Anion recognition by neutral macrocyclic amides

Although amides often serve as anchoring groups in natural and synthetic anion receptors, the structure-affinity relationship studies of amide-based macrocyclic receptors are still very limited. Therefore, we decided to investigate the influence of the size of the macroring on the strength and selectivity of anion binding by uncharged, amide-based receptors. With this aim, we synthesized a series of macrocyclic tetraamides derived from 2,6-pyridinedicarboxylic acid and aliphatic alpha,omega-diamines of different lengths. X-ray analysis shows that all ligands studied adopt expanded conformations in the solid state with the convergent arrangement of all four hydrogen-bond donors. 1H NMR titrations in DMSO solution revealed a significant effect of the ring size on the stability constants of anion complexes; the 20-membered macrocyclic tetraamide 2 is a better anion receptor than its both 18- and 24-membered analogues. This effect cannot be interpreted exclusively in terms of matching between anion diameter and the size of macrocyclic cavity, because 2 forms the most stable complexes with all anions studied, irrespective of their sizes. However, geometric complementarity manifests in extraordinarily high affinity of 2 towards the chloride anion. The results obtained for solutions were interpreted in the light of solid-state structural studies. Taken together, these data suggest that anion binding by this family of macrocycles is governed by competitive interplay between their ability to adjust to a guest, requiring longer aliphatic spacers, and preorganization, calling for shorter spacers. The 20-membered receptor 2 is a good compromise between these factors and, therefore, it was selected as a promising leading structure for further development of anion receptors. Furthermore, the study of an open chain analogue of 2 revealed a substantial macrocyclic effect. X-ray structure of the acyclic model 14 suggests that this may be due to its ill-preorganized conformation, stabilized by two intramolecular hydrogen bonds.     

Sulfate‐Selective Recognition by Using Neutral Dipeptide Anion Receptors in Aqueous Solution

The synthesis of six small peptide anion receptors based on thiourea and squaramide recognition moieties is described. These new receptors bind to tetrahedral sulfate anions with remarkable affinity and selectivity in aqueous solution as shown by NMR spectroscopy. Molecular modelling suggests that selectivity is mediated by a hydrogen bond network incorporating the amide backbone protons in a manner similar to that found in the sulfate‐binding protein.     

Bile acid-based cyclic bisbenzimidazolium receptors for anion recognition: highly improved receptors for fluoride and chloride ions

The anion binding properties of bile acid-based cyclic bisbenzimidazolium receptors 6-8 bridged with m-xylene, p-xylene, and 2,6-dimethylpyridine have been studied. Receptors 6 and 7 exhibit much higher binding affinity for fluoride and chloride ions, respectively, as compared to the imidazolium receptors 1 and 2. Receptor 8, however, shows high selectivity but very low binding affinity for anions due to the presence of pyridyl nitrogen. The single-crystal X-ray structure of imidazolium receptor 10-(Br)2 containing pyridyl spacer reveals the binding pattern.     

Influence of charge on anion receptivity in amide-based macrocycles

Binding and structural aspects of anions with tetraamido/diquaternized diamino macrocyclic receptors containing m-xylyl, pyridine, and thiophene spacers are reported. (1)H NMR studies indicate that the quaternized receptors display higher affinities for anions compared to corresponding neutral macrocycles. The macrocycles containing pyridine spacers consistently display higher affinity for a given anion compared to those with either m-xylyl or thiophene spacers. The m-xylyl- and pyridine-containing receptors exhibit high selectivity for H(2)PO(4)(-) in DMSO-d(6) with association constants, K(a) = 1.09 × 10(4) and >10(5) M(-1), respectively, and moderate selectivity for Cl(-) with K(a) = 1.70 × 10(3) and 5.62 × 10(4) M(-1), respectively. Crystallographic studies for the Cl(-) and HSO(4)(-) complexes indicate that the m-xylyl-containing ligand is relatively elliptical in shape, with the two charges at ends of the major axis of the ellipse. The anions are hydrogen bonded with the macrocycle but are outside the ligand cavity. In the solid state, an unusual low-barrier hydrogen bond (LBHB) was discovered between two of the macrocycle's carbonyl oxygen atoms in the HSO(4)(-) complex. The pyridine-containing macrocycle folds so that the two pyridine units are face-to-face. The two I(-) ions are chelated to the two amides adjacent to a given pyridine. In the structure of the thiophene containing macrocycle with two BPh(4)(-) counterions, virtually no interaction was observed crystallographically between the macrocycle and the bulky anions.     

Strapped and other topographically nonplanar calixpyrrole analogues. Improved anion receptors

Calixpyrroles and related macrocycles are non-aromatic synthetic anion receptors that have attracted considerable attention in recent years. The unfunctionalized, parent calix[4]pyrrole system, also known as octamethylporphyrinogen, may be prepared in one step and in high yield from pyrrole and acetone, and is an effective anion receptor, showing a preference for fluoride, phosphate, carboxylate and chloride anions in organic media. Efforts to improve the anion binding affinity of calix[4]pyrrole and to modify its inherent selectivity have led to the synthesis of a variety of new, modified calixpyrroles. Among the most effective of these are derivatives that contain bridging "straps". In this Feature Article, the preparation and properties of these and other topographically nonplanar calixpyrrole analogues are reviewed from the perspective of the anion recognition chemist.     

2-羟基萘甲醛苯腙衍生物对氟阴离子的高选择性裸眼识别

合成了3种2-羟基萘甲醛苯腙衍生物[1～3;取代基R:H(1),p-NO2(2),2,4-d-NO2(3)],应用紫外-可见吸收光谱研究了其与阴离子的相互作用,通过改变N1-苯环取代基考察了受体分子对阴离子亲合力和选择性的影响.结果表明,乙腈中F-及CH3COO-等阴离子使受体分子吸收光谱发生显著变化,溶液的颜色由黄色...     

Anion receptors: a new class of amide/quaternized amine macrocycles and the chelate effect

A new class of tetraamide macrocyclic receptors for anions with two quaternized amine functionalities exhibited higher affinities for anions compared with the corresponding neutral amides. In two crystal structures of halide complexes of the prototypes with phenyl and pyridine spacers, the anions are held by hydrogen bonding with the amide hydrogens. The pyridine analogues display higher affinities in general than the phenyl systems, a phenomenon which is attributed to the anion version of the chelate effect.     

Bipyrrole- and dipyrromethane-based amido-imine hybrid macrocycles. New receptors for oxoanions

Three new amido-imine-type hybrid macrocycles based on substituted pyrrole units have been synthesized and shown to act as effective receptors for oxoanions in the solid state and in acetonitrile solution. One of the macrocycles in question, compound 15, was characterized by X-ray diffraction analysis as the free macrocycle and as a complex with sulfuric acid. A comparison of the resulting structures reveals that this receptor is capable of undergoing a conformational change and, as a consequence, varying the number of donor sites that can interact with a bound substrate. This system and the other two new receptors described in this work (macrocycles 14 and 16, respectively) display a high affinity toward oxoanions (studied as their tetrabutylammonium (TBA) salts), with association constants on the order of 10(7) M-1 being determined in acetonitrile solution using standard UV-vis spectroscopic titration methods. A competitive titration method was used to determine affinity constants in excess of ca. 10(6) M-1. Two of the receptors (14 and 15) were found to bind acetate, hydrogen sulfate, and dihydrogen phosphate anion well, and the bipyrrole-based receptor (14) was also found to bind the perrhenate anion. In contrast, the bis-dipyrromethane-derived receptor (16) was found to bind chloride anion preferentially. The unusual selectivity displayed by 16 for this spherical anion was rationalized on the basis of single-crystal X-ray diffraction data and DFT modeling calculations, which revealed a rigid structure appropriately suited for chloride anion recognition.     

Pyrrolic and polypyrrolic anion binding agents

This review traces the emergence of pyrrole-based receptors for anion recognition. It outlines how serendipitous findings that the diprotonated form of sapphyrin, a pentapyrrolic expanded porphyrin, formed a centrally-bound complex with fluoride anion made over a decade ago spawned studies of this and other expanded porphyrins as receptors, carriers, and sensors of anions. Further evolutions of the field, including in particular the finding that neutral, non-aromatic oligopyrrole macrocycles, such as the calixpyrroles and calixphyrins, can act as cheap, and easy-to-prepare anion receptors will also be highlighted, as will recent work with acyclic systems, including dipyrrolylquinoxalines (DPQs) and simple derivatives of pyrrole itself.     

Pendant arm pyrrolic amide cleft anion receptors

The propensity of amine, ammonium and amide pendant arm 2,5-diamidopyrrole derivatives to act as anion receptors has been investigated; the anion-coordination ability of these species has been determined by 1H NMR titration techniques revealing a marked selectivity of the amine functionalised receptor for hydrogen sulfate anions.     

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.     

Bis-amidopyrrolyl receptors based on anthracene and carbazole

A new set of diamide receptors containing anthracene and carbazole bridging subunits and either pyrrole or phenyl substituents were synthesised. The four systems produced in this way were shown to bind representative anions in DMSO-d ₆ solution and in the solid state. A higher relative affinity for two test oxoanions, namely dihydrogen phosphate and benzoate, over chloride anion was seen in solution, with the anions in question being studied in the form of their respective tetrabutylammonium salts. However, the specifics of the anion recognition process were seen to depend on structure, with the pyrrole-containing systems displaying higher relative affinities than their corresponding phenyl-containing congeners, and the carbazole receptors proving more effective than the anthracene analogues. Such observations provide support for the notion that both the carbazole NH and the pyrrolic NH protons play an important role in stabilising the receptor-bound anions in solution. Structural analyses of several anion complexes of the diamidopyrrole carbazole receptor reveal that this is not necessarily the case in the solid state; specifically, the pyrrole NH protons are seen to interact with the amide oxygen of another molecule. The net result is an extended one-dimensional coordination polymer.     

N-confused calix[4]pyrroles

This is a first review devoted to N-confused calix[4]pyrroles (NCCPs). NCCPs are a relatively recent arrival to the family of the pyrrole-based anion binding macrocycles, being for the first time identified in 1999. Yet, in a relatively short time these calix[4]pyrrole (CP) isomers attracted attention of the community of research groups interested in anion binding and sensing. This is because they are relatively easy to synthesize, but mainly because they posses anion-binding properties that are different from that of regular calix[4]pyrroles. The difference in anion-binding properties stems from a different binding mode between the NCCP and anion. While the regular CPs adopt in the complex an ideal cone-like conformation where all four pyrroles-NHs engage in hydrogen bonding to the anion, the inverted pyrroles do not allow forming the cone. NCCPs bind anions via a confused cone (CC), by three NH hydrogen bonds with an anion and a CH–anion contact. This different binding mode results also in different anion-binding affinity and selectivity compared to regular CPs. Also, the inverted pyrroles offer a unique possibility for selective chemical modification of the receptor. The corresponding colorimetric sensors were tested for anion binding applications. The results of colorimetric assays for anions are presented and potential applications discussed.     

A Bambusuril Macrocycle that Binds Anions in Water with High Affinity and Selectivity

Synthetic receptors that function in water are important for the qualitative and quantitative detection of anions, which may act as pollutants in the environment or play important roles in biological processes. Neutral receptors are particularly appealing because they are often more selective than positively charged receptors; however, their affinity towards anions in pure water is only in range of 1–10³ L mol^?1. The anion‐templated synthesis of a water‐soluble bambusuril derivative is shown to be an outstanding receptor for various inorganic anions in pure water, with association constants of up to 10⁷ L mol^?1. Furthermore, the macrocycle discriminates between anions with unprecedented selectivity (up to 500 000‐fold). We anticipate that the combination of remarkable affinity and selectivity of this macrocycle will enable the efficient detection and isolation of diverse anions in aqueous solutions, which is not possible with current supramolecular systems.     

Chuan-Cai Fan;Li-Jin Xu;Han-Yuan Gong;%T Neutral C–H bond vs. electron pair of N（sp~2）： A binding site effect study of macrocycle anion receptor

To evaluate the effect of neutral C–H bond or electron pair of nitrogen atom with sp2hybridization（N（sp2）） involving into the same chemical environment for anion binding, two analogous tetracationic imidazolium macrocycles, namely cyclo[2]（2,6-bis-（1H-imidazol-1-yl）pyridine） [2]（1,3-dimethylenebenzene）（14＋）, and cyclo[2]（2,6-bis-（1H-imidazol-1-yl）pyridine）[2]（2,6-di methylenepyridine）（24＋）were studied in detail as small inorganic anion receptors. The guest anions with different shapes are Cl,N3, NO3, and H2PO4. The host–guest interactions were characterized via1 H NMR spectroscopy,electrospray ionization mass spectrometry（ESI-MS） and single crystal X-ray crystallography. The results implied that macrocyclic hosts with similar backbone but two distinct binding sites（14＋with neutral C–H vs. 24＋with N（sp2）） vary markedly in their response to anions, including the binding modes and association constants. The finding will serve to the construction of new anion receptors, even improve insights into the anion binding process in biology.     

Bambus[n]urils: a new family of macrocyclic anion receptors

A recently discovered anion receptor is jointed by three related macrocycles differing in the number of glycoluril units and type of substitution. The synthesis is carried out in nonpolar solvents compared to aqueous media used in the case of the original macrocycle. The size of macrocycle is controlled by a template. A hexameric macrocycle with benzyl substitution binds halide anions with an affinity exceeding 10(9) M(-1) while a tetrameric analog does not bind any of the investigated anions.     

Buried solvent determines both anion-binding selectivity and binding stoichiometry with hydrogen-bonding receptors

[reaction: see text] The crystal structure of a tetraurea picket porphyrin-chloride anion complex has previously shown the anion to be situated between two adjacent ureas and hydrogen bonded via four NH protons (J. Am. Chem. Soc. 1998, 120, 11684-11692). The porphyrin receptor also binds a DMSO molecule and utilizes it as a participant in its anion recognition unit, in a manner similar to enzymes that bind water for use as part of their substrate recognition unit. The bound solvent molecule determines the anion-binding affinity, selectivity, and stoichiometry of binding. With a bound DMSO molecule, the tetraurea picket porphyrin is a highly selective receptor for chloride anion and binds all anions with a 1:1 binding stoichiometry. Absent the buried DMSO molecule, the receptor is selective for phosphate anion and binds chloride and phosphate anions with both 1:1 and 1:2 receptor-anion stoichiometries. Additionally, a remarkable reversal in the selectivity of anion complexation between various picket porphyrin receptors is observed, wherein the binding constant ratios change over 3 orders of magnitude as the receptor's number of urea pickets change from four to two. The latter receptor has no urea pickets available to bind to solvent after complexation with an anion. The results demonstrate that anion complexation with hydrogen-bonding receptors in a competitive solvent is enhanced when a ubiquitous solvent molecule is incorporated into the binding motif. In this way, competitive solvent adds to the overall complexation energy and thereby strengthens binding rather than weakens it, as commonly believed. The results are pertinent to drug design, for they suggest that pharmaceuticals need not be completely desolvated to selectively bind to their biological target when water can be included in the binding motif.     

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-binding behavior of hybrid calixpyrroles

Hybrid calixpyrrole systems are calixpyrrole-like macrocycles that are based on more than one type of small molecule building block. Structurally, these "mixed-breed" macrocycles differ from calixpyrroles in that some pyrrolic units in the latter are replaced by other hetereocyclic units such as furan, thiophene, bipyrrole, and bithiophene. Although several such systems have been reported in recent years, only a few have been studied as possible anion receptors. In this paper, the results of detailed anion binding studies involving several prototypic systems are reported. Taken in concert, these results highlight the fact that some hybrid systems, including compounds 2-5, display anion affinities that are considerably weaker than those of the parent system 1. On the other hand, they also show that compounds 6-8 are good receptors for "Y-shaped" anions, such as carboxylates, and that they bind these species with high affinity. These findings are strongly supported by solid-state structural studies, which reveal an interesting "cross binding mode" for the binding of carboxylate anions by the bis-thiophene, bis-pyrrole system 7.     

Recognition, encapsulation, and selective fluorescence sensing of nitrate anion by neutral C3-symmetric tripodal podands bearing amide functionality

A series of neutral C(3)-symmetric acyclic artificial receptors incorporating amide functionality has been designed, synthesized, and fully characterized. Upon protonation, these conformationally flexible N-bridged tripodal podands 1-5 form in situ cone shape conformation through hydrogen bonding and C-H···π interactions. The protonation-induced interior preorganized cavity is capable of entrapping nitrate anions through the amide N-H bonds to form discrete nitrate complexes (1a-5a), which were fully characterized by NMR, HRESI mass spectra, and single crystal structures. By incorporating suitable fluorophores at each branch of the tripod receptor, the resulting fluorescent receptor 5 selectively recognized nitrate anions by fluorescent quenching in a DMSO solution and displayed one of the highest binding affinities for nitrate anions reported so far in polar media. Receptor 5 represents a unique example of a neutral receptor for the recognition of nitrate anions in polar solvent media by its zwitterionic form. The possible mechanism of proton-induced preorganization of these flexible, acyclic receptors in a convergent cone conformation followed by nitrate complexation has been proposed to rationalize the effective nitrate recognition.