Facile Fluorescence Monitoring of Gut Microbial Metabolite Trimethylamine N-oxide via Molecular Recognition of Guanidinium-Modified Calixarene.

Detection and quantification of trimethylamine N-oxide (TMAO), a metabolite from gut microbial, is important for the disease diagnosis such as atherosclerosis, thrombosis and colorectal cancer. In this study, a novel method was established for the sensing and quantitative detection of TMAO via molecular recognition of guanidinium-modified calixarene from complex matrix. Methods: Various macrocycles were tested for their abilities to serve as an artificial TMAO receptor. Using the optimized receptor, we developed an indicator displacement assay (IDA) for the facile fluorescence detection of TMAO. The quantification of TMAO was accomplished by the established calibration line after excluding the interference from the various interfering substances in artificial urine. Results: Among various macrocycles, water-soluble guanidinium-modified calix[5]arene (GC5A), which binds TMAO in submicromolar-level, was identified as the optimal artificial receptor for TMAO. With the aid of the GC5A•Fl (fluorescein) reporter pair, TMAO fluorescence "switch-on" sensing was achieved by IDA. The fluorescence intensity increased linearly with the elevated TMAO concentration. The detection was not significantly interfered by the various interfering substances. TMAO concentration in artificial urine was quantified using a calibration line with a detection limit of 28.88 ± 1.59 µM, within the biologically relevant low µM range. Furthermore, the GC5A•Fl reporter pair was successfully applied in analyzing human urine samples, by which a significant difference in fluorescence response was observed between the [normal + TMAO] and normal group. Conclusion: The proposed supramolecular approach provides a facile, low-cost and sensitive method for TMAO detection, which shows promise for tracking TMAO excretion in urine and studying chronic disease progression in humans.

Host-Guest Recognition of Pesticides by Calixarenes.

This article is based on a review of the literature and our own experience with toxicological molecules. We explain the nature of calix[n]arenes and as their recognized properties are used to detect compounds of toxicological interest, mainly the most important pesticide families such as organophosphorated, organochlorine compounds, pyrethroid insecticides, carbamate fungicides, and herbicides, using different techniques. In addition, we show the role of the macrocycle and its interactions, and the advantage of using this type of compound for improving conventional techniques, where the phenomenon of recognition is very important, such as chromatography, solid-phased extraction, and the development of specific sensors, among others and Even we also show the use of this macrocycle for detoxication procedures in vivo. In this way, we display as the multiple possibilities of functionalization of the calix[n]arenes makes these versatile molecules in the phenomena of specific recognition. Finally, This review highlights the main analytical methods reported in the literature for determination of plaguicides by host-guest interaction with calixarenes. In this way, among the available analytical tools, chromatographic, and electrochemical-based methods are the most used techniques for the detection and to quantify plaguicides using calixarenes.

Identification of number and type of cations in water-soluble Cs+ and Na+ calix[4]arene-bis-crown-6 complexes by using ESI-TOF-MS.

The treatment of cesium-contaminated wastewater has become one of the biggest issues. The selective Cs+ removal from wastewater containing competitive alkali metal ions such as Na+ is desired to reduce the volume of sludge. Therefore, the present work focused on water-soluble calix[4]arene-bis-crown-6 (W-BisC6) to selectively capture Cs+. For characterization of the complex, UV-vis spectroscopy is commonly used, however, due to the limited availability of information it can be hard to quickly identify the specific structures of some complexes. In this work, the electrospray ionization time of flight spectrometry (ESI-TOF-MS) is successfully utilized to identify the number and type of cations in W-BisC6-cation complexes. ESI-TOF-MS accurately recognized 4 types of complex (W-BisC6-Na+, W-BisC6-Cs+, W-BisC6-2Na+, W-BisC6-Na+-Cs+), and the experimental and simulated results were almost perfectly matched. It also revealed the difficulty of W-BisC6-2Cs+ complex formation under the present conditions. Thus, this technique is significantly helpful for rapid identification of the specific structures of complexes during Cs+-contaminated wastewater treatment.

[Research progress of bonded chiral stationary phases].

Chiral separation is important in biological medicine and other fields. High performance liquid chromatography (HPLC) is widely used in chiral separation and analysis for its economic, rapid and efficient characteristics. Chiral stationary phase (CSP) is the key to achieve chiral resolution in HPLC. Meanwhile, the key to preparing effective CSP is the screening of chiral selector. In recent years, a lot of CSPs with different chiral selectors had been prepared. Silica gel immobilized CSP is especially attached great attention because of its high solvent tolerance and stability. In this paper, the new type of CSPs prepared by using chiral single molecules, polysaccharides, cyclodextrins, macrocyclic antibiotics, crown ethers, calixarenes and alkaloids as chiral selectors are summarized, and the development prospect of immobilized CSPs are also discussed.

Retention behavior of resorcinarene-based cavitands on C8 and C18 stationary phases.

The understanding of the retention behavior of large molecules is an area of interest in liquid chromatography. Resorcinarene-based cavitands are cavity-shaped cyclic oligomers that can create host-guest interactions. We have investigated the chromatographic behavior of two types of cyclic tetramers as analytes in high-performance liquid chromatography. The experiments were performed at four different temperatures (15, 25, 35, 45°C) on two types of reversed stationary phases (C8 and C18 ) from two different manufacturers. We have found a huge difference between the retention of resorcinarenes and cavitands. In some cases, the retention factor of cavitands was even a hundred times larger than the retention factor of resorcinarenes. The retention of methylated derivates was two to four times larger compared to that of demethylated compounds on every column. The opposite retention behavior of the resorcinarenes and cavitands on the two types of stationary phases showed well the difference of the selectivity of the XTerra and BDS Hypersil columns. The retention mechanism was studied by the thermodynamic parameters calculated from the van't Hoff equation.

Quinoline driven fluorescence turn on 1,3-bis-calix[4]arene conjugate-based receptor to discriminate Fe3+ from Fe2+.

The synthesis and characterization of a triazole linked quinoline appended calix[4]arene conjugate, L, and its fluorescence turn on receptor property for Fe(3+) have been demonstrated. The selective and sensitive discrimination of Fe(3+) has been shown using fluorescence and absorption titration experiments. The Fe(3+) binding to L has been further shown by ITC and ESI MS. The mode of binding of Fe(3+) by calix[4]arene conjugate has been shown by absorption, (1)H NMR and visual color change and the species were modeled based on DFT computations. The {L + Fe(3+)} has been shown to label cells with fluorescence imaging. Moreover the utility of this conjugate has been demonstrated by the combination logic gate system.

Chiral recognition in separation science: an overview.

Chiral recognition phenomena play an important role in nature as well as analytical separation sciences. In separation sciences such as chromatography and capillary electrophoresis, enantiospecific interactions between the enantiomers of an analyte and the chiral selector are required in order to observe enantioseparations. Due to the large structural variety of chiral selectors applied, different mechanisms and structural features contribute to the chiral recognition process. This chapter briefly illustrates the current models of the enantiospecific recognition on the structural basics of various chiral selectors.

Analysis of guest binary mixtures by tert-butylcalix[6]arene using host memory of previously bound guests.

A new principle of quantitative and qualitative analysis of binary organic mixtures is offered, which is based on an ability of calixarene receptor for specific polymorphic transitions related to the composition of the analyzed guest mixture. The ability of tert-butylcalix[6]arene to remember selectively some guests bound from headspace both of pure liquids and their binary mixtures is used. The image of guest mixture remains written in metastable polymorphs of host after partial or complete guest elimination from clathrates. The memory was read using differential scanning calorimetry as the enthalpy of exothermic polymorphic transition of host collapse. This enthalpy monotonously changes with the variation of guests' ratio in mixture, unlike the enthalpies of endothermic pseudopolymorphic transitions of guest release. So, the composition of volatile binary mixture can be estimated using only one receptor and only one its parameter even in absence of preferential binding from a binary mixture of guests. This is an example of a genuine molecular recognition.

Tris(triazolyl) calix[6]arene-based zinc and copper funnel complexes: imidazole-like or pyridine-like? A comparative study.

Huisgen dipolar cycloaddition leads straightforwardly to new funnel complexes based on the calix[6]arene macrocycle bearing three functionalized triazoles as coordinating units at the small rim. Coordination to Zn(II) and Cu(I) cations was studied using (1)H NMR and IR spectroscopies and cyclic voltammetry. The nature of the substituents on the triazole ring affects the behavior of the ligands and their coordinating ability and controls the host-guest properties of the metal receptors for exogenous substrates. Depending on their substitution pattern but also on the metal ion and the guest ligand, the triazole-based systems behave either imidazole-like or pyridine-like. The ease of preparation and the versatility of 1,4-disubstituted-1,2,3-triazoles with tunable steric and electronic properties make them promising candidates for further applications from biology to materials.

Quick and efficient extraction of uranium from a contaminated solution by a calixarene nanoemulsion.

This work aims to evaluate the efficiency of a calixarene emulsion for uranium extraction from a contaminated solution prior to apply such a delivery system to uranium skin decontamination. For this purpose, various experimental parameters that can influence the efficiency of the calixarene emulsion on uranium extraction were determined. The results show that the calixarene nanoemulsion effect can be observed after a very short time of contact with uranium-contaminated solution (5 min) and that it is still efficient in case of small volumes of contaminated solution. The pH of the contaminated solution was found to be the most important parameter affecting the calixarene nanoemulsion efficiency with a dramatic reduction of the uranium extraction rate in case of acidification of the contaminated medium. This lack of efficiency can be overcome by buffering the nanoemulsion continuous phase. The obtained results reveal that the calixarene nanoemulsion could represent a promising system for the emergency treatment of uranium cutaneous contamination.

An electrospray ionization tandem mass spectrometric study of p-tert-butylcalix[6]arene complexation with ammonium hydroxide, and ammonium and sodium ions.

The formation of complexes involving p-tert-butylcalix[6]arene with neutral and charged species has been investigated by tandem mass spectrometry combined with electrospray ionization. Complexes of p-tert-butylcalix[6]arene with NH4+ ions were observed in the ratios 1:1, 2:1, and 3:1, together with the complexes of p-tert-butylcalix[6]arene with NH4OH and Na+ ions in the ratios 1:1:1, 2:1:1, and 3:1:1. A single 1:1 complex of p-tert-butylcalix[6]arene with Na+ ions was observed. In addition, a doubly charged complex of p-tert-butylcalix[6]arene with NH4OH, Na+, and NH4+ ions in the ratio 6:1:1:1 was observed. The identity of each complex was determined by mass analysis of product ions formed by the application of a declustering potential over the range 20-220 V and by observation of product ion mass spectra wherein the collision energy was varied from 5 to 50 eV. Fragmentation of the complexes is characterized by the facile loss of the ammonia molecule, sodium and ammonium ions, loss of neutral p-tert-butylcalix[6]arene, and successive neutral losses of C4H8 from the six tert-butyl groups in each p-tert-butylcalix[6]arene molecule.

Sorption characteristics of Cu(II) ions onto silica gel-immobilized calix[4]arene polymer in aqueous solutions: batch and column studies.

In the present study, Cu(II) removal from aqueous solutions by sorption was investigated. Aminopropyl silica gel-immobilized calix[4]arene polymer (APSIC[4]P) was used in sorption as sorbent. During the experimental part of this study, the effect of parameters, such as pH, initial Cu(II) concentration, temperature on Cu(II) removal was observed. In addition, sorption isotherm studies and column studies were made. Maximum Cu(II) removal was obtained at pH 6 and 25 degrees C. In the isotherm studies, Langmuir and Freundlich isotherm models were applied and it was determined that the experimental data confirmed to Langmuir isotherm model. Batch sorption capacity (q0) was calculated as 5.08 mg/g. The capacity value for column study was obtained by graphical integration as 1.14 mg/g. The Thomas and the Yoon-Nelson models were applied to experimental data to predict the breakthrough curves and to determine the characteristics parameters of the column useful for process design.

[Study on the interaction between p-octacarboxyphenylazocalix[8]arene and norfloxacin by fluorescence spectrometry].

In the present paper, p-octacarboxyphenylazocalix[8]arene (CPAC) was used as supramolecular probe according to a reported method. The interaction of CPAC with drug norfloxacin (NFLX) was studied by fluorescence spectrometry. The results show that CPAC can strongly quench the fluorescence of NFLX because of the complex interaction between host and guest molecules in exo-inclusion complex. The spectral changes indicated that the quenching can be considered as static quenching mode. The hydrophobic interaction between the cavity of CPAC and the quinoline ring was the main force to consolidate the exo-inclusive complex CPAC-NFLX stability. The complex constant (K) and binding ratio (n) were determined to be 6. 38 X 10(5) L x mol(-1) and 1, respectively. Further experiment found that the calf thymus DNA and CPAC can combine, leading to the release of NFLX and the enhancement of fluorescence of the reaction system. It is expected that CPAC will be used as drug carrier and releaser.

Phosphorated calix[6]arene derivatives as an ionophore for atropine-selective membrane electrodes.

37,40-bis-[(diethoxy-thiophosphoryl)oxy]-5,11,17, 23,29,35-hexakis(1,1 -dimethyl-ethyl)-calix[6]arene-8,39,41,42-tetrol; 37,38,39,40,41-pentakis-(di-ethoxythiophosphoryl)-oxy]-5,11,17,23,29,35-hexakis (1,1-dimethylethyl)-calix[6]-arene-42-ol; and 37-[(diethoxythiophosphoryl)oxy]-5,11,17,23,29,35-hexakis-(1,1dimethylethyl)-calix[6]arene-38,39,40, 41,42-pentol were introduced as neutral ionophores for atropine-selective electrodes. Practical Nernstian responses were found (54.3, 49.1, and 50.8 mV/decade) for polyvinyl chloride membrane electrodes incorporating these compounds. They exhibited practical linear ranges of 1.9 x 10(-6)-7.9 x 10(-3), 7.9 x 10(-6)-7.9 x 10(-3), and 6.3 x 10(-6)-7.9 x 10(-3) M, respectively. The optimum pH range was 2.5-8.5. The selectivity coefficient values were estimated and interpreted. The electrode performance was correlated to the calixarene structure. Then, the electrode was applied to an actual analysis of pharmaceutical atropine preparations. The recovery values of 18.7 microg/mL-5.5193 mg/mL atropine sulfate were 97.5-99.1%. The corresponding relative standard deviation values ranged between 0.39-0.72% for 5 determinations. The first electrode was applied successfully for analyzing atropine sulfate in injection solution and eye drops.

Absorption and fluorescence spectroscopic study on complexation of Oxazine 1 Dye by calix[8]arenesulfonate.

It has been established by combined absorption and fluorescence measurements that the cationic dye Oxazine 1 (OX) and the polyvalent anionic host calix[8]arenesulfonate (SCA8) form two complexes in simultaneous reactions: OX + SCA8 <--> OX.SCA8 (1), and OX.SCA8 + OX <--> OX(2).SCA8 (2). The equilibrium constants for the two reactions, as functions of the ionic strength (I), and the absorption and fluorescence spectra of the two complex species have been determined by a least-squares fitting method from the experimental data. The variations of the binding constants with the ionic strength could be described on the basis of Debye-Huckel theory. The equilibrium constants are large; their values extrapolated to I = 0 are K(1) = 5.5 x 10(6) M(-1) and K(2) = 4.4 x 10(5) M(-1). The fluorescence of OX undergoes a strong static quenching upon complexation. These results indicate that the complexes are held together by strong electrostatic forces. The addition of non-fluorescent tetramethylammonium chloride to OX-SCA8 mixtures results in a dramatic fluorescent enhancement, which demonstrates the potential applicability of this supramolecular system in fluorescence assays.

The solubilization of the poorly water soluble drug nifedipine by water soluble 4-sulphonic calix[n]arenes.

In this study, the solubilizing effect of 4-sulphonic calix[n]arenes on the poorly water soluble drug nifedipine was investigated. 4-Sulphonic calix[n]arenes are water-soluble phenolic cyclooligomers that form complexes with neutral molecules such as nifedipine. Solubility experiments were performed at 30 degrees C using the Higuchi rotating bottle method. The amount of nifedipine in solution was determined by HPLC. The results showed that the size of the 4-sulphonic calix[n]arenes, the pH of solubility medium, and the concentration of the calix[n]arenes all significantly changed the solubility of nifedipine. 4-Sulphonic calix[8]arene improved the solubility of nifedipine the most, about 3 times the control at 0.008 M and pH 5, followed by 4-sulphonic calix[4]arene, about 1.5 times the control at 0.008 M and pH 5, while in the presence of 4-sulphonic calix[6]arene, the solubility of nifedipine was decreased. The possible mechanisms involving in the complexation between 4-sulphonic calix[4]arenes, 4-sulphonic calix[8]arene and nifedipine may be a combination of hydrogen bonding, hydrophobic bonding, and possibly electron donor-acceptor interactions. However, the degree to which these forces promote the formation of nifedipine:4-sulphonic calix[n]arene complexes with increased solubility was limited by conformational changes in the 4-sulphonic calix[n]arene molecules.

Reorientational dynamics of p-sulfonatocalix[4]arene and of its La(III) complex in water.

The reorientational dynamics of p-sulfonatocalix[4]arene and of its La(III) complex in deuterated water were studied by 1H NMR longitudinal relaxation rates. It is shown that the relaxation is purely dipolar in the non-extreme narrowing regime. The distance between the geminal protons could be determined from the NMR data, giving good agreement with the values generally used in correlation time calculations. The correlation times show an Arrhenius behaviour in good agreement with previously reported data from 13C measurements for a similar uncomplexed calixarene. The Arrhenius energies of activation are identical for the uncomplexed and the complexed calixarenes, suggesting a reorientational motion strongly dependent on the structure of the water cage around the complex. This is also in agreement with a complexation of the La(III) cation in the second sphere of solvation of the sulfonate groups, as shown by molecular dynamics simulations.