Ion‐Pair Recognition by a Heteroditopic Triazole‐Containing Receptor

A new heteroditopic calix[4]diquinone triazole containing receptor capable of recognising both cations and anions through Lewis base and C? H hydrogen‐bonding modes, respectively, of the triazole motif has been prepared. This ion‐pair receptor cooperatively binds halide/monovalent‐cation combinations in an aqueous mixture, with selectivity trends being established by ¹H NMR and UV/Vis spectroscopy. Cation binding by the calix[4]diquinone oxygen and triazole nitrogen donors enhances the strength of the halide complexation at the isophthalamide recognition site of the receptor. Conversely, anions bound in the receptor’s isophthalamide cavity enhance cation recognition. ¹H NMR investigations in solution suggest that the receptor’s triazole motifs are capable of coordinating simultaneously to both cation and anion guest species. Solid‐state X‐ray crystallographic structural analysis of a variety of receptor ion‐pair adducts further demonstrates the dual cation–anion binding role of the triazole group.     

Unexpectedly strong anion–π interactions on the graphene flakes

Interactions of anions with simple aromatic compounds have received growing attention due to their relevancy in various fields. Yet, the anion–π interactions are generally very weak, for example, there is no favorable anion–π interaction for the halide anion F^? on the simplest benzene surface unless the H‐atoms are substituted by the highly negatively charged F. In this article, we report a type of particularly strong anion–π interactions by investigating the adsorptions of three halide anions, that is, F^?, Cl^?, and Br^?, on the hydrogenated‐graphene flake using the density functional theory. The anion–π interactions on the graphene flake are shown to be unexpectedly strong compared to those on simple aromatic compounds, for example, the F^?‐adsorption energy is as large as 17.5 kcal/mol on a graphene flake (C₈₄H₂₄) and 23.5 kcal/mol in the periodic boundary condition model calculations on a graphene flake C₁₁₃ (the supercell containing a F^? ion and 113 carbon atoms). The unexpectedly large adsorption energies of the halide anions on the graphene flake are ascribed to the effective donor–acceptor interactions between the halide anions and the graphene flake. These findings on the presence of very strong anion–π interactions between halide ions and the graphene flake, which are disclosed for the first time, are hoped to strengthen scientific understanding of the chemical and physical characteristics of the graphene in an electrolyte solution. These favorable interactions of anions with electron‐deficient graphene flakes may be applicable to the design of a new family of neutral anion receptors and detectors. © 2012 Wiley Periodicals, Inc.     

Aza‐Bambusurils En Route to Anion Transporters

Previous calculations of anion binding with various bambusuril analogs predicted that the replacement of oxygen by nitrogen atoms to produce semiaza‐bambus[6]urils would award these new cavitands with multiple anion binding properties. This study validates the hypothesis by efficient synthesis, crystallography, thermogravimetric analysis and calorimetry. These unique host molecules are easily accessible from the corresponding semithio‐bambusurils in a one‐pot reaction, which converts a single anion receptor into a potential anion channel. Solid‐state structures exhibit simultaneous accommodation of three anions, linearly positioned within the cavity along the main symmetry axis. The ability to hold anions at a short distance of about 4 Å is reminiscent of natural chloride channels in E. coli, which exhibit similar distances between their adjacent anion binding sites. The calculated transition‐state energy for double‐anion movement through the channel suggests that although these host–guest complexes are thermodynamically stable they enjoy high kinetic flexibility to render them efficient anion channels.     

Dramatic Enhancement of Binding Affinities Between Foldamer‐Based Receptors and Anions by Intra‐Receptor π‐Stacking

As a synthetic model for intra‐protein interactions that reinforce binding affinities between proteins and ligands, the energetic interplay of binding and folding was investigated using foldamer‐based receptors capable of adopting helical structures. The receptors were designed to have identical hydrogen‐bonding sites for anion binding but different aryl appendages that simply provide additional π‐stacking within the helical backbones without direct interactions with the bound anions. In particular, the presence of electron‐deficient aryl appendages led to dramatic enhancements in the association constant between the receptor and chloride or nitrate ions, by up to three orders of magnitude. Extended stacking within the receptor contributes to the stabilization of the entire folding structure of complexes, thereby enhancing binding affinities.     

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.     

Orbital Effect‐Induced Anomalous Anion–π Interactions between Electron‐Rich Aromatic Hydrocarbons and Fluoride

Anion–π interactions generally exist between an anion and an electron‐deficient π‐ring because of the electron‐accepting character of the ring. In this paper, we report orbital effect‐induced anomalous binding between electron‐rich π systems and F^? through anion–π interactions calculated at the MP2/6‐31+G(d,p) and ωB97X‐D/6‐31+G(d,p) levels of theory. We find that anion–π interactions between F^? and electron‐rich π rings increase markedly with increasing number of π electrons and size of the π rings. This is contrary to intuition because anion–π interactions would be expected to gradually decrease because of gradually increasing Coulombic repulsion between the negative charge of the anions and gradually increasing number of π electrons of the aromatic surfaces. Energy decomposition analysis showed that the key to this anomalous effect is the more effective delocalization of negative charge to the unoccupied π* orbitals of larger π rings, which is termed an “orbital effect”.     

Self‐Assembly and Disassembly of Vesicles as Controlled by Anion–π Interactions

Anion–π interactions have been widely studied as new noncovalent driving forces in supramolecular chemistry. However, self‐assembly induced by anion–π interactions is still largely unexplored. Herein we report the formation of supramolecular amphiphiles through anion–π interactions, and the subsequent formation of self‐assembled vesicles in water. With the π receptor 1 as the host and anionic amphiphiles, such as sodium dodecylsulfate (SDS), sodium laurate (SLA), and sodium methyl dodecylphosphonate (SDP), as guests, the sequential formation of host–guest supramolecular amphiphiles and self‐assembled vesicles was demonstrated by SEM, TEM, DLS, and XRD techniques. The intrinsic anion–π interactions between 1 and the anionic amphiphiles were confirmed by crystal diffraction, HRMS analysis, and DFT calculations. Furthermore, the controlled disassembly of the vesicles was promoted by competing anions, such as NO₃^?, Cl^?, and Br^?, or by changing the pH value of the medium.     

Molecular Complexes of Simple Anions with Electron‐Deficient Arenes: Spectroscopic Evidence for Two Types of Structural Motifs for Anion–Arene Interactions

Anion–π interactions between a π‐acidic aromatic system and an anion are gaining increasing recognition in chemistry and biology. Herein, the binding features of an electron‐deficient aromatic system (1,3,5‐trinitrobenzene (TNB)) and selected anions (OH^?, Br^?, and I^?) are examined in the gas phase by using the combined information derived from collision‐induced dissociation experiments at variable energy, infrared multiple‐photon dissociation spectroscopy, and quantum chemical calculations. We provide spectroscopic evidence for two different structural motifs of anion–arene complexes depending on the nature of the anion. The TNB–OR^? complexes (R=H, or alkyl groups which were studied earlier) adopt an anionic σ‐complex structure whereby RO^? attacks the aromatic ring with covalent bond formation, and develops a tetrahedral ring carbon bound to H and OR. The halide complexes rather conform to a structure in which the TNB moiety is hardly altered, and the halogen is placed on an unsubstituted carbon atom over the periphery of the ring at a C–X distance that is appreciably longer than a typical covalent bond length. The ensuing structural motif, previously characterized in the solid state and named weak σ interaction, is now confirmed by an IR spectroscopic assay in the gas phase, in which the sampled species are unperturbed by crystal packing or solvation effects.     

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.     

Ion‐Pairing Assemblies of Porphyrin–AuIII Complexes in Combination with π‐Electronic Receptor–Anion Complexes

Anion complexes of anion‐responsive π‐electronic molecules can behave as pseudo π‐electronic anions providing various ion pairs in combination with countercations. In this study, single crystals of ion‐pairing assemblies comprising porphyrin–Au^III complexes and Cl^? complexes of dipyrrolyldiketone BF₂ complexes were prepared from 1:1 mixtures of anion receptors and the Cl^? salts of cationic porphyrins in solution. In the solid state, the ion pairs formed characteristic assemblies, depending on the substituents of the anion receptors and porphyrin–Au^III complexes. Theoretical calculations on the ion pairs revealed that the stacking structures are stabilized by compensating positive and negative charges as well as π–π interactions.     

1,3‐Alternate Tetraamido‐Azacalix[4]arenes as Selective Anion Receptors

Six tetraaza[1.1.1.1]cyclophane derivatives bearing peripheral amide groups were prepared according to two distinct synthetic strategies that depend on the connection pattern between the aryl units. NMR experiments combined with the X‐ray structures of two tetraamide derivatives 4 b and 10 show that these cavitands adopt a 1,3‐alternate conformation both in solution and in the solid state. Consequently, the four amide groups of the aza[1.1.1.1]‐m,m,m,m‐cyclophane isomer 10 can contribute to the same recognition process towards neutral water molecules or anion guests. NMR experiments, mass spectrometry analyses and single‐crystal X‐ray structures confirm the anion‐binding ability of this receptor. Absorption spectrophotometric titrations in nonpolar solvents provided evidence for the selectivity of 10 to chloride anions in the halide series, with a corresponding association constant K_a reaching 2.5×10⁶ m ^?1.     

CH‐Directed Anion–π Interactions in the Crystals of Pentafluorobenzyl‐Substituted Ammonium and Pyridinium Salts

Simple pentafluorobenzyl‐substituted ammonium and pyridinium salts with different anions can be easily obtained by treatment of the parent amine or pyridine with the respective pentafluorobenzyl halide. Hexafluorophosphate is introduced as the anion by salt metathesis. In the case of the ammonium salt 4 , water co‐crystallisation seems to suppress effective anion–π interactions of bromide with the electron‐deficient aromatic system, whereas with salts 5 and 6 such interactions are observed despite the presence of water. However, due to asymmetric hydrogen‐bonding interactions with ammonium side chains, the anion of 5 is located close to the rim of the pentafluorophenyl group (η¹ interaction). In 6 the CH–anion hydrogen bonding is more symmetric and fixes the anion on top of the ring (η⁶). A similar structure‐controlling effect is observed in case of the 1,4‐diazabicyclo[2.2.2]octane derivatives 7 . Here the position of the anion (Cl, Br, I) is shifted according to the length of the weak CH–halide interaction. The hexafluorophosphate 7 d reveals that this “non‐coordinating” anion can be located on top of an aromatic π system. In the methyl‐substituted pyridinium salts 9 and 10 different locations of the bromide anions with respect to the π system are observed. This is due to different conformations of the mono‐ versus disubstituted pyridine, which leads to different directions of the weak, but structurally important, H_Me? Br bonds.     

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.     

Ion‐Pair Complexation with a Cavitand Receptor

The capability of resorcinarenes to bind anions within the alkyl feet at the lower rim has been exploited as the starting point for developing a new cavitand able to engulf contact ion pairs of primary ammonium salts in chlorinated solvents with association constants (K_ass) in the range of 10³–10⁴ M ^?1. Methylene bridges were introduced into the upper rim to freeze the resorcinarene in the cone conformation with the four H_down protons converging in the lower pocket, thereby maximizing the CH–anion interactions responsible for the anion binding. Four additional phosphate moieties were introduced into the lower rim in close proximity to the anionic site to provide hydrogen‐bonding‐acceptor P?O groups and promote cation complexation at the bottom of the cavitand. The binding ability of the synthesized ligands was analyzed by ¹H NMR spectroscopy and, when possible, by isothermal titration calorimetry (ITC); the data were in agreement when complementary techniques were used.     

Chloride‐Selective Electrodes Based on “Two‐Wall” Aryl‐Extended Calix[4]Pyrroles: Combining Hydrogen Bonds and Anion–π Interactions to Achieve Optimum Performance

The performance of chloride‐selective electrodes based on “two‐wall” aryl‐extended calix[4]pyrroles and multiwall carbon nanotubes is presented. The calix[4]pyrrole receptors bear two phenyl groups at opposite meso‐positions. When the meso‐phenyl groups are decorated with strong electron‐withdrawing substituents, attractive anion–π interactions may exist between the receptor’s aromatic walls and the sandwiched anion. These anion–π interactions are shown to significantly affect the selectivity of the electrodes. Calix[4]pyrrole, bearing a p‐nitro withdrawing group on each of the meso‐phenyl rings, afforded sensors that display anti‐Hofmeister behavior against the lipophilic salicylate and nitrate anions. Based on the experimental data, a series of principles that help in predicting the suitability of synthetic receptors for use as anion‐specific ionophores is discussed. Finally, the sensors deliver excellent results in the direct detection of chloride in bodily fluids.     

Anion–π Slides for Transmembrane Transport

The recognition and transport of anions is usually accomplished by hydrogen bonding, ion pairing, metal coordination, and anion–dipole interactions. Here, we elaborate on the concept to use anion–π interactions for this purpose. Different to the popular cation–π interactions, applications of the complementary π‐acidic surfaces do not exist. This is understandable because the inversion of the aromatic quadrupole moment to produce π‐acidity is a rare phenomenon. Here, we suggest that π‐acidic aromatics can be linked together to produce an unbendable scaffold with multiple binding sites for anions to move along across a lipid bilayer membrane. The alignment of multiple anion–π sites is needed to introduce a cooperative multi‐ion hopping mechanism. Experimental support for the validity of the concept comes from preliminary results with oligonaphthalenediimide (O‐NDI) rods. Predicted by strongly positive facial quadrupole moments, the cooperativity and chloride selectivity found for anion transport by O‐NDI rods were consistent with the existence of anion–π slides. The proposed mechanism for anion transport is supported by DFT results for model systems, as well as MD simulations of rigid O‐NDI rods. Applicability of anion–π slides to achieve electroneutral photosynthesis is elaborated with the readily colorizable oligoperylenediimide (O‐PDI) rods. To clarify validity, scope and limitations of these concepts, a collaborative research effort will be needed to address by computer modeling and experimental observations the basic questions in simple model systems and to design advanced multifunctional anion–π architectures.     

Insights into the Complexity of Weak Intermolecular Interactions Interfering in Host–Guest Systems

The recognition properties of heteroditopic hemicryptophane hosts towards anions, cations, and neutral pairs, combining both cation–π and anion–π interaction sites, were investigated to probe the complexity of interfering weak intermolecular interactions. It is suggested from NMR experiments, and supported by CASSCF/CASPT2 calculations, that the binding constants of anions can be modulated by a factor of up to 100 by varying the fluorination sites on the electron‐poor aromatic rings. Interestingly, this subtle chemical modification can also reverse the sign of cooperativity in ion‐pair recognition. Wavefunction calculations highlight how short‐ and long‐range interactions interfere in this recognition process, suggesting that a disruption of anion–π interactions can occur in the presence of a co‐bound cation. Such molecules can be viewed as prototypes for examining complex processes controlled by the competition of weak interactions.     

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.     

CF3: An Electron‐Withdrawing Substituent for Aromatic Anion Acceptors? “Side‐On” versus “On‐Top” Binding of Halides

The ability of multiple CF₃‐substituted arenes to act as acceptors for anions is investigated. The results of quantum‐chemical calculations show that a high degree of trifluoromethyl substitution at the aromatic ring results in a positive quadrupole moment. However, depending on the polarizability of the anion and on the substitution at the arene, three different modes of interaction, namely Meisenheimer complex, side‐on hydrogen bonding, or anion–π interaction, can occur. Experimentally, the side‐on as well as a η²‐type π‐complex are observed in the crystal, whereas in solution only side‐on binding is found.