Calixarene Phosphonous Acids: Synthesis and Biological Activity

Abstract

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     

Synthesis and Properties of a Series of Novel Calix[6]arene Diazo Derivatives

In this study, seven new compounds p-(4-butyl-phenylazo)calix[6]arene(1), p-(4-(phenylazo)phenylazo)calix[6]arene (2),p-(4-hydroxyphenylazo)calix[6]arene (3),p-{4-[N-(thiazol-2-yl)sulfamoyl]phenylazo\}calix[6]arene(4), p-(4-acetamidophenylazo)calix[6]arene (5),p-(thiazol-2-ylazo)calix[6]arene (6) andp-(2-sulfanylphenylazo)calix[6]arene (7) have been synthesizedfrom calix[6]arene by diazo coupling with the corresponding aromaticamines. UV-Vis, IR, ¹H and ¹³C NMR spectral data have been used to elucidate the structures of the compounds elemental analyses     

Synthesis and amino acid extraction abilities of chiral calix[4]arene triamides containing amino alcohol units

Herein the synthesis and extraction abilities of new d-/l-phenylalaninol substituted p-tert-butylcalix[4]arene triamide derivatives (3 and 4) towards amino acids are reported. These compounds (3 and 4) have been easily synthesized via aminolysis of p-tert-butylcalix[4]arene trimethylester (2) with d-/l-phenylalaninol in methanol-toluen solvent system at one step. The extraction properties of the prepared chiral calix[4]arene triamide derivatives (3 and 4) towards some selected amino acid methylesters are studied by liquid–liquid extraction. Results show that these chiral calix[4]arene triamide derivatives (3 and 4) exhibited a good affinity towards all amino acid species without any remarkably discrimination.     

Synthesis of Oligomer and Styrene Polymer-supported Calix[4]arene Derivatives and Selective Extraction of Fe3+

Five new polymeric compounds containing more than one calix[4]arene have been synthesized by reacting an oligomer with 5,11,17,23-tetrakis[(diethylamino)methyl]-25,26,27,28-tetrahydroxycalix[4]arene (L1), 25,27-dimethyl-26,28-dihydroxy-p-tert-butylcalix[4]arene diketone (L2), and p-nitrocalix[4]arene (L3), and chloromethylated polystyrene with 25,27-dimethyl-26,28-dihydroxy-p-tert-butylcalix[4]arene diketone (L4) and p-nitrocalix[4]arene (L5). These compounds were studied by the selective extraction of Fe³⁺ cation from the aqueous phase into the organic phase and was carried out by using compounds L1–L5. It was observed that the polymer support attached to the lower rim of p-nitrocalix[4]arene was the most efficient carrier of Fe³⁺ in the extraction process.     

Complexation of thiacalix[4]arene methylphosphonic and sulphonic acids with amino acids

In this paper, host–guest complexation process of thiacalix[4]arene tetrakis–methylphosphonic and tetrakis–sulphonic acids with amino acids by HPLC and molecular modelling methods has been studied. It was shown that thiacalix[4]arene tetrakis–methylphosphonic acid due to transformability of macrocyclic skeleton and flexibility of methylphosphonic substituents can adopt its conformation for strong multicentre binding of the amino acids with association constant values 530–10,140 M^? 1 in water.     

Azocalixarenes. 6: Synthesis, complexation, extraction and thermal behaviour of four new azocalix[4]arenes

Four new azocalix[4]arenes {5,11,17,23-tetrakis[(2-hydroxy-5-tert-butylphenylazo)]-25,26,27,28-tetrahydroxycalix[4]arene (1), 5,11,17,23-tetrakis[(2-hydroxy-5-nitro phenylazo)]-25,26,27,28-tetrahydroxycalix[4]arene (2), 5,11,17,23-tetrakis[(2-amino-5-carboxylphenylazo)]-25,26,27,28-tetrahydroxycalix[4]arene (3) and 5,11,17,23-tetrakis[(1-amino-2-hydroxy-4-sulfonicacidnapthylazo)]-25,26,27,28-tetrahydroxycalix[4]arene (4)} have been synthesized from p-tert-butylphenol, p-nitrophenol, p-aminobenzoic acid and 1-amino-2-hydroxy-4-sulphonic acid by diazo coupling reaction with p-aminocalix[4]arene. The resulting ligands (1–4) were treated with three transition metal salts (e.g., CuCl₂·2H₂O, NiCl₂·6H₂O or CoCl₂·6H₂O). Cu(II), Ni(II) and Co(II) complexes of the azocalix[4]arene derivatives were obtained and characterized by UV-vis, IR, ¹H-NMR spectroscopic techniques and elemental analysis. All the complexes have a metal:ligand ratio of 2:1. The Cu(II) and Ni(II) complexes of azocalix[4]arenes are square-planar, while the Co(II) complexes of azocalix[4]arenes are octahedral with water molecules as axial ligands. The solvent extraction of various transition metal cations from the aqueous phase to the organic phase was carried out by using azocalix[4]arenes (1–4). It was found that, azocalix[4]arenes 1, 2 and 3 examined selectivity for transition metal cations such as Ag⁺, Hg⁺ and Hg²⁺. In addition, the thermal stability of metal:azocalix[4]arene complexes were also reported. Dedicated to Prof. Dr. Mustafa Yılmaz on the occasion of his 50th birthday     

Novel Triphenylamine Appended 1,3-Alternate-Calix[4]arenes: Synthesis and Characterization

In the present study, two novel calix[4]arene receptors containing triphenylamine units in 1,3-alternate conformation have been synthesized and characterized in detail. First, the 25,27-dipropoxy-26,28-bis[(3-aminopropyl)oxy]-calix[4]arene 4 and 25,26,27,28-tetra[(3-aminopropyl)oxy]-calix[4]arene 7 were prepared by using convenient reagents. Then, these amino derivatives of calix[4]arene were converted to Schiff base derivatives appended to triphenylamine of calix[4]arene (5 and 8) using 4-formyltriphenylamine via condensation. The 1,3-alternate conformation of the synthesized calix[4]arenes was determined by ¹H and ¹³C NMR analyses. Also, their structures have been characterized by using ¹H and ¹³C NMR, infrared, and elemental analyses.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Synthesis of a water-soluble pillar[6]arene dodecaamine and its selective binding of acidic amino acids in water

A water-soluble pillar[6]arene dodecaamine has been synthesized. ¹H NMR and fluorescence studies indicate that pillar[6]arene dodecaamine could selectively and strongly bind acidic amino acids, i.e. glutamic acid and aspartic acid in water. And the complexation behavior of pillar[6]arene dodecaamine towards acidic tripeptide glutathione and short chain length (C₃ to C₈) dicarboxylic acids in water is also investigated.     

Complexation of Some Amino Acids and Peptides by p-Sulfonatocalix[4]arene and Hexasodium p-Sulfonatocalix[6]arene in Aqueous Solution

The stability constants (log K), the reaction enthalpy( H) and entropy ( S) of the complexesformed between some amino acids (glycine, L-alanine,L-valine, L-leucine, L-phenylalanine, L-tryptophan,L-threonine, and L-lysine) and peptides (glycyl-glycine,glycyl-L-alanine, glycyl-L-leucine, glycyl-L-phenylalanine,L-leucyl-glycine, L-leucyl-L-alanine, glycyl-L-valine,L-leucyl-glycyl-glycine, and glycyl-glycyl-glycine) withp-sulfonatocalix[4]arene and hexasodiump-sulfonatocalix[6]arene in aqueous solutions by meansof calorimetric titration have been investigated. The reportedresults demonstrate that the amino acids and peptides under studyform complexes with both p-sulfonatocalix[4]areneand hexasodium p-sulfonatocalix[6]arene. In the case of theamino acids and peptides the complexation with water-solublecalixarenes in aqueous solution is favored by enthalpiccontributions and disfavored by entropic contributions. However,no influence of the ring size of the calixarenes upon thecomplexation is observed. By comparison with the reaction ofthe sodium salt of phenol-4-sulfonic acid with amino acids amacrocyclic effect in case of the calixarenes is possible.     

Unexplored metallic cation effect in the acidity constants of p-t-butylthiacalix[4]arene,p-t-butylcalix[4]arene and p-t-butylcalix[6]arene in aqueous-organic media

The influence of the metallic cation of the base (Li⁺, Na⁺ or K⁺) was determined on the acid–base constants of p-t-butylthiacalix[4]arene (TC4), p-t-butylcalix[4]arene (CA4) and p-t-butylcalix[6]arene (CA6) in ethanol/water in an large interval of pH values by potentiometry and spectrophotometry. The pK_a values determined by both methods correlate very well and these are characteristic for each macrocycle with influence of the cation of the base without a straight evidence of an effect by the size of the metallic cation. In the case of TC4, pK_a1 and pK_a2 were lower to Li⁺ and Na⁺ than with K⁺. For CA4, an effect of K⁺ on the pK_a2 with respect to Li⁺ was observed. A very different behaviour was observed for CA6 with Li⁺ and K⁺ showing a lower pK_a2 and a higher pK_a3 than with Na⁺. These effects were interpreted on the basis of the interaction/complexation of each cation with each macrocycle.     

Synthesis,crystal structure and complexation behaviour of a thiacalix[4]arene bearing 1,2,3-triazole groups

The structure and complexation behaviour of 1,3-alternate-1,2,3-triazole based on thiacalix[4]arene,1,3-alternate-1 and 2 have been determined by means of X-ray analysis, fluorescence and ¹H NMR spectroscopy. The X-ray results suggested that the nitrogen atom N3 on triazole ring can act as hydrogen bond acceptors in the self-assembly of a supramolecular structure. The fluorescence spectra changes indicated that the thiacalix[4]arene bearing 1,2,3-triazole groups were highly selective for Ag⁺ in comparison with other tested metal ions by enhancement of the monomer emission of pyrene. The ¹H NMR results suggested that Ag⁺ can be strongly bonded by the triazole groups with the cooperation of the ionophoric cavity formed by the two inverted benzene rings and the sulfur atoms of the thiacalix[4]arene.     

Synthesis and Properties of New Thiacalixarene Derivatives with Palladium Ion

Three new thiacalix[4]arene derivatives, 5,11,17,23-tetra-tert-butyl-25,27-di(2-hydroxyethoxy)-26,28-dihydroxythiacalix-{}[4]arene (2), 5,11,17,23-tetra-tert-25, 26,27,28-tetrakis[(methylcarboxyl)methoxy]thiacalix[4]arene (3),5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrakis(2-hydroxy-1-propanoxy)thiacalix[4]arene (4), were synthesized for the first time. The coordination properties of thiacalix[4]arene(1) and its derivatives (2 and 4) were investigated by detecting the interactions betweenthese compounds and two palladium complexes, cis-[Pd(en)(H₂O)₂]²⁺ and cis-[Pd(dtco-3-OH)(H₂O)₂]²⁺, by means of electrospray ionization mass spectrometry (ESI-MS) technique.     

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.     

Synthesis and Properties of Upper Rim Schiff Base Calix[4]arenes

The synthesis and properties of upperrim Schiff base calix[4]arenes are described in thisarticle. Tetrakis-p-bromomethylcalix[4]arene(1) reacts with hexamethylenetetramine to givetetrakis-p-formylcalix[4]arene (2) in highyield. Then upper rim Schiff base calix[4]arenes 3 can be easily synthesized by 2 reacting withappropriate alkylamines. The complexation ability of3 toward transition metals Pb²⁺, Cu²⁺and Co²⁺ was studied by UV-VIS spectrophotometry.     

Extraction Behavior of Amino Acids by Calix[6]arene Carboxylic Acid Derivatives

A series of calixarene carboxylic acid derivatives were synthesized for the extraction of amino acids. A calix[6]arene carboxylic acid derivative showed the highest extractability to the target tryptophan ester. The main driving forcefor the complexation was the interaction between the ammonium cation of the aminoacid and the oxygen atoms of the host molecule. Stripping of amino acids was alsoaccomplished by contacting the organic solution with a fresh acidic solution. Basedon slope and Job method analyses, it was confirmed that the calix[6]arene formsa 1 : 1 complex with the amino acid ester. The structure of the complex between the calix[6]arene and the amino acid was investigated by ¹H-NMR and CD spectra. The calix[6]arene includes a guest molecule in the cavity, and the inclusion induces the asymmetrization of the host molecule. This host compound functions as a novel recognition tool for amino acids.     

Anion influence on extraction and transport of amino acid methyl esters by functionalised calix[4]arene

The liquid–liquid extraction of a series of amino acid methyl esters has been carried out with functionalised calix[4]arene (5,11,17,23-tetrakis(N-methylpiperazino)-25,26,27,28-tetrahydroxycalix[4]arene) from an aqueous phase into a chloroform phase as ion pairs in the presence of picrate ion or tropaeolin 00 as counter ion in order to study the molecular recognition properties of this receptor. The active transport assisted by pH gradient of amino acids as ion pairs through liquid membrane employing the functionalised calix[4]arene as carrier has been investigated. The results showed that the receptor exhibits good extractability towards amino acids and it can also act as carrier through liquid membrane aiming to the separation of amino acids. It was highlighted that the anion nature used as counter ion, the structure of calix[4]arene, and the structure of amino acids are responsible for the experimental results obtained. High yields in both amino acids extraction and transport were obtained for picrate ion used as counter ion.     

The Synthesis of Nitrogen-Containing Calixarene Derivatives and their Interactions with Lead Ions

Several new nitrogen-containingcalixarene derivatives have been synthesized andtheir ion-binding properties investigated byUV spectroscopy and solventextraction. These derivatives include5,11,17,23-tetra-t-butyl-25,26,27,28-tetrakis(piperidinocarbonylmethoxy)calix[4]arene (5),5,11,17,23,29,35,41,47-octa-t-butyl-49,50,51,52,53,54,55,56-octa(piperidinocarbonylmethoxy)calix[8]arene (6) and5,11,17,23,29,35,41,47-octa-t-butyl-49,50,51,52,53,54,55,56-octa(N,N-diethyl-car-bamoyl-methoxy)calix[8]arene(7). The UV spectra of and 7revealed they had an ability to transform tight lead picrate ionpairs into separated ones by complexationwith Pb²⁺ in tetrahydrofuran.Both derivatives give 1 : 1 complexes with Pb²⁺. Extraction studies showed that these derivativescould efficiently extract Pb²⁺ (as picrate salts) from the aqueous phase into chloroform. Theextractability of these derivatives were also compared with that ofthe oxygen-containing ester derivative calix[8]arene 2 and the other two nitrogen-containingcompounds 8 and 9.     

The Synthesis of Ester and Ketone Derivatives of Azocalix[4]arene Containing Chromogenic Groups

Azocalix[4]arenes were prepared by linking 4-ethylaniline, 4-n-butylaniline, 4-acetamide aniline and 2-aminothiazol to calix[4]arene through a diazo-coupling reaction. A new family of azocalix[4]arenes, L1–L12, have been prepared by the incorporation of acetyl, benzoyl, and methyl ketone units to azocalix[4]arene. Characterization of the synthesized compounds was carried using elemental analyses, UV–Vis, IR and ¹H NMR spectroscopic studies.     

Synthetic and NMR Studies on Calix[n]Arene (n = 4,6,8) Triflates,Mesylates, and Tosylates

Abstract

The synthesis and full characterization of eight new calix[n]arene sulfonate esters including their conformational analysis were carried out. While p-tBucalix[6]arene and p-tBu-calix[8]arene esters are conformationally labile in the temperature interval of 25–100°C, p-tBu-calix[4]arene mono-and diesters were isolated as stable conformers at ambient temperature. Two 1,3-functionalised compounds of these derivatives, p-tert-butylcalix[4]arene ditriflate (5) and dimesylate (6) were shown unexpectedly high conformational stability up to 100°C by dynamic NMR measurements. The NMR measurements confirm the pinched-cone conformation for both derivatives. For the dealkylated calix[4]arene derivatives the partial cone conformer of the triesters have been obtained as major products in all cases.     

Preparation of Calix[4]arene Alkylamine Derivatives by Mannich Reaction and use as Phase-Transfer Catalysts for Esterification Reaction

In this study, 5,11,17,23-tetrakis[(N-ethylpiperazine)methyl]-25,26,27,28-tetrahydroxycalix[4]arene (3) and 5,11,17,23-tetrakis[(4-carboethoxy-N-piperidino) methyl]-25,26,27,28-tetrahydroxycalix[4]arene (4) were synthesized in one step according to the Mannich reaction by the treatment of calix[4]arene with a secondary amine (N-ethylpiperazine, ethyl-4-piperidincarboxylate) and formaldehyde. The calix[4]arene derivatives (3, 4) were characterized by a combination of FTIR, ¹H NMR and elemental analyses. The synthesized compounds were used in an esterification reaction as the phase transfer catalyst. The catalytic efficiency of the calix[4]arenes 3 and 4 was evaluated by carrying out the ester-forming reaction of alkali metal carboxylates (sodium butyrate or sodium caprylate) with p-nitrobenzyl bromide. It was observed that the ester-forming reaction of alkali metal carboxylates with p-nitrobenzyl bromide, using calix[4]arene-based catalyst 3 as a phase-transfer catalyst in dichloromethan, provided the best yields.