Synthesis,characterization, and ion‐complexing properties of polymers displaying densely packed arrays of crown‐ethers as lateral substituents

We report the synthesis and ion‐binding properties of four poly(crown‐ethers) displaying either one or two crown‐ethers (15‐crown‐5 or 18‐crown‐6) on every third carbon alongside the backbone. The polymers were synthesized by living anionic ring‐opening polymerization of disubstituted cyclopropane‐1,1‐dicarboxylates monomers. Cation binding of the polychelating polymers and corresponding monomers to Na⁺ and K⁺ was evaluated by picrate extraction and isothermal calorimetry titration. This novel family of poly(crown‐ethers) demonstrated excellent initial binding of the alkali ions to the polymers, with a higher selectivity for potassium. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2337–2345     

The synthesis of novel crown ethers,part X, 4‐propyl‐and 3‐ethyl‐4‐methylchromenone‐crown ethers

Starting from ethyl propionylacetate, and ethyl 2‐ethylacetoacetate we prepared 4‐propyl‐7,8‐, 4‐propyl‐6,7‐, 3‐ethyl‐4‐methyl‐7,8‐ and 3‐ethyl‐4‐methyl‐6,7‐dihydroxy‐2H‐chromenones which were allowed to react with the bis‐dihalides or ditosylates of glycols in DMF/Na₂CO₃ to afford the 6,7‐ and 7,8‐chromenone derivatives of 12‐crown‐4, 15‐crown‐4 and 18‐crown‐6. The products were identified using ir, ¹³C and ¹H nmr, ms and high resolution mass spectroscopy. The cation selectivities of chromenone crown ethers with Li⁺, Na⁺ and K⁺ cations were estimated from the steady state emission fluorescence spectra of free and cation complexed chromenone macrocyclic ethers in acetonitrile.     

The synthesis of novel crown ethers,part ix, 3‐phenyl chromenone‐crown ethers

3‐Phenyl‐ and 3‐(p‐methoxyphenyl)‐7,8‐dihydroxy and ‐6,7‐dihydroxychromenones were prepared from ethyl 3‐oxo‐2‐phenylpropanoate, ethyl 3‐oxo‐2‐(4‐methoxyphenyl)‐propanoate and the trihydroxy benzenes in H₂SO₄. 3‐Aryl‐7,8‐ and 3‐aryl‐6,7‐dihydroxy‐2H‐chromenones reacted with the bis‐dihalides of poly‐glycols in DMF/MeCO₃ to afford 12‐Crown‐4, 15‐Crown‐4 and 18‐Crown‐6‐chromenones. The products were identified with IR, 1H NMR, low and high resolution mass spectroscopy and elemental analysis. Some 1:1 cation association constants, K_b, of the 3‐phenyl chromenone crown ethers with Li⁺, Na⁺, K⁺ and Rb⁺ cations were studied by steady state emission fluorescence spectroscopy; K_b chromenone‐crown complexes displayed crown ether‐cation binding selectivity rules properly in acetonitrile.     

A Highly K+‐Selective Phenylaza‐[18]crown‐6‐Lariat‐Ether‐Based Fluoroionophore and Its Application in the Sensing of K+ Ions with an Optical Sensor Film and in Cells

Herein, we report the synthesis of two phenylaza‐[18]crown‐6 lariat ethers with a coumarin fluorophore ( 1 and 2 ) and we reveal that compound 1 is an excellent probe for K⁺ ions under simulated physiological conditions. The presence of a 2‐methoxyethoxy lariat group at the ortho position of the anilino moiety is crucial to the substantially increased stability of compounds 1 and 2 over their lariat‐free phenylaza‐[18]crown‐6 ether analogues. Probe 1 shows a high K⁺/Na⁺ selectivity and a 2.5‐fold fluorescence enhancement was observed in the presence of 100 mM K⁺ ions. A fluorescent membrane sensor, which was prepared by incorporating probe 1 into a hydrogel, showed a fully reversible response, a response time of 150 s, and a signal change of 7.8 % per 1 mM K⁺ within the range 1–10 mM K⁺. The membrane was easily fabricated (only a single sensing layer on a solid polyester support), yet no leaching was observed. Moreover, compound 1 rapidly permeated into cells, was cytocompatible, and was suitable for the fluorescent imaging of K⁺ ions on both the extracellular and intracellular levels.     

Novel Cesium‐Selective Electrodes Based on Lipophilic 1,3‐Bisbridged Cofacial‐calix[6]crowns

Five bisbridged calix[6]crowns have been investigated as Cs⁺ ionophore in PVC membrane electrodes. As ionophores, three 1,3‐bisbridged calix[6]crown‐4‐ethers( I–III ), 1,3‐bisbridged calix[6]crown‐5‐ether( IV ), and 1,3‐bisbridged calix[6]crown‐6‐ether( V ) have been evaluated. The membranes all give good Nernstian response in the concentration range from 1×10^?7 to 1×10^?1 M of cesium ion. The best detection limits (?log aequation/tex2gif-inf-1.gif=7.08–7.36) are obtained for electrode membranes containing 1,3‐bisbridged cofacial‐calix[6]crown‐4‐ethers( I‐III ), and the values are the lowest compared with those reported previously. The highest selectivity coefficients [ 3.74(Cs/K), 2.63(Cs/Rb)] are obtained for the membrane of 1,3‐bisbridged calix[6]crown‐4‐ether( II ), and these values are also the highest compared with previous reports for Cs⁺‐ISEs. The highest selectivity towards cesium ion is attributed to the geometrically cofacial positions of two crown‐ethers in calix[6]crowns in order to provide the complex of cesium ion and eight oxygens of cofacial crowns.     

An Isomer Specific,Highly Selective Fluorescent Chemosensor for K+ from a Bis‐Naphtho‐15‐Crown‐5 Derivative

Three isomeric series of bis(crown ether)s have been synthesized by condensation of the appropriate formylnaphthocrown with 1,4‐phenylenediacetonitrile. The interaction of these ligands with K⁺ and Na⁺ has been investigated by UV and fluorescence spectroscopic techniques. Among them the bis(crown ether) 2a exhibits excellent K⁺‐selectivity over Na⁺ and a dramatic increase in the fluorescence intensity of chromophores.     

Study of solvent effects on the stability constant and ionic mobility of the dibenzo‐18‐crown‐6 complex with potassium ion by affinity capillary electrophoresis

The effect of solvent on the strength of noncovalent interactions and ionic mobility of the dibenzo‐18‐crown‐6 complex with K⁺ in water/organic solvents was investigated by using affinity capillary electrophoresis. The proportion of organic solvent (methanol, ethanol, propan‐2‐ol, and acetonitrile) in the mixtures ranged from 0 to 100 vol.%. The stability constant, K_KL, and actual ionic mobility of the dibenzo‐18‐crown‐6‐K⁺ complex were determined by the nonlinear regression analysis of the dependence of the effective electrophoretic mobility of dibenzo‐18‐crown‐6 on the concentration of K⁺ (added as KCl) in the background electrolyte (25 mM lithium acetate, pH 5.5, in the above mixed hydro–organic solvents). Competitive interaction of the dibenzo‐18‐crown‐6 with Li⁺ was observed and quantified in mixtures containing more than 60 vol.% of the organic solvent. However, the stability constant of the dibenzo‐18‐crown‐6‐Li⁺ complex was in all cases lower than 0.5 % of K_KL. The log K_KL increased approximately linearly in the range 1.62–4.98 with the increasing molar fraction of organic solvent in the above mixed solvents and with similar slopes for all four organic solvents used in this study. The ionic mobilities of the dibenzo‐18‐crown‐6‐K⁺ complex were in the range (6.1–43.4) × 10^?9 m² V^?1 s^?1.     

Alkaliisocyanacetate. Synthese und Struktur von [K(18‐Krone‐6)](O2CCH2NC)

Alkali‐isocyanoacetates. Synthesis and Structure of [K(18‐crown‐6)](O₂CCH₂NC) The alkali isocyanoacetates M⁺[O₂CCH₂NC]^? (M = Li,Na,K,Cs) ( 1a ‐ d ) are synthesized by reaction of ethyl isocyanoacetate with the respective alkali hydroxides in ethanol and characterized by IR, NMR (¹H, ¹³C), and mass spectrometry (FAB). In alcoholic solution as well as in the gas phase ion pairs and higher aggregated species are observed. In contrast, [K(18‐crown‐6)][O₂CCH₂NC] ( 2 ) which is obtained from 1c and 18‐crown‐6, turns out to be a 1:1 electrolyte in solution (acetone); in the solid, the isocyanoacetate anion binds to K⁺ via the two carboxylate oxygen atoms resulting in an O₈‐coordinated metal atom.     

A Bis‐Oxime Derivative of Diaza‐18‐Crown‐6 as an Ionophore for Silver Ion

A new pendant‐arm derivative of diaza‐18‐crown‐6, containing two oxime donor groups, has been synthesized and incorporated into a polyvinyl chloride (PVC) membrane ion‐selective electrode. The electrode shows selectivity for Ag⁺ ion, with a near Nernstian response. Pb²⁺, Cu²⁺, Hg²⁺, and Tl⁺ are major interfering ions, with Cd²⁺ having minor interference. The electrode shows no potentiometric response for the ions Mg²⁺, Al³⁺, K⁺, Ca²⁺, Ni²⁺, Fe³⁺, and La³⁺, and is responsive to H⁺ at pH<6.     

Synthesis and Optical Properties of 2,13‐Dibenzothiazol‐2′‐yldibenzo[b,k]‐18‐crown‐6

A new crown ether of 2,13‐dibenzothiazol‐2′‐yldibenzo[b,k]‐18‐crown‐6 was synthesized from 2,13‐diformyl‐ dibenzo[b,k]‐18‐crown‐6 with 2‐aminothiophenol. The binding behavior and the optical properties of the crown ether were examined through UV‐visible spectroscopy and fluorescence spectroscopy. When complexed with Na⁺, K⁺, Rb⁺ and Cs⁺ ions, it led to intramolecular charge transfer and caused the changes of the fluorescence spectra. The protonation of the crown ether was also studied.     

Nuclear Magnetic Resonance Study of the Stoichiometry and Stability of Several Li+‐Crown Ether Complexes in Various Acetonitrile‐Nitrobenzene Mixtures

Lithium‐7 NMR spectrometry was used to study the complexation reaction between lithium ions and several 12‐, 15‐ and 18‐membered crown ethers in a number of binary acetonitrile‐nitrobenzene mixtures. Formation constants of the resulting 1:1 complexes in different solvent mixtures were determined by computer fitting of the chemical shift‐mole ratio data. There is an inverse relationship between the complex stability and the amount of acetonitrile in the mixed solvent. Among different sized crown ethers used, 15‐crowns were found to form the most stable Li⁺ complexes in the series. The influence of substitution on the macrocyclic rings on the stability of the resulting complexes is discussed.     

Ag+ selection by aza‐18‐crown‐6 ethers N‐Substituted on heterocyclic aromatics

Substitution on the nitrogen atom, where necessary by high‐pressure S_NAr reactions, of aza‐18‐crown‐6 ethers linked to heterocyclic aromatics has extended the number of potential host compounds for Ag⁺. The complexation of Ag⁺ by the new compounds has been evaluated by liquid membrane ion transport and ion extraction experiments. The nature of the binding sites of these new host compounds for Ag⁺ has been assessed, in DMF/D₂O (4/1), by ¹³C nmr titration experiments with AgClO₄.     

DFT study of the carbon‐ and nitrogen‐pivot lariat crown ethers and their complexes with alkali metal cations: Na+, K+

In this work, a quantum mechanical research of five lariat crown ethers(LCEs), 2‐methoxy‐15‐crown‐5( A ), N‐methoxy‐4‐aza‐15‐crown‐5( B ), N‐methoxy‐4‐aza‐18‐crown‐6( C ), N‐methoxyethyl‐4‐aza‐18‐crown‐6( D ), N,N′‐bis(2‐metho xyethyl)‐4,13‐diaza‐18‐crown‐6( E ), which are based on either 15‐crown‐5 or 18‐crown‐6 frameworks and contain various pendant arms extending from either carbon or nitrogen atoms on the crown frameworks, had been done using density functional theory with B3LYP/6‐31G* method to obtain the electronic and geometrical structures of the LCEs and their complexes with alkali metal ions: Na⁺ and K⁺. The nucleophilicity of LCEs had been investigated by the Fukui functions. For complexes, the match between the cation and cavity size, the status of interaction between alkali metal ions and donor atoms in the LCEs, and the sidearm effect of the LCEs had been analyzed through the other calculated parameters, such as, highest occupied molecular orbital energy, lowest unoccupied molecular orbital energy, and energy gaps. In addition, the enthalpies of complexation reaction had been studied by the calculated thermodynamic data (298 K). The calculated results are all in a good agreement with the experimental data for the complexes. © 2009 Wiley Periodicals, Inc. J Comput Chem 2009     

Aqueous Self‐Assembly and Cation Selectivity of Cobaltabisdicarbollide Dianionic Dumbbells

The anion [3,3′‐Co(C₂B₉H₁₁)₂]^? ([COSAN]^?) produces aggregates in water. These aggregates are interpreted to be the result of C?H???H?B interactions. It is possible to generate aggregates even after the incorporation of additional functional groups into the [COSAN]^? units. The approach is to join two [COSAN]^? anions by a linker that can adapt itself to act as a crown ether. The linker has been chosen to have six oxygen atoms, which is the ideal number for K⁺ selectivity in crown ethers. The linker binds the alkaline metal ions with different affinities; thus showing a distinct degree of selectivity. The highest affinity is shown towards K⁺ from a mixture containing Li⁺, Na⁺, K⁺, Rb⁺ and Cs⁺; this can be indicative of pseudo‐crown ether performance of the dumbbell. One interesting possibility is that the [COSAN]^? anions at the two ends of the linker can act as a hook‐and‐loop fastener to close the ring. This facet is intriguing and deserves further consideration for possible applications. The distinct affinity towards alkaline metal ions is corroborated by solubility studies and isothermal calorimetry thermograms. Furthermore, cryoTEM micrographs, along with light scattering results, reveal the existence of small self‐assemblies and compact nanostructures ranging from spheres to single‐/multi‐layer vesicles in aqueous solutions. The studies reported herein show that these dumbbells can have different appearances, either as molecules or aggregates, in water or lipophilic phases; this offers a distinct model as drug carriers.     

DFT Study for a Series of Less-Symmetrical Crown Ethers and Their Complexes with Alkali Metal Cations

A series of ring‐contracted (14‐crown‐5, 17‐crown‐6) and ring‐enlarged (16‐crown‐5, 17‐crown‐5, 19‐crown‐6, 20‐crown‐6) crown ethers and their complexes with alkali‐metal cations Na⁺ and K⁺ had been explored using density functional theory (DFT) at B3LYP/6‐31G* level in order to reveal the effects of the methylene‐chain length in a crown ether. The nucleophilicity of all crown ethers had been investigated by the Fukui functions. The quantum chemistry parameters, such as the energy gap (ΔE), the highest occupied molecular orbital energy (E_HOMO) and the lowest unoccupied molecular orbital energy (E_LUMO) for less‐symmetrical crown ethers and symmetrical frameworks (15‐crown‐5, 18‐crown‐6) had been calculated. In addition, the thermodynamic energies of complexation reactions had also been studied. The results of the DFT calculations show that the methylene‐chain length plays an important role in determining the structure characters of the crown ethers and also strongly influences the properties of the ethers. Some of the calculated results are in a good agreement with the experimental values.     

Synthesis,alkali metal picrate extraction,and alkali metal cation binding selectivities of some new cage‐annulated polyoxamacrocyclic crown ethers

Five new cage‐annulated crown ethers, i.e., 4a, 4b, 6b, 11a, and 11b, have been synthesized and their respective alkali metal picrate extraction profiles along with that of a previously synthesized host molecule, 6a, have been obtained. These results are compared with the corresponding results obtained for electrospray ionization mass spectrometric (ESI‐MS) measurements of relative binding selectivities displayed by the same hosts toward a series of alkali metal chlorides. Among the crown‐5 hosts studied, 6a displays enhanced avidity toward complexation with K⁺ picrate in liquid‐liquid extraction experiments. Among the three crown‐6 hosts, 4b proved to be the best alkali metal picrate extractant and displayed significant levels of avidity toward complexation with the larger alkali metal cations (i.e., K⁺, Rb⁺, and Cs⁺). The trends in the picrate extraction and the ESI‐MS results obtained herein show several notable similarities and some differences. The similarities generally stem from size‐selective binding properties that are intrinsic to the different cavity sizes of the cage‐annulated macrocycles, whereas the differences reflect the important influence of solvation effects on the binding properties of the macrocycles.     

A Highly K+‐Selective Fluorescent Probe – Tuning the K+‐Complex Stability and the K+/Na+ Selectivity by Varying the Lariat‐Alkoxy Unit of a Phenylaza[18]crown‐6 Ionophore

A desirable goal is to synthesize easily accessible and highly K⁺/Na⁺‐selective fluoroionophores to monitor physiological K⁺ levels in vitro and in vivo. Therefore, highly K⁺/Na⁺‐selective ionophores have to be developed. Herein, we obtained in a sequence of only four synthetic steps a set of K⁺‐responsive fluorescent probes 4 , 5 and 6 . In a systematic study, we investigated the influence of the alkoxy substitution in ortho position of the aniline moiety in π‐conjugated aniline‐1,2,3‐triazole‐coumarin‐fluoroionophores 4 , 5 and 6 [R=MeO ( 4 ), EtO ( 5 ) and iPrO ( 6 )] towards the K⁺‐complex stability and K⁺/Na⁺ selectivity. The highest K⁺‐complex stability showed fluoroionophore 4 with a dissociation constant K_d of 19 mm , but the K_d value increases to 31 mm in combined K⁺/Na⁺ solutions, indicating a poor K⁺/Na⁺ selectivity. By contrast, 6 showed even in the presence of competitive Na⁺ ions equal K_d values (K_d^K+=45 mm and K_d^K+/Na+=45 mm ) and equal K⁺‐induced fluorescence enhancement factors (FEFs=2.3). Thus, the fluorescent probe 6 showed an outstanding K⁺/Na⁺ selectivity and is a suitable fluorescent tool to measure physiological K⁺ levels in the range of 10–80 mm in vitro. Further, the isopropoxy‐substituted N‐phenylaza[18]crown‐6 ionophore in 6 is a highly K⁺‐selective building block with a feasible synthetic route.     

ACE applied to the quantitative characterization of benzo‐18‐crown‐6‐ether binding with alkali metal ions in a methanol–water solvent system

ACE was applied to the quantitative evaluation of noncovalent binding interactions between benzo‐18‐crown‐6‐ether (B18C6) and several alkali metal ions, Li⁺, Na⁺, K⁺, Rb⁺ and Cs⁺, in a mixed binary solvent system, methanol–water (50/50 v/v). The apparent binding (stability) constants (K_b) of B18C6–alkali metal ion complexes in the hydro‐organic medium above were determined from the dependence of the effective electrophoretic mobility of B18C6 on the concentration of alkali metal ions in the BGE using a nonlinear regression analysis. Before regression analysis, the mobilities measured by ACE at ambient temperature and variable ionic strength of the BGE were corrected by a new procedure to the reference temperature, 25°C, and the constant ionic strength, 10 mM . In the 50% v/v methanol–water solvent system, like in pure methanol, B18C6 formed the strongest complex with potassium ion (log K_b=2.89±0.17), the weakest complex with cesium ion (log K_b=2.04±0.20), and no complexation was observed between B18C6 and the lithium ion. In the mixed methanol–water solvent system, the binding constants of the complexes above were found to be about two orders lower than in methanol and about one order higher than in water.     

Nonmonotonic Transient Potential Signals with an 18‐Crown‐6 based Ion‐Selective Electrode in a Flow‐Injection System

The dynamic potential response of an 18‐crown‐6 based ion‐selective electrode towards Li⁺, Na⁺, K⁺ and Ca²⁺, in a flow‐injection system is studied. Different double nonmonotonic transient signals are obtained for the different ions. The influence of the flow‐injection variables and of ion concentration on the signals is studied. Two signal parameters, the relative return rates, are found to be characteristic for each ion and are constant for a concentration range of 1–3 decades. The nonmomotonic transient signals obtained are explained by reference to the theoretical models reported.     

Ion-pair extraction of tetravalent plutonium from hydrochloric acid medium using crown ethers

Ion-pair extraction behaviour of plutonium (IV) from varying concentrations of HCl solution was studied employing crown ethers (benzo-l5-crown-5 (B15C5), 18-crown-6, (18C6), dibenzo-18-crown-6 (DB18C6), dicyclohexano-18-crown-6, (DC18C6), dibenzo-24-crown-8 (DB24C8) and dicyclohexano-24-crown-8 (DCH24C8)) in nitrobenzene as the extractant. Ammonium metavanidate was used as the holding oxidant in the aqueous phase and the conditions necessary for the quantitative extraction of the tetravalent ion were found. The co-extraction of species of the type [HL⁺].[HPu(Cl) ₆ ^– ] and [HL⁺]2·[Pu(Cl) ₆ ^2– ] as ion-pairs (where L represents the crown ether) is suggested.