Synthesis and self-assembly of novel calix[4]arenocrowns: formation of calix[4]areno[2]catenanes

A series of novel calix[4]arenocrowns 1a-c were efficiently synthesized by a one-pot reaction of calix[4]monohydroquinone diacetate 5 with ditosylate 6 and its analogues in the presence of sodium hydroxide. It was found that the calix[4]arenocrowns could form stable pseudorotaxane-type complexes 2a-c with paraquat, and further self-assemble into calix[4]areno[2]catenanes 3a-c with dicationic salt 8 and p-bis(bromomethyl)benzene.     

Synthesis of new calix[4]arenes containing nucleoside bases

A family of novel calix[4]arene derivatives containing nucleoside bases were designed and synthesized. Coupling reaction between para mono- or bis-amino calix[4]arenes 5, 6 or 7 and thymin-1-ylacetic acid in the presence of DCC afforded mono- or bis-thymine-substituted calix[4]arenes 8, 9 or 10 in over 70% yield. Owing to the low solubility of adenine-N⁹-ylacetic acid in DMF and DMSO and the weak nucleophilicity of aminocalix[4]arene derivatives, alternatively, the substitution reaction of bromoacetylated aminocalix[4]arenes derivatives 11, 12, 13 with adenine in the presence of sodium hydride was carried out to synthesize mono- or bis-adenine-substituted calix[4]arenes. Two kinds of isomers 15 and 16 or 17 and 18 were obtained due to the non-regiospecific alkylation of adenine, and their structures have been confirmed by ¹³C NMR and ¹H NMR spectra.     

Capping the upper and lower rims of calix[4]arenes by aryl dinitrile oxide reactions

1,3-Dipolar cycloadditions of upper- and lower-rim diallylcalix[4]arenes (1 and 3) with aryl dinitrile oxides provide a unique and efficient way of capping the calix[4]arenes. When dinitrile oxides reacted with 5-allylcalix[4]arene 7, they underwent a 1,3-dipolar cycloaddition on one side and an electrophilic substitution on the other side, which led to a novel type of asymmetric calix[4]arenes (9 and 12).     

Synthesis of novel calix[4]arenes containing organosilicon groups

Metalation of (RSiMe₂)₃CH (1a R = H, 1b R = Me, 1c R = Ph) with lithium diisopropylamide (LDA) or methyllithium in THF gave organolithium reagents (RSiMe₂)₃CLi, which reacted with the formylated calixarene (2), to give the corresponding 5,17-bis[2,2-bis(organosilyl)-1-ethenyl]-25,26,27,28-tetrapropoxycalix[4]arenes (3a, 3b and 3c) via the Peterson olefination. The compounds (RSiMe₂)₃CLi were treated with 25,26,27,28-tetrakis(4-bromobutoxy)calix[4]arene (4) to give 25,26,27,28-tetrakis[4-(tris(dimethylsilyl)methyl)butoxy] calix[4]arene (5a) and 25,26,27,28-tetrakis[4-(tris(trimethylsilyl)methyl)butoxy] calix[4]arene (5b) via nucleophilic substitution reactions. However the compound 25,26,27,28-tetrakis[4-(tris(dimethylphenylsilyl)methyl)butoxy] calix[4]arene (5c) was not obtained, presumably because (PhSiMe₂)₃C- is highly sterically hindered and the reactivity of its derivatives is low. The compound 5a has potential as a core for dendrimers.     

Functionalisation of the upper rim of calix[4]arene via alcoholysis and hydrosilylation reactions

Metalation of 5,17-dibromo-25,26,27,28-tetra propoxy calix[4]arene (1) with n-BuLi in THF at −78 °C gave organolithium reagent, which reacted with Me₂HSiCl to give 5,17-bis(dimethylsilyl)-25,26,27,28-tetra propoxy calix[4]arene (2). The Si-H groups of calixarene 2 were treated with methanol, ethanol, propanol, butanol, pentanol, hexanol, 2-propanol and 2-methyl propanol in the presence of Karstedt catalyst (platinum(0)-1,3-divinyl-1,1,3,3-tetramethyl disiloxane complex, solution in xylene) to give the corresponding 5,17-bis(alkoxydimethylsilyl)-25,26,27,28-tetra propoxy calix[4]arene (3). Moreover, calixarene 2 was easily functionalized with a variety of alkenes using Karstedt catalyst to give the corresponding organosilylated calix[4]arene (4).     

Calix[4]quinones. Part 4: The ClO2 oxidation of calix[4]arene dialkyl ethers

Except for the special case of calix[4]arene diethyl ether 1, the chlorine dioxide oxidation of dialkyl ethers 2-5 yielded only the corresponding calix[4]diquinone dialkyl ethers 8-11. Chlorine dioxide oxidation of calix[4]arene diethyl ether 1 produced two isomeric products 6 and 7, which were stable enough to be isolated by column chromatography. However, a slow conformational interconversion between isomeric pair 6 and 7 was observed at room temperature, and the equilibrium was reached after 400 h at 18 °C with an amount of 5:3 in favor of syn-isomer.     

Phosphite ligands derived from distally and proximally substituted dipropyloxy calix[4]arenes and their palladium complexes: Solution dynamics, solid-state structures and catalysis

Two bisphosphite ligands, 25,27-bis-(2,2′-biphenyldioxyphosphinoxy)-26,28-dipropyloxy-p-tert-butyl calix[4]arene (3) and 25,26-bis-(2,2′-biphenyldioxyphosphinoxy)-27,28-dipropyloxy-p-tert-butyl calix[4]arene (4) and two monophosphite ligands, 25-hydroxy-27-(2,2′-biphenyldioxyphosphinoxy)-26,28-dipropyloxy-p-tert-butyl calix[4]arene (5) and 25-hydroxy-26-(2,2′-biphenyldioxyphosphinoxy)-27,28-dipropyloxy- p-tert-butyl calix[4]arene (6) have been synthesized. Treatment of (allyl) palladium precursors [(η³-1,3-R,R′-C₃H₄)Pd(Cl)]₂ with ligand 3 in the presence of NH₄PF₆ gives a series of cationic allyl palladium complexes (3a-3d). Neutral allyl complexes (3e-3g) are obtained by the treatment of the allyl palladium precursors with ligand 3 in the absence of NH₄PF₆. The cationic allyl complexes [(η³-C₃H₅)Pd(4)]PF₆ (4a) and [(η³-Ph₂C₃H₃)Pd(4)]PF₆ (4b) have been synthesized from the proximally (1,2-) substituted bisphosphite ligand 4. Treatment of ligand 4 with [Pd(COD)Cl₂] gives the palladium dichloride complex, [PdCl₂(4)] (4c). The solid-state structures of [{(η³-1-CH₃-C₃H₄)Pd(Cl)}₂(3)] (3f) and [PdCl₂(4)] (4c) have been determined by X-ray crystallography; the calixarene framework in 3f adopts the pinched cone conformation whereas in 4c, the conformation is in between that of cone and pinched cone. Solution dynamics of 3f has been studied in detail with the help of two-dimensional NMR spectroscopy.The solid-state structures of the monophosphite ligands 5 and 6 have also been determined; the calix[4]arene framework in both molecules adopts the cone conformation. Reaction of the monophosphite ligands (5, 6) with (allyl) palladium precursors, in the absence of NH₄PF₆, yield a series of neutral allyl palladium complexes (5a-5c; 6a-6d). Allyl palladium complexes of proximally substituted ligand 6 showed two diastereomers in solution owing to the inherently chiral calix[4]arene framework. Ligands 3, 6 and the allyl palladium complex 3f have been tested for catalytic activity in allylic alkylation reactions.     

meso-Indanyl calix[4]pyrrole receptors

Two new meso-indanyl-substituted calix[4]pyrrole receptors, 2 and 3, have been synthesized. A range of calix[4]pyrrole host-neutral molecule complexes crystallise from solutions of 2 in a variety of solvents and the structures of four have been elucidated by X-ray crystallography. The F⁻ and Cl⁻ anion affinities of 2 have been measured in acetonitrile, and are significantly different from the corresponding affinities of the prototypical calix[4]pyrrole, the octamethyl-derivative, 1. ESI-FTICR-MS has been used to determine the relative F⁻ and Cl⁻ anion affinities of receptors 1 and 2 in methanol-acetonitrile solution. Deprotonation of 1 and 2 by fluoride is observed (under the conditions of the MS experiment).     

Multiple catenanes based on tetraloop derivatives of calix[4]arenes

Four novel tetraarylurea calix[4]arenes (4a-d) have been synthesized, substituted by ω-alkenyloxy residues in 3,5-positions of the arylurea residues. The eight alkenyl groups were pairwise connected by olefin metathesis and subsequent hydrogenation. The ring-closure reaction was carried out with heterodimers exclusively formed by 4 with a tetratosylurea calix[4]arene 1, which serves as a template in this reaction step. The potential trans-cavity bridging is entirely suppressed in this way. Bis- and tetraloop calix[4]arenes cannot form dimers due to overlapping loops. However, they readily form heterodimers with open-chain tetraureas, as long as their urea residues can pass through the loops. Thus, five heterodimeric capsules 8a-e with bis[3]catenane structure were synthesized using again the olefin metathesis followed by hydrogenation. Two different strategies were compared for this reaction sequence, starting with heterodimers formed either by tetraloop derivatives 5 with tetraalkenyl tetraureas 6 (pathway A) or by bisloop derivatives 7 with octaalkenyl tetraureas 4 (pathway B). A distinct advantage of one of these pathways was not observed; the bis[3]catenanes were obtained with yields of 20-60%. Heterodimers formed by tetraloop derivatives 5b-d and octaalkenyl ureas 4b-d were converted analogous to three novel cyclic [8]catenanes 9a-c in 30-42% yield. The structure of the novel catenanes was unambiguously proved by ¹H NMR and ESI MS, and for 8a and 9a additionally by single crystal X-ray analysis.     

Novel 2,2′-bipyridine-modified calix[4]arenes: ratiometric fluorescent chemosensors for Zn ion

Two calix[4]arene derivatives with modified bipyridine as binding sites have been designed and synthesized. Compounds 1 and 2 are the first 2,2′-bipyridine-modified calix[4]arene-based sensors that can detect Zn²⁺ selectively with respect to ratiometric fluorescent changes and red shift. A binuclear complex structure has been demonstrated in the binding modes of 1-Zn²⁺ and 2-Zn²⁺ complexes.     

Ullmann coupling reaction of 1,3-bistriflate esters of calix[4]arenes: facile syntheses of monoaminocalix[4]arenes and 4,4′:6,6′-diepithiobis(phenoxathiine)

Treatment of 1,3-bistriflate esters of thiacalix- (6a) and calix[4]arenes 6b with benzylamine in the presence of CuI and K₃PO₄ results in the displacement of a TfO moiety with a benzylamino group, which provides an easy access to monoaminothiacalix[4]arene 4a and its methylene-bridged counterpart 4b. On the other hand, the reaction of 6a in the absence of benzylamine leads to intramolecular dietherification, giving 4,4′:6,6′-diepithiobis(phenoxathiine) 7a.     

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.     

Azobenzene-bridged calix[8]arenes

An azobenzene bridge was introduced into the lower (or smaller) rim of p-tert-butylcalix[8]arene (1) and 1,5-calix[8]crown-3 (2) to form 1,4-singly bridged (3) and 1,5:3,7-doubly bridged (4) calix[8]arene derivatives, respectively. Trans and cis isomers of conformationally rigid 4 were isolated. The quantum yields of the trans-cis photoisomerisation reactions have been measured.     

From calixfurans to heterocyclophanes containing isopyrazole units

Cyclic poly-1,4-diketones 2, obtained by the oxidation of the furan units present in calix[4]furan 1a and calix[6]furan 1c have been converted into the novel heterocyclophanes 4a and 4c containing four and six isopyrazole units, respectively. Solution studies have demonstrated the ability of 4a and 4c to act as ligands for transition metals. The crystal structures of 4a and the coordination compound formed by 4c with 2 equiv. of cis-PtCl₂(DMSO)₂ have been determined. In the solid state 4c is shown to bind aromatic substrates within its cavity.     

Upper rim tetrathiafulvalene-bridged calix[4]arenes

The synthesis of novel upper rim calix[4]arene-tetrathiafulvalene conjugates 1a-d has been performed by bridging the tetrachloromethylated calix[4]arene derivative 4 with the corresponding tetrathiafulvalene-dithiolates. The cyclic voltammetry of 1a-d shows a two-step oxidation behavior, whereas NMR binding titrations showed their binding affinity to pyridinium salts. X-ray structure of 4 features calixarene fixed in the pinched cone conformation; its crystal packing is defined by the network of C-H···Cl weak hydrogen bonds.     

Synthesis of di-substituted calix[4]arene-based receptors for extraction of chromate and arsenate anions

The article describes the synthesis of a family of novel calix[4]arene ionophores, 25,27-bis-(2-aminomethylpyridine-propoxy)-26,28-dihydroxycalix[4]arene (5a), 25,27-bis-(3-aminomethylpyridine-propoxy)-26,28-dihydroxycalix[4]arene (5b) and two chromogenic calix[4]arenes, 5,17-dinitro-25,27-bis-(2-aminomethylpyridine-propoxy)-26,28-dihydroxycalix[4]arene (5c), 5,17-dinitro-25,27-bis-(3-aminomethylpyridine-propoxy)-26,28-dihydroxycalix[4]arene (5d) bearing pyridinium units. In the synthesis, the upper and lower rims of p-tert-butylcalix[4]arene were modified in order to acquire binding sites for the recognition of arsenate and dichromate anions. It has been observed that protonated alkylammonium forms of the ionophores showed high affinity toward dichromate and arsenate anions.     

Water-soluble pentasulfonatocalix[5]arene: selective recognition of ditopic trimethylammonium cations by a triple non-covalent interaction

The inclusion of tetramethylammonium and ditopic trimethylammonium cations by the water-soluble pentasulfonatocalix[5]arene 1 has been studied at neutral pH by ¹H NMR and compared with the homologous tetrasulfonatocalix[4]arene 2. Unlike host 2, host 1 selectively binds the ditopic trimethylammonium ions by three different non-covalent interactions. Remarkably the flexible host 1 exhibits both more efficiency and selectivity in the complexation of ditopic methylammonium ions with respect to similar more preorganised calix[4]arene receptors.     

Complexation thermodynamics of water-soluble calix[4]arene derivatives with lanthanoid(III) nitrates in acidic aqueous solution

Microcalorimetric titrations have been performed in acidic aqueous solution at 25 °C to calculate the complex stability constants (K_S) and thermodynamic parameters (ΔG°, ΔH°, and TΔS°) for the stoichiometric 1:1 complexation of lanthanoid(III) nitrates (La-Gd, Tb) with 5,11,17,23-tetrasulfonato-25,26,27,28-tetrakis(hydroxycarbonylmethoxy)calix[4]arene (2) and 5,11,17,23-tetrasulfonato-thiacalix[4]arene (3). Using the present and previous reported data on water-soluble calix[4]arenesulfonates (1) and structurally related analogues 2 and 3, the complexation behavior is discussed comparatively from the thermodynamic point of view. Possessing four carboxyls at the lower rim of parent calix[4]arenesulfonate (1), the derivative 2 displays the enhanced binding abilities for Sm³⁺. As compared with 1 and 2, p-sulfonatothiacalix[4]arene (3) gives not only the lower binding constants for all of lanthanoid(III) ions but also lower cations selectivity. Thermodynamically, the resulting complexes of lanthanoid(III) ions with 1 and its derivatives 2 and 3 is absolutely entropy-driven in aqueous solution, typically showing larger positive entropy changes. These larger positive entropy changes (TΔS°) and somewhat smaller positive enthalpy changes (ΔH°) are directly contributed to the complexes stability as a compensative consequence.     

Diester intrabridging of p-tert-butylcalix[8]arene and unexpected formation of the monospirodienone derivative

Reaction of p-tert-butylcalix[8]arene 1 with adipoyl chloride in the presence of NaH as the base yielded singly and doubly intrabridged esters 2-4 and 6. Surprisingly, calix[8]arene monospirodienone derivative 7 was also isolated, which was originated by O₂ oxidation. The conditions of this oxidation were optimized leading to a novel synthetic approach to calixarene monospirodienones based on the O₂/NaH/acyl-chloride oxidizing system. Xantheno calix[8]arenes 8-8a were obtained by rearrangement of 7.     

Transglutaminase surface recognition by peptidocalix[4]arene diversomers

A series of N-linked tetrakis(tetrapeptido)calix[4]arene diversomers, 3A-P, has been synthesized by coupling of a cone calix[4]arene tetracarboxylic acid chloride with tetrapeptides 1A-P obtained in a parallel fashion. The inhibition activity of 3A-P towards tissue and microbial transglutaminase was evaluated by in vitro assays with a labeled substrate. Kinetic analysis using one of the most active derivatives (3A) showed a noncompetitive inhibition with respect to the amino acceptor substrate and an uncompetitive inhibition with respect to amino donor substrate. Experimental results are in accordance with an inhibition due to a protein specific surface recognition on a region noncomprising the enzyme active site.