Influence of structural changes on the ion selectivities of magnesium ionophores based on malonic acid diamides

In an investigation of octamethylene bis(malonic acid diamides) and their selectivities for magnesium, it was found that presence of secondary amides within the particular ionophore played a considerable role in the enhancement of magnesium selectivity. Similar effects in other ionophores, i.e. tris(malonic acid diamides), were thus systematically looked at with the help of selectivity measurements with the hope of optimizing the number of secondary and tertiary amides so as to improve the magnesium selectivity. The syntheses of several investigated tris(malonic acid diamide) isologues are equally reported.Deceased in November 1992     

Highly sensitive and selective solid-contact calcium sensor based on Schiff base of benzil with 3-aminosalycilic acid covalently attached to polyacrylic acid amide for health care

Solid-state potentiometric calcium sensors based on newly synthesized Schiff’s base of 3-aminosalycilic acid with benzil [2-hydroxy-3-(2-oxo-1,2-diphenylethylidene)amino) benzoic acid] ionophore I and with isatin [2-hydroxy-3-(2-oxoindolin-3-ylidene amino)benzoic acid] ionophore II ionophores and their covalently attached to polyacrylamide ionophores III and IV, respectively, were developed. The all-solid-state sensors were constructed by the application of a thin film of polymeric membrane cocktail onto gold electrodes that were pre-coated with the conducting polymer poly (3,4-ethylenedioxy-thiophen) as an ion and electron transducer. More than 40 sensors with membranes containing plasticized PVC or poly(butyl methacrylate-co-dodecyl methacrylate as a plasticizer-free membrane matrix were investigated. The constructed sensors contained various amounts of the different ionophores with and without anionic lipophilic additive. The sensor containing 10% of ionophore III and 3% tetra (p-chlorophenyl) borate in acrylate copolymer exhibited a stable potentiometric response over a wide pH range of 4–9. It possessed a linear concentration range of 6 10^?10 to 1 10^?2 mol L^?1 with a Nernstian slope of 28.5 mV/decade and a limit of detection (LOD) of 2 10^?10 mol L^?1. It exhibited a good selectivity for calcium to other cations. The selectivity coefficients towards different mono-, di- and trivalent cations were determined with the fixed interference method (FIM) and separate solution method (SSM). The sensor’s life time is more than 3 months, without significant deterioration in the slope. The proposed sensors were utilized for the determination of calcium concentration in serum. The results were compared with those obtained from routine clinical laboratory electrolyte analyser. The results reveal that the all-solid-state calcium sensor is promising for the point of care testing.     

Synthesis and characterization of 7-deoxycholic amide backbone-based silver(I) ionophores

Four ionophores containing bipyridyl groups on a 7-deoxycholic amide derivative scaffold were designed and synthesized. Potentiometric evaluation of the Poly(vinyl chloride) (PVC) membranes containing those deoxycholic amides bearing bipyridyl moieties with a short linkage showed good affinity to silver(I) ion over alkali, alkaline earth and other transition metal cations. However, two bipyridyl groups flexibly linked to the deoxycholic frame through a long linkage do not result in appreciable potentiometric responses.     

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 of 7-deoxycholic amides or cholanes containing distinctive ion-recognizing groups at C3 and C12 and evaluation for ion-selective ionophores

Tweezer-type ionophores containing C3-bipyridyl and C12-dithiocarbamoyl groups, or C3-bithiophenyl with C12-dithiocarbamoyl groups on a 7-deoxycholic amide or cholane derivatives were designed and synthesized. Potentiometric evaluation of the PVC membranes containing those deoxycholic amides/cholanes linked with unsymmetrically substituted tweezer-type bipyridyl or bithiophenyl with dithiocarbamoyl moieties proved their good affinity and selectivity for silver(I) ion. Especially, ionophores with bithiophenyl moiety on the 3α-position and diphenylaminothioxomethylthioacetyloxy group on 12α-position of cholan-24-amide or cholane reveal the most excellent result with a theoretical slope value of 59 mV/decade.     

Acyclic neutral carrier-based polymer membrane electrode for a stimulant, phentermine.

Groups of dioxadicarboxylic diamides, which were developed as potential ionophores for inorganic cations, were found to act as ionophores for a stimulant, phentermine. Especially, N,N-dioctadecyl-N',N'-dipropyl-3,6-dioxaoctanediamide, which was originally developed as a lead ionophore and is commercially available from Fluka as lead ionophore I, was suitable for making a phentermine-selective electrode. The electrode constructed using this ionophore and bis(2-ethylhexyl) sebacate as a solvent mediator in a poly(vinyl chloride) membrane matrix discriminated between phentermine and analogous compounds more effectively than an electrode based on dibenzo-18-crown-6, a representative ionophore for organic ammonium ions. Moreover, the present electrode showed remarkably little interference by inorganic cations, such as Na+ and K+, as well as lipophilic quaternary ammonium ions including (C2H5)4N+ and (C3H7)4N+. The electrode exhibited a near-Nernstian response to phentermine in the concentration range of 2 x 10(-6) to 1 x 10(-2) M with a slope of 54.8 mV per concentration decade in 0.1 M MgCl2. The lower limit of detection was 7 x 10(-7) M. This electrode was applied to determine phentermine in a cationic-exchange resin complex of this stimulant, which is the general dosage form in medical use.     

Potassium-selective membrane electrodes based on macrocyclic metacyclophanes analogous to calixarenes.

The tetrabutyl ester derived from 9,16,25,32-tetrahydroxy[3.1.3.1]metacyclophane was an excellent ionophore for constructing a K+-selective membrane electrode. This ionophore exhibited a much higher selectivity toward K+ than the structurally similar potassium ionophore IV commercially available from Fluka. In particular, the interference from organic ammonium ions decreased remarkably. Potassium ionophore IV possessed oxygen atoms in the ring structure, while the present ionophore changed the oxygen atoms to carbon atoms. Thus, the removal of oxygen atoms in ring constituents of the metacyclophane acted to reduce the interaction with the NH3+ group of organic ammonium ions. The size of the cavity of the present ionophore was between those of calix[4]arene and calix[6]arene derivatives, which act as Na+ and Cs+ ionophores, respectively, demonstrating that the ability to recognize alkali metal cations was strongly cavity size-dependent. The present K+-selective electrode had less interference from Rb+ and Cs+ than an electrode constructed using valinomycin, but suffered greater interference from Na+.     

Makrocyclische und acyclische neutrale Ionophore. Einfluss des Ringschlusses auf die Kationenselektivität

Macrocyclic and noncyclic neutral ionophores. Effect of the macrocyclic ring on the ion selectivity A series of macrocyclic 3, 6-dioxaoctanedioic diamides was prepared. Their ion selectivity in membranes was compared with nonmacrocyclic analogues. The ion selectivity as well as the capability to extract ions from aqueous solutions to an organic phase decreases with decreasing ring size.     

Potentiometric and theoretical studies of the carbonate sensors based on 3-bromo-4-hexyl-5-nitrotrifluoroacetophenone

Novel carbonate ionophore, trifluoroacetophenone derivative (TFA) substituted by two acceptor substituents in the phenyl ring (3-bromo-4-hexyl-5-nitrotrifluoroacetophenone), was synthesized. Solvent polymeric membrane sensors based on this ionophore exhibited heightened selectivity to carbonate ions in the presence of the most important interfering anions. A wide range of potentiometric properties were studied and compared with those of sensors based on mono-substituted ionophores. Special attention was paid to pH dependence of sensor responses and to elaboration of appropriate conditions for carbonate analysis. A segmented-sandwich membrane method was applied for determination of the stoichiometry of ionophore-carbonate complexes, which was determined to be 1:3, and apparent complex formation constants which were 14.4 and 13.6 for DOS- and NPOE-plasticized membranes, respectively. Theoretical studies on TFA derivatives by semi-empirical (AM1 and PM3) and ab initio(6-31+G*) methods were performed, considering different types of possible ionophore-ion interactions. The formation of hydrogen bonds between carbonate and hydrated TFA was proved to be much more favourable in terms of energy compared to tetrahedral nucleophilic adducts that earlier were postulated to being formed in the membrane phase. The final conclusion on the mechanism of carbonate sensing by TFA-based solvent polymeric membrane sensors was made on the basis of computational data and detailed analysis of the literature.     

A hydrogen ion-selective poly(aniline) solid contact electrode based on dibenzylpyrenemethylamine ionophore for highly acidic solutions.

Hydrogen-ion selective solid contact electrodes based on tribenzylamine, dibenzylnaphthalenemethylamine, and dibenzylpyrenemethylamine ionophores were prepared. With these electrodes, we showed that the response ranges were influenced by the number of phenyl rings in the ionophores. The lower limits for a linear pH response in acidic solutions were pH 2.50, 0.65, and 0.50, respectively. As the number of phenyl rings in the ionophores increased, the slopes of the EMF responses of these electrodes did not change significantly, but their response extended toward an acidic range (shifted to pH 0.50). Thus, their dynamic response range became wider. A solid contact electrode with dibenzylpyrenemethylamine ionophore, in particular, showed the best selectivity, from the interference of cations and anions, and the best reproducibility of the EMF. This electrode was stored in Tris buffer solutions, artificial serum, and hydrofluoric acid solutions for one month without any loss of performance. Their response time was 8 s. Satisfactory results were obtained when it was tested directly with artificial serum (in pH range 6.0 - 8.5) and hydrofluoric acid.     

Solid-phase synthesis of 4(1H)-quinolone and pyrimidine derivatives based on a new scaffold-polymer-bound cyclic malonic acid ester

An efficient method for the preparation of polymer-bound cyclic malonic acid ester starting from Merrifield resin has been developed. Reaction of the resin-bound cyclic malonic acid ester with triethyl orthoformate and subsequent double substitution with nucleophilic reagents, such as arylamine, urea, thiourea, 2-aminobenzothiazoles, or isothiosemicarbazones, afforded the corresponding polymer-bound substituted aminomethylene cyclic malonic acid esters, which upon thermal treament led to 4(1H)-quinolones, 3-substituted uracils and thiouracils, 4H-pyrimido[2,1-b]benzothiazol-4-ones, and 1-(N-alkylidene or benzylideneamino)-1,6-dihydro-2-methylthio-6-oxo-pyrimidines, depending on the structures of the nucleophilic reagents.     

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.     

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 10s 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.     

Potentiometric sensors based on fluorous membranes doped with highly selective ionophores for carbonate

Manganese(III) complexes of three fluorophilic salen derivatives were used to prepare ion-selective electrodes (ISEs) with ionophore-doped fluorous sensing membranes. Because of their extremely low polarity and polarizability, fluorous media are not only chemically very inert but also solvate potentially interfering ions poorly, resulting in a much improved discrimination of such ions. Indeed, the new ISEs exhibited selectivities for CO(3)(2-) that exceed those of previously reported ISEs based on nonfluorous membranes by several orders of magnitude. In particular, the interference from chloride and salicylate was reduced by 2 and 6 orders of magnitude, respectively. To achieve this, the selectivities of these ISEs were fine-tuned by addition of noncoordinating hydrophobic ions (i.e., ionic sites) into the sensing membranes. Stability constants of the anion-ionophore complexes were determined from the dependence of the potentiometric selectivities on the charge sign of the ionic sites and the molar ratio of ionic sites and the ionophore. For this purpose, a previously introduced fluorophilic tetraphenylborate and a novel fluorophilic cation with a bis(triphenylphosphoranylidene)ammonium group, (R(f6)(CH(2))(3))(3)PN(+)P(R(f6)(CH(2))(3))(3), were utilized (where R(f6) is C(6)F(13)). The optimum CO(3)(2-) selectivities were found for sensing membranes composed of anionic sites and ionophore in a 1:4 molar ratio, which results in the formation of 2:1 complexes with CO(3)(2-) with stability constants up to 4.1 × 10(15). As predicted by established theory, the site-to-ionophore ratios that provide optimum potentiometric selectivity depend on the stoichiometries of the complexes of both the primary and the interfering ions. However, the ionophores used in this study give examples of charges and stoichiometries previously neither explicitly predicted by theory nor shown by experiment. The exceptional selectivity of fluorous membranes doped with these carbonate ionophores suggests their use not only for potentiometric sensing but also for other types of sensors, such as the selective separation of carbonate from other anions and the sequestration of carbon dioxide.     

Enzymatic fluorimetric determination of the individual bile acids in blood serum

An enzymatic fluorimetric method is described for the determination of total bile acids (cholic acid and deoxycholic acid), primary bile acids (cholic and chen acids and individual bile acids in serum without prior separation of the acids. Total and primary bile acids are determined by equilibrium procedures by conver of the 3α- and 7α-hydroxy bile acids to 3-oxo and 7-oxo bile acids by α-NAD⁺, in the presence of 3α- and 7α-hydroxysteroid dehydrogenase (HSD), respectively, and measurement of the generated NADH fluorimetrically. Chenodeoxycholic acid is determined with 7α-HSD in the presence of cholic and deoxycholic acids by a differential kinetic procedure, and cholic and deoxycholic acids are calculated by difference. Interferents are removed by treatment of serum with Sachrom rein. Only 1.00 ml of serum is required. Low cost, simplicity and reliability are the main features of the method. The recovery of bile acids added to serum averaged 103% (range 83–122%). The method is suitable for routine use in small clinical laboratories.     

Silver(I) ion selective ionophores containing dithiocarbamoyl moieties on steroid backbone

Tweezer-type and non-tweezer-type ionophores containing dithiocarbamoyl groups on a 7-deoxycholic amide or cholane derivatives were designed and synthesized. Potentiometric evaluation of the poly(vinyl chloride) (PVC) membranes containing those deoxycholic amides/cholanes linked with tweezer-type dithiocarbamoyl moieties showed excellent affinity and selectivity to silver(I) ion over alkali, alkaline earth and other transition metal cations. On the other hand, deoxycholic amides/cholanes substituted with one dithiocarbamoyl group, i.e., non-tweezer-type ionophores, resulted in relatively poor potentiometric sensitivity and detection limits. The enhanced potentiometric properties of newly synthesized tweezer-type dithiocarbamoyl containing ionophores have been further improved by employing silver ion complexing reagent in the internal reference solution, which resulted in greatly reduced detection limit (∼100 ppt) for the electrodes based on them.     

Structural aspects of host molecules acting as ionophores in ion-selective electrodes

Structural aspects of ligand molecules acting as neutral ionophores in ion-selective membrane electrodes are discussed and examples of Li-selective ionophores are presented. The relationship between the structure of ionophore and its complex determined by X-ray and NMR study and the selectivity of ISE was determined.     

Commercially Available Nitrate Ionophores in Potentiometric Sensors are not Superior to Common Ion-exchangers

Nitrate sensing is an important application for potentiometry in environmental applications. Its recognition is by ion-exchangers whose selectivity is governed by the lipophilicity of the ions in solution. Yet, considerable research efforts have been dedicated to the development of such ionophores and some have already been commercialized. This work examines two commercially available nitrate ionophores, nitrate ionophores V and VI, and compares their performance with widely used ion-exchangers by determining the resulting membrane selectivity and complexation to nitrate. Unfortunately, adding a nitrate ionophore to the membrane did not result in improved selectivity. Sandwich membrane experiments indicated that binding interaction is too weak to be measurable, with a logarithmic formation constant of just 1.36±0.14 for ionophore V with nitrate. Ways to improve the reporting of relevant data are suggested.     

Water Hardness Electrodes with Ionophores Containing Oxy- and Ester-Groups

Lipophilic compounds combining oxy- and ester-groups are synthesized and studied as neutral ionophores in plasticized PVC membranes for the development of novel water hardness ion-selective electrodes. Electrodes based on the ionophores studied showed a higher selectivity to calcium over magnesium ions. However, for electrodes based on hexadecyl-4-hydroxybutanoate or decyloxybutanol this preference turned to be rather low: logK_CaMg=–(0.5–0.7). Electrodes with membranes containing hexadecyl-4- hydroxybutanoate, 0.3 M as a neutral ionophore and bis[4-(1,1,3,3-tetramethylbutyl)phenyl]phosphate, 0.01 M as a charged ionophore, in combination with Ca²⁺-selective electrode based on ETH 1001 as ionophore, proved to be suitable for measurements of water hardness, also for the measurement of Mg²⁺ ion content in artificial aquarium fish-breeding water samples and in samples modeling electrolyte composition of blood serum.     

Organic anion recognition of naphthalenesulfonates by steroid-modified beta-cyclodextrins: enhanced molecular binding ability and molecular selectivity

Two beta-cyclodextrin (beta-CD) derivatives bearing steroid groups (1 and 2) were synthesized by the condensation of mono(6-aminoethylamino-6-deoxy)-beta-CD with cholic acid and deoxycholic acid, respectively, and their original conformations and binding behavior to the organic anion of naphthalenesulfonate derivatives were investigated by using 1H NMR spectroscopy and spectrofluorometric titration in combination with computational methods. The 2D NMR experiments reveal that the steroid groups attached to the beta-CD rim could be deeply embedded in the beta-CD cavity to form the intramolecular (for 1) or intermolecular (for 2) inclusion complexes in aqueous solution. Upon complexation with naphthalenesulfonate derivatives, modified beta-CDs display two obviously different binding modes, that is, the competitive inclusion mode and the induced-fit inclusion mode, which is consistent with the results of molecular modeling study. The two modes and the strict size/shape fitting relationship between the hosts and guests reasonably explain the different binding behaviors and molecular selectivity of host beta-CDs 1 and 2 toward the naphthalenesulfonate guests. Therefore, the cholic acid- or deoxycholic acid-modified beta-CDs could effectively recognize the size/shape of guest molecules as compared with the parent beta-CD, giving good molecular selectivity up to 24.9 for the disodium 2,6-naphthalenedisulfonate/disodium 1,5-naphthalenedisulfonate pair by the host 1.