Macrocyclic Ionophores Research Articles

Anion-Selective Electrodes Based On a CH-Hydrogen Bonding Bis-macrocyclic Ionophore with a Clamshell Architecture.

CH-hydrogen bonding provides access to new building blocks for making macrocyclic ionophores with high degrees of preorganization and selective anion recognition. In this study, an anion-binding ionophore in the shape of a clamshell (ClS) was employed that is composed of two cyanostar (CNstar) macrocycles with preorganized cavities linked with a 12-carbon chain. This ionophore allows for anion complexation by CH-hydrogen bonding. The potentiometric performance of membrane-based ion-selective electrodes incorporating this ionophore was evaluated. Different membrane compositions were prepared to determine the optimum concentrations of the ionophore and lipophilic additive in the membrane. The optimized electrode had a slope of -58.2 mV/decade and demonstrated an anti-Hofmeister selectivity pattern toward iodide with a nanomolar detection limit. Electrospray ionization mass spectrometry was employed to study the relative association strengths of ClS with various anions. The observed mass peaks of the ion-ionophore complexes were found to be consistent with the potentiometric selectivity pattern of the corresponding electrodes. Overall, the selectivity of the electrode could be altered by using an ionophore in which the two CNstar macrocycles are linked together with a flexible 12-carbon chain to control the molecularity of the binding event.

Streptomyces sp. M54: an actinobacteria associated with a neotropical social wasp with high potential for antibiotic production.

Streptomyces symbionts in insects have shown to be a valuable source of new antibiotics. Here, we report the genome sequence and the potential for antibiotic production of "Streptomyces sp. M54", an Actinobacteria associated with the eusocial wasp, Polybia plebeja. The Streptomyces sp. M54 genome is composed of a chromosome (7.96Mb), and a plasmid (1.91Kb) and harbors 30 biosynthetic gene clusters for secondary metabolites, of which only one third has been previously characterized. Growth inhibition bioassays show that this bacterium produces antimicrobial compounds that are active against Hirsutella citriformis, a natural fungal enemy of its host, and the human pathogens Staphylococcus aureus and Candida albicans. Analyses through TLC-bioautography, LC-MS/MS and NMR allowed the identification of five macrocyclic ionophore antibiotics, with previously reported antibacterial, antitumor and antiviral properties. Phylogenetic analyses placed Streptomyces sp. M54 in a clade of other host-associated strains taxonomically related to Streptomyces griseus. Pangenomic and ANI analyses confirm the identity of one of its closest relatives as Streptomyces sp. LaPpAH-199, a strain isolated from an ant-plant symbiosis in Africa. In summary, our results suggest an insect-microbe association in distant geographic areas and showcase the potential of Streptomyces sp. M54 and related strains for the discovery of novel antibiotics.

Rethinking Ion Transport by Ionophores: Experimental and Computational Investigation of Single Water Hydration in Valinomycin-K+ Complexes.

Valinomycin is a macrocyclic ionophore that transports K+ across hydrophobic membranes. Its function depends on selectivity, capture, transport, and release of the ion. While thermodynamics clearly indicate that valinomycin binds K+ preferentially over all other alkali ions, characterizing the capture/transport/release of K+ by valinomycin at the molecular level remains a challenge. The bracelet-like structure of valinomycin-K+ (K+VM) has the ion completely enveloped, facilitating transport through the cell membrane. We report that hydration by a single water molecule, (K+VM)(H2O), produces three different conformers, identified by infrared spectroscopy and supporting computational studies. For two minor conformers, the water prevents the ionophore from closing, a conformation that would inhibit diffusion through the membrane. However, the dominant conformer encloses both the ion and the water, replicating the bracelet-like K+VM and arguably enhancing diffusion through the membrane. This potential for active participation of water in transport through the hydrophobic cellular membrane has never been previously considered.

Potentiometric Carboxylate Sensors Based on Carbazole-Derived Acyclic and Macrocyclic Ionophores

Solid-contact ion-selective electrodes with carbazole-derived ionophores were prepared. They were characterized as acetate sensors, but can be used to determine a number of carboxylates. The potentiometric response characteristics (slope, detection limit, selectivity, and pH sensitivity) of sensors prepared with different membrane compositions (ionophore, ionophore concentration, anion exchanger concentration, and plasticizer) were evaluated. The results show that for the macrocyclic ionophores, a larger cavity provided better selectivity. The sensors exhibited modest selectivity for acetate but good selectivity for benzoate. The carbazole-derived ionophores effectively decreased the interference from lipophilic anions, such as bromide, nitrate, iodide, and thiocyanate. The selectivity, detection limit, and linear range were improved by choosing a suitable plasticizer and by reducing the ionophore and anion exchanger concentrations. The influence of the electrode body’s material upon the composition of the plasticized poly(vinyl chloride) membrane, and thus also upon the sensor characteristics, was also studied. The choice of materials for the electrode body significantly affected the characteristics of the sensors.

An Ionophore for High Lithium Loading and Selective Capture from Brine.

The continuous demand and uneven dispersal of natural mineral resources of lithium with a low recycling rate of lithium commodities have forced researchers to look for alternative resources like geothermal brine, brackish brines, and sea brines. But selective lithium-ion extraction and even lithium-ion binding from these aqueous systems is a recognized challenge due to very high hydration energy and the coexistence of other like metal ions but appealing due to economic benefits. Therefore, the designed synthesis of synthetic ionophores with high lithium selectivity is crucial as they can work on dilute conditions without removal of interfering metal ions. However, most of the lithium selective ionophores known in the literature are mononucleated, and no emphasis is given on designing multinucleating ionophore systems to improve the lithium loading capacity which will open up unexplored paths toward the development of a more sustainable and economical extraction process. Herein, we describe a rare fluorogenic macrocyclic ionophore with two binding pockets for selective lithium recognition and extraction among various major alkali and alkaline earth metal ions of oceanic presence through both solid-state and solution studies. Under solid-liquid extraction conditions, this receptor shows a high lithium loading capacity of 135% with LiClO4 and 69.16% with LiCl salt with exclusive selectivity. Under liquid-liquid extraction conditions, this ionophore shows a loading capacity of 27% with 1 M LiCl and 48.57% with 1 M LiClO4 source phase concentration. This new ionophore, therefore, inspiring further to modify and develop a better multinucleating extractant with high lithium loading capacity which is rare in the literature.

Enhanced cation recognition by a macrocyclic ionophore at the air-solution interface probed by mass spectrometry.

Interfacial environments have the potential to drive unexpected events of supramolecular recognition, leading to advances in the development of novel functional materials and molecular sensing techniques. We present experimental evidence for a noticeable enhancement of the cation binding specificity of a prototype calixarene macrocycle (cesium ionophore II) at the air-solution interface, in comparison to bulk solution and to isolated solvent-less conditions. A rationalization of this intriguing finding is outlined, with the support of quantum calculations, in terms of the 'half-solvation' conditions provided by the interface and of conformational effects posed by the backbone structure and the side chains of the macrocyclic ionophore. The investigation involves the introduction of a mass spectrometry method to determine the relative abundances of interfacial complexes that should be of general application in the field and guide future advances in analytical techniques based on molecular recognition.

Conductometric measurements of complexation study between 4-Isopropylcalix[4]arene and Cr3+ cation in THF–DMSO binary solvents

In the present work, the conductometric measurements for complexation process between Cr3+ cation and the macrocyclic ionophore, 4-Isopropylcalix[4]arene (IPC4) were studied in tetrahydrofuran–dimethylsulfoxide (THF–DMSO) binary non-aqueous medium at different temperatures. The results reveal that the stoichiometry of the IPC4–Cr3+ complex in all binary mixed solvents is 1:1. A non-linear behavior was observed for changes of logKf of this complex versus the composition of the binary mixed solvents, which was explained on the basis of changes occurring in the structure of the mixed solvents and also the preferential solvation of the cation, ionophore and the resulting complex in the solution. The thermodynamic parameters (ΔH°c and ΔS°c) for the formation of IPC4–Cr3+ complexes were obtained from the temperature dependence of the stability constant using the van’t Hoff plots. The results obtained in this study, show that the formed complex is enthalpy destabilized, but entropy stabilized and the values of the mentioned parameters are affected strongly by the nature and composition of the binary mixed solvents. The experimental data was tested by using artificial neural network (ANN) program and was in a good agreement with the estimated data.

Fabrication of novel coated pyrolytic graphite electrodes for the selective nano-level monitoring of Cd2+ ions in biological and environmental samples using polymeric membrane of newly synthesized macrocycle

Novel 5-amino-1,3,4-thiadiazole-2-thiol unit based macrocyclic ionophore 5,11,17-trithia-1,3,7,9,13,15,19,20,21-nonaazatetracyclo[14.2.1.14,7.110,13]henicosa-4(20),10(21),16(19)-triene-6,12,18-trithione (M1), was synthesized and characterized. Preliminary studies on M1 have showed that it has more the affinity toward Cd2+ ion. Thus, the macrocyclic ionophore (M1) was used as electroactive material in the fabrication of PVC-membrane electrodes such as polymeric membrane electrode (PME), coated graphite electrode (CGE) and coated pyrolytic graphite electrode (CPGE) were prepared and its performance characteristic were compared with. The electroanalytical studies performed on PME, CGE and CPGE revealed that CPGE having membrane composition M1:PVC:1-CN:NaTPB in the ratio of 7:37:54:2 exhibits the best potentiometric characteristics in terms of detection limit of 7.58×10−9molL−1, Nernstian slope of 29.6mVdecade−1 of activity. The sensor was found to be independent of pH in the range 2.5–8.5. The sensor showed a fast response time of 10s and could be used over a period of 4 months without any significant divergence in its potentiometric characteristics. The sensor has been employed for monitoring of the Cd2+ ion in real samples and also used as an indicator electrode in the potentiometric titration of Cd2+ ion with EDTA.

Comparison of polysiloxane films substituted by undecenyl-cyclam and by naphthyl-cyclam for the design of ISFET devices sensitive to Fe3+ ions

The synthesis and properties of new silicone-based functional materials having attached cyclam macrocycles have been assessed with regard to their application as ion-sensitive membranes of chemical sensors. The preparation process of thin films of the sensitive materials has been designed so that each chemical compound is attached by means of chemical bonds: the macrocyclic ionophore was chemically bound to the silicone polymer and the polymer material was attached to the sensitive surface of the electrochemical devices by means of chemical grafting. The properties of such materials have been evaluated for detection of iron(III) species in water using ion-sensitive field-effect transistor (ISFET) and electrolyte–insulator–semiconductor (EIS) structures, both sensitized by a coating with the functional polymer materials. Two types of cyclam derivatives and two types of synthesis processes have been compared with that respect. The first material, “PDMS-Cyclam”, was prepared by grafting N-10-undecenyl-cyclam to poly(methylhydrosiloxane) (PMHS). The cyclam ionophore of the second material, “PDMS-Naphthyl-Cyclam”, bore a naphthyl pendent group that enhanced the complexing properties for Fe3+ ions. Linear response with respect to the pFe(III)=−Log[Fe3+] was observed over three decades (EIS) or two decades (ISFET) of concentration. A Nernstian response toward Fe3+ ions was observed for the “PDMS-Naphthyl-Cyclam” membrane. These devices exhibit good chemical stability and a long lifetime in aqueous medium.

Synthesis, spectral assignment and application of a recently synthesized macrocyclic ionophore to simultaneous pre-concentration and determination of ultra traces of copper and lead by solid phase extraction-flame atomic absorption spectrometry

Ethyl(2-ethylamino)thiophenol-2,6-pyridinedicarboxylate (ETPD) was synthesized from the reaction of disodium pyridine-2,6-dicarboxylate with 1,2-dibromoethane in methanol, followed by treatment with 2-aminothiophenol. The spectral characterization of ETPD is described in detail. This electron-donating agent was successfully utilized for simultaneous enrichment of ultra trace levels of copper and lead in a wide variety of samples. By passing the aqueous solutions through octadecylsilyl bonded phase membrane disks impregnated with 12 mg of ETPD at flow rates of 45 mL min(-1), Cu and Pb were selectively trapped on the disk surface over the pH range 3.0 to 7.0, whereas most other ions were negligibly retained. Numerous chemical parameters affecting sorption and subsequent elution were also investigated. The target ions were stripped from the disk surfaces by reverse flow, at rates of 12 mL min(-1), and were immediately introduced to the nebulizer of an atomic absorption spectrometer. This inexpensive and off-line method offers enrichment factors of 400 and 300 and detection limits of 2.5 and 0.2 μg L(-1) for copper and lead, respectively. The potential applicability of the method was confirmed by its reliable use in quantification of these elements in some real water samples, industrial effluents, three tea samples and peppers, as well as by comparison with graphite furnace atomic absorption spectrometric determinations.

Thermodynamic study of the complexation of p-isopropylcalix[6]arene with Cs+ cation in dimethylsulfoxide-acetonitrile binary media.

The complexation reactions between the macrocyclic ionophore, p-isopropylcalix[6]arene and Cs+ cation were studied in dimethylsulfoxide–acetonitrile (DMSO-AN) binary non-aqueous solvents at different temperatures using a conductometry method. The conductance data show that the stoichiometry of the (p-isopropylcalix[6]-arene·Cs)+ complex in all binary mixed solvents is 1:1. The stability of the complexes is affected by the composition of the binary solvent media and a non-linear behavior was observed for changes of log Kf of the complex versus the composition of the binary mixed solvents. The thermodynamic parameters (ΔH°c and ΔS°c) for formation of (p-isopropyl-calix[6]arene·Cs)+ complex were obtained from temperature dependence of the stability constant and the obtained results show that the (p-isopropylcalix[6]arene·Cs)+ complex is enthalpy destabilized, but entropy stabilized, and the values of the mentioned parameters are affected strongly by the nature and composition of the binary mixed solvents.

On the Radiation Stability of Crown Ethers in Ionic Liquids

Crown ethers (CEs) are macrocyclic ionophores used for the separation of strontium-90 from acidic nuclear waste streams. Room temperature ionic liquids (ILs) are presently being considered as replacements for traditional molecular solvents employed in such separations. It is desirable that the extraction efficacy obtained with such solvents should not deteriorate in the strong radiation fields generated by decaying radionuclides. This deterioration will depend on the extent of radiation damage to both the IL solvent and the CE solute. While radiation damage to ILs has been extensively studied, the issue of the radiation stability of crown ethers, particularly in an IL matrix, has not been adequately addressed. With this in mind, we have employed electron paramagnetic resonance (EPR) spectroscopy to study the formation of CE-related radicals in the radiolysis of selected CEs in ILs incorporating aromatic (imidazolium and pyridinium) cations. The crown ethers have been found to yield primarily hydrogen loss radicals, H atoms, and the formyl radical. In the low-dose regime, the relative yield of these radicals increases linearly with the mole fraction of the solute, suggesting negligible transfer of the excitation energy from the solvent to the solute; that is, the solvent has a "radioprotective" effect. The damage to the CE in the loading region of practical interest is relatively low. Under such conditions, the main chemical pathway leading to decreased extraction performance is protonation of the macrocycle. At high radiation doses, sufficient to increase the acidity of the IL solvent significantly, such proton complexes compete with the solvent cations as electron traps. In this regime, the CEs will rapidly degrade as the result of H abstraction from the CE ring by the released H atoms. Thus, the radiation dose to which a CE/IL system is exposed must be maintained at a level sufficiently low to avoid this regime.

ChemInform Abstract: Conversion of Dipeptides and a Tetrapeptide to Macrocyclic Ionophores by Means of Cesium-Aided Ring Closure of the N-2-Chloroacetyl Derivatives.

ChemInform Abstract: Conversion of Dipeptides and a Tetrapeptide to Macrocyclic Ionophores by Means of Cesium-Aided Ring Closure of the N-2-Chloroacetyl Derivatives.

An all-solid-state monohydrogen phosphate sensor based on a macrocyclic ionophore

An all-solid-state electrode, containing a synthesized chiral A 2B 2 macrocyclic compound namely (4R,5R,15R,16R)-4,5,15,16-tetraphenyl-3,6,14,17-tetraazatricyclo [13.3.1.18,12] tetracosa-1(23),8,10,12(24)19,21-hexaene-2,7,13,18-tetrone as an ionophore in polyvinyl chloride (PVC)/polyurethane (PU) membrane matrix, has been developed for the selective quantification of monohydrogen phosphate ions. The best performing membrane contained PVC, PU, ionophore, and nitrophenyl octyl ether as a plasticizer in the ratio 32.2:2.6:65.1 (w/w, %). It exhibited a near-Nernstian slope of 31.0 ± 1.0 mV/decade of activity for HPO 4 2− ions in the concentration range of 1.0 × 10 −6 to 1.0 × 10 −2 M at pH 7.4. The detection limit of the electrode was 8.4 × 10 −7 M and the life time was six weeks. The electrode displayed excellent selectivity for monohydrogen phosphate over other anions and the selectivity sequence was determined as HPO 4 2− > SO 4 2− > Ac − > NO 3 − > ClO 4 − > Cl − > I −. The selective electrode for the monohydrogen phosphate ions was evaluated with a standard reference material (SRM 1548) and the titration of the sample solution.

Macrocyclic compound as ionophores in lead(II) ion-selective electrodes with excellent response characteristics

Macrocyclic compounds, such as crown ethers, azacrown ethers, thiacrown ethers, calixarenes and porphyrins, which act as ionophores in lead(II) ion-selective electrodes, are systematically summarized based on the latest literatures. The molecular structure characteristics of the ionophores are generalized. The modification regulations for the substituted ionophores are elaborated with the purpose of improving the response features of the lead(II) ion-selective electrodes assembled by them. It is pointed out that the introduction of pendant moieties which contain soft base coordination centers like N, S and P atoms is in favor of adjusting the cavity size and conformation of the macrocyclic compounds. Furthermore, there is synergic effect between the cavity and the donor sites of the ligand and thus the selective complexation of lead ions is easily realized, resulting in significant avoidance of the interference from other metal ions. The macrocyclic ionophore having the best response characteristics thus far was found to be N,N′-dimethylcyanodiaza-18-crown-6 with the detection limit of 7.0×10−8 (14.5 μg/L), which is one of the uncommon ionophores that can really eliminate the interference from silver and mercury ions. The selectivity coefficients of the ionophore for lead ions over other metal ions, such as alkali, alkaline earth and transition metal ions are in the order of 10−4 or smaller, where the selectivity coefficient of lead(II) over mercury(II) ions is much lower, down to 8.9×10−4. The structure design idea for high-performance ionophore is proposed according to present results. The incorporation of nitrogen atom, especially cyano group or thiocyano group or amino/imino groups, rather than thio atom alone could result in new excellent lead ionophores. The aborative design for metacyclophanes containing aromatic nitrogen atoms with the aim of creating excellent ionophores would also become a potential research trend. The lead(II) ion-selective electrodes have shown widely potential applications in the potentiometric titration, and flow injection potentiometry, and in the direct determination of lead in stack emissions of lead smelters, and assay of lead in rocks, particularly in the direct measurements of trace amount of lead(II) in human hair, blood, edible oil, food, water, and air.

A D2 symmetric tetraamide macrocycle based on 1,1′,4,4′-tetrahydro[3,3′(2 H,2′ H)-spirobiquinoline]-2,2′-dione: synthesis and selectivity for lithium over sodium and alkaline earth ions

Macrocyclic ionophores d, l- 3 and d, l- 4 with four amide carbonyl ligands were synthesized and investigated in lithium ion-selective electrodes. In solvent PVC membranes, ion selectivity of d, l- 3 and d, l- 4 for lithium relative to sodium was observed as log K Li , Na pot = − 1.4 and −1.23, respectively. Spiromacrocycle d, l- 3 and analogue dibenzospiromacrocycle d, l- 4 have similar ion selectivity patterns for alkali metal ions, but d, l- 4 could discriminate against alkaline earth metal ions better than d, l- 3. It is an example of an endopolarophilic/exolipophilic macrocyclic ionophore whose selectivity for monovalent cations over divalent cations is enhanced by thick lipophilic shells.

Evaluation of a supported liquid membrane containing a macrocyclic ionophore for selective removal of strontium from nuclear waste solution

Transport behaviour of Sr(II) across a PTFE flat sheet supported liquid membrane (SLM) containing 4,4′(5′)di- t-butyl-cyclohexano-18-crown-6 (DtBuCH18C6) in 1-octanol as the carrier was investigated. The membrane based separation method was developed for the selective transport of Sr 2+ from aqueous nitrate medium. Linear dependence of the permeability coefficient ( P) on the crown ether concentration suggested that the ligand does not aggregate in the concentration range investigated. The P values increased with HNO 3 concentration as well as with nitrate ion concentration. However, in the presence of 2 M Al(NO 3) 3 in the feed phase, any increase in the HNO 3 concentration showed a decrease in the Sr(II) transport rate. Appreciable acid co-transport was observed in all the experiments which was attributed to the ligand assisted transport of the hydronium ion. A decrease in the transport rate was observed with increase in the membrane pore size. The transport rate was low as only ∼70% migration of Sr 2+ was observed in 24 h. The mechanism of transport has been discussed. A synthetic nuclear waste solution spiked with 85,89Sr tracer containing 1 M nitric acid has also been tested. The selectivity of the crown ether containing membrane is demonstrated as none of the other metal ions present in the synthetic nuclear waste solution could permeate through the PTFE membrane filter.

A Calix[4]imidazolium[2]pyridine as an Anion Receptor

An effective macrocyclic ionophore for F− ions that contains an array of positively charged imidazolium units has been prepared. The calix[4]imidazolium[2]pyridine cation formed a complex with F− ions in a 1:1 stoichiometry, as shown by binding studies using 1H NMR spectroscopic analysis, X-ray crystallographic determination (see structure), and density functional calculations. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z500119_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

A highly selective thallium(I) electrode based on a thia substituted macrocyclic ionophore

A new highly Tl(I)-selective PVC membrane electrode based on tetrathia macrocycle 6,7: 14,15-dibenzo-5,8,13,16-tetraoxo-1,4,9,12-tetrathiacyclohexadecane [Bz 2O 4(16)aneS 4] (I) as membrane carrier, o-nitrophenyloctyl ether ( o-NPOE) as solvent mediator and potassium tetrakis( p-chlorophenyl)borate (KT pClPB) as lipophilic additive has been developed. The best performance was given by the membrane of macrocycle (I) with composition 3:120:1.5:50 (I: o-NPOE:KT pClPB:PVC). This electrode exhibits a Nernstian response to Tl(I) ions in the concentration range 1.0 × 10 −1–2.23 × 10 −6 M with a slope of 58.2 mV/decade of concentration and a detection limit of 1.58 × 10 −6 M. The response time of the sensor is 12 s and can be used over a period of 4 months with good reproducibility. The proposed electrode revealed good selectivity over a wide variety of other cations including alkali, alkaline earth, heavy and transition metals. The electrode works well over a pH range of 3.2–11.5 and in partially non-aqueous medium with up to 30% organic content. The sensor was also used as an indicator electrode in potentiometric titration of Tl(I) ions with KI solution.

Tetraazacyclohexadeca Macrocyclic Ligand as a Neutral Carrier in a Cr Ion-selective Electrode

A polystyrene-based membrane of 2,10-dimethyl-4,12-diphenyl-1,5,9,13-tetraazacyclohexadeca-1,4,9,12-tetraene macrocyclic ionophore was prepared and investigated as Cr(III)-selective electrode. The best performance was observed with the membrane having the polystyrene-ligand-dibutylphthalate-sodiumtetraphenyl borate composition 1:4:1:1 with a Nernstian slope of 19.0 mV per decade of concentration between pH 3.0 and 6.5. This electrode has been found to be chemically inert and of adequate stability with a response time of 20 s and was used over a period of 100 d with good reproducibility (S= 0.3 mV). The membrane works satisfactorily in a partially non-aqueous medium up to a maximum 30% (v/v) content of methanol and ethanol. The potentiometric selectivity coefficient values indicate that the membrane sensor is highly selective for Cr(III) ions over a number of monovalent, divalent and trivalent cations. The membrane electrode has also been successfully used to determine Cr3+ in various food materials.