Arene-based Receptors Research Articles

Development of a Cone Homooxacalix[3]arene-Based Fluorescent Chemosensor for the Selective Detection of Biogenic Ammonium Ions in Protic Solvents.

We report here on the development of a fluorescent cone homooxacalix[3]arene-based receptor with a pyrene unit on the wide rim of the macrocycle (Ox3F) for the selective detection of primary ammonium ions, including those of biological importance. Ox3F was synthesized efficiently via an innovative strategy that enables the regio- and iteroselective wide rim functionalization of the readily available p-tBu-substituted homooxacalix[3]arene precursor. Nuclear magnetic resonance studies and in silico methods highlighted the endo-complexation of primary ammonium ions, including the protonated form of biogenic dopamine, tryptamine, serotonin, mexamine, and 3-iodothyronamine. The binding mode is similar for all guests with the ion deeply inserted into the polyaromatic cavity, enabling the NH3+ head to establish three hydrogen bonds with the ethereal oxygens of the macrocycle. Fluorescence quenching of the pyrene unit was observed following the π-π interaction between the pyrene moiety and the aromatic groups of serotonin, mexamine, and 3-iodothyronamine. No quenching was observed upon complexation of the smaller aromatic neurotransmitter dopamine as well as aliphatic amines and polyamines. This study presents a novel approach for biologically relevant ammonium ion chemosensing with ongoing efforts focused on translating these systems for aqueous environment applications.

Specific Binding of Primary Ammoniums in Aqueous Media by Homooxacalixarenes Incorporated into Micelles.

The development of artificial receptors for efficient recognition of analytes in water is a challenging task. Homooxacalix[3]arene-based receptor 1, which is selective toward primary ammoniums in organic solvents, was transferred into water following two different strategies: direct solubilization and micellar incorporation. Extensive 1H NMR studies showed that recognition of ammoniums is only observed in the case of micellar incorporation, highlighting the beneficial effect of the microenvironment of the micellar core. The selectivity of the system for primary ammoniums over secondary and tertiary ones was also maintained. The hydrophobic effect plays an important role in the recognition properties, which are counterion-dependent due to the energy penalty for the dissociation of certain ammonium salts in the apolar micellar core. This study shows that the straightforward self-assembly process used for the encapsulation of artificial receptors in micelles is an efficient strategy for developing water-soluble nanosized supramolecular recognition systems.

Allosteric binding properties of a 1,3-alternate thiacalix[4]arene-based receptor having phenylthiourea and 2-pyridylmethyl moieties on opposite faces

Thiacalix[4]arene receptors with two thiourea moieties and two 2-pyridyl moieties exhibited a heteroditopic dinuclear receptor with F− and Ag+ ions by a positive allosteric effect.

Dihomooxacalix[4]arene-Based Fluorescent Receptors for Anion and Organic Ion Pair Recognition.

Fluorescent dihomooxacalix[4]arene-based receptors 5a–5c, bearing two naphthyl(thio)ureido groups at the lower rim via a butyl spacer, were synthesised and obtained in the cone conformation in solution. The X-ray crystal structures of 1,3- (5a) and 3,4-dinaphthylurea (5b) derivatives are reported. Their binding properties towards several anions of different geometries were assessed by 1H-NMR, UV-Vis absorption and fluorescence titrations. Structural and energetic insights of the naphthylurea 5a and 5b complexes were also obtained using quantum mechanical calculations. The data showed that all receptors follow the same trend, the association constants increase with the anion basicity, and the strongest complexes were obtained with F−, followed by the oxoanions AcO− and BzO−. Proximal urea 5b is a better anion receptor compared to distal urea 5a, and both are more efficient than thiourea 5c. Compounds 5a and 5b were also investigated as heteroditopic receptors for biologically relevant alkylammonium salts, such as the neurotransmitter γ-aminobutyric acid (GABA·HCl) and the betaine deoxycarnitine·HCl. Chiral recognition towards the guest sec-butylamine·HCl was also tested, and a 5:2 selectivity for (R)-sec-BuNH3+·Cl− towards (P) or (M) enantiomers of the inherently chiral receptor 5a was shown. Based on DFT calculations, the complex [(S)-sec-BuNH3+·Cl−/(M)-5a] was indicated as the more stable.

Specific Binding of Primary Ammonium Ions and Lysine-Containing Peptides in Protic Solvents by Hexahomotrioxacalix[3]arenes.

The binding of ammonium ions by two homooxacalix[3]arene-based receptors was studied using NMR spectroscopy and in silico methods. Both receptors are shown to endocomplex, even in a protic environment, a large variety of primary ammonium ions, including biomolecules. The binding mode is similar for all guests with the ammonium ion deeply inserted into the polyaromatic cavity and its NH3+ head nearly in the plane defined by the three oxygen atoms of the 18-crown-3 moiety, thus enabling it to establish three H-bonds with the ethereal macrocycle. The remarkable electronic, size, and shape complementarity between primary ammonium ions and the two cavity-based receptors leads to an unprecedented specificity for primary ammonium ions over secondary, tertiary, and quaternary ones. These binding properties were exploited for the selective liquid-liquid extraction of primary ammonium salts from water and for the selective recognition of lysine-containing peptides, opening new perspectives in the field of peptide sensing.

A turn-off fluorescence sensor for insensitive munition using anthraquinone-appended oxacalix[4]arene and its computational studies

Herein, a fluorescent oxacalix[4]arene-based receptor, DAQTNOC(5,17-di(N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)acetamide) tetranitrooxacalix[4]arene), was described for the specific recognition of N-methyl-p-nitroaniline (MNA).

Selective recognition of quaternary ammonium ions and zwitterions by using a biomimetic bis-calix[6]arene-based receptor.

Artificial receptors able to recognize efficiently chemical species bearing a quaternary ammonium group have potential applications in the fields of biological and environmental analyses. A possible biomimetic strategy for the elaboration of such receptors consists of associating in close proximity a polyaromatic cavity with a polar binding site. Herein, we show that bis-calix[6]arene 1 behaves as a heteroditopic receptor that can bind biologically relevant quaternary ammonium ions and zwitterions. This host can selectively extract carbamylcholine G3 from water, opening the way for the sensing of this acetylcholine agonist. In some cases, a kinetic selectivity is observed for the shorter guests whereas kinetically stable host-guest complexes can be detected under conditions where they are thermodynamically disfavoured. These results can be rationalized by the unique mode of entrance and escape of the guests into bis-calix[6]arene 1. All these binding properties strongly differ from those reported for related calixarene-based receptors.

Calix[4]arene-based fluorescent probe and the adsorption capacity of its electrospun nanofibrous film for the cesium cation as an adsorbent

Calix[4]arene-based cation receptor 1 has been synthesised by following a multi-step synthetic procedure. The fluorescence properties of 1 upon the addition of various metal ions were investigated by fluorescence spectroscopy. As a result, it was revealed that 1 displayed dramatic quenching effect upon the exposure to Cs+. In contrast, no significant quenching effects were observed upon the addition of other metal ions such as Li+, Na+, K+, Mg2+, Ca2+, Sr2+, Ag+, Zn2+ and Ni2+. Compound 1 was also found by Job plot to form a 1:1 complex with Cs+. In addition, we also prepared 1-embedded electrospun nanofibrous film (NF-1) as an adsorbent for Cs+. NF-1 is proved to adsorb Cs+ effectively from an aqueous solution, indicating that it would be usefully utilised as an adsorbent to remove Cs+.

Synthesis and evaluation of multitopic bisbenzothiazolyl calix[4]arenes for ionic toxicants

Two new benzothiazolyl calix[4]arene-based multitopic molecular receptors L-1 and L-2 have been synthesised and evaluated for recognition of ionic toxicants. The receptors selectively interact with copper, silver and fluoride ion toxicants as assessed through UV-visible, NMR and colorimetric techniques. The stability of L-1:Cu+2 and L-2:Cu+2 complexes was found to be higher than that of complexes formed with Ag+ and F– complexes in the presence of trifluoroacetic acid. Superiority of L-1 over L-2 for analysis of identified toxicants has been determined by measurement of binding constants.

A study of anion binding behaviour of 1,3-alternate thiacalix[4]arene-based receptors bearing urea moieties

Thiacalix[4]arene receptors with two urea moieties exhibited a high affinity towards all of the selected anions.

Functionalized calix[4]arene-based receptor for saccharide recognition

A novel class of functionalized-calix[4]arene such as 1,4-dihydropyridine-calix[4]arene, acridine-calix[4]arene and pyrimidine-calix[4]arene were synthesized using multicomponent reaction. These compounds have been characterized by 1H NMR, 13C NMR and HRMS. Fluorescent and 1H NMR titration investigations reveal that these derivatives have the high binding constant towards the monosaccharide and disaccharide in aqueous solution. The formation of complex was also supported by electrospray mass spectrometry.

Supramolecular assistance for the selective demethylation of calixarene-based receptors.

The selective demethylation of methoxy groups of several multifunctionalized 1,3,5-trimethoxycalix[6]arene-based receptors has been achieved. It is shown in this study that the best reagent is trimethylsilyl iodide (TMSI) and that the conformation adopted by the calixarene core is crucial for both the selectivity and the efficiency of the process. A key feature appears to be the "in" or "out" orientation of the methoxy substituents relative to the macrocyclic cavity. If projected inward, the reaction is slow and not selective. If projected outward, the reaction is fast and selective. A strategy that consists of exploiting the host-guest properties of the receptors to change their conformation and to permit their selective demethylation has been developed. Four cases of such a supramolecular assistance are reported, demonstrating the efficiency of the strategy. Such an allosteric control is highly reminiscent of biological processes allowing selective transformation of multifunctional molecules.

Positive and negative allosteric effects of thiacalix[4]arene-based receptors having urea and crown-ether moieties

Allosteric binding behaviors of heteroditopic receptors bearing the 1,3-alternate conformation based thiacalix[4]arene have been evaluated by absorption and 1H NMR titration experiments.

Fluorescent chemosensors for anions and contact ion pairs with a cavity-based selectivity.

The association of a concave macrocyclic compound to one or multiple fluorophores is an appealing strategy for the design of chemosensors. Indeed, as with biological systems, a cavity-based selectivity can be expected with such fluorescent receptors. Examples of calix[6]arene-based systems using this strategy are rare in the literature, and to our knowledge, no examples of fluorescent receptors that can bind organic contact ion pairs have been reported. This report describes the straightforward synthesis of fluorescent calix[6]arene-based receptors 4a and 4b bearing three pyrenyl subunits and the study of their binding properties toward anions and ammonium salts using different spectroscopies. It was found that receptor 4a exhibits a remarkable selectivity for the sulfate anion in DMSO, enabling its selective sensing by fluorescence spectroscopy. In CDCl3, the receptor is able to bind ammonium ions efficiently only in association with the sulfate anion. Interestingly, this cooperative binding of ammonium sulfate salts was also evidenced in a protic environment. Finally, a cavity-based selectivity in terms of size and shape of the guest was observed with both receptors 4a and 4b, opening interesting perspectives on the elaboration of fluorescent cavity-based systems for the selective sensing of biologically relevant ammonium salts such as neurotransmitters.

An induced-fit process through mechanical pivoting of aromatic walls in host–guest chemistry of calix[6]arene aza-cryptands

The per-ipso-nitration of a TMPA-capped calix[6]arene has been achieved. The substitution of the six bulky tBu substituents for nitro groups has a strong impact on the behavior of the ligand during guest recognition. The complexation of the aza cap (by H(+) or Cu(+)) associated with the encapsulation of a guest triggers an induced-fit process leading to the loss of the cone conformation of the host in favor of alternate conformations. Such a "pivoting" response of one or two walls of the calixarene core induces a large mechanical motion of the corresponding aromatic units. This stands in strong contrast with the "breathing" phenomena previously identified with other calix[6]arene-based complexes that expand or shrink the size of their cone as a function of the guest. Because of the covalently attached rigid TMPA cap, three arene units of this new calixarene host have a restricted mobility, which forces it to respond in a different manner to a supramolecular stress.

A study of allosteric binding behaviour of a 1,3-alternate thiacalix[4]arene-based receptor using fluorescence signal.

A novel heteroditopic thiacalix[4]arene receptor L possessing 1,3-alternate conformation, which contains two pyrene moieties attached to the lower rim via urea linkages together with a crown ether moiety appended at the opposite side of the thiacalix[4]arene cavity, has been synthesized. The complexation behaviour of receptor L was studied by means of fluorescence spectra and (1)H NMR titration experiments in the presence of K(+) ions and a variety of other anions. The results suggested that receptor L can complex efficiently via the urea cavity or the crown ether moiety, and a positive/negative allosteric effect operating in receptor L was observed.

Supramolecular Assistance for the Selective Monofunctionalization of a Calix[6]arene Tris-carboxylic Acid-Based Receptor

The selective functionalization of macrocyclic receptors remains extremely challenging because it generally requires the transformation of one and only one functional group among several identical groups. Recently, some of us described that the host-guest properties of a calix[6]arene-based Zn complex could be exploited for its selective monofunctionalization. Herein, we report on the extension of this synthetic strategy to a calix[6]arene-based receptor displaying a different recognition pattern with its guest. More precisely, a calix[6]arene tris-carboxylic acid-based receptor bearing three azido groups at the large rim was selectively monofunctionalized through an intramolecular thermal Huisgen reaction with a hexynNH3(+) ion accommodated into the cavity. This work shows that the monofunctionalization methodology can also be performed efficiently with host-guest systems involving ionic/H-bonding interactions, and it is thus not limited only to the use of metal-ligand interactions. In other words, this supramolecular methodology can be used as a general tool for the selective functionalization of molecular receptors.

Experimental and computational studies of anion recognition by pyridine-functionalised calixarenes

Calix[4]arene-based receptors linked to amide and pyridine moieties have been synthesised in four steps from calix[4]arene, and characterised by 1H and 13C NMR spectroscopy. The recognition properties of these receptors towards different anions were evaluated using 1H NMR and computational studies. The receptors show modest selectivities towards dihydrogen phosphate versus carboxylates.

Electrospun nanofibers and multi-responsive supramolecular assemblies constructed from a pillar[5]arene-based receptor

Multi-responsive supramolecular polymers have been constructed from pillar[5]arene-based receptors. Significantly, nanofibers, nanosized supramolecular polymers based on pillararenes, have been successfully fabricated employing an electrospinning technique for the first time.

Calix[4]arene-based fluorescent receptor for selective turn-on detection of Hg2+ ions

A new fluorescent molecular receptor 3 based on the cone confirmation of calix[4]arene appended with 2-[4-(N,N-dimethylaminophenyl)iminoethoxy] moieties was synthesised, which exhibits selective fluorescence ‘Turn-On’ response in the presence of only Hg2+ ions among the various metal ions tested with a detection limit up to the nanomolar range. The fluorescence behaviour of receptor 3 in the presence of Hg2+ ions is attributed to the alteration in electronic properties of 3, i.e. working of intramolecular charge transfer (ICT) phenomenon on Hg2+ ions complexation. The nitrogen atoms of the imino moieties got involved in the coordination with mercury ions, which enhances the electron-withdrawing ability of imino nitrogen atoms and, hence, leads to an ICT process consequently resulting in the appearance of an emission band at 444 nm.