Crown Ether Type Research Articles

Chiral recognition and discrimination studies of tyrosine enantiomers on (-)-18-crown-6-tetracarboxylic acid as a chiral selector by nuclear magnetic resonance spectroscopy and docking simulations.

Considering the substantial significance of chiral biomolecules, such as amino acids, in our daily routines, we performed chiral recognition and discrimination of tyrosine (Tyr) enantiomers on (-)-(18-crown-6)-2,3,11,12-tetracarboxylic acid [(-)-18-C-6-TA] as crown-ether type chiral selector (CS) by nuclear magnetic resonance (NMR) spectroscopy and docking simulations. In this study, successful discrimination of the enantiomers of Tyr was achieved, as evidenced by the proton chemical shift differences (ΔΔδ) of Tyr enantiomers observed in the 1 H NMR spectra with (-)-18-C-6-TA CS. We compared the results of these two techniques with the findings obtained from high performance liquid chromatography (HPLC) investigations. In both NMR and HPLC experimental and docking simulation studies, a stronger interaction between the L-Tyr enantiomer with (-)-18-C-6-TA CS than the D-Tyr was consistently observed. Also, the binding energy differences (ΔΔEL-D ) found in simulation data that correspond to enantioselectivity aligned well with the NMR experimental result.

Synthesis, α‐Glucosidase Inhibitory Activity, and Molecular Docking Studies of Tri(benzo)‐5‐azacrownophanes with a γ‐Piperidone Moiety

AbstractMulticomponent reactions (MCR) are power tools in modern organic synthesis. These reactions have many advantages over single component reactions, including saving time and chemicals. Moreover, compounds with complicated structures can be synthesized based on simple substrates and one‐step reactions, without the tedious work of separating intermediate compounds. Taking full advantage of this tool, over the past 10 years we have synthesized novel crown compounds with the successful introduction of different bioactive moieties into molecules. As part of our ongoing research, this study reports on the synthesis of a new type of crown ether based on a three component reaction of an aldehyde, a ketone, and ammonium acetate in dry solvent, at specific temperature. The structure of the new compounds was identified using physical‐chemical methods of analysis including IR, 1H & 13C NMR, HRMS and single‐X ray diffraction. The effects of the newly synthesized azacrown ethers on the enzyme α‐glucosidase were then explored and they were shown to be potential candidates in the search for new antidiabetic drugs. Among five tested compounds, two compounds are active again the enzyme α‐glucosidase and expressed IC50 values of 407.17±9.01 μM and 345.90±6.75 μM. Molecular docking studies were also performed to investigate the binding mode of the synthetic compounds to α‐glucosidase. Finally, ADMET parameters were assessed to investigate the relationship between structure and biological activities.

Synthesis of crown ether-based microporous organic networks: A new type of efficient adsorbents for chlorophenols.

Microporous organic networks (MONs) are a booming class of functional materials in elimination of environmental pollutants. However, the limit varieties of MONs still restrict their broad applications. Here we report the synthesis of a novel type of crown ether (CE)-based MONs via the coupling between brominated 18-crown-6 ether and different aromatic alkynyls. The constructed CE-based MONs integrates the good conjugation property of MONs and the inherent host-guest binding sites of CE, allowing the ultrafast and efficient adsorption and removal of a typical environmental priority pollutant 2,4,6-trichlorophenol (2,4,6-TCP). The hydrophobic CE-based MONs can also address the recovery challenge of unstable discrete CE in most organic and inorganic solvents. All CE-based MONs displayed fast adsorption kinetics (< 3min) and large adsorption capacities (229.1-341.7mgg-1) for 2,4,6-TCP. The CE-based MONs also gave stable adsorption capacities for 2,4,6-TCP in pH range of 4.0-6.0, NaCl concentration of 0-40mgL-1, HA concentration of 0-30mgL-1, or H2O2 ratio of <5%. Density functional theory calculation, Fourier transform infrared and X-ray photoelectron spectra evaluation revealed adsorption process involved hydrophobic, π-π and hydrogen bonding interactions. The CE-based MONs also showed favorable reusability and good adsorption for other toxic chlorophenols. This work highlights the potential of CE-based MONs in contaminants elimination.

Achiral Molecular Recognition of Substituted Aniline Position Isomers by Crown Ether Type Chiral Stationary Phase.

To understand the selectivity of the crown ether type chiral stationary phase (CSP), the retention selectivity for aniline and the positional isomers of substituted anilines were studied. In various substituted isomers, except nitroaniline, a remarkable decrease of retention due to steric hindrance was observed for the 2-substituted isomer. To determine the detailed molecular recognition mechanism, quantum chemical calculations were performed for the aggregates between the crown ether and the anilines. The results suggested that the 20-Crown-6, which includes a phenyl-substituted 1,1′-binaphthyl moiety, interacts with alkyl and aryl amines in an unconventional form different from the proposed one for 18-Crown-6.

Adsorption of Gadolinium (Gd3+) Ions on the Dibenzo Crown Ether (DBCE) and Dicyclo Hexano Crown Ether (DCHCE) Grafted on the Polystyrene Surface: Insights from All Atom Molecular Dynamics Simulations and Experiments

All atom molecular dynamics simulations and experiments were performed to understand the adsorption behavior of gadolinium (Gd3+) ion on the crown ethers grafted polystyrene (PS) surface. Two different types of crown ethers, viz., dibenzo crown ether (DBCE) and dicyclo hexano crown ether (DCHCE), were grafted separately on the PS surface to understand the adsorption behavior. We investigate the roles of Gd3+ ion concentration and grafting density (ρs) of the crown ether on the adsorption behavior of Gd3+ ion on the PS surface. The adsorption of Gd3+shows an increasing trend with increasing salt concentration, for all cases of crown ether grafting densities. The adsorption behavior follows the Langmuir isotherm model. The maximum amount of Gd3+ ion adsorption was observed to be 1.83 mg/g for DBCE and 2.02 mg/g for DCHCE at ρs = 2.07 mol/nm2. The maximum amount of Gd3+ ion adsorption on DBCE coated PS beads, in batch experiments, was found to be 1.76 mg/g, which is in good agreement with the theoretical res...

The Asymmetry is Derived from Mechanical Interlocking of Achiral Axle and Achiral Ring Components –Syntheses and Properties of Optically Pure [2]Rotaxanes–

Rotaxanes consisting of achiral axle and achiral ring components can possess supramolecular chirality due to their unique geometrical architectures. To synthesize such chiral rotaxanes, we adapted a prerotaxane method based on aminolysis of a metacyclophane type prerotaxane that had planar chirality, which is composed of an achiral stopper unit and a crown ether type ring component. The prerotaxanes were well resolved using chiral HPLC into a pair of enantiomerically pure prerotaxanes, which were transferred into corresponding chiral rotaxanes, respectively. Obtained chiral rotaxanes were revealed to have considerable enantioselectivity.

Chiral separation using chiral crown ethers as chiral selectors in chirotechnology

This article reviews the enantiomer separation using two typical chiral crown ethers as chiral selectors in chirotechnology. The coated chiral crown ether type chiral stationary phase (CSP) derived from bis-(1,1′-binaphthyl)-22-crown-6 and the covalently bonded chiral crown ether type CSP derived from (18-crown-6)-2,3,11,12-tetracarboxylic acid (18-C-6-TA) in the term of their suitability and applicability are discussed and compared in chiral HPLC. It was shown that the covalently bonded type CSP using 18-C-6-TA as a chiral selector has been widely applied for resolving various chiral primary amines in chiral HPLC. Furthermore, this article focuses on the enantiomer separation and their applications using (+)- and/or (−)-18-C-6-TA as chiral selectors for capillary electrophoresis as well as a chiral solvating agent for nuclear magnetic resonance spectroscopy.

Crown Ether Complexes of Alkali-Metal Chlorides from SO2.

The structures of alkali-metal chloride SO2 solvates (Li-Cs) in conjunction with 12-crown-4 or 1,2-disila-12-crown-4 show strong discrepancies, despite the structural similarity of the ligands. Both types of crown ethers form 1:1 complexes with LiCl to give [Li(1,2-disila-12-crown-4)(SO2 Cl)] (1) and [Li(12-crown-4)Cl]⋅4 SO2 (2). However, 1,2-disila-12-crown-4 proved unable to coordinate cations too large for the cavity diameter, for example, by the formation of sandwich-type complexes. As a result, 12-crown-4 reacts exclusively with the heavier alkali-metal chlorides NaCl, KCl and RbCl. Compounds [Na(12-crown-4)2 ]Cl⋅4 SO2 (3) and [M(12-crown-4)2 (SO2 )]Cl⋅4 SO2 (4: M=K; 5: M=Rb) all showed S-coordination to the chloride ions through four SO2 molecules. Compounds 4 and 5 additionally exhibit the first crystallographically confirmed non-bridging O,O'-coordination mode of SO2 . Unexpectedly, the disila-crown ether supports the dissolution of RbCl and CsCl in the solvent and gives the homoleptic SO2 -solvated alkali-metal chlorides [MCl⋅3 SO2 ] (6: M=Rb; 7: M=Cs), which incorporate bridging μ-O,O'-coordinating moieties and the unprecedented side-on O,O'-coordination mode. All compounds were characterised by single-crystal X-ray diffraction. The crown ether complexes were additionally studied by using NMR spectroscopy, and the presence of SO2 at ambient temperature was revealed by IR spectroscopy of the neat compounds.

The Electrochemical Sugar Recognition Using a β-Cyclodextrin Assembled on the Gold Electrode

Introduction Cyclodextrin has a hydrophobic field inside of its structure and includes various molecules to form complexes. The inclusion occurs when the size of the cyclodextrin cavity matches that of the guest molecules. Therefore, a molecule recognition probe which is not soluble to water can be dissolved in an aqueous solution by the inclusion of cyclodextrin. This type of sensing using a cyclodextrin complex is widely researched. Hayashita’s group conduct alkali metal ion recognition using crown ether type azo probe and sugar recognition using boronic acid type azo probe. Both of them utilize the cyclodextrin inclusion ability. Moreover, electrochemical molecule recognition, which involves fixing cyclodextrin on electrodes and utilizing the inclusion ability, is also widely researched. purpose In our laboratory we have various probes that utilize cyclodextrin and in our experiments we conduct an electrochemical molecular recognition by impedance measurements in aqueous solutions. We composed β-CyD whose alkyl chains were stretched (β-CyD-R10SH) and we also modified the gold electrode with it. This improved the coverage and stabilization of the modification to CyD gold electrode by van der Waals forces of each other alkyl chain. We successfully improved sensitivity of the carbohydrate recognition. In addition, we succeeded in recognition of phosphoric acid salts such as ATP by having the dipicolylamino group included. In this study, my purpose was to find an electrochemical molecular recognition by impedance measurements of monosaccharide such as D-fructose, D-glucose and D-galactose, disaccharide, trisaccharides, tetrasaccharide, polysaccharides and the rare sugar based on the impedance measurements. Materials and Method Synthesis of β -CyD-(CH2)10S(CH2)11CH3 ( β -CyD-R10SH ): Primary amino was introduced at the 6th carbon of cyclodextrin by the Appel reaction, nucleophilic substitution reaction and the Staudinger reaction. A solution of the Synthesized heptakis(6-deoxy-6-amino)-b-cyclodextrin and 11-(thiododecyl)undecanoic acid were stirred for 18 hours with DCC, in order to create a white powder (β-CyD-R10SH). Modification: modification was conducted in 3 steps. First, β-CyD-R10SH was attached onto the gold electrode by the SAM method. Second, the octadecanthiol was attached onto the gold electrode to fill gaps among β-CyD-R10SH. Third, 1-pyreneboronic acid was included by β-CyD-R10SH. Measurement: EIS were measured while adding sugar solution using the modified electrode prepared above. Through the results of measurements, the relationship between concentration and charge transfer resistance was investigated by making a Nyquist plot. Results and Discussion Modification of β-CyD-R10SH and 1-octadecanethiol to the gold disk electrode was identified by a decrease of the current response of CV. The Nyquist plots at that point with the inclusion of 1-pyreneboronic acid were shown in Fig. 2 when sugar was added to the solution. With the addition of D-fructose and D-psicose, the increase in charge transfer resistance (Rct) was observed. This confirmed the inclusion of 1-pyreneboronic acid / Bp-amido-adamantane and monosaccharide / rare sugar recognition. However, with the addition of D-psicose when 1-pyreneboronic acid was used as a probe, the increase in charge transfer resistance (Rct) was not observed. It showed that using an appropriate probe for each molecule was necessary. Conclusion We conduct an electrochemical molecular recognition using modified cyclodextrin on gold electrode by impedance measurements. The results mentioned above indicate that the method is applicable to recognition of various molecules by changing probes and show high sensitivity. Figure 1

Novel C1-symmetric chiral crown ethers bearing rosin acids groups: synthesis and enantiomeric recognition for ammonium salts

Four types of novel C1-symmetric chiral crown ethers including 28-crown-8, 20-crown-6, 17-crown-5 and 14-crown-3 (9a–m) were synthesized and their enantiodiscriminating abilities with protonated primary amines (10–14) were examined by 1H NMR spectroscopy. 20-crown-6 crown ethers exhibited good chiral recognition properties toward these guests and showed different complementarity to some chiral guests, indicating that 20-crown-6 crown ethers could be used as a chiral NMR solvating agent to determine the enantiopurity of these guests. In addition, the binding model and binding site between the hosts and guests were also studied by the computational modeling and experimental calculation.

Capsules with Highly Active Pores and Interiors: Versatile Platforms at the Nanoscale

Spherical porous capsules offer new exciting approaches in chemistry, materials sciences, and in context of physical and biological phenomena. The underlying concepts are reported with particular emphasis on metal oxide based capsules of the {M132 } Keplerate type which display-due to their exceptional structural features and easy variation/derivatization as well as exchange of building units-an unmatched range of properties and offer unique opportunities for investigating a variety of basic aspects of nanoscience, including the discovery of some new phenomena, especially those related to hydrophobicity issues that are of significance for everyday life. This relies in particular on the existence of a large number of flexible crown ether type pores/channels and the possibility of changing the interior from completely hydrophilic to completely hydrophobic due to the presence of numerous easily exchangeable internal ligands/functionalities; the capsules can even be constructed so that they enclose a large number of highly active Lewis and Brønsted acid sites. The manifold of possible applications/uses are outlined as subtitles with reference to results as well as possible future studies. There are, among many others, options to control passing cations under different internal frames allowing also their separations, to conduct studies about hydrophobic recognitions and clustering of biological interest in water, controlled internal ion transport, nanoscale dewetting, and to carry out basic as well as new types of reactions under confined conditions.

Development of Chemically Bonded Crown Ether Stationary Phases in Capillary Ion Chromatography

Three types of crown ethers (i.e. 1-aza-15-crown-5-ether, 1-aza-18-crown-6-ether and 2-aminomethyl-18-crown-6-ether) were chemically bonded to silica gels via a simple 2-step reaction and the resulted stationary phases were evaluated for the separation of both anions and cations in capillary ion chromatography. It was found that the chemically bonded stationary phases were most stable and relatively sharper peaks were obtained when a mixture of toluene:acetonitrile = 7:3 was used as the reaction solvent in the second step reaction. The size of crown ether cavity as well as the presence of nitrogen atom within the cavity affected the retention behaviors of the ions. As for the separation of anions, it was found that the eluent cations were trapped on the stationary phases and acted as the anion-exchange site, viz. the anions were separated in the ion-exchange mode. Without the obstruction of nitrogen atom, 2-aminomethyl-18-crown-6-ether could easily form complexes with metal cations, and the retention as well as elution order were dependant on the complex formation constant between crown ether and the metal cations. Eluent with higher pH favored the retention and separation of the metal cations.

Synthesis and microbiological evaluation of several benzocaine derivatives

Abstract Starting from benzocaine, a well-known anaesthetic, ten derivatives were synthesized and characterized by UV–vis, IR, NMR, and elemental analysis. Most of the compounds contain residues with recognized biological activity, like nicotinic acid (vitamin B3 or PP), biotin (vitamin B7 or H), lipoic acid (thioctic acid), adamantine, as well as other residues of crown-ether type, benzofurazane, naphtylurea, di- and tri-nitrobenzene, and a nitroxide radical. The biological evaluation of the obtained compounds included hydrophobicity (lipophobicity) assay, total antioxidant and microbiological activity tests.

Ligand dependent self-assembly of hydroxido-bridged dicopper units templated by sodium ion

Crown-ether like interaction of two neutral [Cu2(μ-OH)(μ-L(1))] (H3L(1) = 2-(2'-hydroxyphenyl)-1,3-bis[4-(2-hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazolidine) fragments, around a central Na(+) cation as self-assembly template, led to the formation of [Na{Cu2(μ-OH)(μ-L(1))}2]ClO4 (1). Di-tert-butyl group substituted H3L(2) {2-(3,5-di-tert-butyl-2-hydroxyphenyl)-1,3-bis[4-(3,5-di-tert-butyl-2-hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazolidine} conversely yields only [Cu2(μ-OH)(μ-L(2))]·1.5H2O (2), by discarding aggregation around the Na(+) ion. The crown-ether type aggregate 1 exhibits ferromagnetic interactions within the double oxido-phenoxido [Cu2] fragments and weak antiferromagnetic interactions are mediated by the ONa(+)O bridges. Complex 2 registers only weak antiferromagnetic interactions within the oxido-phenoxido bridged [Cu2] entity. UV-visible and emission titration spectroscopy establish the interaction of cationic complex 1 with calf thymus DNA in Tris buffer and it cleaves supercoiled pBR322 DNA from in situ generated ROS.

Click-immobilized K+-selective ionophore for potentiometric and optical sensors

Clickable crown ether type of K+-selective ionophore was synthesized for the first time. The ionophore can be easily immobilized in azide-modified poly (vinyl chloride) (N3PVC) matrix by azide-alkyne Huisgen cycloaddition (“click chemistry”) for the fabrication of potentiometric and optical sensors. Formation of the triazole linkers in the polymer matrix decreases the solubility of functionalized PVC significantly. Azidation of PVC for 12 h followed by Cu(I) catalyzed cycloaddition can produce ionophore grafted PVC with good solubility and film forming property. The solid-contact electrode prepared with plasticized functional polymer exhibited Nernstian response to potassium ion from 10−6 to 10−1 M, good selectivity and improved lifetime. Such ionophore grafted polymer has also been used to prepare optical sensors with ETH 5294 as chromoionophore. The measuring range and selectivity of the optode are comparable to the ones of ion-selective electrode.

ChemInform Abstract: Photochemical Approach to the Preparation of Lariat Crown Ethers Containing Peptide Sidearms.

New types of lariat type crown ethers containing peptide sidearms were prepared by using a novel strategy employing single electron transfer (SET)-induced photocyclization reactions of -silylether terminated phthalimides. Reactions of chiral substrates in this series produced diastereomeric mixtures of crown ether products as a result of the formation of new stereogenic center generation in the photocyclization process.

Manganese(III)-Assisted Specific Intramolecular Addition

Oligomethylene-tethered ω-alkenyl 3-oxobutanoates and 3-oxobutanamides underwent manganese(III)-mediated oxidative intramolecular addition to produce dihydrofuran-fused macrolides and macrocyclic amides from 8 to 26 members. A similar reaction of the oligooxamethylene-tethered ω-alkenyl 3-oxobutanoates also gave dihydrofuran-fused crown ether type macrolides which had a phase-transfer ability with sodium and potassium pi-crates. The manganese(III)-assisted specific intramolecular addition could be explained by the π-complexation of the ω-alkenyl part with the manganese(III) enolate.

Complexation of alkali metal cations by crown-ether type podands with applications in solvent extraction: insights from quantum chemical calculations

The complexation behavior of nine polyether type podands with a varying number of oxygen donor atoms (4-10) towards the alkali metal cations Li(+), Na(+) and K(+) was studied by quantum chemical methods at the DFT-B3LYP level of theory using the all-electron split-valence 6-311++G(d,p) basis set. The optimized structures of the complexes show a regular increase in the mean cation-oxygen distance with the coordination number. OC-CO dihedral angles of the podand arms were also found to increase with the coordination number and with the size of the cation. Maximum values for the number of strong cation-oxygen interactions (effective coordination numbers) were found for each cation (six for Li(+), seven for Na(+) and eight for K(+)). The calculated values for thermodynamic parameters relative to the binding of free and solvated cations to the podands allowed the assessment of binding constants in vacuum, in water and in dichloromethane. The estimated cation extraction constants mimic the experimental extraction trends, but their values are much larger than experimental values. Scale factors were determined to correct the values effectively. For each podand the ratios between the calculated extraction constants of Li(+) (or Na(+)) and the corresponding ones for K(+) (seen as extraction selectivities) compare acceptably with the corresponding experimental values.

Photochemical Approach to the Preparation of Lariat Crown Ethers Containing Peptide Sidearms

New types of lariat type crown ethers containing peptide sidearms were prepared by using a novel strategy employing single electron transfer (SET)-induced photocyclization reactions of <TEX>$\alpha$</TEX>-silylether terminated phthalimides. Reactions of chiral substrates in this series produced diastereomeric mixtures of crown ether products as a result of the formation of new stereogenic center generation in the photocyclization process.

Synthesis and structure of new crown ethers with 1,4-phenylene and 1,4-naphthylene units

The synthesis of monomers and dimers of some new crown ether type macrocycles with 1,4-phenylene and 1,4-naphthylene units are reported. The structural investigations of the compounds were carried out by NMR spectra, MS measurements and the single crystal X-ray solid state molecular structure of one compound.