A Halogen Bonding [2]Rotaxane Shuttle for Chloride-Selective Optical Sensing.

The first example of a [2]rotaxane shuttle capable of selective optical sensing of chloride anions over other halides is reported. The rotaxane was synthesised via a chloride ion template-directed cyclisation of an isophthalamide macrocycle around a multi-station axle containing peripheral naphthalene diimide (NDI) stations and a halogen bonding (XB) bis(iodotriazole) based station. Proton NMR studies indicate the macrocycle resides preferentially at the NDI stations in the free rotaxane, where it is stabilised by aromatic donor-acceptor charge transfer interactions between the axle NDI and macrocycle hydroquinone moieties. Addition of chloride ions in an aqueous-acetone solvent mixture induces macrocycle translocation to the XB anion binding station to facilitate the formation of convergent XB⋅⋅⋅Cl- and hydrogen bonding HB⋅⋅⋅Cl- interactions, which is accompanied by a reduction of the charge-transfer absorption band. Importantly, little to no optical response was induced by addition of bromide or iodide to the rotaxane, indicative of the size discriminative steric inaccessibility of the interlocked cavity to the larger halides, demonstrating the potential of using the mechanical bond effect as a potent strategy and tool in chloride-selective chemo-sensing applications in aqueous containing solvent environments.

Coupling Photoresponsive Transmembrane Ion Transport with Transition Metal Catalysis.

Artificial ion transporters have been explored both as tools for studying fundamental ion transport processes and as potential therapeutics for cancer and channelopathies. Here we demonstrate that synthetic transporters may also be used to regulate the transport of catalytic metal ions across lipid membranes and thus control chemical reactivity inside lipid-bound compartments. We show that acyclic lipophilic pyridyltriazoles enable Pd(II) cations to be transported from the external aqueous phase across the lipid bilayer and into the interior of large unilamellar vesicles. In situ reduction generates Pd(0) species, which catalyze the generation of a fluorescent product. Photocaging the Pd(II) transporter allows for photoactivation of the transport process and hence photocontrol over the internal catalysis process. This work demonstrates that artificial transporters enable control over catalysis inside artificial cell-like systems, which could form the basis of biocompatible nanoreactors for applications such as drug synthesis and delivery or to mediate phototargeted catalyst delivery into cells.

Exploiting the Catenane Mechanical Bond Effect for Selective Halide Anion Transmembrane Transport.

The first examples of [2]catenanes capable of selective anion transport across a lipid bilayer are reported. The neutral halogen bonding (XB) [2]catenanes were prepared via a chloride template-directed strategy in an unprecedented demonstration of using XB⋅⋅⋅anion interactions to direct catenane assembly from all-neutral components. Anion binding experiments in aqueous-organic solvent media revealed strong halide over oxoanion selectivity, and a marked enhancement in the chloride and bromide affinities of the catenanes relative to their constituent macrocycles. The catenanes additionally displayed an anti-Hofmeister binding preference for bromide over the larger iodide anion, illustrating the efficacy of employing sigma-hole interactions in conjunction with the mechanical bond effect to tune receptor selectivity. Transmembrane anion transport studies conducted in POPC LUVs revealed that the catenanes were more effective anion transporters than the constituent macrocycles, with high chloride over hydroxide selectivity, which is critical to potential therapeutic applications of anionophores. Remarkably these outperform existing acyclic halogen bonding anionophores with regards to this selectivity. Record chloride over nitrate anion transport selectivity was also observed. This represents a rare example of the direct translation of intrinsic anion binding affinities to anion transport behaviour, and demonstrates the key role of the catenane mechanical bond effect for enhanced anion transport selectivity.

Squaramide-Based Heteroditopic [2]Rotaxanes for Sodium Halide Ion-Pair Recognition.

A series of squaramide-based heteroditopic [2]rotaxanes consisting of isophthalamide macrocycle and squaramide axle components are synthesized using an alkali metal cation template-directed stoppering methodology. This work highlights the unprecedented sodium cation template coordination of the Lewis basic squaramide carbonyls for interlocked structure synthesis. Extensive quantitative 1 H NMR spectroscopic anion and ion-pair recognition studies reveal the [2]rotaxane hosts are capable of cooperative sodium halide ion-pair mechanical bond axle-macrocycle component recognition, eliciting up to 20-fold enhancements in binding strengths for bromide and iodide, wherein the Lewis basic carbonyls and Lewis acidic NH hydrogen bond donors of the squaramide axle motif operate as cation and anion receptive sites simultaneously in an ambidentate fashion. Notably, varying the length and nature of the polyether cation binding unit of the macrocycle component dramatically influences the ion-pair binding affinities of the [2]rotaxanes, even overcoming direct contact NaCl ion-pair binding modes in polar organic solvents. Furthermore, the cooperative ion-pair binding properties of the squaramide-based heteroditopic [2]rotaxanes are exploited to successfully extract solid sodium halide salts into organic media.

Alkali Metal Halide Ion-Pair Binding in Conformationally Dynamic Halogen Bonding Heteroditopic [2]Rotaxanes.

A series of heteroditopic halogen bonding (XB) [2]rotaxanes were prepared via a combination of passive and active metal template-directed strategies. The ability of the [2]rotaxanes to bind alkali metal halide ion-pairs was investigated by extensive 1 H NMR titration studies, wherein detailed analysis of cation, anion and ion-pair affinity measurements indicate dramatic positive cooperative enhancements in halide anion association upon either Na+ or K+ pre-complexation. This study demonstrates that careful consideration of multiple, parallel and competing binding equilibria is essential when interpreting observed 1 H NMR spectral changes in ion-pair receptor systems, especially those which exhibit dynamic behaviour. Importantly, in comparison to XB [2]catenane analogues, these neutral XB heteroditopic [2]rotaxane host systems demonstrated that despite their relatively weaker cation and anion binding affinities, they exhibit a notably higher level of positive cooperativity for alkali metal halide ion-pair binding, highlighting the role of greater co-conformational adaptive behaviour in mechanically-bonded hosts for the purposes of charged species recognition.

Halogen bonding relay and mobile anion transporters with kinetically controlled chloride selectivity.

Selective transmembrane transport of chloride over competing proton or hydroxide transport is key for the therapeutic application of anionophores, but remains a significant challenge. Current approaches rely on enhancing chloride anion encapsulation within synthetic anionophores. Here we report the first example of a halogen bonding ion relay in which transport is facilitated by the exchange of ions between lipid-anchored receptors on opposite sides of the membrane. The system exhibits non-protonophoric chloride selectivity, uniquely arising from the lower kinetic barrier to chloride exchange between transporters within the membrane, compared to hydroxide, with selectivity maintained across membranes with different hydrophobic thicknesses. In contrast, we demonstrate that for a range of mobile carriers with known high chloride over hydroxide/proton selectivity, the discrimination is strongly dependent on membrane thickness. These results demonstrate that the selectivity of non-protonophoric mobile carriers does not arise from ion binding discrimination at the interface, but rather through a kinetic bias in transport rates, arising from differing membrane translocation rates of the anion-transporter complexes.

Dynamic Metalloporphyrin-Based [2]Rotaxane Molecular Shuttles Stimulated by Neutral Lewis Base and Anion Coordination.

A series of dynamic metalloporphyrin [2]rotaxane molecular shuttles comprising of bis-functionalised Zn(II) porphyrin axle and pyridyl functionalised macrocycle components are prepared in high yield via active metal template synthetic methodology. Extensive variable temperature 1 H NMR and quantitative UV-Vis spectroscopic titration studies demonstrate dynamic macrocycle translocation is governed by an inter-component co-ordination interaction between the macrocycle pyridyl and axle Zn(II) metalloporphyrin, which serves to bias a 'resting state' co-conformation. The dynamic shuttling behaviour of the interlocked structures is dramatically inhibited by the addition of a neutral Lewis base such as pyridine, but can also be tuned via post-synthetic rotaxane demetallation of the porphyrin axle core to give free-base, or upon subsequent metallation, Ni(II) [2]rotaxane analogues. Importantly, the Lewis acidic Zn(II) porphyrin axle component is also capable of coordinating anions which induces mechanical bond shuttling behaviour resulting in a novel optical sensing response.

Multistate Redox-Switchable Ion Transport Using Chalcogen-Bonding Anionophores.

Synthetic supramolecular transmembrane anionophores have emerged as promising anticancer chemotherapeutics. However, key to their targeted application is achieving spatiotemporally controlled activity. Herein, we report a series of chalcogen-bonding diaryl tellurium-based transporters in which their anion binding potency and anionophoric activity are controlled through reversible redox cycling between Te oxidation states. This unprecedented in situ reversible multistate switching allows for switching between ON and OFF anion transport and is crucially achieved with biomimetic chemical redox couples.

Halogen-Bonding Heteroditopic [2]Catenanes for Recognition of Alkali Metal/Halide Ion Pairs.

The first examples of halogen bonding (XB) heteroditopic homo[2]catenanes were prepared by discrete Na+ template-directed assembly of oligo(ethylene glycol) units derived from XB donor-containing macrocycles and acyclic bis-azide precursors, followed by a CuI -mediated azide-alkyne cycloaddition macrocyclisation reaction. Extensive 1 H NMR spectroscopic studies show the [2]catenane hosts exhibit positive cooperative ion-pair recognition behaviour, wherein XB-mediated halide recognition is enhanced by alkali metal cation pre-complexation. Notably, subtle changes in the catenanes' oligo(ethylene glycol) chain length dramatically alters their ion-binding affinity, stoichiometry, complexation mode, and conformational dynamics. Solution-phase and single-crystal X-ray diffraction studies provide evidence for competing host-separated and direct-contact ion-pair binding modes. We further demonstrate the [2]catenanes are capable of extracting solid alkali-metal halide salts into organic media.

Allosteric and Electrostatic Cooperativity in a Heteroditopic Halogen Bonding Receptor System.

A halogen bonding (XB) heteroditopic receptor, consisting of a 1,3-bis-iodo-triazole benzene XB anion binding site covalently appended via a flexible methylene group with two benzo-15-crown-5 (B15C5) cation binding moieties, and its hydrogen bonding receptor analogue, are used to delineate the mechanisms of cooperativity for alkali metal halide ion-pair recognition. Extensive cation, anion and ion-pair 1 H NMR titration investigations demonstrate the combination of allosteric pre-organisation, via 1 : 1 stoichiometric intramolecular potassium and rubidium metal cation bis-B15C5 sandwich complexation, in concert with favourable electrostatics and XB potency, results in a remarkable enhancement of halide anion binding affinity by a factor of at least 700. By contrast, a notably diminished halide anion affinity enhancement factor of just 15 is observed with the corresponding 1 : 1 stoichiometric sodium cation complexed receptor system, where the smaller sized cation singly occupies one B15C5 unit and only an electrostatic contribution to cooperativity is possible. These observations serve to illustrate that allosteric pre-organisation capability, electrostatic attraction and XB mediated anion recognition are important strategic design features to incorporate in future high-fidelity heteroditopic ion-pair receptor development.

Anti-Hofmeister Anion Selectivity via a Mechanical Bond Effect in Neutral Halogen-Bonding [2]Rotaxanes.

Exceptionally strong halogen bonding (XB) donor-chloride interactions are exploited for the chloride anion template synthesis of neutral XB [2]rotaxane host systems which contain perfluoroaryl-functionalised axle components, including a remarkably potent novel 4,6-dinitro-1,3-bis-iodotriazole motif. Halide anion recognition properties in aqueous-organic media, determined via extensive 1 H NMR halide anion titration experiments, reveal the rotaxane host systems exhibit dramatically enhanced affinities for hydrophilic Cl- and Br- , but conversely diminished affinities for hydrophobic I- , relative to their non-interlocked axle counterparts. Crucially, this mechanical bond effect induces a binding selectivity which directly opposes Hofmeister bias. Free-energy analysis of this mechanical bond enhancement demonstrates anion recognition by neutral XB interlocked host systems as a rare and general strategy to engineer anti-Hofmeister bias anion selectivity in synthetic receptor design.

Anion Recognition with Antimony(III) and Bismuth(III) Triaryl-Based Pnictogen Bonding Receptors.

The synthesis and characterisation of a library of acyclic antimony(III) and bismuth(III) triaryl pnictogen bonding (PnB) receptor systems are reported. In the first-generation receptor series, quantitative 1 H NMR chloride titration experiments in THF solvent media reveal halide anion binding potency is intimately correlated with both the electronic-withdrawing nature of the aryl- substituent and the polarisability of the PnB donor. Further extensive anion binding investigations with the most potent Sb- and Bi-based PnB receptors: 1⋅Sb2CF3 and 1⋅Bi2CF3 , reveal novel selectivity profiles, both displaying Cl- selectivity relative to the heavier halides and, impressively, to a range of highly basic oxoanions. The synthesis and preliminary chloride anion binding studies of a series of novel tripodal tris-proto-triazole triaryl Sb(III) and Bi(III) mixed PnB-HB receptor systems are also described. Whereas parent triphenyl Sb(III) and Bi(III) compounds are incapable of binding Cl- in THF solvent media, the PnB-triazole HB host systems exhibit notable halide affinity.

Selective Potassium Chloride Recognition, Sensing, Extraction, and Transport Using a Chalcogen-Bonding Heteroditopic Receptor.

Chalcogen bonding (ChB) is rapidly rising to prominence in supramolecular chemistry as a powerful sigma (σ)-hole-based noncovalent interaction, especially for applications in the field of molecular recognition. Recent studies have demonstrated ChB donor strength and potency to be remarkably sensitive to local electronic environments, including redox-switchable on/off anion binding and sensing capability. Influencing the unique electronic and geometric environment sensitivity of ChB interactions through simultaneous cobound metal cation recognition, herein, we present the first potassium chloride-selective heteroditopic ion-pair receptor. The direct conjugation of benzo-15-crown-5 ether (B15C5) appendages to Te centers in a bis-tellurotriazole framework facilitates alkali metal halide (MX) ion-pair binding through the formation of a cofacial intramolecular bis-B15C5 M+ (M+ = K+, Rb+, Cs+) sandwich complex and bidentate ChB···X- formation. Extensive quantitative 1H NMR ion-pair affinity titration experiments, solid-liquid and liquid-liquid extraction, and U-tube transport studies all demonstrate unprecedented KCl selectivity over all other group 1 metal chlorides. It is demonstrated that the origin of the receptor's ion-pair binding cooperativity and KCl selectivity arises from an electronic polarization of the ChB donors induced by the cobound alkali metal cation. Importantly, the magnitude of this switch on Te-centered electrophilicity, and therefore anion-binding affinity, is shown to correlate with the inherent Lewis acidity of the alkali metal cation. Extensive computational DFT investigations corroborated the experimental alkali metal cation-anion ion-pair binding observations for halides and oxoanions.

Neutral isocyanide-templated assembly of pillar[5]arene [2] and [3]pseudorotaxanes.

Unprecedented pillar[5]arene-isocyanide pseudorotaxane complexes are reported. Extensive 1H-NMR experiments reveal remarkably strong binding affinities of alkyl diisocyanide guests (Ka > 105 M-1 in CDCl3) by pillar[5]arenes. Characterised by multinuclear 1H and 13C-NMR spectroscopy and single-crystal X-ray diffraction, it is demonstrated that pillar[5]arenes are capable of encapsulating a series of alkyl diisocyanides wherein either [2]- or [3]pseudorotaxanes can be formed by varying the alkyl chain length. Moreover, electron-deficient aryl isocyanides, are demonstrated to form inclusion complexes within the cavities of pillar[5]arenes stabilised by multiple C-H⋯π interactions.

Redox-Switchable Chalcogen Bonding for Anion Recognition and Sensing.

Inspired by the success of its related sigma-hole congener halogen bonding (XB), chalcogen bonding (ChB) is emerging as a powerful noncovalent interaction with a plethora of applications in supramolecular chemistry and beyond. Despite its increasing importance, the judicious modulation of ChB donor strength remains a formidable challenge. Herein, we present, for the first time, the reversible and large-scale modulation of ChB potency by electrochemical redox control. This is exemplified by both the switching-ON of anion recognition via ChB oxidative activation of a novel bis(ferrocenyltellurotriazole) anion host and switching-OFF reductive ChB deactivation of anion binding potency with a telluroviologen receptor. The direct linking of the redox-active center and ChB receptor donor sites enables strong coupling, which is reflected by up to a remarkable 3 orders of magnitude modulation of anion binding strength. This is demonstrated through large voltammetric perturbations of the respective receptor ferrocene and viologen redox couples, enabling, for the first time, ChB-mediated electrochemical anion sensing. The sensors not only display significant anion-binding-induced electrochemical responses in competitive aqueous-organic solvent systems but can compete with, or even outperform similar, highly potent XB and HB sensors. These observations serve to highlight a unique (redox) tunability of ChB and pave the way for further exploration of the reversible (redox) modulation of ChB in a wide range of applications, including anion sensors as well as molecular switches and machines.

Hydroxy Groups Enhance [2]Rotaxane Anion Binding Selectivity.

We report the synthesis of two [2]rotaxanes containing an interlocked three dimensional binding cavity formed from a pyridinium bis(amide) axle component containing two phenol donors, and an isophthalamide based macrocycle. In the competitive solvent mixture 1 : 1 CDCl3 : CD3 OD, one of the receptors exhibits a much higher selectivity preference for chloride than an analogous rotaxane without the hydroxy groups. X-ray crystal structures reveal the chloride anion guest encapsulated within the interlocked binding cavity, though not all of the hydrogen bond donors are utilised. Computational semi-empirical simulations indicate that secondary intermolecular interactions occur between the axle hydroxy hydrogen bond donors and the [2]rotaxane macrocycle components, contributing to a more preorganised binding pocket, which may be responsible for the observed enhanced selectivity.

Organotelluroxane molecular clusters assembled via Te⋯X- (X = Cl-, Br-) chalcogen bonding anion template interactions.

The synthesis and characterisation of two novel molecular organotelluroxane clusters, comprising of an inorganic Te8O6X4 (X = Cl, Br) core structure are described. The integration of highly electron withdrawing 3,5-bis-trifluoromethylphenyl groups to the constituent Te(IV) centres is determined to be crucial in the chalcogen bonding (ChB) halide template directed assembly. Characterised by multi-nuclear 1H, 125Te, 19F NMR, UV-Vis, IR spectroscopies and X-ray crystal structure analysis, the discrete molecular clusters exhibit excellent organic solvent solubility and remarkable chemical stability. Furthermore, preliminary fluorescence investigations reveal the telluroxanes exhibit aggregation induced emission (AIE) behaviour in organic aqueous solvent mixtures.

Selective Extraction, Recovery, and Sensing of Hydroquinone Mediated by a Supramolecular Pillar[5]quinone Quinhydrone Charge-Transfer Complex.

Intermolecular interactions between an electron-rich aromatic hydroquinone (HQ) with its electron deficient counterpart, benzoquinone (BQ), result in the formation of a quinhydrone charge-transfer complex. Herein, we report a novel quinhydrone-type complex between pillar[5]quinone (P[5]Q) and HQ. Characterized by a suite of spectroscopic techniques including 1H NMR, UV-visible, and FTIR together with PXRD, SEM, BET, CV, and DFT modeling studies, the stability of the complex is determined to be due to an electron-proton transfer reaction coupled with a complementary donor-acceptor interaction. The selectivity of P[5]Q toward HQ over other dihydroxybenzene isomers allows for not only the naked-eye detection of HQ but also its selective liquid-liquid extraction and recovery from aqueous media.

Charge neutral halogen bonding tetradentate-iodotriazole macrocycles capable of anion recognition and sensing in highly competitive aqueous media.

A series of neutral tetradentate halogen bonding (XB) macrocycles, comprising of two bis-iodotriazole XB donors were synthesised in 60-70% yields via a stepwise CuAAC-mediated cyclisation strategy. Extensive 1H NMR anion titration experiments reveal halide binding affinities are critically dependent on the substitution pattern of the xylyl spacer unit. The meta-substituted macrocycle remarkably displays cooperative tetradentate XB-halide anion recognition in highly competitive 40% aqueous-organic D2O/acetone-d6 (40 : 60, v/v) solvent mixtures. Integration of para-xylyl and naphthyl spacer units generates extended macrocyclic cavities, capable of selective oxalate recognition. Furthermore, preliminary fluorescence exeperiments reveal dicarboxylate specific sensing can be achieved through monitoring of the naphthylene centred emission.

Halogen Bonding Heteroditopic Materials for Cooperative Sodium Iodide Binding and Extraction.

A series of novel heteroditopic halogen bonding (XB) receptor functionalised silica based materials, containing mono- and bis-iodotriazole benzo-15-crown-5 groups are investigated for the cooperative binding and extraction of sodium halide ion-pair species from aqueous solution. Characterisation of the XB materials by CHN elemental analysis, 13 C CP/MAS NMR and ATR-FTIR spectroscopies confirms and quantifies the successful incorporation of the ion-pair receptor frameworks to the silica material. ICP-MS solid-liquid extraction studies demonstrate the bidentate XB functionalised material is capable of NaI extraction from water. Importantly, cooperative XB-mediated sodium halide ion-pair binding is determined to be crucial to the material's extraction capabilities, impressively demonstrating a two-fold enhancement in sodium iodide extraction efficiency relative to a heteroditopic hydrogen bonding receptor functionalised silica material analogue.