Anion binding by pyrrole–pyridine-based macrocyclic polyamides

The synthesis, characterisation and anion-binding properties of new pyrrole–pyridine-based macrocyclic polyamides 7a and 7b are presented. Chloride anion templation in the macrocyclisation reaction has been shown to control [1 + 1] acylation. The anion-binding properties of the receptors have been determined by UV–vis titrations in a DMSO solution and compared with systems with a similar design. The new receptors have been found to display a 10-fold selectivity for hydrogensulphate, dihydrogenphosphate and acetate anions over other anions studied.     

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.     

Conformational control of selectivity and stability in hybrid amide/urea macrocycles

The anion-binding properties of two similar hybrid amide/urea macrocycles containing either a 2,6-dicarboxamidophenyl or a 2,6-dicarboxamidopyridine group are compared. Significant differences in anion affinity and mode of interaction with anions are attributed to the presence of intramolecular hydrogen bonds in the pyridine system. In fact, remarkably, the phenyl macrocycle undergoes amide hydrolysis under neutral conditions in DMSO/water. The anion binding abilities of the receptors are compared to those of acyclic analogues of the macrocycles that show that the phenyl receptor behaves in a similar fashion to acyclic urea-containing receptors (i.e., showing little selectivity amongst oxo anions), whilst the pyridine-containing receptor shows a high affinity and selectivity for carboxylates.     

Ring Size Determines the Conformation,Global Aromaticity and Photophysical Properties of Macrocyclic Oligofurans

In π-conjugated macrocycles, there is a trade-off between the global and local expression of effects such as aromaticity, with the outcome of the trade-off determined by the geometry and aromaticity of the constituent units. Compared with other aromatic rings, the aromatic character of furan is relatively small, and therefore global effects in macrocyclic furans are expected to be more pronounced. Following our introduction of macrocyclic oligofuran, we present the first synthesis of a series of π-conjugated bifuran macrocycles of various ring sizes, from trimer to hexamer, and characterize them using both computational and experimental methods. The properties of macrocyclic oligofurans change considerably with size: The smaller trimer is rigid, weakly emissive and planar as revealed by its single crystal structure, and displays global antiaromaticity. In contrast, the larger pentamer and hexamer are flexible, emissive, have non-planar structures, and exhibit local aromaticity. The results are supported by NICS and ACID calculations that indicate the global antiaromaticity of planar furan macrocycles, and by transient absorption measurements showing sharp absorption band for the trimer and only the internal conversion decay pathway.     

Anion binding versus intramolecular hydrogen bonding in neutral macrocyclic amides

Although amide groups are important hydrogen-bond donors in natural and synthetic anion receptors, studies on structure-affinity relationships of amide-based macrocyclic receptors are still very limited. Therefore, we synthesized a series of macrocyclic tetraamides 5-8 derived from 1,3-benzenedicarboxylic (isophthalic) acid and aliphatic alpha,omega-diamines of different lengths. (1)H NMR titrations in DMSO solution show that the anion affinity of these receptors decreases with increasing size of the macrocycle irrespective of the anion, and this suggests a minor role of geometric complementarity. Comparison with their previously studied pyridine congeners reveals that the isophthalic acid based macrocycles are less potent, in contrast to what was found for simple model diamides. Combined theoretical and experimental structural studies were carried out to determine the reasons behind this behaviour. The results show that the unexpectedly low anion binding ability of the isophthalic acid-based receptors is due to the self-complementary nature of the isophthalic bis-amide fragments: when two such moieties are present within a sufficiently flexible macrocycle, they adopt syn-anti conformations and bind each other by two strong intramolecular hydrogen bonds that close the macrocyclic cavity. Nevertheless, anion binding is able to break these hydrogen bonds and switch a macrocycle into a convergent all-syn conformation. Despite the ill-preorganized conformation, 20-membered receptor 6 is better than either its open-chain analogue (macrocyclic effect) and/or its isomer having differently placed carbonyl groups. The crystal structures of four anion complexes of the macrocyclic receptors are reported. X-ray studies and solution NMR data confirmed the inclusive nature of the complexes and pointed to strong involvement of aromatic CH hydrogen atoms in anion binding.     

Induced fit interanion discrimination by binding-induced excimer formation

The synthesis, photophysical, and anion-binding properties of a series of di-, tri-, and tetrapodal anion-binding hosts based on aminopyridinium units with pyrenyl reporter groups are described. The ditopic mesitylene-derived calix[4]arene-based host 4 binds strongly to dicarboxylates, particularly malonate, in a 2:1 anion:host ratio but is essentially nonemissive in the presence of all anions except chloride because of intramolecular quenching by the pyridinium units. Addition of chloride results in a conformational change, giving an initial increase in emission assigned to intramolecular excimer formation. Further chloride addition also results in an increase in the intensity of the pyrenyl monomer emission as chloride binding reduces the acceptor ability of the pyridinium groups. This behavior is not exhibited by control compounds 5 and 6, which lack the ditopic geometry and calixarene spacer unit; however, tripodal 6 forms 1:2 anion:host complexes with a range of anions.     

Macrocyclic Eu3+ chelates show selective luminescence responses to anions

A series of lanthanide-containing macrocycles, Eu2-Eu5, exhibited unique luminescent responses in the presence of strong hydrogen-bond-accepting anions (F-, CH3COO-, and H2PO4-) in dimethyl sulfoxide. The macrocycles examined herein were designed to include a lanthanide chelate, aromatic spacers that function as antennae, thiourea groups as anion-binding units, and an alkyl or aryl linker between the thioureas that tailors the size and rigidity of the macrocycle. The anion-induced change in the emission intensity (lambda(exc) = 272 nm; lambda(em) = 614 nm) varied across the series of macrocycles and was dependent on the basicity of the anion. The largest luminescence response was observed in Eu(2), whereby the emission increased 77% upon the addition of 8 equiv of fluoride. A change in luminescence was not observed when exciting Eu3+ directly (lambda(exc) = 395 nm) over the course of anion titration experiments with all of the anions studied. These macrocycles contain only slight variations in structure, and insights into the mechanism of the anion interaction have been gained through monitoring of anion titrations via luminescence, absorbance, and luminescence lifetime measurements. In addition, model compounds (2-5) lacking the Eu3+ moiety were synthesized to study the binding pockets of Eu2-Eu5 using absorbance and 1H NMR spectroscopy. These studies indicate that the anions interact with the thiourea moiety of Eu2-Eu5, and the luminescent response is controlled by changes in the morphology of the macrocycle binding pocket.     

Elite new anion ligands: polythioamide macrocycles

Prototypes for a new class of polythioamide-based macrocycles have been synthesized and anion-binding capabilities assessed. Results indicate higher anion binding for H(2)PO(4)(-), HSO(4)(-), and F(-) for monocycles, but somewhat lessened binding capabilities for bicycles compared with amide corollaries.     

Slow anion exchange,conformational equilibria,and fluorescent sensing in venus flytrap aminopyridinium-based anion hosts

The synthesis, anion binding, and conformational properties of a series of 3-aminopyridinium-based, tripodal, tricationic hosts for anions are described. Slow anion and conformational exchange on the (1)H NMR time scale at low temperature, coupled with NMR titration, results in a high level of understanding of the anion-binding properties of the compounds, particularly with respect to significant conformational change resulting from induced fit complexation. Peak selectivity for halides, particularly Cl(-), is observed. The approach has been extended to dipodal and tripodal podands based on 3-aminopyridinium "arms" containing photoactive anthracenyl moieties. The 1,3,5-tripodal host shows a remarkable selectivity for acetate over other anions, in contrast to the analogous unsubstituted tris(3-aminopyridinium) analogue, despite the fact that low-temperature (1)H NMR experiments reveal a total of four acetate-binding conformations. Photodimerization of anthracene units results in the formation of potential fluorescent anion sensors.     

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.     

Anion-templated calix[4]arene-based pseudorotaxanes and catenanes

We present the rational design and anion-binding properties of the first anion-templated pseudorotaxanes and catenanes in which the "wheel" component is provided by a calix[4]arene macrobicyclic unit. The designs and syntheses of two new calix[4]arene macrobicycles, 2 and 3, are presented, and the abilities of these new species both to bind anions and to undergo anion-dependent pseudorotaxane formation are demonstrated. Furthermore, it is shown that performing ring-closing metathesis reactions on some of these pseudorotaxane assemblies gives novel catenane species 14 and 15, in which the yield of interlocked molecule obtained is critically dependent on the presence of a suitable anion template, namely, chloride. Exchange of the chloride anion in catenane 14 a for hexafluorophosphate gives catenane 14 d, which contains a unique anion-binding domain defined by the permanently interlocked hydrogen-bond-donating calix[4]arene macrobicycle and pyridinium macrocycle fragments. The anion-binding properties of this domain are presented, and shown to differ from non-interlocked components.     

Self-assembled, kinetically locked, Ru(II)-based metallomacrocycles: physical, structural, and modeling studies

By using a "complex as ligand approach," the metal-ion-templated self-assembly of heterometallic tetranuclear metallomacrocycles containing kinetically locked Ru(II) centers is described. Depending on the metal-ion template employed in the self-assembly process, the final macrocycle can be kinetically labile or inert. Electrochemical studies reveal that the kinetically inert macrocycles display reversible Ru(III/II) oxidation couples. The crystal structure of a kinetically inert Ru2Re2 macrocycles reveals a structurally complex palmate anion-binding pocket. Host-guest studies carried out with the same macrocyle in organic solvents reveals that the complex functions as a luminescent sensor for anions and that binding affinity and luminescent modulation is dependent on the structural nature and charge of the guest anion. Computational density functional theory (DFT) studies support the hypothesis that the luminescence of the macrocycle is from a 3MLCT state and further suggests that the observed guest-induced luminescence changes are most likely due to modulation of nonradiative decay processes.     

Double armed crown ethers and armed macrocycles as a new series of metal-selective reagents: a review

Various double armed crown ethers and related macrocycles are presented as metal-selective reagents characterized by macrocyclic ligands and metal-ligating sidearms. They exhibit unique metal binding and recognition functions via macroring-sidearm cooperative action. Since they form three dimensional complexes suitable for metal-sensing and separation, we can develop a new series of metal-selective reagents via armed macrocycle strategy. Polymerization and immobilization of the armed macrocycles further enhance the usefulness in analytical science. This review focuses primarily on the molecular design, host-guest chemistry, and analytical applications of the armed macrocycles, and clearly indicates that these macrocycles provide new options in designing a metal-selective reagent.     

Arene Phosphorus-Containing Macrocyclic Crown Ethers: Last Studies

Abstract

The data on the synthesis, structures, and chemical properties of macrocyclic compounds containing endo-cyclic atoms of tri- and pentavalent phosphorus are summarized. Methods for the synthesis of the described macrocycles are reported. Peculiarities of structure, chemical properties, particularly formation of complexes, catalytic activity, and practical applications are analyzed. The bibliography includes 155 references.     

A novel conformationally adaptive macrocyclic tetramaleimide with flipping pyrene sidewalls

The synthesis, structure, and properties of pyrene-based conformationally adaptive macrocycles are described. This new type of conformationally adaptive macrocycle was constructed through Perkin reaction,followed by imidization. By changing the condensation partner as the linking unit, a family of conjugated macrocycles with different sizes of the cavity was synthesized, which provide a simple and modular synthetic strategy towards the conformationally adaptive macrocycles. Furthermore, the macr...     

1,1'-Binaphthyl-substituted macrocycles as receptors for saccharide recognition

The preparation of receptors for saccharide recognition in a natural environment has been an unmet goal for a long time. We present herein the synthesis and binding properties of (R,S)-1,1'-binaphthyl-substituted macrocycles as receptors for saccharide recognition in water/acetonitrile (1:1) and in DMSO. Porphyrin and metalloporphyrin macrocycles with two to four 1,1'-binaphthyl substituents and multiple hydroxy groups generate a binding site for saccharides that incorporates hydrogen-bonding hydroxy groups together with the aromatic hydrophobic pocket. The specificity for di- and trisaccharides is governed by the cavity size. The mechanism of binding has been studied by 1H NMR spectroscopy and the role of H-bonding and CH-pi interactions has been evaluated; the ability to bind saccharides has been demonstrated by the surface plasmon resonance (SPR) technique. The application of these macrocyclic receptors to sensor development is also presented.     

New Chiral Macrocyclic Compounds from D-Mannitol

We have recently reported the synthesis of new chiral macrocyclic polyhydroxyethers by reduction of cyclodextrins 1. These compounds display appreciable conformational freedom in solution as it occurs with the ionophores. Our chiral macrocycles may be considered as built by units of alditol (1 → 4) alditols. Such units, conveniently substituted, prepared by us by reduction of disaccharide derivatives2, are possible synthons for the synthesis of other macrocyclic polyhydroxyethers in which the nature and number of alditol (1 → n) alditol components can be varied at will. We are interested in the preparation and the structural studies of these type of receptors since the synthesis of new chiral macrocycles is a topic of interest and the building of chiral cavities may be of importance in the study of host-guest interactions. We now report on the preparation, from D-mannitol, a readily available starting material with C₂symmetry, and tetraethylene glycol, of the chiral macrocycles 1, 2, and 3, as model compounds in exploring the synthesis of more complex macrocyclic polyhydroxyethers derived from alditol (1 → n) alditol. Other macrocyclic compounds from D mannitol have been previously synthesised.     

Synthesis of Carbohydrate Based Macrolactones and Their Applications as Receptors for Ion Recognition and Catalysis

Glycomacrolactones exhibit many interesting biological properties, and they are also important in molecular recognitions and for supramolecular chemistry. Therefore, it is important to be able to access glycomacrocycles with different sizes and functionality. A new series of carbohydrate-based macrocycles containing triazole and lactone moieties have been designed and synthesized. The synthesis features an intramolecular nucleophilic substitution reaction for the macrocyclization step. In this article, the effect of some common sulfonate leaving groups is evaluated for macrolactonization. Using tosylate gave good selectivity for monolactonization products with good yields. Fourteen different macrocycles have been synthesized and characterized, of which eleven macrocycles are from cyclization of the C1 to C6 positions of N-acetyl D-glucosamine derivatives and three others from C2 to C6 cyclization of functionalized D-glucosamine derivatives. These novel macrolactones have unique structures and demonstrate interesting anion binding properties, especially for chloride. The macrocycles containing two triazoles form complexes with copper sulfate, and they are effective ligands for copper sulfate mediated azide-alkyne cycloaddition reactions (CuAAC). In addition, several macrocycles show some selectivity for different alkynes.     

Solid‐Phase Parallel Synthesis of Functionalised Medium‐to‐Large Cyclic Peptidomimetics through Three‐Component Coupling Driven by Aziridine Aldehyde Dimers

The first solid‐phase parallel synthesis of macrocyclic peptides using three‐component coupling driven by aziridine aldehyde dimers is described. The method supports the synthesis of 9‐ to 18‐membered aziridine‐containing macrocycles, which are then functionalized by nucleophilic opening of the aziridine ring. This constitutes a robust approach for the rapid parallel synthesis of macrocyclic peptides.     

New strategy and methods for constructing artificial macrocyclic anion receptors. Selective binding of tetrahedral oxoanions

A new rational strategy for assembling highly selective neutral macrocyclic anionic receptors proposed by the authors is considered. The strategy includes preliminary theoretical modeling of supramolecular complexes, analysis of synthetic paths for receptor preparation, selection and synthesis of building blocks followed by their cyclocondensation under thermo-dynamic control in the presence of acid corresponding to the target template anion, which provides anion-induced combinatorial selection of the macrocyclic ligand in the emerging dynamic combinatorial library. Analysis of the properties of the obtained anion receptors showed that the number of hydrogen bonds formed between the receptor and the guest anion mainly determines the binding energy. The receptor selectivity for a particular anion is determined by the nature of coordination sites, their geometry in the macrocyclic cavity, and the overall conformation rigidity of the macrocycle. Using the developed strategy and novel synthetic approaches, a large series of highly selective anion receptors with record binding constants (up to 10^p7 L mol^p-1 in both highly and weakly solvating media) was constructed and the structures of the host—guest complexes were studied in detail by both experimental and theoretical methods