Ionophore Structure Research Articles

Predicting the Potentiometric Sensitivity of Membrane Sensors Based on Modified Diphenylphosphoryl Acetamide Ionophores with QSPR Modeling.

While potentiometric, plasticized membrane sensors are known as convenient, portable and inexpensive analytical instruments, their development is time- and resource-consuming, with a poorly predictable outcome. In this study, we investigated the applicability of the QSPR (quantitative structure–property relationship) method for predicting the potentiometric sensitivity of plasticized polymeric membrane sensors, using the ionophore chemical structure as model input. The QSPR model was based on the literature data on sensitivity, from previously studied, structurally similar ionophores, and it has shown reasonably good metrics in relating ionophore structures to their sensitivities towards Cu2+, Cd2+ and Pb2+. The model predictions for four newly synthesized diphenylphosphoryl acetamide ionophores were compared with real potentiometric experimental data for these ionophores, and satisfactory agreement was observed, implying the validity of the proposed approach.

Investigating Structural Property Relationships to Enable Repurposing of Pharmaceuticals as Zinc Ionophores

The importance of zinc in biology has gained greater recognition in recent years due to its essential contributions to the function of many endogenous enzymes. Disruption of zinc homeostasis may be useful in treating pathological conditions, such as Alzheimer’s, and for antiviral purposes. Despite the growth of knowledge and increased interest in zinc, little is known about the structure and function of zinc ionophores. In this study we analyse the Cambridge Structural Database and solution complexation studies found in the literature to identify key functional groups which may confer zinc ionophorism. Pharmaceuticals, nutraceuticals and amino acids with these functionalities were selected to enable us to explore the translatability of ionophoric activity from in vitro assays to cellular systems. We find that although certain species may complex to zinc in the solid and solution states, and may carry ions across simple membrane systems, this does not necessarily translate into ionophoric activity. We propose that the CSD can help refine key functionalities but that ionophoric activity must be confirmed in cellular systems.

Antimicrobial agent triclosan is a proton ionophore uncoupler of mitochondria in living rat and human mast cells and in primary human keratinocytes

Triclosan (TCS) is an antimicrobial used widely in hospitals and personal care products, at ~10 mm. Human skin efficiently absorbs TCS. Mast cells are ubiquitous key players both in physiological processes and in disease, including asthma, cancer and autism. We previously showed that non-cytotoxic levels of TCS inhibit degranulation, the release of histamine and other mediators, from rat basophilic leukemia mast cells (RBL-2H3), and in this study, we replicate this finding in human mast cells (HMC-1.2). Our investigation into the molecular mechanisms underlying this effect led to the discovery that TCS disrupts adenosine triphosphate (ATP) production in RBL-2H3 cells in glucose-free, galactose-containing media (95% confidence interval EC50 = 7.5-9.7 µm), without causing cytotoxicity. Using these same glucose-free conditions, 15 µm TCS dampens RBL-2H3 degranulation by 40%. The same ATP disruption was found with human HMC-1.2 cells (EC50 4.2-13.7 µm), NIH-3 T3 mouse fibroblasts (EC50 4.8-7.4 µm) and primary human keratinocytes (EC50 3.0-4.1 µm) all with no cytotoxicity. TCS increases oxygen consumption rate in RBL-2H3 cells. Known mitochondrial uncouplers (e.g., carbonyl cyanide 3-chlorophenylhydrazone) previously were found to inhibit mast cell function. TCS-methyl, which has a methyl group in place of the TCS ionizable proton, affects neither degranulation nor ATP production at non-cytotoxic doses. Thus, the effects of TCS on mast cell function are due to its proton ionophore structure. In addition, 5 µm TCS inhibits thapsigargin-stimulated degranulation of RBL-2H3 cells: further evidence that TCS disrupts mast cell signaling. Our data indicate that TCS is a mitochondrial uncoupler, and TCS may affect numerous cell types and functions via this mechanism. Copyright © 2015 John Wiley & Sons, Ltd.

Selective transport of zinc and copper ions by synthetic ionophores using liquid membrane technology

This work highlights the role of synthetic carrier (ionophore) in the separation of heavy metal ions. A new series of ionophores; 4,4′-nitrophenyl-azo-O,O′-phenyl-3,6,9-trioxaundecane-1,10-dioate (R1), bis[4,4′nitro-phenylazo-naphthyl-(2,2-dioxydiethylether)] (R2) 1,8-bis-(2-naphthyloxy)-3,6-dioxaoctane (R3), 1,11-bis-(2-naphthyloxy)-3,6,9-trioxaunde-cane (R4), 1,5-bis-(2-naphthyloxy)-3-oxa-pentane (R5) have been synthesized and used as extractant as well as carrier for the transport of various metal ions (Na+, K+, Mg2+, Ni2+, Cu2+ and Zn2+) through liquid membranes. Effect of various parameters such as metal ion concentration, ionophore concentration, liquid–liquid extraction, back extraction, comparison of transport efficiency of BLM and SLM and different membrane support (hen’s egg shell and PTFE) have been studied. In BLM ionophores (R2–R5) transport Zn+ at greater extent and the observed trend for the transport of Zn2+ is R2 > R4 > R3 > R5 respectively. Further transport efficiency is increased in SLM. In egg shell membrane ionophores (R2–R5) transport Zn+ due to their non-cyclic structure and pseudo cavity formation while ionophore R1 transports Cu2+ ions at greater extent due to its cyclic structure and cavity size. Among the membrane support used egg shell membrane is found best for the transport of zinc ions because of its hydrophobic nature and exhibits electrostatic interactions between positively charged zinc ions and –COOH group of egg shell membrane. Thus structure of ionophores, hydrophobicity and porosity of the membrane support plays important role in separation of metal ions.

New polymeric membrane cadmium(II)-selective electrodes using tripodal amine based ionophores

Fabrication of PVC membrane electrodes incorporating selective neutral carriers for Cd 2+ was reported. The ionophores were designed to have different topologies, donor atoms and lipophilicity by attaching tripodal amine (TPA) units to the lipophilic anthracene (ionophore I) and p-tert-butylcalix[4]arene (ionophores II, III and IV). The synthesized ionophores were incorporated to the plasticized PVC membranes to prepare Cd(II) ion selective electrodes (ISEs). The membrane electrodes were optimized by changing types and amounts of ionic sites and plasticizers. The selectivity of the membranes fabricated from the synthesized ionophores was evaluated, the relationship between structures of ionophores and membrane characteristics were explored. The ionophore IV which composed of two opposites TPA units on the calix[4]arene compartment showed the best selectivity toward Cd 2+. The best membrane electrode was fabricated from ionophore IV (10.2 mmol kg −1) with KTpClPB (50.1 mol% related to the ionophore) as an ion exchanger incorporated in the DOS plasticized PVC membrane (1:2; PVC:DOS). The Cd-ISE fabricated from ionophore IV exhibited good properties with a Nernstian response of 29.4 ± 0.6 mV decade −1 of activity for Cd 2+ ions and a working concentration range of 1.6 × 10 −6–1.0 × 10 −2 M. The sensor has a fast response time of 10 s and can be used for at least 1 week without any divergence in potential. The electrode can be used in the pH range of 6.0–9.0. The proposed electrodes using ionophores III and IV were employed as a probe for determining Cd 2+ from the oxidation of CdS QDs solution and the real treatment waste water sample with excellent results.

2,2′-Dipyridyl-6,6′-dicarboxylic acid diamides: Synthesis, complexation and extraction properties

New ligands for complexing of the post-transition metals – diamides of 2,2′-bipyridyl-6,6′-dicarboxylic acid were developed, synthesised and characterised. They were proposed to be effective extractants towards americium. The structures of the amides were studied in solid as well as in solution. The extraction of Am and lanthanides depending on diamide structure, chlorinated cobalt dicarbollide (CCD) – diamide ratio, type of diluent was studied. The optimal conditions for Am/REE separation were determined. The properties of new potentiometric sensors on the base of 2,2′-dipyridyl-6,6′-dicarboxylic acid diamides were studied. The correlation structure vs. properties of ionophores (i.e. extractants), their sensitivity and selectivity in sensor analysis and extraction are discussed.

Isoguanine octamer: From bowl to ball

Isoguanine (2-oxo-6-amino-guanine, isoG) can form the higher-order self-pairing ionophore structures by regulating the concentration of metal ions. The metal ion coordinated isoG-tetrads adopt bowl-like shape with the metal ion located at the bottom of the bowl. The present study of the formation of the H-bonded octamers ((isoG 4–M +) 2; M + = Na +, K +) illustrates that the bowl-shaped isoG 4–M + complexes are able to form the extraordinary ball-shaped octamers (isoG 4–M +) 2 H-bonded through the H(N6) and N7 sites. A moderate energy barrier predicted for the process of separating the ball-shaped octamer into two bowl-shaped tetrads and the unique structural features of the octamer suggests a possibility towards construction of the self-assembled isoG nanostructures.

Use of Tin (IV) Porhyrins as Ionophores for the Construction of Phthalate‐Selective Electrodes: Influence of the Structure and Membrane Composition on their Response Properties

AbstractTin(IV) porphyrins derivatives were used as ionophores for phthalate selective electrodes preparation. The influence of ionophore structure and membrane composition (amount of incorporated ionic sites) on the electrode response, selectivity and long‐term stability were studied. Poly(vinyl chloride) polymeric membranes plasticized with o‐NPOE (o‐nitrophenyloctylether) and containing Sn(IV)‐tetraphenylporphyrin (TPP) dichloride (Sn(IV)[TPP]Cl2) or Sn(IV)‐octaethylporphyrin (OEP) dichloride (Sn(IV)[OEP]Cl2), and in some cases incorporating lipophilic cationic (tetraocthylammonium bromide ‐ TOABr) and anionic (sodium tetraphenylborate – NaTPB and potassium tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate‐KTFPB) additives, were prepared and their potentiometric characteristics compared. Both ionophores are shown to operate via a neutral mechanism, and the addition of 10 mol % of lipophilic quaternary ammonium salt derivative to the membrane is required to achieve optimal electrode performance. The potentiometric units prepared, with Sn(IV)[TPP]Cl2 (Type A) or Sn(IV)[OEP]Cl2 (Type B) without additives, presented a slope of −52.8 mV dec−1 and −58.8 mV dec−1 and LLLR of 9.9×10−5 mol L−1 and 9.9×10−6 mol L−1, respectively. The units prepared using the same metalloporphyrins and incorporating 10% mol TOABr presented a slope of −55.0 mV dec−1 and −57.8 mV dec−1 and LLLR of 5.0×10−7 mol L−1 and 3.0×10−7 mol L−1. Their analytical usefulness was assessed by potentiometric determinations of phthalate in water and industrial products providing results that presented recoveries of about 100%.

Gallium(III)‐Schiff Base Complexes as Novel Ionophores for Fluoride Selective Polymeric Membrane Electrodes

AbstractGallium(III)‐Schiff base complexes are examined as potential ionophores for the development of fluoride ion‐selective polymeric membrane electrodes. To probe the effect of ionophore structure, several different salen and salophen compounds have been synthesized and tested in plasticized poly(vinyl chloride) membranes (H21–5). A salophen ligand structure highly substituted with t‐butyl groups (H21) was found to be optimal with respect to membrane compatibility, and its corresponding Ga(III) complex yields membrane electrodes with greatly enhanced potentiometric selectivity for fluoride ion over a host of other anions. Addition of lipophilic anionic sites into the membrane phase provides optimized response and selectivity, indicating that the Ga1 ionophore functions as a charge carrier. The use of dioctylsebacate as the membrane plasticizer helps reduce any dimer‐monomer equilibria in the membrane phase, yielding sensors with rapid and fully reversible EMF response. Optimal potentiometric detection of fluoride is achieved in solutions buffered to relatively low pH values (pH 3.0), to reduce anionic response to hydroxide. The use of gallium(III)‐Schiff base complexes is shown to offer a promising research direction to ultimately achieve polymeric membrane fluoride sensors that exhibit potentiometric response equivalent to the classical lanthanum fluoride‐based solid state type membrane electrode.

Visible and FTIR Microscopic Observation of Bisthiourea Ionophore Aggregates in Ion-Selective Electrode Membranes

Since conventional response models for ionophore-based ISEs are based on the assumption of a homogeneous membrane phase, they cannot accurately predict the response of membranes containing self-aggregating ionophores. However, meaningful conclusions about the relationship between ionophore structure and potentiometric responses can only be drawn if ionophore aggregation is properly recognized. This study demonstrates that dark field visible microscopy and FTIR microspectroscopy are valuable tools for the observation of such ionophore self-aggregation and, thereby, the development of new ionophore-based ISEs. Sulfate selective electrodes with solvent polymeric membranes containing bisthiourea ionophores that differ only by peripheral nonpolar substituents were shown to exhibit very different interferences from the sample pH. On one hand, optimized electrodes based on an ionophore with a phenyl substituent on each thiourea group (1) do not respond to pH at all and function well as sulfate-selective electrodes. On the other hand, membranes containing a more lipophilic ionophore with two additional hexyl-substituted adamantyl groups (2) exhibit severe pH interference at pH values as low as pH 5. The observation of membranes containing ionophore 2 with dark field visible microscopy and FTIR microspectroscopy shows supramolecular aggregation, and explains the startling difference between the potentiometric responses of the two types of electrodes.

Synthesis and characterization of novel ionophores of double-armed penta-crown ethers

Unique structures of novel ionophores of double-armed penta-crown ethers were successfully synthesized. Diaza 18-crown-6 was designed as the parent crown ring. The penta-crown ethers were prepared by the reaction of trimethylolpropane triacrylate (TMPTA) with diaza 18-crown-6 and further with 1-aza crown ethers through the Michael reaction. The newly synthesized penta-crown ethers were characterized by 1H NMR, 13C NMR, FAB mass spectrum, IR and elemental analyses, respectively.

Ionophore-based ion-selective potentiometric and optical sensors.

This paper describes ion-selective electrodes (ISEs) and optodes with a focus on the fundamental mechanisms, response characteristics, and recognition elements (ionophores) described to date for these sensors. The topics covered review the most frequently encountered ideas about ionophore-based sensors, including the theoretical and experimental parameters that influence response, typical ionophore structures, useful membrane compositions, and applications. Since these sensors are applicable in a number of fields, such as clinical, environmental, and process monitoring, as well as more novel approaches such as microfluidic-based systems and micro/nanoprobes, this article provides descriptions that are oriented toward a more general audience. Furthermore, a large portion of this review describes the ionophore component itself in hopes of inspiring ideas in readers of how novel molecular architectures with new ionic targets or improved selectivity can be developed.

Potentiometric coefficients of ion-selective electrodes. Part III. Organic ions (IUPAC Technical Report)

Abstract Potentiometric selectivity coefficients, K A,B pot, have been collected for ionophore-based ion-selective electrodes (ISEs) for organic ions reported during 1988-1998. In addition to the actual numerical values of K A,B pot together with the methods and conditions for their determination, response slopes, linear ranges, chemical compositions, and ionophore structures for the ISE membranes are tabulated.

Potentiometric selectivity coefficients of ion-selective electrodes. Part II. Inorganic anions (IUPAC Technical Report)

Abstract Potentiometric selectivity coefficients, K A,B pot have been collected for ionophore-based ion-selective electrodes (ISEs) for inorganic anions reported during 1988-1998. In addition to the actual numerical values of K A,B pot together with the methods and conditions for their determination, response slopes, linear concentration (activity) ranges, chemical compositions, and ionophore structures for the ISE membranes are tabulated.

Durability of membranes containing uranyl salophenes

Potentiometric, spectroscopic and microscopic studies concerning polymer membranes based on uranyl salophenes were performed. Uranyl salophenes—group of Schiff base complexes—revealed very good recognition abilities toward some hydrophilic anions and appeared to be very promising ionophores for phosphate-selective electrodes. The influence of the ionophore structure and polymer matrix composition on the durability and selectivity of PVC based membrane of phosphate-selective electrodes was investigated. The interaction of uranyl salophenes with water and Cl −, NO 3 −, H 2PO 4 − anions was examined. When the membranes were conditioned in phosphate solution, the formation of a water–UO 2–salophene complex, insoluble in both water and organic phase, and next the decomposition of the ionophore occurred. These results gave the explanation of the mechanism of deterioration of phosphate-selective membranes.

Durability of phosphate-selective CHEMFETs

Lipophilic uranyl salophenes derivatives I and II were used as ionophores in membranes of phosphate-selective CHEMFETs. High selectivity for H 2PO 4 − over other anions was obtained for these sensors. The influence of the ionophore structure on the sensor durability was investigated. CHEMFETs based on derivative II exhibited better long-term stability due to the better solvation of this ionophore in the membrane phase. The microsensor durability can be improved decreasing the amount of the ammonium salt in the membrane to 5% mol, with only little decrease of initial selectivity.

Durable phosphate-selective electrodes based on uranyl salophenes

Lipophilic uranyl salophenes derivatives were used as ionophores in durable phosphate-selective electrodes. The influence of the ionophore structure and membrane composition (polarity of plasticizer, the amount of incorporated ionic sites) on the electrode selectivity and long-term stability were studied. The highest selectivity for H 2PO 4 − over other anions tested was obtained for lipophilic uranyl salophene III (with t-butyl substituents) in poly(vinylchloride)/ o-nitrophenyl octyl ether (PVC/ o-NPOE) membrane containing 20 mol% of tetradecylammonium bromide (TDAB). Moreover, phosphate-selective electrodes based on this derivative exhibited the best long-term stability (2 months). The electrode durability can be improved decreasing the amount of the ammonium salt in membrane to 5 mol%.

Uranyl salophenes as ionophores for phosphate-selective electrodes

Anion selectivities of poly(vinylchloride) (PVC) plasticized membranes containing uranyl salophene derivatives were presented. The influence of the membrane components (i.e. ionophore structure, dielectric constant and structure of plasticizer, the amount of incorporated ammonium salt) on its phosphate selectivity was investigated. The highest selectivity for H 2PO 4 − over other anions tested was obtained for lipophilic uranyl salophene III (without ortho-substituents) in PVC/ o-nitrophenyl octylether ( o-NPOE) membrane containing 20 mol% of tetradecylammonium bromide (TDAB). Ion-selective electrodes (ISEs) based on these membranes exhibited linear response in the range 1–4 of pH 2PO 4 − with a slope of 59 mV/decade. The introduction of ortho-methoxy substituents in ionophore structure decreased the phosphate selectivity of potentiometric sensors.

Selectivity of potentiometric ion sensors.

Selectivities of solvent polymeric membrane ion-selective electrodes (ISEs) are quantitatively related to equilibria at the interface between the sample and the electrode membrane. However, only correctly determined selectivity coefficients allow accurate predictions of ISE responses to real-world samples. Moreover, they are also required for the optimization of ionophore structures and membrane compositions. Best suited for such purposes are potentiometric selectivity coefficients as defined already in the 1960s. This paper briefly reviews the basic relationships and focuses on possible biases in the determination of selectivity coefficients. The traditional methods to determine selectivity coefficients (separate solution method, fixed interference method) are still the same as those originally proposed by IUPAC in 1976. However, several precautions are needed to obtain meaningful data. For example, errors arise when the response to a weakly interfering ion is also influenced by the primary ion leaching from the membrane. Wrong selectivity coefficients may be also obtained when the interfering agent is highly preferred and the electrode shows counterion interference. Recent advances show how such pitfalls can be avoided. A detailed recipe to determine correct potentiometric selectivity coefficients unaffected by such biases is presented.

Electrospray ionization mass spectrometry with in-source collision-induced dissociation of monensin factors and related metabolites

Monensins are a series of polyether ionophore antibiotic factors produced by Streptomyces cinnamonensis. Three monensin factors and four metabolites of monensin A isolated from cattle feces were investigated by electrospray ionization mass spectrometry (ESI-MS). In-source collision-induced dissociation (CID) of the alkali metal and ammonium molecular ion adducts of monensin produce strikingly different mass spectra, with the alkali metal complexes exhibiting little dissociation and the ammoniated forms characterized by extensive fragmentation of the polyether skeletal structure with the production of several structurally diagnostic ions. The observed fragmentation of ammoniated monensin primarily involves opening of the cyclic ether rings and consecutive H2O losses. The propensity of ammoniated monensin derivatives toward skeletal fragmentation may involve the complexation of the thermally labile NH4+ ion through multiple hydrogen-bonding interactions with the polyether complexing oxygens resulting in decreased stability of the resultant complex. Comparison of the in-source CID spectra associated with the structurally similar compounds evaluated provides for the proposal of a general scheme for the fragmentation of ammoniated monensins and related compounds, the consistency of which indicates the usefulness of ESI-MS with in-source CID in ionophore structure elucidation. © 1998 John Wiley & Sons, Ltd.