Synthesis of a [2]rotaxane incorporating a "magic sulfur ring" by the thiol-ene click reaction

The mild and highly efficient thiol-ene click reaction has been used to construct a rotaxane incorporating dibenzo-24-crown-8 (DB24C8) and a dibenzylammonium-derived thread in high yield under the irradiation of UV light. A rotaxane containing a disulfide linkage in the macrocycle was also synthesized by the thiol-ene click reaction. It has been demonstrated that the formation of the [2]rotaxane with the disulfide bond in the macrocycle occurs by a mechanism that is different to the threading-followed-by-stoppering process. The successful construction of a rotaxane directly from its constituent components, the macrocycle containing a disulfide linkage and the dibenzylammonium hexafluorophosphate salt, suggests that the space within the macrocycle incorporating the disulfide linkage is smaller than the phenyl unit and a plausible reaction mechanism has been proposed as follows: A small amount of the initiator forms two radicals upon the absorption of UV irradiation; the radicals act as a "key" to "unlock" the disulfide bond in the macrocycle. The resulting crown ether like moiety in the macrocycle is clipped around the ammonium ion center in the dumb-bell-shaped compound. The [2]rotaxane is generated upon recombination of the disulfide linkage.     

Synthesis of triazolium-based mono- and tris-branched [1]rotaxanes using a molecular transporter of dibenzo-24-crown-8

We report a diverted route to [1]rotaxane and tris-branched [1]rotaxane that are devoid of any efficient template and which could not be obtained by classical straightforward strategies. The described chemical route relies on the utilization of a “macrocycle transporter”, which is able first to bind a macrocycle, second to link temporarily a triazolium-containing molecular axle, and third to deliver the macrocycle around the new docked axle through molecular machinery in a [1]rotaxane structure. The extended encircled thread is eventually cleaved by an amine or a triamine to afford the triazolium-containing [1]rotaxanes, releasing at the same time, the macrocycle transporter as a recyclable species.     

Active‐Metal Template Synthesis of a Halogen‐Bonding Rotaxane for Anion Recognition

The synthesis of an all‐halogen‐bonding rotaxane for anion recognition is achieved by using active‐metal templation. A flexible bis‐iodotriazole‐containing macrocycle is exploited for the metal‐directed rotaxane synthesis. Endotopic binding of a Cu^I template facilitates an active‐metal CuAAC iodotriazole axle formation reaction that captures the interlocked rotaxane product. Following copper‐template removal, exotopic coordination of a more sterically demanding rhenium(I) complex induces an inversion in the conformation of the macrocycle component, directing the iodotriazole halogen‐bond donors into the rotaxane’s interlocked binding cavity to facilitate anion recognition.     

Homo- and hetero-[3]rotaxanes with two pi-systems clasped in a single macrocycle

Here we present the first synthesis of a [3]rotaxane with two dumbbell components threaded through a single gamma-cyclodextrin macrocycle. This synthesis is carried out in two steps: first one dumbbell is synthesized threaded through the macrocycle to give a [2]rotaxane, then a second dumbbell is synthesized through the remaining cavity of the [2]rotaxane. We have synthesized a hetero- [3]rotaxane with one stilbene and one cyanine dye threaded through gamma-cyclodextrin, which exhibits quantitative energy transfer between the two encapsulated dyes. The stilbene [2]rotaxane intermediate in this synthesis has a remarkably high affinity for suitably shaped hydrophobic guests in aqueous solution, facilitating the synthesis of [3]rotaxanes and suggesting possible applications in sensors.     

Electrochemically switchable hydrogen-bonded molecular shuttles

A series of [2]rotaxanes containing succinamide and naphthalimide hydrogen-bonding stations for a benzylic amide macrocycle is described. Electrochemical reduction and oxidation of the naphthalimide group alters its ability to form hydrogen bonds to the macrocycle to such a degree that redox processes can be used to switch the relative macrocycle-binding affinities of the two stations in a rotaxane by over 8 orders of magnitude. The structure of the neutral [2]rotaxane in solution is established by (1)H NMR spectroscopy and shows that the macrocycle exhibits remarkable positional integrity for the succinamide station in a variety of solvents. Cyclic voltammetry experiments allow the simultaneous stimulation and observation of a redox-induced dynamic process in the rotaxane which is both reversible and cyclable. Model compounds in which various conformational and co-conformational changes are prohibited demonstrate unequivocally that the redox response is the result of shuttling of the macrocycle between the two stations. At room temperature in tetrahydrofuran the electrochemically induced movement of the macrocycle between the two stations takes approximately 50 micros.     

Optically probing molecular shuttling motion of [2]rotaxane by a conformation-adaptive fluorophore

A bistable [2]rotaxane with a conformation-adaptive macrocycle bearing a 9,14-diphenyl-9,14-dihydrodibenzo[a,c]phenazine (DPAC) unit was synthesized, which could be utilized to optical probe the molecular shuttling motion of the functionalized rotaxane system. The UV–vis, ¹H NMR and PL spectroscopic data clearly demonstrated that the DPAC ring was interlocked onto the thread and the fluorescence intensity of the DPAC unit in the macrocycle was effectively regulated by the location change of the macrocycle along the thread under acid/base stimulation, which was attributed to the modulation of the intramolecular photo-induced electron transfer between the DPAC unit and the methyltriazole (MTA) unit. This bistable rotaxane system containing a conformation-adaptive fluorophore unit in the macrocycle moiety opens an alternative way to design functional bistable mechanically interlocked molecules.     

Effects of Axle‐Core,Macrocycle, and Side‐Station Structures on the Threading and Hydrolysis Processes of Imine‐Bridged Rotaxanes

Imine‐bridged rotaxanes are a new type of rotaxane in which the axle and macrocyclic ring are connected by imine bonds. We have previously reported that in imine‐bridged rotaxane 5 , the shuttling motion of the macrocycle could be controlled by changing the temperature. In this study, we investigated how the axle and macrocycle structures affect the construction of the imine‐bridged rotaxane as well as the dynamic equilibrium between imine‐bridged rotaxane 5 and [2]rotaxane 7 by using various combinations of axles ( 1 A , B ), macrocycles ( 2 a – e ), and side‐stations (XYL and TEG). In the threading process, the flexibility of the macrocycle and the substituent groups at the para position of the aniline moieties affect the preparation of the threaded imines. The size of the imine‐bridging station and the macrocyclic tether affects the hydrolysis of the imine bonds under acidic conditions.     

Dynamic Control of Chiral Space Through Local Symmetry Breaking in a Rotaxane Organocatalyst

We report on a switchable rotaxane molecular shuttle that features a pseudo‐meso 2,5‐disubstituted pyrrolidine catalytic unit on the axle whose local symmetry is broken according to the position of a threaded benzylic amide macrocycle. The macrocycle can be selectively switched (with light in one direction; with catalytic acid in the other) with high fidelity between binding sites located to either side of the pyrrolidine unit. The position of the macrocycle dictates the facial bias of the rotaxane‐catalyzed conjugate addition of aldehydes to vinyl sulfones. The pseudo‐meso non‐interlocked thread does not afford significant selectivity as a catalyst (2–14 % ee), whereas the rotaxane affords selectivities of up to 40 % ee with switching of the position of the macrocycle changing the handedness of the product formed (up to 60 % Δee).     

Squaraine-derived rotaxanes: highly stable, fluorescent near-IR dyes

Squaraines are fluorescent, near-IR dyes with promising photophysical properties for biomedical applications. A limitation with these dyes is their inherent reactivity with nucleophiles, which leads to loss of the chromophore. Another drawback is their tendency to form nonfluorescent aggregates in water. Both problems can be greatly attenuated by encapsulating the dye inside an amide-containing macrocycle. In other words, the squaraine becomes the thread component in a Leigh-type rotaxane, a permanently interlocked molecule. Two new rotaxanes are described: an analogue with four tri(ethyleneoxy) chains on the squaraine to enhance water solubility, and a rotaxane that has an encapsulating macrocycle with transposed carbonyl groups. An X-ray crystal structure of the latter rotaxane shows that the macrocycle provides only partial protection of the electrophilic cyclobutene core of the squaraine thread. The stabilities of each compound in various solvents, including serum, were compared with a commercially available cyanine dye. The squaraine rotaxane architecture is remarkably resistant to chemical and photochemical degradation, and likely to be very useful as a versatile fluorescent scaffold for constructing various types of highly stable, near-IR imaging probes.     

Synthesis of a [2]rotaxane incorporating a Ni(II)-salen moiety: evidence of ring-opening-and-closing protocol

[reaction: see text] We have synthesized a [2]rotaxane from a crown-ether-like macrocycle that undergoes ring opening and closing through cleavage and formation of imino bonds of a salen moiety; the self-assembly of this macrocycle and a dumbbell-shaped rodlike component, followed by addition of nickel acetate, afforded, after counterion exchange, a [2]rotaxane that is stabilized through coordination of the Ni ion to the macrocycle's salen moiety.     

Anion-induced shuttling of a naphthalimide triazolium rotaxane

The anion-templated synthesis of a rotaxane structure, incorporating the new naphthalimide triazolium motif, is described and the interlocked host shown to exhibit selective, uni-directional, anion-induced shuttling. Initial pseudorotaxane investigations demonstrate the ability of a naphthalimide triazolium threading component to form interpenetrated assemblies with counter-anion-dependent co-conformations. (1)H NMR studies reveal that the shuttling behaviour of the analogous rotaxane host system is controlled by selective anion binding and by the nature of the solvent conditions. Complete macrocycle translocation only occurs upon the recognition of the smaller halide anions (chloride and bromide). The rotaxane solid-state crystal structure in the presence of chloride is in agreement with the solution-phase co-conformation. The sensitivity of the axle naphthalimide absorbance band to the position of the macrocycle component within the interlocked structure enabled the molecular motion to be observed by UV/Vis spectroscopy, and the chloride-induced shuttling of the rotaxane was reversed upon silver hexafluorophosphate addition.     

En route to a molecular sheaf: active metal template synthesis of a [3]rotaxane with two axles threaded through one ring

We report that a 2,2':6',2″-terpyridylmacrocycle-Ni complex can efficiently mediate the threading of two alkyl chains with bulky end groups in an active metal template sp(3)-carbon-to-sp(3)-carbon homocoupling reaction, resulting in a rare example of a doubly threaded [3]rotaxane in up to 51% yield. The unusual architecture is confirmed by X-ray crystallography (the first time that a one-ring-two-thread [3]rotaxane has been characterized in the solid state) and is found to be stable with respect to dethreading despite the large ring size of the macrocycle. Through such active template reactions, in principle, a macrocycle should be able to assemble as many axles in its cavity as the size of the ring and the stoppers will allow. A general method for threading multiple axles through a macrocycle adds significantly to the tools available for the synthesis of different types of rotaxane architectures.     

Clipping and stoppering anion templated synthesis of a [2]rotaxane host system

A new [2]rotaxane host system containing nitro-isophthalamide macrocycle and polyether functionalised pyridinium axle components is prepared via clipping and stoppering synthetic methodologies using chloride anion templation. After removing the chloride anion template, (1)H NMR titration experiments reveal the unique interlocked host cavity to be highly selective for binding chloride and bromide in preference to basic oxoanions in competitive aqueous solvent mixtures. The rotaxane host system proved to be a superior anion complexant in comparison to the individual macrocycle and axle components. The anion binding affinity of the novel rotaxane is also investigated via molecular dynamics simulations and in general the structural data obtained corroborates the experimental solution anion recognition behaviour.     

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.     

Hydrogen bond-assembled fullerene molecular shuttle

A novel [2]rotaxane has been prepared in which fullerene C(60) behaves as both a stopper and a photoactive unit. The amphiphilic nature of the rotaxane thread can be used to shuttle the macrocycle from close to the fullerene spheroid (in nonpolar solvents) to far away (in polar solvents). The differing location of the macrocycle in dichloromethane and dimethyl sulfoxide gives rise to effects detectable by (1)H NMR and time-resolved spectroscopy.     

Switchable dual binding mode molecular shuttle

[Structure: see text] Protonation controls the location of a dual binding mode macrocycle in a [2]rotaxane. In the neutral form, amide-amide hydrogen bonds hold the macrocycle over a dipeptide residue; when the thread is protonated, polyether-ammonium cation interactions dominate and the macrocycle changes position.     

Investigating the effect of macrocycle size in anion templated imidazolium-based interpenetrated and interlocked assemblies

The effect of varying the size of the macrocycle component on the formation of anion templated imidazolium interpenetrated assemblies is investigated. Two different approaches to reducing the macrocycle size are undertaken and the stabilities of the resulting pseudorotaxanes incorporating substituted imidazolium threading components studied using (1)H NMR spectroscopy. Novel imidazolium axle containing interlocked rotaxane host structures are synthesised using chloride anion templated amide condensation and 'stoppering' methods, and the anion recognition properties of the 'stoppered' rotaxane investigated.     

Threading-followed-by-shrinking protocol for the synthesis of a [2]rotaxane incorporating a Pd(II)-salophen moiety

This communication describes a new protocol for the construction of [2]rotaxanes: "threading-followed-by-shrinking". This approach involves the threading of a rodlike unit through a crown ether-like macrocycle and then shrinking the size of the macrocycle's cavity through coordination of a transition-metal ion by a salophen moiety in the macrocycle. The self-assembly of the macrocycle and a thread, followed by addition of palladium acetate, afforded the [2]rotaxane, which contains a palladium(II)-salophen moiety, after counterion exchange. This [2]rotaxane was characterized fully by NMR and IR spectroscopic, mass spectrometric, and elemental and X-ray crystallographic analyses.     

Triggering a [2]rotaxane molecular shuttle through hydrogen sulfide

A novel chemically-controlled [2]rotaxane molecular shuttle was successfully designed and synthesized. A H₂S-responsive bulk barrier was introduced between the two identical recognition stations of the [2]rotaxane to prevent dynamic shuttling of the macrocycle. Upon addition of H₂S, the complete intramolecular cascade reaction occurs in a controllable manner, resulting in removal of the bulk barrier and the shuttling motion of the macrocycle between the two stations recovers.     

Squaraine Rotaxane as a Reversible Optical Chloride Sensor

A mechanically interlocked squaraine rotaxane is comprised of a deep‐red fluorescent squaraine dye inside a tetralactam macrocycle. NMR studies show that Cl^? binding to the rotaxane induces macrocycle translocation away from the central squaraine station, a process that is completely reversed when the Cl^? is removed from the solution. Steady‐state fluorescence and excited‐state lifetime measurements show that this reversible machine‐like motion modulates several technically useful optical properties, including a three‐fold increase in deep‐red fluorescence emission that is observable to the naked eye. The excited states were characterized quantitatively by time‐correlated single photon counting, femtosecond transient absorption spectroscopy, and nanosecond laser flash photolysis. Cl^? binding to the rotaxane increases the squaraine excited singlet state lifetime from 1.5 to 3.1 ns, and decreases the excited triplet state lifetime from >200 to 44 μs. Apparently, the surrounding macrocycle quenches the excited singlet state of the encapsulated squaraine dye and stabilizes the excited triplet state. Prototype dipsticks were prepared by adsorbing the lipophilic rotaxane onto the ends of narrow, C18‐coated, reverse‐phase silica gel plates. The fluorescence intensity of a dipstick increased eighteen‐fold upon dipping in an aqueous solution of tetrabutylammonium chloride (300 mM ) and was subsequently reversed by washing with pure water. It is possible to develop the dipsticks for colorimetric determination of Cl^? levels by the naked eye. After dipping into aqueous tetrabutylammonium chloride, a dipstick’s color slowly fades at a rate that depends on the amount of Cl^? in the aqueous solution. The fading process is due primarily to hydrolytic bleaching of the squaraine chromophore within the rotaxane. That is, association of Cl^? to immobilized rotaxane induces macrocycle translocation and exposure of the electrophilic C₄O₂ core of the squaraine station, which is in turn attacked by the ambient moisture to produce a bleached product.