Synthesis and properties of mono-O-[(N-(aminoalkyl)aminocarbonyl)-methoxy]thiacalix[4]arenes and novel mono-O-bridged bisthiacalix[4]arene

A simple method for thiacalix[4]arene O-monoamide preparation with high yields using 5,11,17,23-tetra-tert-butyl-28-(ethoxycarbonyl)methoxy-2,8,14,20-tetrathiacalix[4]arene reaction with diaminoalkanes is reported. The solid state cyclization reaction of the acylethylenediamines function of 5,11,17,23-tetra-tert-butyl-28-O-[(N-(2-aminoethyl)aminocarbonyl)-methoxy]thiacalix[4]arene leading to the formation of the 5,11,17,23-tetra-tert-butyl-28-[2-methoxy-imdazoline]thiacalix[4]arene compound is described for the first time for the calixarene macrocycle family. Finally, preliminary results show that O-mono-amide-thiacalixarene derivatives are promising candidates for the production of self-assembled materials and efficient precursors for the synthesis of bisthiacalix[4] arenes.     

Supramolecular self-assemblies of stereoisomers of p-tert-butyl thiacalix[4]arenes functionalized with hydrazide groups at the lower rim with some metal cations

Novel p-tert-butyl thiacalix[4]arenes functionalized with hydrazide groups at the lower rim in cone, partial cone and 1,3-alternate conformations were synthesized and their receptor properties toward metal ions of p- (Al³⁺, Pb²⁺) and d- (Fe³⁺, Co³⁺, Ni²⁺, Cu²⁺, Ag⁺, Cd²⁺) elements were investigated by picrate extraction and dynamic light scattering (DLS). It was shown that the p-tert-butyl thiacalix[4]arenes functionalized with hydrazide groups are effective extractants of soft metal cations. The complex stoichiometry depended on the receptor configuration. All the p-tert-butyl thiacalix[4]arene derivatives with hydrazide fragments were able to form nanoscale aggregates but did not show self-association abilities.     

p-tert-Butyl thiacalix[4]arenes functionalized at the lower rim by o-, m-, p-amido and o-, m-, p-(amidomethyl)pyridine fragments as receptors for α-hydroxy- and dicarboxylic acids

A series of new p-tert-butyl thiacalix[4]arenes with o-, m-, p-amido and o-, m-, p-(amidomethyl)pyridine substituents at the lower rim in cone, partial cone, and 1,3-alternate conformations were synthesized. The ability of the obtained compounds to recognize the α-hydroxy (glycolic, tartaric) and dicarboxylic (oxalic, malonic, succinic, fumaric, and maleic) acids was investigated by UV-vis spectroscopy. Also, the efficiency and selectivity of binding, the association constants log K_a (10² to 10⁷ M⁻¹) and the stoichiometry were determined for the complexes of p-tert-butyl thiacalix[4]arenes with the acids. The receptors based on p-tert-butyl thiacalix[4]arenes with (amidomethyl)pyridine substitutes are most efficient in complexation in many cases.     

Synthesis and conformational behaviour of lower-rim tetraacetylated thiacalix[4]arenes

The acylation of thiacalix[4]arenes with AcCl or Ac₂O gave the corresponding lower-rim tetraacetoxy derivatives. In contrast to classical calix[4]arenes, tetraacetylated thiacalix[4]arenes are conformationally mobile in solution and represent a thermodynamic equilibrium of three different conformers at room temperature. As proven by a dynamic ¹H NMR study, conformational preferences of acetylated thiacalix[4]arenes considerably depend on the upper-rim substitution. Hence, t-Bu thiacalixarene prefers 1,3-alternate and 1,2-alternate conformations (43% and 38%, respectively), while the upper-rim unsubstituted compound adopts preferably the partial cone conformation (70%).     

Solvent extraction and self-assembly of nanosized aggregates of p-tert-butyl thiacalix[4]arenes tetrasubstituted at the lower rim by tertiary amide groups and monocharged metal cations in the organic phase

New p-tert-butyl thiacalix[4]arenes functionalized with morpholide and pyrrolidide groups at the lower rim in cone, partial cone, and 1,3-alternate conformations were synthesized, and their receptor properties for monocharged cations (alkali metal and silver ions) were studied using the picrate extraction method and dynamic light scattering (DLS). To evaluate the ability of the p-tert-butyl thiacalix[4]arene derivatives to recognize metal ions, liquid-liquid extraction of their picrate salts has been carried out in a mutually saturated water-dichloromethane system. The degrees of extraction and the extraction constants for monocharged metal cations (Li⁺, Na⁺, K⁺, Cs⁺) have been determined. The ability of the systems, consisting of host and guest molecules, to self-assembly was proved by DLS using a Zetasizer Nano ZS particle size analyzer. It was shown that all the investigated thiacalix[4]arenes are able to form nanoscale particles with silver cations under the experimental conditions. The pyrrolidide derivative in the cone conformation showed both self-association and aggregation processes with lithium cations. The degree of extraction for all the investigated systems that formed nanoscale aggregates in the organic phase was more than 67% and the extraction constants, log K_ex determined by the picrate extraction method, more than 6.     

Synthesis of New Photoswitchable Tectons Based on Thiacalix[4]arene Azo Derivatives in the 1,3-<Emphasis Type="Italic">Alternate Conformation</Emphasis>

The paper describes the first synthesis of molecular tectons, a series of ligands based on thiacalix[4]arenes in the 1,3-alternate stereoisomeric form containing photoswitchable azo groups in the side chain and carboxyl groups as potential binding sites for the synthesis of photoswitchable complexes and coordination polymers. In the case of p-tert-butylcalixarenes, the convergent approach is preferred.     

(1+1) or (2+2) Coupling for bis(tosyloxyethoxy)benzenes with calix[4]arene and thiacalix[4]arene

As bifunctional reagents, bis(tosyloxyethoxy)benzenes can react with p-tert-butylcalix[4]arene or p-tert-butylthiacalix[4]arene to afford intramolecularly bridged (1+1) or intermolecularly bridged (2+2) products. It was found that the bridging pattern strongly depended on the structure of bis(tosyloxyethoxy)benzene and the kind of calixarene. For the ortho-isomer of bis(tosyloxyethoxy)benzene, intramolecularly bridged calix[4]arene and thiacalix[4]arene were the main products. For the para-isomer, the bridging reaction was in a (2+2) fashion. As for the meta-isomer, double thiacalix[4]arene and intramolecularly bridged calix[4]crown were synthesized.     

Novel dendritic cores based on thiacalix[4]arene derivatives

Thiacalix[4]arenes possessing carboxylic groups were used for the design of potential dendritic cores with amino surface groups. The known tetraacetic acid in the 1,3-alternate conformation gave the desired product in very low yield because of steric hindrance on thiacalix[4]arene moiety. Therefore, synthetic strategy based on withdrawing of the carboxyl groups via benzylic spacer from the thiacalix[4]arene moiety was successfully applied for the realization of novel thiacalix[4]arenes bearing two or four protected lysine units.     

Azocalixarenes.8: synthesis and investigation of the absorption spectra of di-substituted azocalix[4]arenes containing chromogenic groups

The synthesis of series of chromogenic di-substituted azocalix[4]arene derivatives is described. A ketone moiety as a different chelating agent is grafted on the lower rim of p-tert-butylcalix[4]arenes. Eight novel azocalix[4]arenes (1–8) are prepared by linking 2-, 3- and 4-nitroaniline, 4-phenylazoaniline, 3- and 4-chloroaniline or 2- and 4-methylaniline to 25,27-diacetonyloxy-26,28-dihydroxy-11,23-di-(tert-butyl)calix[4]arene through a diazo-coupling reaction, and characterized by UV–Vis, FT-IR and ¹H-NMR spectroscopic techniques and elemental analysis, consecutively. The absorption spectra of the di-substituted azocalix[4]arenes are discussed, according to effect of varying pH and solvent upon the absorption ability of azocalix[4]arenes. The colors of these azocalix[4]arenes are compared with respect to nature of their aromatic rings and substituents there in. Concentration effects on the visible absorption maxima of these compounds are also reported.     

Structure–Activity Relationship of the Thiacalix[4]arenes Family with Sulfobetaine Fragments: Self-Assembly and Cytotoxic Effect against Cancer Cell Lines

Regulating the structure of macrocyclic host molecules and supramolecular assemblies is crucial because the structure–activity relationship often plays a role in governing the properties of these systems. Herein, we propose and develop an approach to the synthesis of the family of sulfobetaine functionalized thiacalix[4]arenes with regulation of the self-assembly and cytotoxic effect against cancer cell lines. The dynamic light scattering method showed that the synthesized macrocycles in cone, partial cone and 1,3-alternate conformations form submicron-sized particles with Ag⁺ in water, but the particle size and polydispersity of the systems studied depend on the macrocycle conformation. Based on the results obtained by ¹H and ¹H-¹H NOESY NMR spectroscopy and transmission electron microscopy for the macrocycles and their aggregates with Ag⁺, a coordination scheme for the Ag⁺ and different conformations of p-tert-butylthiacalix[4]arene functionalized with sulfobetaine fragments was proposed. The type of coordination determines the different shapes of the associates. Cytotoxic properties are shown to be controlled by the shape of associates, with the highest activity demonstrated by thiacalix[4]arenes in partial cone conformation. This complex partial cone/Ag⁺ is two times higher than the reference drug imatinib mesylate. High selectivity against cervical carcinoma cell line indicates the prospect of their using as components of new anticancer system.     

Dimeric water embedded within a hydrophobic cavity of tetra-(p-tert-butyl)thiacalix[4]arene

X-ray crystallographic analysis and density functional B3LYP/6-31G(d) calculation confirm that dimeric water is embedded within a hydrophobic cavity of tetra-(p-tert-butyl)thiacalix[4]arene and stabilized by hydrogen bondings of aromatic π?H₂O(1) and methyl?H₂O(2) in the dimeric water inclusion complex with binding energies of 1.4 and 0.9 kcal mol⁻¹ respectively, and by hydrogen bonding formed between H₂O(2) and four phenolic OH groups from an adjacent tetra-(p-tert-butyl)thiacalix[4]arene, with binding energy of 3.8-4.2 kcal mol⁻¹.     

New synthetic approach to aminoethoxy derivatives of <Emphasis Type="Italic">p</Emphasis>-(<Emphasis Type="Italic">tert</Emphasis>-butyl)calix[4]arene

A new procedure has been proposed for the synthesis of mono- and bis(2-aminoethoxy)-p-(tertbutyl) calix[4]arenes from the corresponding mono- and bis[2-(1,3-dioxoisoindol-2-yl)ethoxy]-p-(tert-butyl)-calix[4]arenes.     

Synthesis and Crystal Structure of p-tert-Butylthiacalix[8]arene: A New Member of Thiacalixarenes

Even though it was obtained in poor yield, p-tert-butylthiacalix[8]arene (TC8A) has been synthesized as a new member of thiacalix[n]arenes by the terephthalate-induced cyclization of a mixture of acyclic oligomers, which was obtained by the reaction between p-tert-butylphenol and sulfur with CaO in ethylene glycol/diphenyl ether system. Slow evaporation of the chloroform solution of TC8A afforded guest-free crystals consisting of TC8A itself. The close-packed crystal structure of TC8A resembles that of p-tert-butylcalix[8]arene (C8A) closely, containing a plated loop molecular structure.This revised version was published online in July 2005 with a corrected issue number.     

Composition of thiacalix[4]arene complexes with monovalent metal ions in the gas phase: MALDI mass spectrometry

MALDI-TOF mass spectrometry was used to study the reaction of p-tert-butylthiacalix[4]arene (1) and a number of its derivatives disubstituted at the lower rim (2—9) with monovalent metal salts (Li, Na, K, Cs, Cu, Ag) in the gas phase. It was shown that the thiacalixarenes under study bind the metal ions through the substitution of hydrogen atoms of the hydroxy groups. The reactions of silver and copper salts with the thiacalix[4]arenes were found to form the cluster ions, which represent the macrocycle dimers with several metal ions, while the formation of such clusters is impossible in the case of alkali metal salts. The peak intensities of the cluster ions increase in the weakly basic medium, reaching in some cases 100%.     

Pentakis-thiacalix[4]Arenes with Nitrile Fragments: Receptor Properties toward Cations of Some s-and d-metals and Self-assembly of Nanoscale Aggregates

Pentakis-thiacalix[4]arenes containing thiacalix[4]arene fragments in cone, partial cone and 1,3-alternate conformations as their central core have been obtained. Their interaction with cations of s- and d-metals gives supramolecular assemblies whose composition depends on the conformation of pentakis-thiacalix[4]arenes and the nature of the ‘guests’.     

Regioselective ipso formylation of p-tert-butylcalix[4]arene

A convenient procedure for direct introduction of one formyl group into p-tert-butylcalix[4]arenes through ipso substitution is described.     

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.     

Synthesis and heteronuclear inclusion properties of a novel thiacalix[4]arene-based hard-soft receptor with 1,3-alternate conformation

A novel thiacalix[4]arene ditopic receptor with 1,3-alternate conformation and possessing two complexation sites for hard and soft cations, 5,11,17,23-tetra-tert-butyl-25,27-bis[(N,N-diethylaminocarbonyl)methoxy]-26,28-bis[(pyridylmethyl)oxy]-2,8,14,20-tetrathiacalix[4]arene is prepared. Regioselective synthesis of distal-bis[(N,N-diethylaminocarbonyl)methoxy]thiacalix[4]arene is accomplished by a protection-deprotection method using benzyl groups as a protecting group. The deprotection of benzyl group was succeeded in the presence of solid superacid (Nafion-H) under refluxing benzene. Its complexation behavior is examined by ¹H-NMR titration experiments. The formation of 1:2 homo- and heteronuclear complexes demonstrates that the preorganization, subtle conformational changes and affinity have a pronounced effect on the complexation of the receptor.     

Synthesis and Conformational Characteristics of Benzyl-Substituted p-tert-Butylcalixarenes

(m-Methylbenzyloxy)-, bis(p-methylbenzyloxy)-, and bis(m-methylbenzyloxy)-p-tert-butylcalix[4]arenes were prepared by reactions of p-tert-butylcalix[4]arene with p- and m-methylbenzyl bromides in the presence of alkali metal carbonates. Silylation of these derivatives gave (m-methylbenzyloxy)bis(trimethylsilyloxy)-, bis(m-methylbenzyloxy)bis(trimethylsilyloxy)-, and bis(p-methylbenzyloxy)bis(trimethylsilyloxy)-p-tert-butylcalix[4]arenes. With phase-transfer catalysis, bis(p-methylbenzyloxy)bis(2-propenyloxy)- and bis(m-methylbenzyloxy)bis(2-propenyloxy)-p-tert-butylcalix[4]arenes were obtained. Alkylation of the monosubstituted calixarene yields the corresponding trisubstituted derivative.     

Unique self-assembly patterns based on thiacalix[4]arene-silver interactions

Novel self-assembled supramolecular networks were prepared by the interactions of thiacalix[4]arenes bearing simple alkyl groups on the lower rim (4×MeO-, 4×n-PrO-) with silver triflate. Contrary to the classical calix[4]arenes (with CH₂ bridges between the aromatic moieties), the presence of four sulfur atoms enables the formation of S-Ag-S connections between the individual molecules leading to the coordination topology so far unknown in calixarene chemistry. These systems form infinite 1-D coordination polymeric structures in the solid state, where the thiacalixarene moieties are preorganized in a side-by-side arrangement. Interestingly, the linear coordination polymers were obtained using both the conformational immobilised (4×n-PrO, cone, 1,3-alternate conformers) and the conformational mobile (4×MeO) thiacalix[4]arenes, which indicates the generality of this behaviour in thiacalixarene series.