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Targeting the cancer cell mitochondrion is a promising approach for developing novel anticancer agents. The experimental anticancer agent N,N′-bis(3,5-dichlorophenyl)urea (SR4) induces apoptotic cell death in several cancer cell lines by uncoupling mitochondrial oxidative phosphorylation (OxPhos) using a protein-free mechanism. However, the precise mechanism by which SR4depolarizes mitochondria is unclear because SR4lacks an acidic functional group typically found in protein-independent uncouplers. Recently, it was shown that structurally related thioureas can facilitate proton transport across lipid bilayers by a fatty acid-activated mechanism, in which the fatty acid acts as the site of protonation/deprotonation and the thiourea acts as an anion transporter that shuttles deprotonated fatty acids across the phospholipid bilayer to enable proton leak. In this paper, we show that SR4-mediated proton transport is enhanced by the presence of free fatty acids in the lipid bilayer, indicating that SR4uncouples mitochondria through the fatty acid-activated mechanism. This mechanistic insight was used to develop a library of substituted bisaryl ureas for structure–activity relationship studies and subsequent cell testing. It was found that lipophilic electron-withdrawing groups on bisaryl ureas enhanced electrogenic proton transport via the fatty acid-activated mechanism and had the capacity to depolarize mitochondria and reduce the viability of MDA-MB-231 breast cancer cells. The most active compound in the series reduced cell viability with greater potency than SR4and was more effective at inhibiting adenosine triphosphate production.

Transmission-line faults can be located by comparing the arrival time of fault-generated pulses. Global positioning system (GPS) receivers provide a time base that can be used along with the information from digital fault recording.

Lanthanide-doped upconversion nanoparticles (UCNPs) can convert low-energy near-infrared (NIR) light into high-energy visible light, making them valuable for broad applications. UCNPs often suffer from poor light-harvesting capabilities, which can be significantly improved by incorporating organic dye antennas. However, the dye-sensitized upconversion systems are prone to severe photobleaching in an ambient atmosphere. Here, we present a synergistic approach to mitigate photobleaching by introducing triplet state quencher cyclooctatetraene (COT). COT effectively suppresses the generation of singlet oxygen by quenching the triplet states of the dye and consumes the existing singlet oxygen through oxidant reactions. The inclusion of COT extends the half-life of IR806 by 4.7-times by preventing the oxidation of its poly(methylene) chains. Without significantly affecting emission intensity and dynamics, COT effectively stabilized dye-UCNPs, demonstrating a notable 3.9-fold increase in half-life under continuous laser irradiation. Our findings suggest a new strategy to enhance the photostability of near-infrared dyes and dye-sensitized upconversion nanohybrids.

Many synthetic and supramolecular chiral polymeric systems are known to exhibit the “majority rules effect” (MRE), a positive nonlinear response in which a small enantiomeric excess (ee) of the chiral building blocks leads to unproportionally large chiroptical signals near zero ee. In contrast, the opposite “racemate rules effect” (RRE), a negative nonlinear response in which the chiroptical signals are flat near zero ee, while giving large nonlinear chiroptical responses to eeat high values, has only been occasionally observed. The origin of this unusual eedependence remains elusive largely because few systems have been established that exhibit this effect. Herein, we present a design approach that enables the development of chiral supramolecular polymers with a pronounced negative nonlinear response akin to RRE. This is achieved by in situ generating a bidentate inducer for supramolecular polymerization that exists in both meso- and homochiral forms upon reacting with chiral guests. The presence of the meso-inducer creates an aggregate structure that has a little response in the circular dichroism (CD) spectra as a function of eeat a particular wavelength, but a homochiral inducer gives large changes in response to eeat this wavelength. This allowed for an RRE-like response to be observed when the CD intensity of the supramolecular polymers was plotted against the eeof the chiral guests that generate the meso- and homochiral inducers without the necessity of the racemic guest preferentially being incorporated into the polymer.

Generation of chemical gradients across biological membranes of cellular compartments is a hallmark of all living systems. Here we report a proof-of-concept prototype transmembrane pumping system in liposomes. The pump uses fatty acid to fuel chloride transport, thus generating a transmembrane chloride gradient. Addition of fatty acid to phospholipid vesicles generates a transmembrane pH gradient (pHin< pHout), and this electrochemical H+potential is harnessed by an anionophore to drive chloride efflux via H+/Cl–cotransport. Further addition of fatty acid efficiently fuels the system to continuously drive chloride transport against the concentration gradient, up to [Cl–]in65 mM | [Cl–]out100 mM, and is 1400 times more efficient than using an external fuel. Based on our findings from dissecting the H+/Cl–flux process with the use of different liposomal fluorescence assays, and supported by additional liposome-based 13C NMR and DLS studies; we proposed that the presence of an anionophore can induce asymmetric distribution of fatty acid, and contribute to another Cl–flux mechanism in this system.

Transmembrane anion transport has been the focus of a number of supramolecular chemistry research groups for a number of years. Much of this research is driven by the biological relevance of anion transport and the search to find new treatments for diseases such as cystic fibrosis, which is caused by genetic problems leading to faulty cystic fibrosis transmembrane conductance regulator (CFTR) channels, which in turn lead to reduced chloride and bicarbonate transport through epithelial cell membranes. Considerable effort has been devoted to the development of new transporters, and our group along with others have been searching for combinations of organic scaffolds and anion binding groups that produce highly effective transporters that work at low concentration. These compounds may be used in the future as “channel replacement therapies”, restoring the flux of anions through epithelial cell membranes and ameliorating the symptoms of cystic fibrosis.

Perturbations in cellular chloride concentrations can affect cellular pH and autophagy and lead to the onset of apoptosis. With this in mind, synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here, we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol. Liposomal and cellular transport activity of the squaramides is shown to correlate with cell death activity, which is attributed to caspase-dependent apoptosis. One ion transporter was also shown to cause additional changes in lysosomal pH, which leads to impairment of lysosomal enzyme activity and disruption of autophagic processes. This disruption is independent of the initiation of apoptosis by the ion transporter. This study provides the first experimental evidence that synthetic ion transporters can disrupt both autophagy and induce apoptosis.

Recent elegant examples illustrate the power of charge density analysis, employed in a systematic way, to link electron density distribution to molecular structure. This leads to new insights into important chemical systems and the effects of systematic modifications to them. The advances made in extracting the electron density distribution from standard resolution X-ray diffraction data and the subsequent use of this information in systematic studies are also described.

Square peg in a round ball: Squaramides are shown to be potent transmembrane anion transporters for both chloride and bicarbonate, performing better than the thiourea and urea analogues. Studies into the nature of this transport point to a mobile carrier mechanism, where the squaramide delivers the anion cargo across the lipid bilayer (see scheme, green sphere=anion). These drug‐like molecules provide a platform for the development of a new generation of anion‐transport systems.

A ditopic ion‐pair receptor (1), which has tunable cation‐ and anion‐binding sites, has been synthesized and characterized. Spectroscopic analyses provide support for the conclusion that receptor 1binds fluoride and chloride anions strongly and forms stable 1:1 complexes ([1⋅F]−and [1⋅Cl]−) with appropriately chosen salts of these anions in acetonitrile. When the anion complexes of 1were treated with alkali metal ions (Li+, Na+, K+, Cs+, as their perchlorate salts), ion‐dependent interactions were observed that were found to depend on both the choice of added cation and the initially complexed anion. In the case of [1⋅F]−, no appreciable interaction with the K+ion was seen. On the other hand, when this complex was treated with Li+or Na+ions, decomplexation of the bound fluoride anion was observed. In contrast to what was seen with Li+, Na+, K+, treating [1⋅F]−with Cs+ions gave rise to a stable, host‐separated ion‐pair complex, [F⋅1⋅Cs], which contains the Cs+ion bound in the cup‐like portion of the calix[4]pyrrole. Different complexation behavior was seen in the case of the chloride complex, [1⋅Cl]−. Here, no appreciable interaction was observed with Na+or K+. In contrast, treating with Li+produces a tight ion‐pair complex, [1⋅Li⋅Cl], in which the cation is bound to the crown moiety. In analogy to what was seen for [1⋅F]−, treatment of [1⋅Cl]−with Cs+ions gives rise to a host‐separated ion‐pair complex, [Cl⋅1⋅Cs], in which the cation is bound to the cup of the calix[4]pyrrole. As inferred from liposomal model membrane transport studies, system 1can act as an effective carrier for several chloride anion salts of Group 1 cations, operating through both symport (chloride+cation co‐transport) and antiport (nitrate‐for‐chloride exchange) mechanisms. This transport behavior stands in contrast to what is seen for simple octamethylcalix[4]pyrrole, which acts as an effective carrier for cesium chloride but does not operates through a nitrate‐for‐chloride anion exchange mechanism.

The article discusses the Highlander Radmarathon in Hohenems, western Austria, billed as one of Austria's toughest sportives that takes in high Austrian passes and scenery. It details that the 187-kilometre race includes 4-kilometre climbing at Hochtannberg and Furkajoch passes and is matched by a relax and friendly atmosphere. The article also describes the ride experiences of 60-year-old German cyclist Roland Grubel, and Austrian cyclists Iris Nasahl and Gunar Nasahl.

Complexation of dihydrogen phosphate by an anion receptor containing six hydrogen bond donor groups has been shown to reduce the pKaof the bound anionic species to such an extent that addition of further aliquots of dihydrogen phosphate result in deprotonation of the bound species with the resultant formation of a monohydrogen phosphate receptor complex. X‐ray crystallographic studies confirm monohydrogen phosphate complex formation in the solid state. In this way, this study explains the formation of complexes with unusual stoichiometries when investigating the binding of dihydrogenphosphate anion to hydrogen‐bonding receptors.

1,3‐Diindolylureas and thioureas have been synthesised and their anion complexation properties in solution studied. Whilst diindolylthioureas showed only moderate affinities and selectivities, diindolylureas show remarkably high affinity for dihydrogen phosphate in solution for an acyclic, neutral receptor in water/[D6]DMSO mixtures. These easy‐to‐make compounds adopt relatively planar conformations in the solid‐state and are able to donate four hydrogen bonds and yet not fill the coordination sphere of carbonate or phosphate, allowing two or three receptors to bind to each anion in the solid‐state.

Calix[4]pyrrole–chloride interactions are affected not only by the choice of countercation in halogenated solvents, but show a specific dependence on the way in which these cations are bound within the electron rich, bowl‐like calix[4]pyrrole cavity formed upon chloride anion complexation. In dichloromethane, the affinities of simple meso‐octamethylcalix[4]pyrrole (1) for methyl‐, ethyl‐, and n‐butylammonium chlorides are on the order of 105, 104, and 102M−1, respectively, as determined from isothermal titration calorimetry (ITC) analyses. These cation‐dependent anion affinity effects, while clearly evident, are less pronounced in other halogenated solvents, such as 1,2‐dichloroethane. Support for the proposed cation complexation selectivity is provided by solid state X‐ray crystallographic analyses.

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 conditionsin 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.

Acyclic molecules containing amides, ureas, and pyrrole groups have proven to be effective and selective anion-binding agents. In this Account, the structural chemistry of isophthalamide anion complexes, ortho-phenylenediamine based bis-ureas, and amidopyrroles, as well as anion-triggered deprotonation processes in neutral anion receptor systems, are discussed.

A bispyrrol-2-yl-2,5-diamidopyrrole has been synthesized and shown to have a significantly higher affinity for oxo-anions than previous generation 2,5-diamidopyrroles.

Simple bis-urea compounds based on ortho-phenylenediamine function as excellent receptors for carboxylate anions in DMSO-d6–0.5% water solution. By varying the functional groups in these compounds, the binding affinity of carboxylate anions can be modulated. Solid-state studies illustrate the cleft-like arrangement of the DDDD hydrogen bond array in the carboxylate complexes of these compounds.

The anion binding behaviour of a number of pyrrolylamidourea and thiourea compounds have been studied in DMSO solution. Mono-amidothioureapyrrole compounds were found to be deprotonated by basic anions such as fluoride, acetate, benzoate or dihydrogenphosphate with the structure of the deprotonated species elucidated by X-ray crystallography. 2,5-Bis-amidoureapyrroles were synthesized and found to be effective anion receptors for a range of putative anionic guests.

No Abstract

Amidopyrroles have been employed in a variety of anion receptors and sensors. 2,5-Bisamidopyrroles show selective oxo-anion complexation properties in organic solution whilst bis-amides containing dipyrrolylmethane groups form strong complexes with dihydrogen phosphate anions in mixtures of DMSO-d6and water. Deprotonation of the 2,5-bisamidopyrrole unit can lead to interesting solid-state structures including the formation of orthogonal hydrogen bonded dimers. Amidopyrrole groups have also been employed in receptors for ion-pairs and in membrane transport agents for HCl.

Four examples of bis-amidopyrrole derivatives of pyrrole-2,5-diacetic acid have been prepared. The reaction of diethyl pyrrole-2,5-diacetate with a large excess 24 equiv. of N,N-dimethylethylenediamine gave N,N′-bis2-dimethylaminoethyl-1H-pyrrole-2,5-diacetamide 1. Three further examples, N,N′-bis2-2-pyridylethyl-1H-pyrrole-2,5-diacetamide 2, N,N′-bis2-pyridylmethyl-1H-pyrrole-2,5-diacetamide 3 and N,N′-dibenzyl-1H-pyrrole-2,5-diacetamide 4, were prepared in a one pot procedure by converting pyrrole-2,5-diacetic acid into the N-hydroxysuccinimide ester and then reacting this with four equivalents of the appropriate amine, 2-2-aminoethylpyridine, 2-aminomethylpyridine or benzylamine, respectively. Compounds 1–4are shown to be effective anion receptors in acetonitrile-d3solution, with comparable binding affinities to those found for simple pyrrole-2,5-dicarboxamides, despite possessing a more flexible hydrogen bonding array.

A 2,5-diamidopyrrole-capped macrobicycle was synthesized and its chloride salt binding ability evaluated in polar and apolar organic solvents. X-ray crystal structures of the receptor and its sodium chloride complex were obtained and in the latter structure the salt is bound as a contact ion-pair.

Anion recognition chemistry has grown from its beginnings in the late 1960s with positively charged ammonium cryptand receptors for halide binding to, at the end of the millennium, a plethora of charged and neutral, cyclic and acyclic, inorganic and organic supramolecular host systems for the selective complexation, detection, and separation of anionic guest species. Solvation effects and pH values have been shown to play crucial roles in the overall anion recognition process. More recent developments include exciting advances in anion‐templated syntheses and directed self‐assembly, ion‐pair recognition, and the function of anions in supramolecular catalysis.

Die Chemie der Anionenerkennung hat sich seit ihren Anfängen in den späten sechziger Jahren des 20. Jahrhunderts stark entwickelt. Anfangs waren nur positiv geladene Ammonium-Cryptanden als Rezeptoren für Halogenid-Ionen bekannt. Nun, am Ende des Millenniums, sind eine Vielzahl geladener und neutraler, cyclischer und acyclischer, anorganischer und organischer supramolekularer Wirte für die selektive Komplexierung, den Nachweis und die Trennung anionischer Gastmoleküle verfügbar. Bei der Anionenerkennung spielen Solvatationseffekte und der pH-Wert eine entscheidende Rolle. In jüngerer Zeit wurden wichtige Fortschritte bei Synthesen mit anionischen Templaten, der durch Anionen gesteuerten Selbstorganisation, der Ionenpaarerkennung und der Funktion von Anionen bei der supramolekularen Katalyse erzielt.

This review looks back to the birth of modern supramolecular chemistry with the formation of simple crown ether-alkali metal complexes through to more recent self–assembling molecular systems. The final section of this review speculates on what the future may hold for supramolecular assemblies. This includes new catalysts, self–replicating molecular systems, complexes that might be used for data storage, and the creation of molecular motors.

This perspective examines the mechanisms by which electrochemical recognition of various charged and neutral guest species by redox-active receptor molecules takes place. Particular emphasis is given to the intramolecular signalling pathway employed in each case. These include electrostatic interactions (through space or through conju-gated bonds), conformational changes in the redox centre in complexation and guest interference to an already present communication pathway in the host.

The synthesis of a new calixarene-capped calixpyrrole 2has been achieved using p- tert-butylcalix[4]arene tetramethyl ketone 1as a template. Using this approach, the stereochemistry at the calixpyrrole meso-carbons is automatically defined. The X-ray crystal structure of 2has been elucidated and reveals hydrogen bonding between the pyrrole NH groups and the oxygens at the lower rim of the calixarene. NMR studies confirm the importance of these interactions in solution.

New tris-benzoyl-, tris-ferrocenoyl- and bis-ferrocenoyl p-tert-butylcalix[5]arene esters have been synthesised (1-3 respectively) by reaction of the parent calixarene with the appropriate acid chloride. X-ray crystal structures of all three compounds have been determined with the structure of 2 revealing an ethanol guest molecule bound deep in the cavity of the calix[5]arene. The electrochemical properties of 2 have been extensively investigated using rotating disk electrode, cyclic and square wave voltammetric techniques. Electrochemical evidence is presented suggesting 2 has the capability of detecting neutral polar guest molecules, such as dimethylformamide, in dichloromethane solutions.

The synthesis of two bis-amidinium calixarenes 3and 4has been achieved. Compounds 3and 4self-assemble with carboxylate salts viaamidinium-carboxylate salt bridges producing ditopic receptor species.

Anew type of solid support for HPLC separationof nucleotides, oligonucleotides, N‐protected amino acids, and perfluorinated biphenyls is revealed in the form of two distinct calix[4]pyrrole‐modified silica gels (below).

The synthesis, metal, ammonium and alkyl ammonium cation coordination chemistry and electrochemical recognition studies of new diester-and diamide-calix[4]arenediquinone receptors are described. In addition the synthesis and coordination properties of a novel diamide benzo-15-crown-5-calix[4]arene molecule is reported.

The calix[4]pyrroles are a class of old but new heterocalixarene analogues that show interesting anion and neutral substrate binding properties. Calix[4]pyrroles are easy to make and functionalize. As such, they have been employed in the production of separation media for anionic and neutral species. Calixpyrroles also provide useful precursors for the generation of novel calixpyridinopyrroles and calixpyridines.

Membrane transport proteins fulfill important regulatory functions in biology with a common trait being their ability to respond to stimuli in the environment. Various small-molecule receptors, capable of mediating transmembrane transport, have been successfully developed. However, to confer stimuli-responsiveness on them poses a fundamental challenge. Here we demonstrate photocontrol of transmembrane transport and electric potential using bis(thio)ureas derived from stiff-stilbene. UV–vis and 1H NMR spectroscopy are used to monitor E–Zphotoisomerization of these bis(thio)ureas and 1H NMR titrations reveal stronger binding of chloride to the (Z)-form than to the (E)-form. Additional insight into the binding properties is provided by single crystal X-ray crystallographic analysis and DFT geometry optimization. Importantly, the (Z)-isomers are much more active in transmembrane transport than the respective (E)-isomers as shown through various assays. As a result, both membrane transport and depolarization can be modulated upon irradiation, opening up new prospects toward light-based therapeutics as well as physiological and optopharmacological tools for studying anion transport-associated diseases and to stimulate neuronal activity, respectively.

The selective and efficient capture of phosphopeptides is critical for comprehensive and in-depth phosphoproteome analysis. Here we report a new switchable two-dimensional (2D) supramolecular polymer that serves as an ideal platform for the enrichment of phosphopeptides. A well-defined, positively charged metallacycle incorporated into the polymer endows the resultant polymer with a high affinity for phosphopeptides. Importantly, the stimuli-responsive nature of the polymer facilitates switchable binding affinity of phosphopeptides, thus resulting in an excellent performance in phosphopeptide enrichment and separation from model proteins. The polymer has a high enrichment capacity (165 mg/g) and detection sensitivity (2 fmol), high enrichment recovery (88%), excellent specificity, and rapid enrichment and separation properties. Additionally, we have demonstrated the capture of phosphopeptides from the tryptic digest of real biosamples, thus illustrating the potential of this polymeric material in phosphoproteomic studies.

A pyrrolylamidothiourea deprotonates in the presence of oneequivalent of not onlyfluoride, but alsoacetate, benzoate or dihydrogen phosphate in DMSO solution with structural studies using synchrotron radiation confirming thiourea deprotonation in the solid state.

A macrocyclic amidourea shows anion dependent binding modes with a variety of different putative anionic guests.

The role of solvent (and other species) in the formation of networks from tetrakis(thiourea)platinum(ii) cations and croconate anions is examined, with crystallisations from DMSO giving rise to a structure containing solvent filled channels.

A simple bis-urea containing anion receptor, synthesised from ortho-phenylenediamine, has been shown to have excellent selectivity for carboxylates in solution, with a crystal structure elucidation of the benzoate complex showing four hydrogen bonds between the receptor and anion in the solid state.

Steric interactions in 1,3-dicarboxamidoanthraquinones have been employed to ‘twist’ isophthalamide-like anion binding sites; the crystal structure of the fluoride complex of a bis-3,5-dichlorophenylamide derivative shows the receptor acting as a ‘hydrogen-bonding corner’ in a ‘2 2’ fluoride containing molecular box.

Anion complexation studies on a series of platinumii tetrakispyrrolylpyridine salts demonstrate the importance of CH–anion hydrogen bonds in coordinating anionic guests in solution and the solid-state.

An amidopyrrole with appended imidazole group can bind and co-transport HCl−across vesicle membranes much more effectively than an analogue with an appended pyridyl group.

Two amido-pyrrole cleft anion receptors bearing two ferrocene reporter groups have been synthesised and crystallographically characterised; the receptors contain either a non-conjugated or conjugated link between the anion-binding amido-pyrrole unit and the ferrocene reporter groups. The anion binding affinities and electrochemical behaviour of the receptors in the absence and presence of anions have been studied by 1H NMR titration techniques and cyclic voltammetry using a Pt microdisc working electrode, respectively.

Crystals of the title complex, C28H36N4·C2H6OS, undergo a phase transition between room temperature and 198 K, as determined by X‐ray diffraction techniques. A monoclinic form is observed at room temperature, while a triclinic modification is found at 198 K, with Z′ changing from 1 to 2. Differential scanning calorimetry (DSC) of the calix­pyrrole–di­methyl sulfoxide complex revealed a series of phase changes between 273 and 243 K. The transition from the room‐temperature monoclinic form to the low‐temperature triclinic form is reversible, as determined by changes in the cell dimensions from remeasuring selected reflections at room temperature and at temperatures below 223 K. The uncomplexed calix­[4]­pyrrole mol­ecule shows no phase changes occurring between room temperature and 233 K, the low‐temperature limit of the DSC.

The use of simple 2,5-diamidopyrrole derivatives as anion receptors has been investigated. Reaction of 3,4-diphenylpyrrole-2,5-dicarboxylic acid chloride with n-butylamine or aniline has produced two new amidic cleft anion receptors 1and 2. The anion-coordination ability of these species has been determined by 1H NMR titration techniques. Crystal structures of 1and 2have been elucidated, revealing a continuous hydrogen bonding network formed by 1and dimerization of 2via NH⋯O and CH⋯O hydrogen bonds.

The intense yellow colour of the 4-nitrophenolate anion 2, in MeCN or CH₂Cl₂ solution, dissipates upon complex formation with meso-octamethylcalix[4]pyrrole 1; the complex may be used as a colourimetric sensor for halide anions, such as fluoride, that displace the phenolate anion thereby restoring the yellow colour, characteristic of free 4-nitrophenolate anion, to solutions containing 1, 2 and the anion in question.

The intense yellow colour of the 4-nitrophenolate anion 2, in MeCN or CH2Cl2 solution, dissipates upon complex formation with meso-octamethylcalix[4]pyrrole 1; the complex may be used as a colourimetric sensor for halide anions, such as fluoride, that displace the phenolate anion thereby restoring the yellow colour, characteristic of free 4-nitrophenolate anion, to solutions containing 1, 2 and the anion in question.

Condensation of isophthaloyl dichloride and pentafluoroaniline or 2,3,5,6-tetrafluoroaniline results in the formation of imide linked ‘4 + 4’ macrocycles.