. Due to the unique properties of benzimidazoles, such as fluorescence and metal coordination, this new type of molecular shuttle may find further applications in developing functional molecular machines and materials.     

Calix[4]arene‐Based Rotaxane Host Systems for Anion Recognition

The synthesis, structure and anion binding properties of the first calix[4]arene‐based [2]rotaxane anion host systems are described. Rotaxanes 9? Cl and 12? Cl, consisting of a calix[4]arene functionalised macrocycle wheel and different pyridinium axle components, are prepared via adaption of an anion templated synthetic strategy to investigate the effect of preorganisation of the interlocked host’s binding cavity on anion binding. Rotaxane 12? Cl contains a conformationally flexible pyridinium axle, whereas rotaxane 9? Cl incorporates a more preorganised pyridinium axle component. The X‐ray crystal structure of 9? Cl and solution phase ¹H NMR spectroscopy demonstrate the successful interlocking of the calix[4]arene macrocycle and pyridinium axle components in the rotaxane structures. Following removal of the chloride anion template, anion binding studies on the resulting rotaxanes 9? PF₆ and 12? PF₆ reveal the importance of preorganisation of the host binding cavity on anion binding. The more preorganised rotaxane 9? PF₆ is the superior anion host system. The interlocked host cavity is selective for chloride in 1:1 CDCl₃/CD₃OD and remains selective for chloride and bromide in 10 % aqueous media over the more basic oxoanions. Rotaxane 12? PF₆ with a relatively conformationally flexible binding cavity is a less effective and discriminating anion host system although the rotaxane still binds halide anions in preference to oxoanions.