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.     

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 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.     

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.     

A Halogen‐Bonding Bis‐triazolium Rotaxane for Halide‐Selective Anion Recognition

A systematic study on the anion‐binding properties of acyclic halogen‐ and hydrogen‐bonding bis‐triazolium carbazole receptors is described. The halide‐binding potency of halogen‐bonding bis‐iodotriazolium carbazole receptors was found to be far superior to their hydrogen‐bonding bis‐triazolium‐based analogues. This led to the synthesis of a mixed halogen‐ and hydrogen‐bonding rotaxane host containing a bis‐iodotriazolium carbazole axle component. The rotaxane’s anion recognition properties, determined by ¹H NMR titration experiments in a competitive aqueous solvent mixture, demonstrated the preorganised halogen‐bonding interlocked host cavity to be halide‐selective, with a strong binding affinity for bromide.     

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 Discrimination by Tetra-Iodotriazole Halogen Bonding Interlocked Hosts

Whilst the exploitation of interlocked host frameworks for anion recognition is widely established, examples incorporating halogen bond donor groups are still relatively rare. Through the integration of a novel tetra(iodotriazole)-pyridinium motif into macrocycle and axle components, a family of halogen bonding catenane and rotaxanes are constructed for anion recognition studies in a competitive aqueous-organic solvent mixture. Importantly, the degree of anion selectivity displayed is dictated by the topological nature and charged state of the respective interlocked host cavity. All the interlocked hosts exhibit iodide anion selectivity over other halides and sulfate, with the level of discrimination being the greatest with the mono-cationic rotaxane. Arising from greater electrostatic interactions working in tandem with halogen bonding and hydrogen bonding, the di-cationic rotaxane displays stronger anion association at the expense of a relatively lower degree of iodide selectivity.     

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.     

Orthogonal Halogen‐Bonding‐Driven 3D Supramolecular Assembly of Right‐Handed Synthetic Helical Peptides

Peptide‐mediated self‐assembly is a prevalent method for creating highly ordered supramolecular architectures. Herein, we report the first example of orthogonal C?X???X?C/C?X???π halogen bonding and hydrogen bonding driven crystalline architectures based on synthetic helical peptides bearing hybrids of l ‐sulfono‐γ‐AApeptides and natural amino acids. The combination of halogen bonding, intra‐/intermolecular hydrogen bonding, and intermolecular hydrophobic interactions enabled novel 3D supramolecular assembly. The orthogonal halogen bonding in the supramolecular architecture exerts a novel mechanism for the self‐assembly of synthetic peptide foldamers and gives new insights into molecular recognition, supramolecular design, and rational design of biomimetic structures.     

Polymeric Halogen‐Bond‐Based Donor Systems Showing Self‐Healing Behavior in Thin Films

The synthesis and comprehensive characterization of a systematic series of cleft‐type anion receptors imbedded into a polymeric architecture is presented. For the first time, isothermal calorimetric titrations on polymeric halogen‐bond‐based donors were exploited to evaluate the dependence of the anion affinity on different key parameters (i.e. monomeric versus polymeric receptor, halogen versus hydrogen bonding, charge assistance). The combination of these donor systems with a copolymer bearing accepting carboxylate groups led to supramolecular cross‐linked polymer networks showing excellent intrinsic self‐healing behavior. FT‐Raman spectroscopy and nano‐indentation measurements were utilized to clarify the thermally induced self‐healing mechanism based on the formation of halogen bonds. These first self‐healing materials based on halogen bonds pave the way for new applications of halogen‐bond donors in polymer and material science.     

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.     

Selective Sensing of Phosphates by a New Bis‐heteroleptic RuII Complex through Halogen Bonding: A Superior Sensor over Its Hydrogen‐Bonding Analogue

The selective phosphate‐sensing property of a bis‐heteroleptic Ru^II complex, 1 [PF₆]₂, which has a halogen‐bonding iodotriazole unit, is demonstrated and is shown to be superior to its hydrogen‐bonding analogue, 2 [PF₆]₂. Complex 1 [PF₆]₂, exploiting halogen‐bonding interactions, shows enhanced phosphate recognition in both acetonitrile and aqueous acetonitrile compared with its hydrogen‐bonding analogue, owing to considerable amplification of the Ru^II‐center‐based metal‐to‐ligand charge transfer (MLCT) emission response and luminescence lifetime. Detailed solution‐state studies reveal a higher association constant, lower limit of detection, and greater change in lifetime for complex 1 in the presence of phosphates compared with its hydrogen‐bonding analogue, complex 2 . The ¹H NMR titration study with H₂PO₄^? ascertains that the binding of H₂PO₄^? occurs exclusively through halogen‐bonding or hydrogen‐bonding interactions in complexes 1 [PF₆]₂ and 2 [PF₆]₂, respectively. Importantly, the single‐crystal X‐ray structure confirms the first ever report on metal‐assisted second‐sphere recognition of H₂PO₄^? and H₂P₂O₇^2? with 1 through a solitary C?I???anion halogen‐bonding interaction.     

Halogen‐ and Hydrogen‐Bonded Salts and Co‐crystals Formed from 4‐Halo‐2,3,5,6‐tetrafluorophenol and Cyclic Secondary and Tertiary Amines: Orthogonal and Non‐orthogonal Halogen and Hydrogen Bonding,and Synthetic Analogues of Halogen‐Bonded Biological Systems

Co‐crystallisation of, in particular, 4‐iodotetrafluorophenol with a series of secondary and tertiary cyclic amines results in deprotonation of the phenol and formation of the corresponding ammonium phenate. Careful examination of the X‐ray single‐crystal structures shows that the phenate anion develops a C?O double bond and that the C?C bond lengths in the ring suggest a Meissenheimer‐like delocalisation. This delocalisation is supported by the geometry of the phenate anion optimised at the MP2(Full) level of theory within the aug‐cc‐pVDZ basis (aug‐cc‐pVDZ‐PP on I) and by natural bond orbital (NBO) analyses. With sp² hybridisation at the phenate oxygen atom, there is strong preference for the formation of two non‐covalent interactions with the oxygen sp² lone pairs and, in the case of secondary amines, this occurs through hydrogen bonding to the ammonium hydrogen atoms. However, where tertiary amines are concerned, there are insufficient hydrogen atoms available and so an electrophilic iodine atom from a neighbouring 4‐iodotetrafluorophenate group forms an I???O halogen bond to give the second interaction. However, in some co‐crystals with secondary amines, it is also found that in addition to the two hydrogen bonds forming with the phenate oxygen sp² lone pairs, there is an additional intermolecular I???O halogen bond in which the electrophilic iodine atom interacts with the C?O π‐system. All attempts to reproduce this behaviour with 4‐bromotetrafluorophenol were unsuccessful. These structural motifs are significant as they reproduce extremely well, in low‐molar‐mass synthetic systems, motifs found by Ho and co‐workers when examining halogen‐bonding interactions in biological systems. The analogy is cemented through the structures of co‐crystals of 1,4‐diiodotetrafluorobenzene with acetamide and with N‐methylbenzamide, which, as designed models, demonstrate the orthogonality of hydrogen and halogen bonding proposed in Ho’s biological study.     

Selective Recognition of Phenazine by 2,6‐Dibutoxylnaphthalene‐Based Tetralactam Macrocycle

A 2,6‐dibutoxylnaphthalene‐based tetralactam macrocycle was designed and synthesized. This macrocycle shows highly selective recognition to phenazine – a well‐known secondary metabolite in bacteria and an emerging disinfection byproduct in drinking water. In contrast, the macrocycle shows no binding to the structurally similar dibenzo‐1,4‐dioxin. It was revealed that hydrogen bonding, π‐π and σ‐π interactions are the major driving forces between phenazine and the new tetralactam macrocycle. A perfect complementarity in electrostatic potential surfaces may explain the high selectivity. In addition, the macrocycle shows fluorescent response to phenazine, demonstrating its potential in fluorescent detection of phenazine.     

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.     

A Halogen‐Bond‐Induced Triple Helicate Encapsulates Iodide

The self‐assembly of higher‐order anion helicates in solution remains an elusive goal. Herein, we present the first triple helicate to encapsulate iodide in organic and aqueous media as well as the solid state. The triple helicate self‐assembles from three tricationic arylethynyl strands and resembles a tubular anion channel lined with nine halogen bond donors. Eight strong iodine???iodide halogen bonds and numerous buried π‐surfaces endow the triplex with remarkable stability, even at elevated temperatures. We suggest that the natural rise of a single‐strand helix renders its linear halogen‐bond donors non‐convergent. Thus, the stringent linearity of halogen bonding is a powerful tool for the synthesis of multi‐strand anion helicates.     

Chalcogen Bonding Ion-Pair Cryptand Host Discrimination of Potassium Halide Salts

A series of chalcogen, halogen and hydrogen bonding heteroditopic macrobicyclic cryptands are reported and their potassium halide ion-pair recognition properties investigated. Saliently, the co-bound potassium cation was determined to be crucial in switching on the bromide and iodide recognition properties of the respective cryptand receptor. Importantly, the nature of the sigma-hole mediated interaction employed in the anion recognition component is demonstrated to significantly augment the ion-pair binding behaviour, markedly so for the halogen bonding analogue. Most notably the incorporation of a chelating chalcogen bonding donor motif significantly improves the selectivity towards KBr over KI, relative to halogen and hydrogen bonding analogues.     

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.     

Phenylene‐Bridged Core‐Modified Planar Aromatic Octaphyrin: Aromaticity,Photophysical and Anion Receptor Properties

The synthesis of a planar expanded meso porphyrin with an intramolecular para‐phenylene‐bridged core is reported. The planarity of the octaphyrin macrocycle was confirmed by single‐crystal X‐ray structural analysis, in which the bridged para‐phenylene unit deviated by 27° from the mean macrocyclic plane. Spectroscopic analyses and theoretical calculations suggested that the macrocycle was Hückel aromatic and followed a major [34 π] single‐conjugation pathway, which indicated that the bridging para‐phenylene unit was not involved in the macrocyclic conjugation. Analysis of the photophysical properties of this system by steady‐state absorption/fluorescence spectroscopy and transient absorption spectroscopy revealed moderate enhancement in the parameters of the octaphyrin as compared to its non‐bridged octaphyrin congeners, which was attributed to the planarity and rigidity of the macrocycle as imposed by the bridging para‐phenylene unit. Preliminary anion‐binding studies revealed that the protonated macrocycle bound selectively with chloride ions through N?H???Cl hydrogen‐bonding interactions.