Selective Anion Binding Research Articles

A charge-neutral organic cage selectively binds strongly hydrated sulfate anions in water.

In biological systems, enzymes and transport proteins can bind anions in aqueous media solely by forming hydrogen bonds with charge-neutral motifs. Reproducing this functionality in synthetic systems presents challenges and incurs high costs, particularly when targeting strongly hydrated anions such as sulfate. Here we report a [2.2.2]urea cryptand (cage), synthesized in one pot, that selectively binds sulfate in a mixture of dimethyl sulfoxide and water and in water with affinities in the micromolar to millimolar range. The neutral cage bearing six urea groups donates 12 strong hydrogen bonds to encapsulate a sulfate anion, showing favourable enthalpy even in pure water. Sulfate binding can be further enhanced by using micelles to provide a low-polarity microenvironment. The cage finds utility in analysing divalent anions in water and beverage samples or in removing sulfate. The work demonstrates the achievability of robust and selective anion binding in water with minimal synthetic efforts, by using neutral NH hydrogen bonds akin to those found in biology.

Anion-templated synthesis of a switchable fluorescent [2]catenane with sulfate sensing capability.

Anion templation strategies have facilitated the synthesis of various catenane and rotaxane hosts capable of strong and selective binding of anions in competitive solvents. However, this approach has primarily relied on positively charged precursors, limiting the structural diversity and the range of potential applications of the anion-templated mechanically interlocked molecules. Here we demonstrate the synthesis of a rare electroneutral [2]catenane using a powerful, doubly charged sulfate template and a complementary diamidocarbazole-based hydrogen bonding precursor. Owing to the unique three-dimensional hydrogen bonding cavity and the embedded carbazole fluorophores, the resulting catenane receptor functions as a sensitive fluorescent turn-ON sensor for the highly hydrophilic sulfate, even in the presence of a large excess of water. Importantly, the [2]catenane exhibits enhanced binding affinity and selectivity for sulfate over its parent macrocycle and other acyclic diamidocarbazole-based receptors. We demonstrate also, for the first time, that the co-conformation of the catenane may be controlled by reversible acid/base induced protonation and deprotonation of the anionic template, SO42-. This approach pioneers a new strategy to induce molecular motion of interlocked components using switchable anionic templates.

Remote control of anion binding by CH-based receptors.

We show that the substitution of tetra(benzimidazole)resorcin[4]arenes with electron withdrawing groups on the upper rim enhances anion binding at the opposite edge by more than three orders of magnitude. Moreover, selective anion binding at either the OH/NH or CH binding sites is demonstrated.

A photoactivated chiral molecular clamp rotated by selective anion binding.

Developing chiral molecular platforms that respond to external fields provides opportunities for designing smart chiroptical materials. Herein, we introduce a molecular clamp whose chiral properties can be turned on by photoactivation. Selective anion binding achieves rational tuning of the conformations and chiroptical properties of the clamp, including circular dichroism and circularly polarized luminescence. Cyanostilbene segments were conjugated to chiral amines with a rotatable axis. Negligible chiroptical signals were significantly enhanced through a light illumination-induced isomerization. Binding with halide ions (F-, Cl- and Br-) enables chiroptical inversion and subsequent amplification of the resulting opposite handedness state by photo treatment. In contrast, the larger I- and NO3 - ions failed to achieve chiroptical inversion. Also the handedness inversion was hampered in conformationally locked amines. Density-functional theory-based computational studies and experimental results reveal a structural transformation that proceeds from a butterfly-like open geometry to a closed V-shaped state initiated by four hydrogen bonds and the rotatable axis. This work illustrates design protocols for use in smart chiroptical molecular platforms mediated by photo treatment and anion binding.

Generation of N-heterocyclic carbenes (NHC) in aqueous solutions of zwitterionic imidazolium surfactant micelles

N-heterocyclic carbenes (NHCs) are important compounds that are often prepared and used in water free environment. Herein we investigate transient formation of a NHC in the headgroup of zwitterionic imidazolium sulfonate surfactants of the type 3-(1-alkyl-1H-imidazol-3-ium-3-yl)propane-1-sulfonate (ImS3-n) in water. As demonstrated by a series of 1H NMR experiments, the formation of the NHC reactive species is accelerated above the critical micelle concentration of these surfactants due to an increased local concentration of the hydroxide or deuteroxide ions (OH−/OD−) responsible for deprotonation of C(2)-H. The rate of NHC formation can be modulated by the nature and concentration of the anions of added salts, reflecting the selectivity of anion binding to the zwitterionic micelle surface. Analogous anion binding affects are observe in the NMR chemical shifts of the C(2)-H signal of the imidazolium headgroup of the surfactants. The NHCs generated at the surface of ImS3-n micelles promote the selective oxidation of 4-nitrobenzaldehyde to 4-nitrobenzoic acid, a reaction known to be catalyzed by nucleophilic carbenes. Below the cmc or in the presence of a short-chain non-micelle-forming analogue, 3-(1-methyl-1H-imidazol-3-ium-3-yl)propane-1-sulfonate (ImS3-1), no selective oxidation of 4-nitrobenzaldehyde takes place. The results demonstrate the importance of the micellar microenvironment for controlling the reactivity and selectivity of chemical reactions involving NHC species in aqueous media and can ultimately lead to greener catalytic systems.

Molecular dynamics study of Cl− permeation through cystic fibrosis transmembrane conductance regulator (CFTR)

The recent elucidation of atomistic structures of Cl− channel CFTR provides opportunities for understanding the molecular basis of cystic fibrosis. Despite having been activated through phosphorylation and provided with ATP ligands, several near-atomistic cryo-EM structures of CFTR are in a closed state, as inferred from the lack of a continuous passage through a hydrophobic bottleneck region located in the extracellular portion of the pore. Here, we present repeated, microsecond-long molecular dynamics simulations of human CFTR solvated in a lipid bilayer and aqueous NaCl. At equilibrium, Cl− ions enter the channel through a lateral intracellular portal and bind to two distinct cationic sites inside the channel pore but do not traverse the narrow, de-wetted bottleneck. Simulations conducted in the presence of a strong hyperpolarizing electric field led to spontaneous Cl− translocation events through the bottleneck region of the channel, suggesting that the protein relaxed to a functionally open state. Conformational changes of small magnitude involving transmembrane helices 1 and 6 preceded ion permeation through diverging exit routes at the extracellular end of the pore. The pore bottleneck undergoes wetting prior to Cl− translocation, suggesting that it acts as a hydrophobic gate. Although permeating Cl− ions remain mostly hydrated, partial dehydration occurs at the binding sites and in the bottleneck. The observed Cl− pathway is largely consistent with the loci of mutations that alter channel conductance, anion binding, and ion selectivity, supporting the model of the open state of CFTR obtained in the present study.

Azacrown-calixpyrrole isosteres: receptors and sensors for anions.

Calix[4]pyrroles (CPs) and polyammonium azacrowns (ACs) are well-known receptors for anions. CPs bind anions by directional hydrogen bonds that do not always work well for aqueous analytes. The positive charge in polyammonium ACs allows for a stronger but non-directional anion-ammonium electrostatic attraction but lack selectivity. Bridging the gap between CPs and ACs could increase affinity and potentially preserve the selectivity of anion binding. We have synthesized a flexible calixpyrrole-azacrown near isosteric receptor and incorporated an environmentally sensitive dansyl fluorophore to enable fluorescence measurements. Anion binding was evaluated using NMR and fluorescence titrations. The isosteric receptor shows a strong affinity for aqueous phosphates and phosphonates (Na+ salts) in the order HAsO42- > H2PO4- > H2P2O72- > glyphosate2- > AMP- > methylphosphonate- ≫ ADP2- or ATP3- but does not bind halides. This is in stark contrast to CP which shows a strong preference for halides over oxyanions. The anion binding by the new receptor was accompanied by analyte-specific changes in fluorescence intensity and spectral width and by a wavelength shift. These parameters were used in qualitative and quantitative sensing of aqueous anions. By applying machine-learning algorithms, such as linear discriminant analysis and support vector machine linear regression, this one sensor can differentiate between 10 different analytes and accurately quantify herbicide glyphosate and methylphosphonate, a product of sarin, soman or cyclosarin hydrolysis. In fact, glyphosate can be quantified even in the presence of competing anions such as orthophosphate (LODs were ≤ 1 μM).

Turn-on fluorescent capsule for selective fluoride detection and water purification.

It has been a long-standing challenge to develop organic molecular capsules for selective anion binding in water. Here, selective recognition of aqueous fluoride was achieved through triple protonation of a hemicryptophane (L), which is composed of a fluorescent cyclotriveratrylene (CTV) cap and tris(2-aminoethyl)amine (tren) as the anion binding site. Fluoride encapsulation by [3H-L]3+ was evidenced by 1H NMR, 19F NMR, LC-MS, and X-ray crystallography. In addition, [3H-L]3+ exhibited a 'turn-on' fluorescence signal (λ em = 324 nm) upon fluoride addition. An apparent association constant K A = (7.5 ± 0.4) × 104 M-1 and a detection limit of 570 nM fluoride were extracted from the fluorescence titration experiments in citrate buffer at pH 4.1. To the best of our knowledge, [3H-L]3+ is the first example of a metal-free molecular capsule that reports on fluoride binding in purely aqueous solutions with a fluorescence response. Finally, the protonated capsule was supported on silica gel, which enabled adsorptive removal of stoichiometric fluoride from water and highlights real-world applications of this organic host-guest chemistry.

Oligopyrrolic Cages: From Classic Molecular Constructs to Chemically Responsive Polytopic Receptors.

"Functional molecular systems", discrete and self-assembled constructs where control over molecular recognition, structure, bonding, transport, release, catalytic activity, etc., is readily achieved, are a topic of current interest. Within this broad paradigm, oligopyrrolic cages have garnered attention due to their responsive recognition features. Due to the presence of slightly polar pyrrole subunits which can also behave as hydrogen-bonding donors, these oligopyrrolic cages are potential receptors for various polarized species. In this Account, we summarize recent advances involving the syntheses and study of (1) covalent oligopyrrolic macrobicyclic cages, (2) oligopyrrolic metallacages, and (3) oligopyrrolic noncovalently linked cages. Considered in concert, these molecular constructs have allowed advances in applied supramolecular chemistry; to date, they have been exploited for selective guest encapsulation studies, anion binding and ion-channel formation, and gas absorption, among other applications. While key findings from others will be noted, in this Account will focus on our own contributions to the chemistry of discrete oligopyrrolic macrocycles and their use in supramolecular host-guest chemistry and sensing applications. In terms of specifics, we will detail how oligopyrrole cages with well-defined molecular geometries permit reversible guest binding under ambient conditions and how the incorporation of pyrrole subunits within larger superstructures allows effective control over anion/conjugate acid binding activity under ambient conditions. We will also provide examples that show how derivatization of these rudimentary macrocyclic cores with various sterically congested β-substituted oligopyrroles can provide entry into more complex supramolecular architectures. In addition, we will detail how hybrid systems that include heterocycles other than pyrrole, such as pyridine and naphthyridine, can be used to create self-assembled materials that show promise as gas-absorbing materials and colorimetric reversible sensors. Studies involving oligopyrrolic polymetallic cages and oligopyrrolic supramolecular cages will also be reviewed. First, we will discuss all-carbon-linked oligopyrrolic bicycles and continue on to present systems linked via amines and imines linkages. Finally, we will summarize recent work on pyrrolic cages created through the use of metal centers or various noncovalent interactions. We hope that this Account will provide researchers with an initial foundation for understanding oligopyrrolic cage chemistry, thereby allowing for further advances in the area. It is expected that the fundamental design and recognition principles made in the area of oligopyrrole cages, as exemplified by our contributions, will be of general use to researchers targeting the design of functional molecular systems. As such, we have structured this Account so as to summarize the past while setting the stage for the future.

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 : CD3OD, 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.

Macrocyclic Polyoxometalates: Selective Polyanion Binding and Ultrahigh Proton Conduction.

The rational development of an anion templation strategy for the construction of macrocycles has been historically limited to small anions, but large polyoxoanions can offer unmatched structural diversity and ample binding sites. Here we report the formation of a {Mo22 Fe8 } macrocycle by using the Preyssler anion, [NaP5 W30 O110 ]14- ({P5 W30 }), as a supramolecular template. The {Mo22 Fe8 } macrocycle displays selective anion binding behavior in solution. In the solid state, the 1 : 2 host-guest complex, {P5 W30 }2 ⊂{Mo22 Fe8 }, transports protons more effectively, through an extended hydrogen-bonding network, than a related 1 : 1 complex where the guest is completely encapsulated. The results highlight the great potential this anion templation approach has in producing macrocyclic systems for selective anion recognition and proton conduction purposes.

Macrocyclic Polyoxometalates: Selective Polyanion Binding and Ultrahigh Proton Conduction

The rational development of an anion templation strategy for the construction of macrocycles has been historically limited to small anions, but large polyoxoanions can offer unmatched structural diversity and ample binding sites. Here we report the formation of a {Mo22Fe8} macrocycle by using the Preyssler anion, [NaP5W30O110]14− ({P5W30}), as a supramolecular template. The {Mo22Fe8} macrocycle displays selective anion binding behavior in solution. In the solid state, the 1 : 2 host–guest complex, {P5W30}2⊂{Mo22Fe8}, transports protons more effectively, through an extended hydrogen-bonding network, than a related 1 : 1 complex where the guest is completely encapsulated. The results highlight the great potential this anion templation approach has in producing macrocyclic systems for selective anion recognition and proton conduction purposes.

Knotting matters: orderly molecular entanglements.

Entangling strands in a well-ordered manner can produce useful effects, from shoelaces and fishing nets to brown paper packages tied up with strings. At the nanoscale, non-crystalline polymer chains of sufficient length and flexibility randomly form tangled mixtures containing open knots of different sizes, shapes and complexity. However, discrete molecular knots of precise topology can also be obtained by controlling the number, sequence and stereochemistry of strand crossings: orderly molecular entanglements. During the last decade, substantial progress in the nascent field of molecular nanotopology has been made, with general synthetic strategies and new knotting motifs introduced, along with insights into the properties and functions of ordered tangle sequences. Conformational restrictions imparted by knotting can induce allostery, strong and selective anion binding, catalytic activity, lead to effective chiral expression across length scales, binding modes in conformations efficacious for drug delivery, and facilitate mechanical function at the molecular level. As complex molecular topologies become increasingly synthetically accessible they have the potential to play a significant role in molecular and materials design strategies. We highlight particular examples of molecular knots to illustrate why these are a few of our favourite things.

Fluorinated leaning pillar[6]arene: synthesis, structure and selective iodide anion binding by anion-π interactions.

Anion recognition has continuously attracted significant attention due to its important role in environmental and biological sciences. Here, we have designed and synthesized an electron-deficient fluorinated leaning pillar[6]arene 1 that contains two tetrafluoro-benzene units. The electron-deficient fluorinated leaning pillar[6]arene 1 is capable of selectively recognizing iodide anions to form a host-guest complex with 1 : 1 stoichiometry driven by anion-π interactions. Our work ascribes this selective recognition to the preorganization of macrocycles, suitable cavity size, and the effect of anion-π interactions. The innovative application of this macrocycle offers us a new avenue for the design of selective receptors for anions and electron-deficient macrocyclic arenes.

Recognition competes with hydration in anion-triggered monolayer formation of cyanostar supra-amphiphiles at aqueous interfaces.

The triggered self-assembly of surfactants into organized layers at aqueous interfaces is important for creating adaptive nanosystems and understanding selective ion extraction. While these transformations require molecular recognition, the underlying driving forces are modified by the local environment in ways that are not well understood. Herein, we investigate the role of ion binding and ion hydration using cyanosurf, which is composed of the cyanostar macrocycle, and its binding to anions that are either size-matched or mis-matched and either weakly or highly hydrated. We utilize the supra-amphiphile concept where anion binding converts cyanosurf into a charged and amphiphilic complex triggering its self-organization into monolayers at the air–water interface. Initially, cyanosurf forms aggregates at the surface of a pure water solution. When the weakly hydrated and size-matched hexafluorophosphate (PF6−) and perchlorate (ClO4−) anions are added, the macrocycles form distinct monolayer architectures. Surface-pressure isotherms reveal significant reorganization of the surface-active molecules upon anion binding while infrared reflection absorption spectroscopy show the ion-bound complexes are well ordered at the interface. Vibrational sum frequency generation spectroscopy shows the water molecules in the interfacial region are highly ordered in response to the charged monolayer of cyanosurf complexes. Consistent with the importance of recognition, we find the smaller mis-matched chloride does not trigger the transformation. However, the size-matched phosphate (H2PO4−) also does not trigger monolayer formation indicating hydration inhibits its interfacial binding. These studies reveal how anion-selective recognition and hydration both control the binding and thus the switching of a responsive molecular interface.

Sensing and Catalysis Using Functionalized Oxoporphyrinogens

Simple oxoporphyrinogen (OxP) derivatives are excellent colorimetric sensors for a variety of analytes including anions, acidity and enantiomeric excess. More recently, this family of compounds has grown to include rim-functionalized compounds, which also exhibit colorimetric properties. In this work, we have prepared differently rim-functionalized OxPs and we will present their properties with respect to sensing, including selective anion binding, ion pair sensing andcoupled sensing of other important polluting species. The sensing properties of OxPs rely on intermolecular hydrogen bonding interactions which, in turn, imply their possible applications in organocatalysis. These properties will be described with an emphasis on the identity of macrocyclic substituents, and how catalytic activity of the OxP macrocycles is established. Structural aspects of OxPs influencing their sensing and organocatalytic activities will be discussed.

Electron deficient imine-based receptor for selective colorimetric recognition of cyanide ion through aromatic [sbnd]CH•••anion interactions

An electron withdrawing natured di-nitro substituted, imine based receptor L has been designed and synthesized. Naked-eye colorimetric experiment and UV–vis spectrometric studies reveals that the receptor L selectively binding the cyanide anion through C–H•••cyanide interaction. On the other hand, benzene analogue of receptor does not show any color and spectral change with cyanide ion. Though the receptor L do not have any strong traditional hydrogen bonding donor moieties, the obtained exclusive selectivity of L towards cyanide can be explained with help of Hay et al. theoretical postulates. Electron withdrawing natured functionalizations on the aromatic moiety of L is significantly enhanced the strength and selectivity of anion sensor L. Particularly, upon nitro substitution at 2nd and 4th phenyl ring of L, the un substituted aromatic –C–H groups are rehabilitated into relatively more acidic i.e. The aryl group having nitro functionalities that contributes to selective anion binding in cyanide complex of L through CH•••cyanide ion interactions. Detailed molecular electrostatic potential (MEP) map analysis supports our spectroscopy findings. To the best of our knowledge this is a first report of colorimetric sensing of cyanide majorly inclined by non-traditional aromatic-C–H•••cyanide interaction.

Selective Anion Binding Drives the Formation of AgI8L6 and AgI12L6 Six-Stranded Helicates.

Here we describe the formation of an unexpected and unique family of hollow six-stranded helicates. The formation of these structures depends on the coordinative flexibility of silver and the 2-formyl-1,8-napthyridine subcomponent. Crystal structures show that these assemblies are held together by Ag4I, Ag4Br, or Ag6(SO4)2 clusters, where the templating anion plays an integral structure-defining role. Prior to the addition of the anionic template, no six-stranded helicate was observed to form, with the system instead consisting of a dynamic mixture of triple helicate and tetrahedron. Six-stranded helicate formation was highly sensitive to the structure of the ligand, with minor modifications inhibiting its formation. This work provides an unusual example of mutual stabilization between metal clusters and a self-assembled metal–organic cage. The selective preparation of this anisotropic host demonstrates new modes of guiding selective self-assembly using silver(I), whose many stable coordination geometries render design difficult.

Molecular Recognition and Hydration Energy Mismatch Combine To Inform Ion Binding Selectivity at Aqueous Interfaces.

There is a critical need for receptors that are designed to enhance anion binding selectivity at aqueous interfaces in light of the growing importance of separation technologies for environmental sustainability. Here, we conducted the first study of anion binding selectivity across a series of prevalent inorganic oxoanions and halides that bind to a positively charged guanidinium receptor anchored to an aqueous interface. Vibrational sum frequency generation spectroscopy and infrared reflection absorption spectroscopy studies at the water-air interface reveal that the guanidinium receptor binds to an oxoanion series in the order SO42- > H2PO4- > NO3- > NO2- while harboring very weak interactions with the halides in the order I- > Cl- ≈ Br-. In spite of large dehydration penalties for sulfate and phosphate, the more weakly hydrated guanidinium receptor was selective for these oxoanions in contradiction to predictions made from ion partitioning alone, like the Hofmeister series and Collins's rules. Instead, sulfate binding is likely favored by the suppression of dielectric screening at the interface that consequently boosts Coulombic attractions, and thus helps offset the costs of anion dehydration. Geometric factors also favor the oxoanions. Furthermore, the unique placement of iodide in our halide series ahead of the stronger hydrogen-bond acceptors (Cl-, Br-) suggests that the binding interaction also depends upon single-ion surface partitioning from bulk water to the interface. Knowledge of the anion binding preferences displayed by a guanidinium receptor sheds light on the receptor architectures needed within designer interfaces to control selectivity.

Synthesis of i-Corona[6]arenes for Selective Anion Binding: Interdependent and Synergistic Anion-π and Hydrogen-Bond Interactions.

i-Corona[3]arene[3]tetrazines were synthesized from the nucleophilic aromatic substitution reaction of resorcinol and its derivatives with 3,6-dichlorotetrazine in a one-pot fashion under mild conditions. All of the resulting macrocycles adopted 1,3,5-alternate conformation irrespective of the nature of the substituents on both upper- and lower-rims. i-Corona[3]arene[3]tetrazine was found to self-regulate its macrocyclic conformation and cavity to recognize anions with binding constants spanning from 26 M-1 to 2.2×103 M-1 depending on the structure of the anions. The selective binding resulted from a significant interdependent and synergistic effect between multiple tetrazine π/anion and Caryl -H/anion hydrogen bond interactions. Taking advantage of synergistic effect revealed, a cyanobenzene-embedded i-corona[3]arene[3]tetrazine was designedly synthesized and highly selective and very strong affinity toward nitrate with a binding constant of 2.2×105 M-1 was achieved.