Halotriazolium Axle Functionalised [2]Rotaxanes for Anion Recognition: Investigating the Effects of Halogen‐Bond Donor and Preorganisation

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 ¹H 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 ¹H 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.     

An All‐Halogen Bonding Rotaxane for Selective Sensing of Halides in Aqueous Media

The synthesis and anion binding properties of the first rotaxane host system to bind and sense anions purely through halogen bonding, is described. Through a combination of polarized iodotriazole and iodotriazolium halogen bond donors, a three‐dimensional cavity is created for anion binding. This rotaxane incorporates a luminescent rhenium(I) bipyridyl metal sensor motif within the macrocycle component, thus enabling optical study of the anion binding properties. The rotaxane topology was confirmed by single‐crystal X‐ray structural analysis, demonstrating halogen bonding between the electrophilic iodine atoms and chloride anions. In 50 % H₂O/CH₃CN solvent mixtures the rotaxane host exhibits strong binding affinity and selectivity for chloride, bromide, and iodide over a range of oxoanions.     

A Potent Halogen‐Bonding Donor Motif for Anion Recognition and Anion Template Mechanical Bond Synthesis

The covalent attachment of electron deficient perfluoroaryl substituents to a bis‐iodotriazole pyridinium group produces a remarkably potent halogen bonding donor motif for anion recognition in aqueous media. Such a motif also establishes halogen bonding anion templation as a highly efficient method for constructing a mechanically interlocked molecule in unprecedented near quantitative yield. The resulting bis‐perfluoroaryl substituted iodotriazole pyridinium axle containing halogen bonding [2]rotaxane host exhibits exceptionally strong halide binding affinities in competitive 50 % water containing aqueous media, by a factor of at least three orders of magnitude greater in comparison to a hydrogen bonding rotaxane host analogue. These observations further champion and advance halogen bonding as a powerful tool for recognizing anions in aqueous media.     

Iodide Recognition and Sensing in Water by a Halogen‐Bonding Ruthenium(II)‐Based Rotaxane

The synthesis and anion‐recognition properties of the first halogen‐bonding rotaxane host to sense anions in water is described. The rotaxane features a halogen‐bonding axle component, which is stoppered with water‐solubilizing permethylated β‐cyclodextrin motifs, and a luminescent tris(bipyridine)ruthenium(II)‐based macrocycle component. ¹H NMR anion‐binding titrations in D₂O reveal the halogen‐bonding rotaxane to bind iodide with high affinity and with selectively over the smaller halide anions and sulfate. The binding affinity trend was explained through molecular dynamics simulations and free‐energy calculations. Photo‐physical investigations demonstrate the ability of the interlocked halogen‐bonding host to sense iodide in water, through enhancement of the macrocycle component’s Ru^II metal–ligand charge transfer (MLCT) emission.     

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. ¹H 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.     

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.     

A Chiral Halogen‐Bonding [3]Rotaxane for the Recognition and Sensing of Biologically Relevant Dicarboxylate Anions

The unprecedented application of a chiral halogen‐bonding [3]rotaxane host system for the discrimination of stereo‐ and E/Z geometric isomers of a dicarboxylate anion guest is described. Synthesised by a chloride anion templation strategy, the [3]rotaxane host recognises dicarboxylates through the formation of 1:1 stoichiometric sandwich complexes. This process was analysed by molecular dynamics simulations, which revealed the critical synergy of halogen and hydrogen bonding interactions in anion discrimination. In addition, the centrally located chiral (S)‐BINOL motif of the [3]rotaxane axle component facilitates the complexed dicarboxylate species to be sensed via a fluorescence response.     

Iodide‐Induced Shuttling of a Halogen‐ and Hydrogen‐Bonding Two‐Station Rotaxane

The first example of utilizing halogen‐bonding anion recognition to facilitate molecular motion in an interlocked structure is described. A halogen‐bonding and hydrogen‐bonding bistable rotaxane is prepared and demonstrated to undergo shuttling of the macrocycle component from the hydrogen‐bonding station to the halogen‐bonding station upon iodide recognition. In contrast, chloride‐anion binding reinforces the macrocycle to reside at the hydrogen‐bonding station.     

Dual Role of the 1,2,3‐Triazolium Ring as a Hydrogen‐Bond Donor and Anion–π Receptor in Anion‐Recognition Processes

Several bis(triazolium)‐based receptors have been synthesized as chemosensors for anion recognition. The central naphthalene core features two aryltriazolium side‐arms. NMR experiments revealed differences between the binding modes of the two triazolium rings: one triazolium ring acts as a hydrogen‐bond donor, the other as an anion–π receptor. Receptors 9²⁺?2BF₄ ^? (C₆H₅), 11²⁺?2BF₄ ^? (4‐NO₂?C₆H₄), and 13²⁺?2BF^4? (ferrocenyl) bind HP₂O₇^3? anions in a mixed‐binding mode that features a combination of hydrogen‐bonding and anion–π interactions and results in strong binding. On the other hand, receptor 10²⁺?2 BF₄ ^? (4‐CH₃O?C₆H₄) only displays combined Csp₂?H/anion–π interactions between the two arms of the receptors and the bound anion rather than triazolium (CH)⁺???anion hydrogen bonding. All receptors undergo a downfield shift of the triazolium protons, as well as the inner naphthalene protons, in the presence of H₂PO₄^? anions. That suggests that only hydrogen‐bonding interactions exist between the binding site and the bound anion, and involve a combination of cationic (triazolium) and neutral (naphthalene) C?H donor interactions. Theoretical calculations relate the electronic structure of the substituent on the aromatic group with the interaction energies and provide a minimum‐energy conformation for all the complexes that explains their measured properties.     

Mechanical Bond Enhanced Lithium Halide Ion-Pair Binding by Halogen Bonding Heteroditopic Rotaxanes**

A family of novel halogen bonding (XB) and hydrogen bonding (HB) heteroditopic [2]rotaxane host systems constructed by active metal template (AMT) methodology, were studied for their ability to cooperatively recognise lithium halide (LiX) ion-pairs. ¹H NMR ion-pair titration experiments in CD₃CN:CDCl₃ solvent mixtures revealed a notable “switch-on“ of halide anion binding in the presence of a co-bound lithium cation, with rotaxane hosts demonstrating selectivity for LiBr over LiI. The strength of halide binding was shown to greatly increase with increasing number of halogen bond donors integrated into the interlocked cavity, where an all-XB rotaxane was found to be the most potent host for LiBr. DFT calculations corroborated these findings, determining the mode of LiX ion-pair binding. Notably, ion-pair binding was not observed with the corresponding XB/HB macrocycles alone, highlighting the cooperative, heteroditopic, rotaxane axle-macrocycle component mechanical bond effect as an efficient strategy for ion-pair recognition in general.     

Chalcogen Bond Mediated Enhancement of Cooperative Ion‐Pair Recognition

A series of heteroditopic receptors containing halogen bond (XB) and unprecedented chalcogen bond (ChB) donors integrated into a 3,5‐bis‐triazole pyridine structure covalently linked to benzo‐15‐crown‐5 ether motifs exhibit remarkable cooperative recognition of halide anions. Multi‐nuclear ¹H, ¹³C, ¹²⁵Te and ¹⁹F NMR, ion pair binding investigations reveal sodium cation–benzo‐crown ether binding dramatically enhances the recognition of bromide and iodide halide anions, with the chalcogen bonding heteroditopic receptor notably displaying the largest enhancement of halide binding strength of over two hundred‐fold, in comparison to the halogen bonding and hydrogen bonding heteroditopic receptor analogues. DFT calculations suggest crown ether sodium cation complexation induces a polarisation of the sigma hole of ChB and XB heteroditopic receptor donors as a significant contribution to the origin of the unique cooperativity exhibited by these systems.     

Nitrate Anion Recognition in Organic–Aqueous Solvent Mixtures by a Bis(triazolium)acridine‐Containing [2]Rotaxane

The synthesis of a novel [2]rotaxane host system containing a bis(triazolium)acridine‐based axle component is reported. ¹H NMR anion‐binding titrations reveal that the rotaxane is able to recognise selectively the NO₃^? anion over a range of more basic oxoanions (AcO^?, HCO₃^? and H₂PO₄^?) in a competitive organic–aqueous solvent mixture.     

Chloride‐Anion‐Templated Synthesis of a Strapped‐Porphyrin‐Containing Catenane Host System

The synthesis, structure and anion‐recognition properties of a new strapped‐porphyrin‐containing [2]catenane anion host system are described. The assembly of the catenane is directed by discrete chloride anion templation acting in synergy with secondary aromatic donor–acceptor and coordinative pyridine–zinc interactions. The [2]catenane incorporates a three‐dimensional, hydrogen‐bond‐donating anion‐binding pocket; solid‐state structural analysis of the catenane?chloride complex reveals that the chloride anion is encapsulated within the catenane’s interlocked binding cavity through six convergent CH????Cl and NH???Cl hydrogen‐bonding interactions and solution‐phase ¹H NMR titration experiments demonstrate that this complementary hydrogen‐bonding arrangement facilitates the selective recognition of chloride over larger halide anions in DMSO solution.     

Halogen‐ and Hydrogen‐Bonding Catenanes for Halide‐Anion Recognition

Halogen‐bonding (XB) interactions were exploited in the solution‐phase assembly of anion‐templated pseudorotaxanes between an isophthalamide‐containing macrocycle and bromo‐ or iodo‐functionalised pyridinium threading components. ¹H NMR spectroscopic titration investigations demonstrated that such XB interpenetrated assemblies are more stable than analogous hydrogen bonding (HB) pseudorotaxanes. The stability of the anion‐templated halogen‐bonded pseudorotaxane architectures was exploited in the preparation of new halogen‐bonding interlocked catenane species through a Grubbs’ ring‐closing metathesis (RCM) clipping methodology. The catenanes’ anion recognition properties in the competitive CDCl₃/CD₃OD 1:1 solvent mixture revealed selectivity for the heavier halides iodide and bromide over chloride and acetate.     

Host–Guest Chemistry: Oxoanion Recognition Based on Combined Charge‐Assisted C−H or Halogen‐Bonding Interactions and Anion⋅⋅⋅Anion Interactions Mediated by Hydrogen Bonds

Several bis‐triazolium‐based receptors have been synthesized and their anion‐recognition capabilities have been studied. The central chiral 1,1′‐bi‐2‐naphthol (BINOL) core features either two aryl or ferrocenyl end‐capped side arms with central halogen‐ or hydrogen‐bonding triazolium receptors. NMR spectroscopic data indicate the simultaneous occurrence of several charge‐assisted aliphatic and heteroaromatic C?H noncovalent interactions and combinations of C?H hydrogen and halogen bonding. The receptors are able to selectively interact with HP₂O₇^3?, H₂PO₄^?, and SO₄^2? anions, and the value of the association constant follows the sequence: HP₂O₇^3?>SO₄^2?>H₂PO₄^?. The ferrocenyl end‐capped 7²⁺?2 BF₄ ^? receptor allows recognition and differentiation of H₂PO₄^? and HP₂O₇^3? anions by using different channels: H₂PO₄^? is selectively detected through absorption and emission methods and HP₂O₇^3? by using electrochemical techniques. Significant structural results are the observation of an anion???anion interaction in the solid state (2:2 complex, 6²⁺? [ H₂P₂O₇ ] ^2? ), and a short C?I???O contact is observed in the structure of the complex [ 8 ²⁺][SO₄]_0.5[BF₄].     

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.     

Halogen Bonding between Anions and Iodoperfluoroorganics: Solution‐Phase Thermodynamics and Multidentate‐Receptor Design

The interactions of iodoperfluoroarenes and ‐alkanes with anions in organic solvent were studied. The data indicates that favorable halogen‐bonding interactions exist between halide anions and the monodentate model compounds C₆F₅I and C₈F₁₇I. These data served as a basis for the development of preorganized multidentate receptors capable of high‐affinity anion recognition. Several new receptor architectures were prepared, and the multidentate‐iodoperfluorobenzoate‐ester design, as described in a preliminary communication, was evaluated in more detail. Computation was employed to better interpret the structure–activity relationships arising from these studies. Investigations of the thermodynamics of anion binding (by van't Hoff analysis) and solvent effects reveal details of these halogen bonding interactions.     

Increased Halide Recognition Strength by Enhanced Intercomponent Preorganisation in Triazolium Containing [2]Rotaxanes

Three triazolium‐based [2]rotaxanes containing different sized axle and macrocycle components were synthesised in good yields (40–57 %) through chloride anion templation. The anion recognition properties of the interlocked receptor systems were investigated using ¹H NMR titration experiments: all three rotaxanes display impressive selectivities for halide anions over the more basic oxoanion acetate. The rotaxanes incorporating shorter, more rigid axle components with aryl‐substituted triazolium groups display substantially higher anion binding affinities than those with longer, bis‐alkyl‐substituted heterocycles, which is attributed to the increased intercomponent preorganisation afforded by the smaller axle component. Computational DFT and molecular dynamics simulations composed of unconstrained and umbrella sampling simulations corroborate the experimental observations.     

Easily‐prepared Hydroxy‐containing Receptors Recognize Anions in Aqueous Media

Despite their ready availability, O?H groups have received relatively little attention as anion recognition motifs. Here, we report two simple hydroxy‐containing anion receptors that are prepared in two facile steps followed by anion exchange, without the need for chromatographic purification at any stage. These receptors contain a pyridinium bis(amide) motif as well as hydroxyphenyl groups, and bind mono‐ and divalent anions in 9:1 CD₃CN:D₂O, showing a selectivity preference for sulfate. Notably, a “model” receptor that does not contain hydroxy groups shows only very weak sulfate binding in this competitive solvent mixture. In the solid state, X‐ray crystallographic studies show that the receptors tend to form extended assemblies with anions; however, ¹H and DOSY NMR studies as well as molecular dynamics simulations show that only 1:1 complexes are present in solution. Molecular dynamics simulations suggest that one of the receptors suffers from competing intramolecular hydrogen bonding, while another binds partially‐hydrated anions, with the receptor's O?H groups forming hydrogen bonds to water molecules within the anion's coordination sphere.     

Bistable or Oscillating State Depending on Station and Temperature in Three‐Station Glycorotaxane Molecular Machines

High‐yield, straightforward synthesis of two‐ and three‐station [2]rotaxane molecular machines based on an anilinium, a triazolium, and a mono‐ or disubstituted pyridinium amide station is reported. In the case of the pH‐sensitive two‐station molecular machines, large‐amplitude movement of the macrocycle occurred. However, the presence of an intermediate third station led, after deprotonation of the anilinium station, and depending on the substitution of the pyridinium amide, either to exclusive localization of the macrocycle around the triazolium station or to oscillatory shuttling of the macrocycle between the triazolium and monosubstituted pyridinium amide station. Variable‐temperature ¹H NMR investigation of the oscillating system was performed in CD₂Cl₂. The exchange between the two stations proved to be fast on the NMR timescale for all considered temperatures (298–193 K). Interestingly, decreasing the temperature displaced the equilibrium between the two translational isomers until a unique location of the macrocycle around the monosubstituted pyridinium amide station was reached. Thermodynamic constants K were evaluated at each temperature: the thermodynamic parameters ΔH and ΔS were extracted from a Van′t Hoff plot, and provided the Gibbs energy ΔG. Arrhenius and Eyring plots afforded kinetic parameters, namely, energies of activation E_a, enthalpies of activation ΔH^≠, and entropies of activation ΔS^≠. The ΔG values deduced from kinetic parameters match very well with the ΔG values determined from thermodynamic parameters. In addition, whereas signal coalescence of pyridinium hydrogen atoms located next to the amide bond was observed at 205 K in the oscillating rotaxane and at 203 K in the two‐station rotaxane with a unique location of the macrocycle around the pyridinium amide, no separation of ¹H NMR signals of the considered hydrogen atoms was seen in the corresponding nonencapsulated thread. It is suggested that the macrocycle acts as a molecular brake for the rotation of the pyridinium–amide bond when it interacts by hydrogen bonding with both the amide NH and the pyridinium hydrogen atoms at the same time.