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A preparative method for the synthesis of optically pure N-(1-phenylethyl)amides of inherently chiral (cR)- and (cS)-dibenzoyloxy-calix[4]arene acetic acids has been developed. Their absolute stereochemical configuration was determined by X-ray diffraction analysis.

The Host-Guest complexation of octakis(diphenoxyphosphoryloxy)tetramethylcalix[4]resorcinarene, 5,17-bis-(N-tolyliminomethyl)-25,27-dipropoxycalix[4]arene and 5,11,17,23-tetrakis(diisopropoxyphosphonyl)-25,26,27,28-tetrapropoxycalix[4]arene with a series of 11 phenols (phenol, p-fluorophenol, p-chlorophenol, p-bromophenol, pyrogallol, p-cresol, p-aminophenol, p-nitrophenol, salicylic aldehyde, guaiacol and veratrole) has been studied by the high-performance liquid chromatography (RP HPLC) method. Chromatographic characteristics and log P of industrial phenols have been determined. Using the relationship of the phenol retention factor k’ vs the calixarene concentration in the mobile phase the stability constants of the supramolecular complexes K A (29-331 M -1 ) have been determined. The stability constants of the calixarene complexes show that the Host-Guest interaction strongly depends on the nature of the substituents in the Host and Guest molecules. Calixresorcinarene functionalized by diphenoxyphosphoryl groups and calixarene containing tolyliminomethyl groups formed more stable complexes with some phenols compared to calixarene functionalized by diisopropoxyphosphonyl groups. In accordance with the molecular modeling data the complexation does not change the C2v flattened-cone conformation of the calixarene skeleton. The Host-Guest complexes are stabilized by the intermolecular hydrogen bonds of phenolic OH groups with oxygen atoms of P = O groups at the upper rim, and OH groups at the lower rim of the macrocycle. Hydrophobic interactions also participate in the complexation.

In the present work, the derivatives of calix[4]arene, thiacalix[4]arene, and sulfonylcalix[4]arene bearing four methylene(phenyl)phosphinic acid groups on the upper rim of the macrocycle were synthesized and studied as inhibitors of human protein tyrosine phosphatases. The inhibitory capacities of the three compounds towards PTP1B were higher than those for protein tyrosine phosphatases TC–PTP, MEG1, MEG2, and SHP2. The most potent sulfonylcalix[4]arene phosphinic acid displayed Ki value of 32 nM. The thiacalix[4]arene phosphinic acid was found to be a low micromolar inhibitor of PTP1B with selectivity over the other PTPs. The kinetic experiments showed that the inhibitors compete with the substrate for the active site of the enzyme. Molecular docking was performed to explain possible binding modes of the calixarene-based phosphinic inhibitors of PTP1B.

All three possible inherently chiral (cS)-propyloxy-octyloxy-calix[4]arene acetic acids were synthesized and their absolute configuration was proved. Complexation of the calix[4]arene acetic acids with a number of chiral compounds have been studied by molecular modeling and 1H NMR spectroscopy and enantioselectivity of binding of R- and S-forms of 2-aminobutanol was found.

The Mitsunobu alkylation of 4-tert-butylcalix[4]arene with (S)-(2-diphenylthiophosphinoferrocenyl)methanol followed by desulfuration of the thiophosphine unit using tris(dimethylamino)phosphine afforded enantiomerically pure calixarene mono- and di(ferrocenylphosphine) ligands in high yields. The calixarene mono(ferrocenylphosphine) ligands exhibited good catalytic activity but low atropoenantioselectivity when used in the asymmetric Suzuki–Miyaura coupling reaction of 1-naphthaleneboronic acid and 1-bromo-2-methylnaphthalene. However, the di(ferrocenylphosphine) ligand displayed both good catalytic activity and enantioselectivity (ee values up to 86 %) when employed in the asymmetric Tsuji–Trost allylic alkylation of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate.

The aim of the research was to study a potential antithrombotic sodium salt of calix[4]arene-methylenebis-phosphonic acid (С-145) — on activation and aggregation of platelets in vivo, as well as on proliferation and apoptosis of endothelial cells in the cell culture. Effects of calix[4]arene С-145 estimated in vitro after addition to the platelet rich plasma, and in vivo after intravenous injection into rabbit bloodstream in equivalent amounts (46 μM). Aggregation of platelets was induced by adenosine diphosphate and detected using aggregometer Solar AP2110. Platelet shape and cytoplasmic granularity were monitored on COULTER EPICS XL Flow Cytometer. The level of tissuetype plasminogen activator — tPA — was estimated using enzyme-linked immunosorbent assay ELISA. Effects of calix[4]arene C-145 on culture of endotelial cells cells was studied using 3-(4,5-Dimethylthiazol2-yl)-2,5-Diphenyltetrazolium Bromide — MTT-test. The population of proliferative pool of cells (G2/ M+S) was determined using flow cytometry. Aggregometry and flow cytometry showed that calix[4]arene C-145 did not activate platelets nor affect their aggregation in vitro. However intravenous injection of calix[4]arene C-145 into the bloodstream of healthy rabbits leads to strong inhibition of platelet aggregation and changes of shape and granularity of most of the platelets after 2 hours of administration. Any additional appearance of endothelial cells activation marker tPA in vivo and any inhibition of calix[4]arene C-145 on proliferation of endothelial cells in cell culture did not observe. So calix[4]arene C-145 had strong anti-platelet effect in vivo that was not a result of their direct action on platelets or endothelial cells in vitro. This allowed to assume the possibility of calix[4]arene C-145 use as an effective antithrombotic agent., Целью работы было изучение действия потенциального антитромботического агента — натриевой соли каликс[4]арен-метилен-бисфосфоновой кислоты — каликс[4]арена С-145 на активацию и агрегацию тромбоцитов in vivo, а также на пролиферацию и апоптоз эндотелиоцитов в тканевой культуре. Эффекты каликс[4]арена С-145 оценивали in vitro после добавления в плазму крови, богатую тромбоцитами, а также in vivo после внутривенного введения в кровоток кролика в эквивалентных количествах (46 μМ). Агрегацию тромбоцитов индуцировали ADP и определяли с помощью агрегометра Solar AP2110. Форму и гранулярность цитоплазмы тромбоцитов устанавливали проточным цитометром COULTER EPICS XL. Уровень активатора плазминогена тканевого типа — tPA — измеряли методом иммуноэнзимного анализа ELISA. Эффекты каликс[4] арена C-145 на культуру эндотелиоцитов изучали с помощью 3-(4,5-диметилтиазол-2-ил)-2,5диметилтетразолия бромида — МТТ-теста. Популяцию пролиферативного пула (G2/M+S) клеток эндотелия определяли с применением цито метрии. Методами агрегатометрии и цитометрии установлено, что каликс[4]арен С-145 не активирует тромбоциты и не влияет на их агрегацию in vitro. Однако уже через два часа после введения каликс[4]арена С-145 здоровым лабораторным кролям тромбоциты теряли способность агрегировать, а пул интактных тромбоцитов уменьшался в два раза. В то же время не наблюдали выброса в плазму крови маркера активации эндотелиоцитов tPA in vivo, а также ингибирования пролиферации эндотелиоцитов в культуре клеток. Таким образом, каликс[4]арен С-145 обладает значительным антитромбоцитарным эффектом in vivo, не действуя непосредственно на тромбоциты и эндотелиоциты in vitro. Такие свойства каликсарена позволяют рассматривать возможность его применения в качестве эффективного антитромботического агента.

International audience; A facile method for the preparation of enantiomerically pure inherently chiral calix[4]arene phosphonic acid (cR,pR)-7 in four steps starting from the readily available and previously synthesized (cS)-enantiomer of calix[4]arene acetic acid 1 or its methyl ester 2 was developed. The first tests of this unique calixarene Brönsted acid with inherent chirality in organocatalysis of the aza-Diels–Alder reaction of imines with Danishefsky’s diene and epoxide ring opening by benzoic acid were performed. The calixarene phosphonic acid (cR,pR)-7 shows good catalytic activities but with low enantioselectivities in these reactions.

A method for the synthesis of calix[4]arenes possessing methylenebisphosphonic acid groups capable of forming supramolecular complexes with amino acids, and anchoring 3-methylsulfidopropoxy groups ...

All six possible stereoisomers of calix[4]arenes with four different substituents on the lower rim of the macrocycle have been synthesized by stepwise alkylation of the hydroxyl groups of tert-butylcalix[4]arene using (R)- or (S)-1-phenylethylamide groups as chiral auxiliaries. They form three enantiomeric pairs, as confirmed by the values of their specific rotation.

Host-Guest complexation of calixarene-bis-hydroxymethylenediphosphonic acid with 17 amino acids in water solution had been studied by the RP HPLC and molecular modelling methods. It had been shown the binding constants of the complexes are depended on the nature of the amino acid residue, log P and pKa of the acids. The complexation is mainly determined by the electrostatic interactions between the positively charged nitrogen atom of the amino acid and the negatively charged oxygen atom of phosphonic acid residue of the calixarene, the Host-Guest p-p, СН-p and solvophobic interactions.

Water-soluble cationic calixarenes readily form aggregates in water. The properties of these aggregates, however, markedly vary along with alterations in the molecular structure. In a set of our recent studies, such aggregates were examined by various methods, and first of all using acid–base indicator dyes. The latter acted in fact as monoprotic acids exhibiting one color transition, and their pKa shifts against the values in water were relatively close for different calixarenes. In the present paper, we report the behavior of a much more complicated dye, fluorescein, and two relative compounds, in aqueous solutions of two cationic calix[4]arenes. The last named possess four choline groups on the upper rim and the sole difference is the length of the alkoxy groups at the lower rim: O(CH2)2CH3 and O(CH2)7CH3. In water, both calixarenes form aggregates of similar size and with similar zeta-potential. However, their influence on the acid–base and tautomeric equilibria of fluorescein clearly demonstrate that the aggregates of the long-tailed calixarene resemble the common micelles of colloidal surfactants to a higher degree than those of tetrapropyloxy compound.

The synthetic approaches to mono-isopropoxytrihydroxycalix[4]arenes bearing two or three diphenylphosphino groups at the upper macrocycle rim were elaborated. Due to reactive hydroxyl groups at the lower rim capable of binding with silica gel surface, the calixarenes, especially the enantiomerically pure inherently chiral diphosphinocalixarene, are promissing ligands for creation of hybride organic–inorganic metallocomplexing catalysts of organic (asymmetric) reactions.

This interdisciplinary study, performed with participation of research workers of Palladin Institute of Biochemistry and Institute of Organic Chemist­ry of NAS of Ukraine, is devoted to analysis of biochemical effects of some calixarene methylene bisphosphonic acids (cyclic phenol oligomers) on two well-known biological phenomenons – Mg2+-dependent ATP hydrolysis (myosin subfragment-1 of myometrium smooth muscle was used as an example) and fibrin polymerization. Calix[4]arene С-97 (calix[4]arene methylene bisphosphonic acids) is a macrocyclic substance, which contains intramolecular highly ordered lipophilic cavity formed by four aromatic rings, one of which is functionalized at the upper rim with methylene bisphosphonic group. At concentration of 100 µM, this substance was shown to effectively inhibit ATPase activity of pig myometrium myosin subfragment-1 (inhibition coefficient І0.5 = 83 ± 7 µM). At the same time, this calix[4]arene causes significant (vs. control) increase of myosin subfragment-1 hydrodynamic diameter, which may indicate formation of an intermolecular complex between calixa­rene and myosin head. Computer simulation methods (docking and molecular dynamics with addition of grid technologies) enabled to elucidate the grounds of intermolecular interactions between calix[4]arene С-97 and myometrium myosin subfragment-1, that involve hydrophobic, electrostatic and π-π-stacking interactions, some of which are close to the ATPase active centre. In view of the ability of calixarenes to penetrate into the cell and their low toxicity, the results obtained may be used as a basis for further development of a new generation of supramolecular effectors (starting from the above mentioned substances, in particular calix[4]arene С-97) for regulation of smooth muscle contractile activity at the level of ATP dependent actin-myosin interaction. Calix[4]arenes bearing two or four methylenebisphosphonic acid groups at the macrocyclic upper rim have been studied with respect to their effects on fibrin polymerization. The most potent inhibitor proved to be calix[4]arene tetrakis-methylene-bis-phosphonic acid (C-192), in which case the maximum rate of fibrin polymerization in the fibrinogen + thrombin reaction decreased by 50% at concentrations of 0.52·10-6 M (IC50). At this concentration, the molar ratio of the compound to fibrinogen was 1.7 : 1. For the case of desAB fibrin polymerization, the IC50 was 1.26·10-6 M at a molar ratio of C-192 to fibrin monomer of 4 : 1. Dipropoxycalix[4]-arene bis-methylene-bis-phosphonic acid (C-98) inhibited fibrin desAB polymerization with an IC50 = 1.31·10-4 M. We hypothesized that C-192 blocks fibrin formation by combining with polymerization site ‘A’ (Aa17–19), which ordinarily initiates protofibril formation in a ‘knob-hole’ manner. This suggestion was confirmed by an HPLC assay, which showed a host–guest inclusion complex of C-192 with the synthetic peptide Gly-Pro-Arg-Pro, an analogue of site ‘A’. Further confirmation that the inhibitor was acting at the initial step of the reaction was obtained by electron microscopy, with no evidence of protofibril formation being evident. Calixarene C-192 also doubled both the prothrombin time and the activated partial thromboplastin time in normal human blood plasma at concentrations of 7.13·10-5 and 1.10·10-5 M, respectively. These experiments demonstrate that C-192 is a specific inhibitor of fibrin polymerization and blood coagulation and can be used for the design of a new class of antithrombotic agents.

Calixarenes substituted at the upper rim by electron-deficient pentafluorophenyl groups have been synthesized by reaction of hexafluorobenzene with organolithium derivatives of calixarenes. The single crystal structures indicate stacking interactions between the two perfluorinated aromatic rings. The thermodynamic characteristics of the flattened cone-flattened cone inversion process have been studied using dynamic NMR and quantum chemical methods. The calculated activation free energy for tetra(pentafluorophenyl)-substituted species is higher than that derived for tetraphenyl calixarene. The calixarenes substituted at the upper rim by electron-deficient pentafluorophenyl groups are potential hosts for anion recognition.

The cone shaped сalix[4]arene hydroxyphosponous, ketophosphonous, methylenebisphosphonous, and hydroxymethylenebisphosphonous acids are specific inhibitors of glutathione S-transferase, ATPases of smooth muscle cells, fibrin polymerization processes

The interaction of inherently chiral calix[4]arene carboxilic acids and their amides with amino acids in the organic phase has been studied using electron spectroscopy. It was found that the chiral calix[4]arenes are able of enantioselective recognition of L- and D-forms of amino acids. Stability constants of the calixarene – amino acid supramolecular complexes were determined and mechanism of the host-guest interaction was examined by molecular modeling method.

The preparative methods for the synthesis of imidazolium and pyridinium room temperature task-specific ionic liquids possessing thiacalix[4]arene complexing groups in cationic or anionic fragments of the molecule are described. The cationic imidazolium and pyridinium derivatives of tetrabuthoxythiacalixarene existing in the conformation 1,3-alternate are capable to bind “soft” metal cations due to cooperative cation-π and ion–dipole interactions with spatially contiguous benzene rings and oxygen atoms of the thiacalixarene platform. The cone-shaped imidazolium salts of the tetrahydroxythiacalix[4]arene sulfonic acid can chelate cations of transition metals, lanthanides, and actinides by oxygen and sulfur atoms at the lower rim of macrocycle.

Both enantiomers of inherently chiral dipropoxy-p-tert-butylcalix[4]arene carboxylic acids with AABH substitution patterns have been prepared by the stereoselective reactions of 25,26-dipropoxy-p-tert-butylcalix[4]arene with enantiomerically pure (S)- or (R)-N-(1-phenylethyl)bromoacetamide, separation of the diastereomers by recrystallization, and removal of the chiral auxiliary groups. The absolute configurations of the obtained compounds have been established by X-ray analysis.

A series of dipropoxy-, tripropoxy- and tetrapropoxycalix(4)arenes bearing one or two fragments of α-hydroxymethylphosphonic acid at the upper rim of the macrocycle was prepared by the reaction of the corresponding mono- and di-formylcalixarenes with sodium salts of dialkyl phosphites or with trialkyl (tristrimethylsilyl)phosphites followed by dealkylation (desilylation) of the ester derivatives. The conformations of the macrocyclic skeleton and the stereoisomeric forms of the compounds obtained were investigated by 1 H NMR. The resulting α- hydroxymethylphosphonic acids were found to be able to inhibit the activity of glutathione S- transferase in vitro.

The study of the aqueous solutions of the cationic hexameric calixarene 5,11,17,23,29,35-hexakis (N,N-dimethyl-N-hydroxyethylammoniummethylene)-37,38,39,40,41,42-hexametoxycalix[6]arene hexachloride demonstrates their colloidal nature. Within the concentration range from 1 × 10–5 to 0.01 M, this compound forms positively charged aggregates of a much larger size as compared with those of tetrameric cationic calix[4]arene previously studied by us. The aggregation was confirmed both by DLS and TEM experiments; the last method revealed that the 102 to 103 nm sized particles consist of smaller primary aggregates. These aggregates manifest themselves in displaying alteration of absorption spectra and marked shifts of apparent ionization constants of common acid–base indicators. These shifts resemble those registered in micellar solutions of cationic surfactants and cationic polyelectrolyte brushes. The pCl measurements also confirm the formation of calixarene aggregates. The dye associations with the calixarene...

Monosodium salt of p-tert-butylcalix[4]arene reacts with alkyl halides or aroyl chlorides in DMF formed the cone-shaped monoalkyloxycalix[4]arenes or 1,3-diacyloxycalix[4]arenes, respectively. Diacyloxycalix[4]arenes are easily transformed into monoacyloxycalix[4]arenes in the partial cone conformation by interaction with NaOMe. The influence of intramolecular hydrogen bonding on course of alkylation and acylation reactions as well as the structure of the synthesized compounds in solution and crystalline state are discussed.

By sulfonylation of tetra(p-tert-butyl)-27-propoxy-25-[N-(1-phenylethyl)carbamoylmethoxy]calix[4] arene diastereomeric inherently chiral calixarenes with the ABCH substitution at the lower rim were synthesized and separated by column chromatography. The alkylation of these compounds afforded the corresponding calixarenes with the ABCD substitution type. The absolute configuration of compounds was established by XRD analysis.

Cup-shaped calix[4]arenes bearing one or two ketocyanine fluorophore fragments at the wide rim of the macrocycle are synthesized by condensation of formyl calix[4]arenes with arylmethylene(hetarylmethylene)cyclopentanones in the presence of the ionic liquid, dimethylammonium dimethylcarbamate (DIMCARB) and characterized using UV–vis and fluorescence spectroscopy. Strong positive solvatofluorochromism for the calixarene ketocyanines is observed.

Macrocyclic amphiphilic molecules based on calix[4]arenes are highly attractive for controlled supramolecular assembly of DNA into small nanoparticles, since they present a unique conical architecture and can bear multiple charged groups. In the present work, we synthesized new amphiphilic calixarenes bearing cationic groups at the upper rim and alkyl chains at the lower rim. Their self-assembly in aqueous solution was characterized by fluorescent probes, fluorescence correlation spectroscopy, dynamic light scattering, gel electrophoresis and atomic force microscopy. We found that calixarenes bearing long alkyl chains (octyl) self-assemble into micelles of 6 nm diameter at low critical micellar concentration and present the unique ability to condense DNA into small nanoparticles of about 50 nm diameter. In contrast, the short-chain (propyl) analogues that cannot form micelles at low concentrations failed to condense DNA, giving large polydisperse DNA complexes. Thus, formation of small DNA nanoparticles is hierarchical, requiring assembly of calixarenes into micellar building blocks that further co-assemble with DNA into small virus-sized particles. The latter showed much better gene transfection efficiency in cell cultures relative to the large DNA complexes with the short-chain analogues, which indicates that gene delivery of calixarene/DNA complexes depends strongly on their structure. Moreover, all cationic calixarenes studied showed low cytotoxicity. Thus, this work presents a two-step hierarchical assembly of small DNA nanoparticles for gene delivery based on amphiphilic cone-shaped cationic calixarenes.

Molecular modeling, synthesis, and structural investigations of the phosphorus-containing (thia)calixarenes and their supramolecular complexes with biorelevant or ecologically hazardous molecules and ions are discussed within the context of cationic and molecular recognition, extraction properties, and bioactivity.

A family of amphiphilic alkoxycalix[4]arenes bearing phosphonyl groups directly attached to para positions of the aromatic rings is synthesized by the Arbuzov reaction of para -bromoalkoxycalix[4]arenes with alkyl esters of phosphorus (III) acid in the presence of NiBr 2 . Amphiphilicity of the calixarene phosphonates is controlled by varying the quantities of the hydrophilic phosphoryl groups at the upper rim and the hydrophobic alkyl groups at the lower rim. Complexation of the calixarenes with benzene derivatives and iso- butanol in solutions is studied by RP HPLC and IR spectroscopy methods. Langmuir-Blodgett films of the calixarene phosphonates are prepared. Physical characteristics and complexation of the films with volatile organic molecules are characterized.

Inhibition of Yersinia protein tyrosine phosphatase by calix[4]arene mono-, bis-, and tetrakis(methylenebisphosphonic) acids as well as calix[4]arene and thiacalix[4]arene tetrakis(methylphosphonic) acids have been investigated. The kinetic studies revealed that some compounds in this class are potent competitive inhibitors of Yersinia PTP with inhibition constants in the low micromolar range. The binding modes of macrocyclic phosphonate derivatives in the enzyme active center have been explained using computational docking approach. The results obtained indicate that calix[4]arenes are promising scaffolds for the development of inhibitors of Yersinia PTP.

Both enantiomers of inherently chiral calixarene carboxylic acids with ABCD substitution patterns have been prepared by the benzoylation of 25-propoxy-27-(R)-N-(α-phenylethyl)amidomethyloxycalix[4]arene followed by resolution of the diastereomers formed, monobromination of them and removal of the benzoyl and α-phenylethylamide auxiliary groups. The absolute configuration of the calixarenes obtained has been established by X-ray analysis. Preliminary study of the chiral recognition properties of calixarene carboxylic acid was performed.

The addition of calix[4]arenes to MeCN/H2O or MeOH/MeCN/THF/H2O mobile phases improves LC separation of benzene or uracil derivatives on Separon SGX C18 or Separon SGX NH2 supports. Structure of the calixarenes and their host–guest supramolecular complexes with the analytes are discussed in context of the LC separation.

Proximal heteroalkylation of monoalkyl ethers of calix[4]arenes or p - tert -butylcalix[4]arenes in NaH/CH 3 CN or NaOH/DMSO, respectively, was applied for synthesis of inherently chiral calixarenes with ABHH substitution pattern. The introduction by the method of ( R )- or ( S )- N -(α-phenylethyl)acetamide chiral auxiliary group gives mixtures of diastereomeric derivatives of inherently chiral calixarenes, which were separated by column chromatography. The chiral calixarenes were thoroughly characterized by 1 H, 13 C NMR, and X-ray diffraction methods.

Application of calixarene derivatives in bio-medical researches is reviewed in this article. Antiviral, bactericidal, antithrombothic, antituberculosis, anticancer activity as well as specific protein complexation, membranotropic properties and toxicity of modified calixarenes are discussed.

Extraction properties of lariat crown ethers were studied. Dibenzo-substituted crown ethers of a new class, with electron-donor side phosphoryl groups -P(O)R2 (R = iso-C3H7O, n-C4H9O, C6H5), were proposed as extracting agents. The oxygen atoms of the phosphoryl groups form additional bonds with metal ions in the extractable complexes. Extraction of 31 metals from 0.01–7 M HNO3 with five diphosphorylated derivatives of 18-crown-6 and 21-crown-7 was studied. Diphosphorylated endoreceptors were prepared by introduction of organophosphorus fragments into the structure of dibenzo crown ethers. The extraction properties of these compounds depend on the electron-donor properties of the phosphoryl oxygen. If the sum of the reaction constants of the substituents at the phosphorus atom of these groups is −1.77 or more negative, the phosphoryl oxygen is coordinated with the metal of the extracted metal salts and the endoreceptos are effective and selective extracting agents for the following metals (the maximal distribution ratio is given): Tl (1.1) ≈ Rb (1.1) 103). In this case, the extraction ability of diphosphorylated dibenzo crown ether increases by a factor of 102–103 as compared to that of the unsubstituted analogs. The resulting compounds can be used as endoreceptors of new generation with unique extraction properties.

The reaction of calix[4]arene monoalkyl ethers with 1(S)-camphor-10-sulfonyl chloride yields 1,2- or 1,3-alkoxy-1(S)-camphorsulfonyloxycalixarenes depending on the nature of the base used. In the presence of triethylamine only 1,3-substituted derivatives are formed. Two diastereomers of the 1,2-substituted calixarenes with clockwise and anticlockwise arrangement of alkyl and camphorsulfonyl groups at the narrow rim are formed in the presence of sodium hydride or potassium carbonate. Due to chiral induction of the camphorsulfonyl group the 1,2-substitution is diastereoselective. The ratio of diastereomers formed is dependent on the alkyl groups at the calixarene narrow rim.

Monoester derivatives of thiacalix[4]arene tetrakis(methylphosphonic) acid were found to be capable of inhibiting protein tyrosine phosphatase 1B. In addition, these compounds can strongly bind to human serum albumin.

Calix[4]arenes bearing a methoxy and an R or S α-phenylethylacetamido group at the narrow rim of macrocycles are stereoselectively acylated with 1 equiv of trichloroacetyl isocyanate to give chiral asymmetrically substituted calix[4]arenecarbamates in preparative yields and high diastereomeric excess.

[structure: see text] Chiral calix[4]arene alpha-aminophosphonic acids were obtained through diastereoselective Pudovik-type addition of sodium ethyl phosphites to the chiral calixarene imines, removal of chiral auxiliary groups, and mild dealkylation of phosphonate fragments. The diacids obtained show inhibitory activity toward porcine kidney alkaline phosphatase that depends considerably on the absolute configuration of the alpha-carbon atoms.

The synthesis of new calix[4]arenes bearing two or four tetrazole liganting groups at the upper rim is decribed. The structures of tetrakis-tetrazolecalix[4]arene and its palladium dichloride (2:2) complex are examined by X-ray crystallography.

Calix[4]arenes, functionalized at the wide rim with two or four N 2 -sulfonylamidine groups were prepared. In the crystalline state, the bowl shaped calix[4]arene-bis- N -sulfonyltrifluoromethylacetamidine 3b is associated through intermolecular hydrogen bonds, NH⋯O S, while the phenyl rings of the Ph–SO 2 -fragments are hosted in the cavities of the nearby molecules of 3b . Calixarene 4b influences Ca 2+ transport in Mg 2+ , ATP-dependent calcium pumps.

Complexation of isoleucine with bis (dihydroxyphosphorylhydroxymethyl) dipropoxycalix[4]arene was studied by titration calorimetry, NMR and UV–VIS spectroscopies and in terms of molecular modeling. The experimental data allowed to infer the occurrence of two heterogeneous non-equivalent calixarene moieties complexed by a single isoleucine molecule. The association constants were calculated to be 25,000±3000 and 1700±300 for the (1:1) and (2:1) calixarene–isoleucine complexes, respectively.

The host–guest complexation of the upper rim diisopropoxyphosphoryl derivatives of dipropoxy- or tetrapropoxycalix[4]arenes and the upper rim unsubstituted parent calixarenes with uracil and 5-amino-, 5-chloro-, 5-nitro-, 6-methyl and 6-amino-1,3-dimethyluracil in methanol–acetonitrile–tetrahydrofuran–water (15:10:5:70, v/v( solution was investigated by reversed-phase high-performance liquid chromatography. The association constants of the 1:1 host–guest complexes of the uracils with the calixarenes within the range 1200–54 300 M−1 were calculated from the relationship between the capacity factor of the uracil solutes and concentration of the calixarenes in the mobile phase. The association constants were dependent on the nature of uracil guests, the manner of the lower rim substitution of the calixarene skeleton and the number of the phosphoryl groups at the upper rim. Molecular dynamics (MD( simulations of host–guest interactions were performed. Based on the MD trajectories, the atomic partition to the net molecular solvent-exposed surface was analysed for the separate host and guest molecules and for the complexes. Copyright © 2005 John Wiley & Sons, Ltd.

An effective method of 5,11,17,23-tetra-tert-butyl-25,26-dialkoxy-27,28-dihydroxy-calix[4]arenes and 25,26,27,28-tetraalkoxycalix[4]arenes synthesis by alkylation of tetrahydroxycalix[4]arenes in a DMSO-NaOH medium was developed.

Calix[4]arenedialkyl ethers 3 react with an excess of acylisocyanates to give selectively monoacylated products 4. Intramolecular hydrogen bonds and steric effects of the acylcarbamate fragments are most likely responsible for the high selectivity of this monoprotection. [reaction: see text]

The synthesis and structure of new tetrahydroxythiacalix[4]arenes, existing in the cone conformation and possessing reactive bromide, chloromethyl or diorganylphosphoryl groups on the upper rim of the macrocycle are described. The molecular structure of tetrakis(diisopropoxyphosphorylmethyl)thiacalix[4]arene was examined by X-ray crystallography.

Calix[4]arene phosphonous acids possessing two or four dihydroxyphosphoryl groups linked with the para-positions of the macrocyclic skeleton directly or by an aminomethyl spacer have been synthesised and their complexation with the herbicides2,4-dichlorophenoxyacetic acid (2,4-D) or atrazine (AT) in water has been investigated by the reversed phase HPLC method. The association constants of the 1 : 1 guest–host complexes of the herbicides (guest) with the calixarenes (host) in the range 772–5077 M-1 (2,4-D) and 2513–6785 M-1 (AT) have been determined from the relationship between the capacity factor of the guest and concentration of the calixarene host in the mobile phase. The association constants are dependent on the conformation and stereochemical mobility of the calixarene skeleton, the number of the dihydroxyphosphoryl groups at the upper rim, as well as the acid-base properties of the guest. Hydrophobic, electrostatic, and π-π-aromatic interactions in the guest–host complexes are discussed.

The host–guest complexation of tetrapropoxycalix[4]arene with uracil, 5-amino-, 5-methyl-, 5-ethyl-, 5-chloro-, 5-nitro-, 6-methyl-, 1,3-dimethyl-, 6-amino-1-methyl- and 6-amino-1,3-dimethyluracil, adenine and 9-methyladenine in methanol–acetonitrile–tetrahydrofuran–water (15:10:5:70, v/v) solution was investigated by reversed-phase high-performance liquid chromatography. The association constants of the 1:1 host–guest complexes of the guests with the calixarene host within the range 3250–54300 M−1 were determined from the capacity factor of the guest and concentration of the calixarene host in the mobile phase. Molecular dynamic (MD) simulation of the host–guest interaction was performed. Basing on the MD trajectories atomic partition to the net molecular solvent-exposed surface was analyzed for the separated guest and host molecules and for the complex. Copyright © 2003 John Wiley & Sons, Ltd.