Inclusion of Organic Cations by Calix[n]arenes

Calix[n]arenes represent an interestingclass of preorganized aromatic hostsexhibiting an enhanced ability forcation- interaction. Recent resultsobtained with the complexation of variouscalix[n]arenes and five structural typesof organic cations, namely ammonium ions,quaternary ammonium ions, phosphonium ions,iminium ions and tropylium ions are reviewed.The influence of both the guest structure and theshape and flexibility of the hosts on the complexstability in the gas phase and (mainly) in solutionis considered.     

Chiral Heteroditopic Baskets Designed from Triazolated Calixarenes and Short Peptides

Cone calix[4]arenes and calix[6]arenes bearing two, three, and four short peptide units each having two chiral carbon atoms were prepared. The syntheses were performed by using an efficient modular approach that includes the Ugi preparation of the azido‐peptide followed by its reactions with the propargylated calixarenes under CuAAC (Cu^I‐catalyzed azide–alkyne cycloaddition) conditions. The three novel multitopic hosts were probed for their ability to bind metal ions by UV titration, and showed the highest complexation efficiency towards copper(II) and lead(II). These two cations possessed quite different complexation modes with copper(II) bound predominantly by multiple‐triazole sites, in contrast to lead(II), which is stabilized mainly by multiple interactions with amide groups of the peptide units. Circular dichroism data for the free chiral hosts, their equimolar mixtures with copper(II) perchlorate and lead(II) perchlorate, and for tertiary mixtures of all three compounds showed the formation of mono‐ and binuclear complexes, or a switching behavior, depending on the structure of the host and the addition order of the cations.     

Synthesis of nucleobase-calix[4]arenes via click chemistry and evaluation of their complexation with alkali metal ions and molecular assembly

In this study, calix[4]arene derivatives (11–14) bearing a single nucleobase (adenine, thymine, cytosine or guanine) were synthesised via click chemistry. The complexation ability of the synthesised derivatives with alkali metal ions was measured using MALDI-TOF mass spectrometry, and their molecular assembly in CDCl₃ was determined using ¹H NMR. Calix[4]arene derivatives (11–14) formed 1:1 complexes with all alkali metal ions and the rank order for the complexation selectivity was Rb⁺ > Cs⁺ > K⁺ ? Na⁺ > Li⁺. The attachment of nucleobase at the upper rim of calix[4]arene had little effect on its complexation selectivity for alkali metal ions. Thymine-, adenine- and guanine-calix[4]arenes formed self-assembled structures in CDCl₃ via base–base interactions. In addition, adenine-calix[4]arene (11) bound to thymine-calix[4]arene (12) to form a discrete species via Hoogsteen hydrogen bonding.     

Cation- and anion-assisted binding of triethylenediamine by zinc bisporphyrinates

The complexation of zinc calix[4]arene or calix[4]pyrrole bisporphyrinates with alkali metal cations, halide anions, and triethylenediamine was studied by ¹H NMR spectroscopy. It was established that the binding of molecules and/or charged particles by various fragments of calix[4]arene and calix[4]pyrrole porphyrins are interrelated processes. This makes it possible to use one process (for example, complexation of the calix[4]arene fragment of the macrocycle with alkali metal cations or complexation of the calix[4]pyrrole fragment with halide ions) as a tool for controlling another process (complexation of the porphyrin fragments of the macrocycle with neutral molecules).     

Heterodimer of tetraaryl- and tetratosylurea calix[4]arenes: first single crystal X-ray analysis and guest encapsulation properties in CDCl3

The first single crystal X-ray analysis of the heterodimer of tetraaryl- and tetratosylurea calix[4]arenes was reported, which revealed the real pattern of the hydrogen bonds. Moreover, the heterodimer showed good encapsulation abilities for some organic molecules in CDCl₃.     

Synthesis, NMR, X-ray structural analyses and complexation studies of new Ag selective calix[4]arene based dipodal hosts—a co-complexation of neutral and charged species

New podands based on the p-tert-butylcalix[4]arene unit with substitution at the lower rim incorporating imine units, have been synthesized in high yield by simple condensation method. These podands have been shown to extract and transport Ag⁺ selectively over alkali, alkaline earth metal cations, Zn²⁺, Pb²⁺ and Hg²⁺ ions, from neutral aqueous phase to organic phase. In all the ligands the calix unit has been found to be present in a cone conformation except for the one having pyridine as end group, at the ortho position. It has been isolated in two conformations; cone and 1,2-alternate. To the best of our knowledge, this may be the first 1,3-lower rim substituted calix[4]arene to exist in a 1,2-alternate conformation and is among a few known compounds with this conformation in the general class of calix[4]arenes. A complex of this ligand, which happens to be the highest extractant of Ag⁺ has been isolated and characterized using mass, ¹H and ¹³C NMR spectroscopy's and elemental analysis. The spectroscopic evidence and molecular modelling studies performed on the complex suggest a participation of the imine and pyridine nitrogens and two of the ether oxygens in coordination to the metal ion. The X-ray crystal structures of three of the ligands establish the formation of inclusion complexes with polar acetonitrile solvent molecules. The ¹H and ¹³C NMR spectra of all the compounds, taken in CDCl₃, show the presence of acetonitrile molecules in the cavity of the calix[4]arene, indicating inclusion of the neutral guest molecules in the solution phase as well. For one of the podands X-ray crystal structure has shown a formation of clatharate complex of chloroform with the ligand which has rarely been found in the case of calix[4]arenes.     

Synthesis of novel p-tert-butyl-calix[4]arene derivatives and their cation binding ability: chromogenic effect upon side arms binding

A series of novel double-armed calix[4]arene derivatives, i.e. 5,11,17,23-tetra-tert-butyl -25,27-bis[2-[(2-hydroxy-5-(4-nitroazo)benzylidene)amino]ethoxy]-26,28-dihydroxy-calix[4]-arene (4), 5,11,17,23-tetra-tert-butyl-25,27-bis[2-[(2-hydroxy-5-(2-nitroazo)benzylidene) amino]ethoxy]-26,28-dihydroxycalix[4]arene (5), 5,11,17,23-tetra-tert-butyl-25,27-bis[2-[(2-hydroxy-5-(4-chloroazo)benzylidene)amino]ethoxy]-26,28-dihydroxycalix[4]arene (6), have been synthesized as an selective chromoionophore for Na⁺. The complexation behavior of ligands 4-6 with alkali metal ions Na⁺, K⁺, Rb⁺and Cs⁺ has been evaluated by using UV-Vis spectrometry in CH₃CN-H₂O (99:1/V:V) solution at 25°C. The UV-Vis spectra show that the complexation of 4-6 with Na⁺exhibits obvious bathochromic shifts (λ_max 379→480 nm) and there is a unique color change in the solution from yellow to red upon complexation. The binding constants for Na⁺ are higher than that of other alkali metal ions, giving the highest cation selectivity up to 7 for Na⁺/K⁺. The binding ability and photophysical behavior of alkali cations by calix[4]arene derivatives 4-6 are discussed from the point of view of substituted effects at the lower rim of parent calix[4]arene and size-fit concept between host calix[4]arenes and guest cations.     

A paradigm shift in the construction of heterobimetallic complexes: synthesis of group 2 & 4 metal-calix[6]arene complexes

Deprotonation of calix[6]arenes with barium in methanol followed by the addition of [Ti(OPr(i))(4)] or [Zr(OBu(n))(4)] is effective in the formation of novel dimeric 2:1 barium-titanium(IV)/zirconium(IV) calix[6]arene complexes. In these complexes a central Ti(IV)/Zr(IV) coordinated in the exo-position connects the two calix[6]arenes in the 1,3-alternate conformation, each with an endo-barium sharing common phenolate groups with the titanium/zirconium centre and participating in cation-pi interactions. A homometallic barium calix[6]arene dimer was also prepared wherein the calix[6]arenes are in the 1,3-alternate conformation with each coordinating one endo- and one exo-barium centre. The exo-barium cations connect the two calix[6]arenes through bridging methanol ligands. In this and the heterometallic complexes, cation-pi complexation of the Ba(2+) ion within the 1,3 alternate conformation of calix[6]arene facilitates the formation of the dimeric complexes in methanol. In contrast, the smaller Sr(2+) ion did not form similar complexes in methanol, and the formation of an analogous 2:1 strontium-titanium calixarene complex required the use of the more sterically demanding donor alcohol, isopropanol, the resulting complex being devoid of cation-pi interaction. The results show (i) that a subtle interplay of solvation strength, coordination array type and cavity/cation size influences the accessibility of heterobimetallic complexes based on calix[6]arenes, and (ii) a synergistic endo-exo binding behaviour.     

Fullerene encapsulation with calix[5]arenes

This paper presents the synthesis of the fullerene hosts based on the calix[5]arenes and their binding properties. Calix[5]arenes 1a, 2, 3a bind C₆₀ or C₇₀ in organic solvents. The solvent effect of the fullerene complexation was clearly observed; the association constant decreases in a solvent with high solubility for C₆₀. Covalently linked double-calix[5]arenes 4-6 were also investigated on their binding properties for fullerenes in organic solvents. Their binding abilities for both C₆₀ and C₇₀ are extremely high in toluene solution. Higher binding selectivity toward C₇₀ is observed by all the double-calix[5]arenes. The selectivity of 5a toward C₇₀/C₆₀ is highest in toluene with a value of 10. The structures of the supramolecular complexes of the calix[5]arene hosts and C₆₀ or C₇₀ were investigated by using ¹H and ¹³C NMR studies. The molecular mechanics calculation and X-ray structure reveal that the interior of the calix[5]arene is complementary to the exterior of C₆₀ molecule. In contrast, the host-guest complexes of C₇₀ with the simple calix[5]arenes take many conformational options due to its less symmetric shape. The molecular mechanics calculation and our chemical shift simulation nicely worked to estimate the reliable structures; the calix[5]arene cavity takes up C₇₀ molecule, and the C₇₀ molecule tilts significantly from the C5 axis of the calix[5]arene. In the case of the host-guest complex of C₇₀ with the double-calix[5]arene, the molecular dynamics simulation of the host-guest complex represented the realistic movement of the bound C₇₀ inside the cavity. The combination of the molecular dynamics simulation and the chemical shift simulation of the host-guest complex suggested that the C₇₀ molecule rapidly moves inside the cavity.     

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.     

Recognition of guests bearing donor and acceptor hydrogen bonding groups by heteroditopic calix[4]arene receptors

The synthesis of new hosts specifically designed for the recognition of neutral guests bearing donor-acceptor hydrogen bonding groups is described. These hosts are characterized by the presence of two distinct binding region in close proximity: the rigid π-donor cavity and the H-bond donor N-methylene-N′-phenylureido group inserted onto the upper rim of the calix[4]arene skeleton. The binding abilities of these receptors were investigated toward a series of neutral ditopic organic molecules in CDCl₃ solution by ¹H NMR spectroscopy. The results obtained show that rigidity of the calix[4]arene apolar cavity is the control element in determining efficiency. In fact, compared with the more rigid 2, host 10, where the rigidity of the cone structure is maintained by hydrogen bonding of the OH of the lower rim, a decrease of efficiency of almost one order of magnitude was observed. The cooperative effect of the two binding region of host 2 was verified with different classes of ditopic guests. Good efficiency in the recognition of urea derivatives and dimethylsulfoxide was achieved.     

Thermodynamics of sublimation of calix[4]arene complexes with solvent molecules

The inclusion of small neutral organic guests (C₆H₁₄, CH₂Cl₂, CH₃OH) by calix[4]arene receptors was found by ¹H NMR spectroscopy and microanalysis. The studied calix[4]arenes can form stable intramolecular complexes with solvent molecules which keep the stoichiometric composition without changing under conditions of the sublimation experiment. The saturated vapour pressures of calix[4]arenes and complexes of calix[4]arenes with solvent molecules were determinated for the first time by the Knudsen’s effusion method in the wide temperature range. The changing of standard thermodynamic parameters of complexation by transfer process from condensed state to vapour phase was estimated. It was shown that the large flexibility of the calixarene ligand structure corresponds to a strongly negative entropic contribution as well as negative enthalpy term to the Gibbs energy of formation of host–guest complexes in the gas phase.     

Synthesis of Ionizable Calix[4]arenes for Chelation of Selected Divalent Cations

Two sets of functionalised calix[4]arenes, either with a 1,3-crown ether bridge or with an open-chain oligo ether moiety in 1,3-position were prepared and further equipped with additional deprotonisable sulfonamide groups to establish chelating systems for selected cations Sr²⁺, Ba²⁺, and Pb²⁺ ions. To improve the complexation behaviour towards these cations, calix[4]arenes with oligo ether groups and modified crowns of different sizes were synthesized. Association constants were determined by UV/Vis titration in acetonitrile using the respective perchlorate salts and logK values between 3.2 and 8.0 were obtained. These findings were supported by the calculation of the binding energies exemplarily for selected complexes with Ba²⁺.     

A Quantum Chemical Study on Recognition of Nitro-phenols by Calix[n]arenes

A PM3 calculation in vacuum of the inclusion complexation ofo-, m-, p-nitro-phenol with calix[n]arenes is performedsuccessfully. The pathways for inclusion process are describedand the most probable structures of the 1:1 complex are soughtthrough a potential energy scan. The energy differences betweenthe inclusion complexes and the hosts, by calculation, show thatthe most stable complexation is calix[4]-p-nitro phenol andcalix[6]-m-nitro phenol.     

Conformational features and recognition properties of a conformationally blocked calix[7]arene derivative

The shaping of a calix[7]arene macrocycle into cone-like structure 3, through exhaustive alkylation of doubly bridged calix[7]arene derivative 2 with bulky groups, has been investigated. Conformational details about the structure adopted by calix[7]arene derivative 3 in solution have been obtained by using chemical shift surface maps, as previously reported by our group. Thus, chemical shift contour plots indicated that 3 adopted a cone-shaped structure in solution analogous to that adopted by the known p-tert-butylcalix[7]arene heptacarboxylic acid derivative 4. Interestingly, the X-ray structure of derivative 3 showed a high degree of similarity to the theoretical structure, which confirmed the validity of the contour plots method. The preorganized calix[7]arene host 3 showed interesting recognition abilities toward both organic and alkali cations. In fact, an unprecedented endo-cavity complexation of linear and branched alkyl ammonium cations with a larger calix[7]arene host was evidenced. A comparable affinity for branched tBuNH(3)(+) and linear nBuNH(3)(+) guests was observed.     

Inclusion behavior of water-soluble thiacalix- and calix[4]arenes towards substituted benzenes in aqueous solution

Inclusion abilities of thiacalix- and calix[4]arenetetrasulfonate (3 and 4) towards mono-substituted benzenes were investigated in neutral aqueous solution. In general, the hosts regioselectively encapsulated the guests from the aromatic moiety except the complexation of toluene by 4, in which the guest penetrated from either the aromatic or the methyl group. Stabilities of the inclusion complexes increased with the electron-withdrawing ability of the substituent on the guest, suggesting pi-pi electronic interaction between the host and guest. In spite of the lower electron density of the aromatic ring, thiacalix[4]arene 3 showed higher inclusion ability than calix[4]arene 4, suggesting that the size rather than the electron density of the calix framework is a more important factor in determining the inclusion ability.     

Potassium Sensing Calix[4]arene Crown Ethers

1,3-Alternate calix[4]arene crown-5 (1) and corresponding biscrown-5 (2) were synthesized and the complexation behavior with alkali metal ions examined. For both 1 and 2, potassium ion was selectively extracted from aqueous phase into organic phase over other alkali metal ions based on two phase extraction experiment. The complexation ratio between calix[4]arene biscrown-5 (2), in which two crown cavities connect to the calix[4]arene framework by 1,3-alternate fashion and potassium metal ion is found to 1:1 by proton NMR spectroscopy and extraction equilibria. Association constants (logK_a) for 1 and 2 were determined to give 2.51 and 3.49, respectively.     

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.     

New artificial receptors from selectively functionalized calix[4]arenes

Abstract

The development of new synthetic methods for the monoalkylation of calix[4]arenes at the lower rim allows the synthesis of a new class of trihydroxamate siderophores. Three chelating hydroxamic acid units are introduced through a sequence of reactions which blocks the macrocycle in the cone conformation. The new ligands obtained form neutral 1:1 complexes (FeL) with iron (III), which are stable in EtOH/H₂O 9:1 at pH 2–7. Calix[4]arene bis-crown ethers are prepared by exploiting the selective 1,2-(proximal) functionalization of calix[4]arenes at the lower rim. These ligands are, however, less effective in complexing alkali metal cations compared with the 1,3-calix[4]arene crown-ethers which, in their partial cone structure, offer a better shielding for the complexed cations. Rigid upper rim-bridged calix[4]arenes potentially useful for the inclusion of neutral molecules are prepared by exploiting the selective 1,3-diformylation of calix[4]arene at the upper rim. Finally a new chloromethylation method for calix[4]arenes blocked in the cone conformation is described together with the synthesis of new cavitands.     

Potassium selective calix[4]semitubes

A new class of ionophore consisting of two calix[4]arene units linked through the lower rim by two ethylene chains, in combination with propyl ether and phenolic functional groups, has been developed. These calix[4]semitube molecules exhibit remarkable selectivity and fast complexation kinetics for potassium over all Group 1 metal cations. Molecular modelling studies, using structural models derived from crystallographic data, suggest the potassium cation is complexed by a horizontal, side-on route and not through the calix[4]arene annulus. The length of the bridging alkylene chain between the respective calix[4]arenes of the semitube structure dictates the strength and selectivity of alkali metal cation binding.