Ab initio and density functional studies of cooperative hydrogen bonding in calix[4]-and calix[6]arenes

The cone conformation of C ₄ symmetry is shown by the Hartree-Fock method (3-21G basis) to be the predominant conformer of calix[4]arene; the compressed cone of C ₂ symmetry is the major conformer of calix[6]arene. Using quantum chemical methods we calculated hydrogen bond cleavage energies for calix[4]-(ab initio and density functional methods) and calix[6]arene (ab initio), and also for the complex of calix[4]arene with carbon disulfide. These energies along with structural data point to the cooperative effect of hydrogen bonds. The results of these studies provided an explanation to the greater conformational lability of calix[6]arene compared with calix[4]arene molecules. It is also predicted that the nucleophilic substitution reaction involving calix[6]arene in the presence of weak bases and in aprotic solvents, as well as in the gas phase, will occur via diastereomeric transition states.     

Bridge-disubstituted calix[4]arenes obtained via a new preparative route. Synthesis and structural study

A series of calix[4]arenes bearing various substituents including alkyl, p-bromobenzyl, carboxy and allyl at opposite methylene bridges has been synthesized via successive metallation followed by nucleophilic substitution. In a first step, mono-lithiated calix[4]arenes react with terminal bromoalkanes to give 2-alkylated calix[4]arenes or with CO₂ the respective calixarene-2-carboxylic acid in good yields. A second lithiation step of the monosubstituted products with subsequent attachment of both polar and non-polar substituents yields several new diametrally bridge-disubstituted calix[4]arenes. 2D-NMR measurements establish the disubstituted calixarenes to predominantly adopt the 1,2-alternate conformation in solution. First examples of X-ray crystal structures of the new type of disubstituted calix[4]arenes are described featuring the calix[4]arene also in the rare 1,2-alternate conformation.     

A facial microwave-assisted synthesis, spectroscopic characterization and preliminary complexation studies of calix[4]pyrroles containing the hydroxamic-acid moiety

The synthesis, spectroscopic characterization and preliminary complexation properties of functionalized calix[4]pyrroles are described. To date, two generalized preparative approaches have been pursued (i) modifying the basic pyrrole-plus-ketone synthesis of calix[4]pyrrole by using microwave irradiation protocol, (ii) the basic meso-tetra(methyl) meso-tetra(p-nitrophenyl) calix[4]pyrrole skeleton was functionalized to give hydroxamic acids, especially in the meso-position of the macrocycles. The structures of novel calix[4]pyrrole hydroxamic acid derivatives were confirmed on the basis of various physico-chemical techniques such as elemental analysis, FT-IR, ¹H NMR and FAB-Mass. The results of preliminary studies on the extraction of vanadium (V) with the host calix[4]pyrrole hydroxamic acids were elucidated by significant examination of UV–Vis spectroscopy and ICP-AES. Single crystal structure of basic meso-tetra(methyl) meso-tetra (p-nitro phenyl) calix[4]pyrrole moiety has also been reported.     

Effect of the glutaraldehyde derivatives of Calix[n]arene as cross-linker reagents on lipase immobilization

Synthesis of the glutaraldehyde derivatives calix[n]arene (n = 4,6,8) (Calix[n]-GA) and using as cross-linkers for immobilization of Candida rugosa lipase (CRL) have been discussed in this paper. The amino functional calix[n]arene derivatives (Calix[n]-NH ₂) were synthesized via reduction of dinitrile, hexanitrile and octanitrile derivatives of calix[n]arenes. These amino functional calix[n]arene derivatives (Calix[n]-NH ₂) were converted to their aldehyde derivativatives with glutaraldehyde. The calix[n]arene derivatives were used in lipase immobilization in order to see the role of calix[n]arene binding site on the lipase activitiy and stability. The activity recovery of calix[n]arene-supported lipases (Calix[n]-CRL) based on the Calix[4]-CRL, Calix[6]-CRL and Calix[8]-CRL reaches to 53.5, 66.1 and 76.4%, respectively.     

Mass spectroscopic investigation of bis-1,3-urea calix[4]arenes and their ability to complex N-protected α-amino acids

We report the ability of urea’s appended onto the upper-rim of conformationally locked ‘cone’ calix[4]arenes to show a preference for binding specific N-protected α-amino acids. Superior complexation (as judged by mass spectroscopy) between N-protected α-amino results and bis-1,3-N-benzylureas calix[4]arenes was observed when methylene bridges were present between the calix[4]arene ‘host’ and the urea motif. Interestingly we also demonstrate that subjecting mixtures of structurally diverse N-Fmoc-α-amino acids to a single bis-1,3-N-benzylurea derived calix[4]arene allows, in some cases, the calix[4]arene ‘host’ to selectively ‘pick out’ and complex a specific N-Fmoc amino acid from the mixture.     

Stereochemical control of calixarenes useful as rigid and conformationally diversiform platforms for molecular design

Stereochemical problems and related functions of calix[4]arenes, calix[6]arenes and their chiral derivatives have been reviewed. In p-tert-butylcalix[4]arene (1H₄) and its mono-, di-, tri-, and tetra-O-alkyl derivatives (1H₃R, 1H₂R₂,1HR₃, and 1R₄, respectively), 23 different homologues can exist (including 1H₄). We found that the OH group in the unmodified phenol unit is permeable through the calix[4]arene ring. Thus, several conformational isomers become equivalent after the ‘oxygen-through-the-annulus’ rotation of the OH group and the number of possible homologues is reduced to 13 (including 1H₃). We report in this paper the syntheses of all of these possible conformational isomers using a protection-deprotection method with a benzyl group and metal template effects. On the other hand, all possible chiral isomers that can be derived from calix[4]arene by modification of the OH groups have been systematically classified. Molecular asymmetry can be generated not only by different substituents but also by conformational isomerism. The numbers of chiral isomers are 17 for tetra-O-substituted calix[4]arenes, 9 for tri-O-substituted calix[4]arenes, 3 for di-O-substituted calix[4]arenes, and 0 for mono-O-substituted calix[4]arenes. Chiral calix[4]arenes can also be designed by the introduction of a substituent into the m-position of a phenol unit or by the use of a dissymmetric ‘stapling reaction’ in proximal phenol units. In p-tert-butylcalix[6]arene, the conformational behaviour is totally different from that in p-tert-butylcalix[4]arene. A large degree of conformational freedom remains in the framework, and both ‘oxygen-through-the-annulus rotation’ and ‘para-substituent-through-the-annulus rotation’ can take place. However, when metal cations are bound to calix[6]aryl esters, the conformation is changed to a cone type. Bridging and capping are powerful methods to immobilize the conformation of calix[6]arenes. In addition, definitive evidence for ring immobilization was obtained from the absence of racemization in the chiral calix[6]arene. A successful example of chiral recognition for α-amino acid derivatives was achieved by using chiral homooxacalix[3]arene which has ‘pseudo C₂ symmetry’. These examples indicate that calixarenes serve as rigid and conformationally diversiform platforms for the design of novel functional supramolecules.     

Direct access to upper rim substituted mono- and diaryloxy calix[4]arenes via bis(spirodienone) route

A seemingly ipso-like nucleophilic substitution of the upper rim of p-tert-butylcalix[4]arene is accomplished by an indirect method involving calix[4]arene derived bis(spirodienone). This method not only provides both mono and 1,3-diaryloxy calixarenes but also enables the synthesis of upper rim monothio substituted calix[4]arenes. A modification of the methodology can be successfully extended for the selective synthesis of mono- and 1,3-diquinone calix[4]arenes having free hydroxyl groups at the lower rim, in fewer steps.     

Inherently chiral biscalixarene cone–cone conformers consisting of calix[4]arene and calix[5]arene subunits

Inherently chiral biscalixarenes with hetero-cavities were synthesized by a covalent assembly of p-tert-butylcalix[5]arene with a 1,3-substituted calix[4]arene via 1,3-alkylation reaction and subsequent desymmetrization. The racemates were resolved by chiral HPLC method. ¹H NMR spectra, VT-NMR spectra, and theoretical calculations support that the calix[5]arene subunit of the inherently chiral calix[4][5]arene ester adopts a cone-in conformation, with the aromatic ring bearing the CH₂CO₂Et group tilting inward the calix[5]arene cavity. By contrast, such a cone-in structural feature of the calix[5]arene subunit disappears for the corresponding inherently chiral calix[4][5]arene carboxylic acid, due to the intramolecular hydrogen bonding between the carboxyl group and an ethereal oxygen of the glycolic chain.     

Efficient ZnCl2 assisted synthesis of calix[4]pyrroles catalysed by Brønsted acidic ionic liquids

A facile and efficient protocol is reported for the synthesis of calix[4]pyrroles and N-confused calix[4]pyrroles in moderate to excellent yields by one-pot condensation of ketones and pyrrole in the presence of catalytic amount of nontoxic acidic ionic liquids. In this reaction the products were obtained in short reaction time with selectivity of regular calix[4]pyrroles.     

Synthesis of calix[4]arene alkylamine derivatives as new phase-transfer catalysts for esterification reaction

This study reports the synthesis of calix[4]arene-based phase-transfer catalysts derived from the reaction of 5,17-di-tert-butyl-25,27,26,28-tetrahydroxycalix[4]arene with N-ethylpiperazine, diallylamine or 4-benzylpiperidine. The catalytic efficiency of the calix[4]arenes alkylamine derivatives was evaluated by carrying out the ester-forming reaction of alkali metal carboxylates (sodium butyrate or sodium caprylate) with p-nitrobenzyl bromide. It has been observed that the ester-forming reaction of alkali metal carboxylates with p-nitrobenzyl bromide, using the N-ethylpiperazine amine derivative of calix[4]arene as a phase-transfer catalyst in dichloromethane at 25 °C, provided the best yields.     

Highly efficient synthesis of N-confused meso-tetraspirocyclohexyl calix[4]pyrrole using Brønsted acidic ionic liquids as catalysts

An efficient, green and novel protocol is described for high yield synthesis of N-confused meso-tetraspirocyclohexyl calix[4]pyrrole. In aqueous solution, the condensation of pyrrole and cyclohexanone in the presence of Brønsted acidic ionic liquid catalysts afforded N-confused calix[4]pyrrole in up to 62.5% yield which represents a ∼threefold yield improvement over existing protocol and makes significant quantity of N-confused calix[4]pyrrole readily available.     

X-ray guided H NMR analysis of pinched cone calix[4]arenes

The analysis of structural parameters of azobenzene- and stilbene-bridged calix[4]arene obtained from AM1 calculation are in good agreement with those obtained from X-ray crystallography. The bridge longer than 9.0 Å such as p,p-trans-azobenzene and p,p-trans-stilbene cannot be constructed over the narrow rim of calix[4]arene through two ethylene oxide linkers. The m,m-stilbene bridge is the most promising photo switch because its shorter cis stereoisomer (5.85 Å) allows calix[4]arene to assume the perfect cone conformation, whilst its longer trans stereoisomer (8.00 Å) forces calix[4]arene to adapt a pinched cone conformation. The pinched cone conformation has longer distances between the neighbouring phenoxyl groups causing the weaker intramolecular hydrogen bonding and the upfield shifts of the phenolic proton signals to below 7.00 ppm. This upfield shift is useful for quick identification of pinched cone conformation of new calix[4]arene compounds.     

Regioselective ipso-nitration of calix[4]arenes

A novel protection/deprotection method leading to the regioselective ipso-substitution of calix[4]arenes is described. The introduction of nosyl (p-nitrobenzenesulfonyl) groups into the lower rim of partly alkylated tert-butylcalix[4]arenes leads subsequently to the exclusive ipso-nitration of the alkylated phenol rings, while the protecting groups can be easily removed in the next step. This method gives dialkoxy- or trialkoxy-substituted calix[4]arenes with nitro groups on the alkylated rings and tert-butyl groups on the remaining ones. The above substitution pattern is complementary to the isomers so far known in the chemistry of calix[4]arenes and could be used in the design of novel type of calixarene-based receptors.     

Tuning the anion binding properties of calixpyrroles by means of p-nitrophenyl substituents at their meso-positions

Extended cavity calix[4]pyrroles and a calix[6]pyrrole were synthesized by cyclization of 5-methyl-5-(4-nitrophenyl)dipyrromethane with acetone in the presence of acid. The solid-state structures of the novel macrocycles were determined by X-ray crystallography. The host-guest chemistry of these receptors towards halide ions was investigated in solution by ¹H NMR titration techniques and compared with those of the meso-octamethylcalix[4]pyrrole and meso-dodecamethylcalix[6]pyrrole. The binding of chloride anions was observed to occur with different affinities on the two faces of the novel calix[6]pyrrole derivative described here.     

Analytical applications of nano-baskets of calix[4]pyrroles

Calix[4]pyrrole is one such class which holds a great promise in the fields of sensors and their unique behavior as sensors owes to its structural flexibility. Anion binding ability of calix[4]pyrrole has been modified in a variety of ways. Introduction of electron releasing and electron withdrawing groups at the meso position or at β-pyrrolic positions leads to calix[4]pyrrole with deep cavities and fixed walls which shows increased selectivity and modified binding effects. Strapping of calix[4]pyrrole is another way to modify its structural behavior which is responsible for its binding behavior. Choice of strap could play a profound role not only in increasing the intrinsic anion binding affinity of calix[4] pyrrole, but also in modulating the receptor anion stoichiometry, thereby modifying potentially the inherent anion binding selectivity. Calix[n]pyrroles with extended cavities have also been synthesized. Such as calix[3]bipyrrole binds bromide substantially with high affinity than calix[4]pyrrole. Calix[4]pyrrole has also been used to produce anion sensors that can report the presence of anion by means of a color change. The medium effect on the complexation of calix[4]pyrrole and anion has been investigated in various solvents. Calix[4]pyrrole has also been used to increase the ionic conductivity of solid polymer electrolyte by anion complexation of the metal salt. Calix[4]pyrrole has been used to obtain optical sensors using surface plasmon resonance technique. Composite films of cellulose acetate containing calix[4]pyrrole has also been reported which has potential usage in packaging, storage and preservation. In nut shell, calix[4]pyrrole can be modified in a variety of ways to form versatile sensors which can be used in variety of ways in various areas.     

Synthesis and crystal structure of 15α,20α-di(4-hydroxylphenyl)calix[4]pyrroles and 10α,20β-di(4-hydroxylphenyl)calix[4]pyrroles

In the presence of methanesulfonic acid as catalyst, the condensation reactions of 5,5′-dialkyldipyrromethanes with p-hydroxyacetophenone in methanol resulted in a mixture of the unexpected polysubstituted 15α,20α-di(4-hydroxylphenyl)calix[4]pyrroles and the expected 10α,20β-di(4-hydroxylphenyl)calix[4]pyrroles in comparable lower yields. The crystal structures of the new calix[4]pyrroles and their oxyacetate derivatives were successfully determined by X-ray diffraction and the intermolecular interactions in the solid state is briefly discussed.     

Self-assembled calix[4]arenequinhydrone on the platinum electrode by cathodic reduction of calix[4]arenediquinone

The electrochemical reduction of di(methoxy-p-tert-butyl)calix[4]arenediquinone led to its calix[4]arenedihydroquinone. The presence of both in the solution refers to the generation of calix[4]arenequinhydrone charge-transfer complex at the electrode surface through a donor/acceptor process type. Self-assembled adlayers of calix[4]arenequinhydrone was obtained by partial electrochemical reduction. Electrochemical deposition of the last form was achieved on the platinum disk electrode at ?1.16?V versus SCE (saturated calomel electrode) in aprotic solution by cathodic reduction of the starting substrate. The deposit was first characterized by cyclic voltammetry (CV) in electrolytic solution and then in electrolyte support solution and finally in a ferricyannure solution. The self-assembled product was characterized by MALDI-TOF Mass and IR spectroscopy techniques. It was observed too by SEM technique. Calix[4]arenequinhydrone is observed on the electrode surface as hexangular prisms with a length of few micrometers.     

Information transfer in calix[4]arenes: influence of upper rim substitution on alkaline metal complexation at the lower rim

Novel calix[4]arene amides have been synthesized and their interaction with alkaline cations has been evaluated through extracting aqueous solutions of Li-, Na- and K-picrates with solutions of calix[4]arene amides in CH₂Cl₂. Electron-withdrawing groups on the upper rim of the calix[4]arene scaffold were found to have a negative effect on the absolute amount of metal ions extracted. The decreased extraction ability is accompanied by a higher selectivity towards sodium cations.     

p-Sulfonic acid calix[n]arenes as homogeneous and recyclable organocatalysts for esterification reactions

Esterification yields were significantly improved using calix[n]arenes catalysts under simple conditions. p-Sulfonic acid calix[4]arene and p-sulfonic acid calix[6]arene were powerful organocatalysts in several esterification reactions, which showed activity comparable or even superior to other well-established acids catalysts, such as, sulfuric acid, p-toluenesulfonic acid, and p-hydroxybezenesulfonic acid described in the literature.     

Preorganization of diglycolamides on the calix[4]arene platform and its effect on the extraction of Am(III)/Eu(III)

Different diglycolamide (DGA)-substituted calix[4]arene-based extractants were synthesized and evaluated for the extraction of Am(III) and Eu(III), representative trivalent actinide and lanthanide ions, respectively. On the narrow rim of the calix[4]arene platform, the DGA moiety was either 1,3-di- or tetrasubstituted with a varying spacer length between the oxygen and amide nitrogen atom. In addition, DGA groups were appended both to the wide rim and to both rims of calix[4]arenes and their efficiencies were compared for Am(III) and Eu(III) extraction at three different feed acidities. The extraction and separation efficiencies strongly depended on the N-alkyl substituent as well as the spacer length. 1,3-Di-DGA-substituted calix[4]arenes are inferior extractants to the corresponding tetra-DGA-substituted ones. Narrow rim DGA-functionalized derivatives resulted in high extraction efficiencies, while the wide rim DGA-functionalized calix[4]arenes showed practically no extraction.