Novel potentiometric copper (II) selective membrane sensors based on cyclic tetrapeptide derivatives as neutral ionophores

Two novel membrane sensors sensitive and reasonably selective for Cu²⁺ ions are described. These are based on the use of newly synthesized cyclic tetrapeptide derivatives as neutral ionophores and sodium tetraphenylborate (NaTPB) as an anionic excluder in plasticized PVC membranes. The sensors exhibit fast and stable near-Nernstian response over the concentration range 1.0 × 10⁻⁶ mol l⁻¹ to 1.0 × 10⁻² mol l⁻¹ Cu²⁺ with a cationic slope of 30.2-25.9 mV per decade at pH 4.5-7 with a lower detection limit of 0.05-0.13 μg ml⁻¹. Effects of plasticizers, lipophilic salts and various foreign common ions are tested. The sensors display long life-span, long term stability, high reproducibility, and short response time. Selectivity of both sensors is significantly high for Cu²⁺ over Fe³⁺, Al³⁺, Zn²⁺, Cd²⁺, Hg²⁺, Ni²⁺, Co²⁺, Mn²⁺, alkaline earth and alkali metal ions. The sensors are used for direct measurement of copper content in different rocks and industrial wastewater samples from electroplating factories. The results agree fairly well with data obtained using atomic absorption spectrometry.     

High selectivities in defective MFI membranes

Two polycrystalline MFI membranes with significant flow through defects (non-zeolitic pores that are gaps between the crystals) are shown to have high ideal and mixture selectivities. The membranes were characterized at room temperature by permporosimetry, pervaporation, separations, and single-gas permeation. These measurements indicate that one membrane (B-ZSM-5) had a relatively large number of smaller defects, whereas the second membrane (silicalite-1) had a smaller number of somewhat larger defects. The relative contributions of these defects to the overall flux changed dramatically in the presence of n-alkanes and SF₆. These molecules caused adsorption-induced expansion of the crystals, and this expansion shrank the defect sizes and thus changed the membrane permeation characteristics. The B-ZSM-5 membrane had 90% of its helium flux through defects at room temperature, but it had a H₂/SF₆ideal selectivity as high as 260 because of SF₆-induced swelling that stopped 99% of the flux through the defects. In contrast, the silicalite-1 membrane had only 9% of its helium flux through defects, but the defects were large enough that crystal swelling only decreased the flux through them by 30%. Thus its selectivities were lower. These studies show that n-hexane, n-pentane, n-butane, n-propane, and SF₆ swell MFI crystals when they adsorb, but benzene and CO₂ do not. The changes in membrane microstructure due to crystal expansion not only significantly affect membrane separation ability, but also have implications on how to select appropriate characterization techniques for evaluating MFI membrane quality.     

Synthesis of glycosylated porphyrins as neutral ionophores for a berberine-sensitive electrode

For preparing a berberine-sensitive electrode, 5,10,15,20-tetrakis[2-(2,3,4,6-tetraacetyl-β-D-glucopyranosyl)-1-O-phenyl]porphyrin (T(o-glu)PPH₂) was synthesized from the reaction of pyrrole with ortho-acetylglycosylated benzaldehyde by Lindsay’s method. The electrode based on T(o-glu)PPH₂ with an optimized membrane composition exhibits Nernstian response to berberine in the concentration range 2.4 × 10^–7–5.0 × 10^–3 mol L^–1, with a pH range from 3.9 to 10.2, and a fast response time of 30 s. The electrode shows fair selectivity towards berberine with respect to common co-existing species. T(o-glu)PPH₂ shows better potentiometric response characteristics comparing to chloro[5,10,15,20-tetrakis[2-(2,3,4,6-tetraacetyl-β-D-glucopyranosyl)-1-O-phenyl]-porphinato]-manganese (MnT(o-glu)PPCl) and better selectivity towards berberine than tetraphenylporphyrin (TPPH₂). The effect of the composition of the electrode membrane has been studied and the experimental conditions optimized. The contents of berberine in pharmaceutical tablets were determined by direct potentiometry and the results agreed with values obtained by the pharmacopoeia method. Received: 17 July 2000 / Revised: 18 September 2000 / Accepted: 23 October 2000     

Synthesis of glycosylated porphyrins as neutral ionophores for a berberine-sensitive electrode

For preparing a berberine-sensitive electrode, 5,10,15,20-tetrakis[2-(2,3,4,6-tetraacetyl-beta-D-glucopyranosyl)-1-O- phenyl]porphyrin (T(o-glu)PPH2) was synthesized from the reaction of pyrrole with ortho-acetylglycosylated benzaldehyde by Lindsay's method. The electrode based on T(o-glu)PPH2 with an optimized membrane composition exhibits Nernstian response to berberine in the concentration range 2.4 x 10(-7)-5.0 x 10(-3) mol L-1, with a pH range from 3.9 to 10.2, and a fast response time of 30 s. The electrode shows fair selectivity towards berberine with respect to common co-existing species. T(o-glu)PPH2 shows better potentiometric response characteristics comparing to chloro[5,10,15,20-tetrakis[2-(2,3,4,6-tetraacetyl-beta-D- glucopyranosyl)-1-O-phenyl]-porphinato]-manganese (MnT(o-glu)PPCl) and better selectivity towards berberine than tetraphenylporphyrin (TPPH2). The effect of the composition of the electrode membrane has been studied and the experimental conditions optimized. The contents of berberine in pharmaceutical tablets were determined by direct potentiometry and the results agreed with values obtained by the pharmacopoeia method.     

Influence of the dielectric constant of the medium on the selectivities of neutral carrier ligands in electrode membranes

The selectivities of potassium and calcium ion-selective liquid membrane electrodes, based on neutral carrier ligands, have been studied in relation to the dielectric constant of the membrane solvent. Potentiometric measurements have shown that the selectivity for monovalent cations is favoured by a low dielectric constant, and that for divalent cations by a high dielectric constant of the solvent. This is in good agreement with theoretical predictions. The size of the calcium-selective ligand has also been estimated.     

Carbonate ion selective electrodes with trifluoroacetophenone derivatives in potentiometric clinical analyser

Properties of six derivatives of 1-trifluoroacetylbenzene: [4-(n-butyl)- (1), 4-(n-hexadecyl)- (2), 4-dodecyloxy- (3), 4-(n-dodecylsulfonyl)- (4), N,N-dioctyl-4-trifluoroacetylbenzamide (5), octyl-p-trifluoroacetylbenzoate (6)] as neutral carriers for carbonate ion were examined and compared. The sensitivity towards carbonate ion was for (3) pH dependent. This eliminates (3) from practical applications in clinical analysis. When measuring CO(3)(2-) within the physiological range of human blood using as carriers compounds 1 and 2 the interference of chloride must be taken into account. In the case of carriers 4, 5, 6 this effect is negligible. Electrodes with membranes containing as carriers 2, 4, 5 and 6 were tested in an automatic potentiometric clinical analyser Microlyte 6, KONE. To avoid contamination by atmospheric CO(2) of three aqueous standards (TES, NaCl, NaHCO(3)), pH was adjusted by coulomeric generation of H(+) or OH(-) in a system devoid of carbon dioxide. Recovery of HCO(3)(-) calculated from measured CO(3)(2-) and pH, was investigated in a series of aqueous solutions and spiked bovine serum samples. The correlation between added and recovered concentration of HCO(3)(-) was linear with the intercept close to 0 and slope equal to 1 in aqueous solutions for all ligands and in bovine serum samples only in the case of ligand (2).     

Lead(II)-polyethoxylate-tetraphenyl borate compounds as ionophores in membranes of selective electrodes

Lead-selective electrodes were proposed on the basis of tetraphenyl borates of lead(II) complexes of polyhydroxyethylated nonylphenols with various number of hydroxyethyl groups. The composition and some physicochemical properties of the ionophores were determined. Electroanalytical properties of the proposed selective electrodes were examined.     

Electromotive behaviour of anion selective membranes with triorganotin acetates as ionophores and nucleophiles as additives

The electromotive behaviour of neutral carrier based Cl^–-selective electrodes can be improved if lipophilic nucleophiles are added to the membrane phase containing triorganotin acetates as anion carriers. The addition of about 50 mol-% octadecanethiol to diethyl-n-hexyltin acetate as ionophore leads to improved sensor response times and to slopes of the electrode response function close to the Nernstian behaviour.     

Fluorescent iminodiacetamide derivatives as potential ionophores for optical zinc ion-selective sensors.

Fluorescent sensor molecules were synthesized by conjugation of iminodiacetamide derivatives with fluorescent moieties of different structures and their UV-visible and fluorescent properties were characterized in acetonitrile solvent. The fluorescent measurements revealed that the N-(2-naphthyl) and N-phenyl derivatives exhibit a distinct zinc ion-selectivity over alkali and alkaline earth metal ions, while N-(anthrylmethyl) and N-(3-methoxyphenyl) derivatives do not possess any ion-selectivities. In contrast to the fluorescent measurements, all ligands show Zn(2+) selectivity over Ca(2+) and Mg(2+) ions in plasticized PVC membranes using potentiometric signal transduction. This observation found for N-(anthrylmethyl) and N-(3-methoxyphenyl) derivatives can be ascribed to the more hindered interaction between the signalling group of the ionophore and the central metal ion in PVC membranes than in acetonitrile solution upon complexation. From the fluorescent measurements it can also be concluded that the ligands with metal ions form complexes mainly with 2:1 stoichiometry (L(2)M). On complex formation a considerable decrease in the fluorescent intensity was observed for all ligands except the N-(anthrylmethyl) derivative, where a 25 - 30 fold fluorescence enhancement was found, which is explained by the photoinduced electron transfer (PET) mechanism. All ionophores exhibited serious hydrogen ion interference, therefore complexation-induced spectral changes were measured in aprotic acetonitrile solution.     

Symmetrical, unsymmetrical and bridged calix[4]arene derivatives as neutral carrier ionophores in poly (vinyl chloride) membrane sodium selective electrodes

The complexing ability of a range of 19 symmetrical, unsymmetrical and bridged calix[4]arene derivatives having ester, ketone, amide, amine and thioether functionalities were determined by the picrate extraction method. On incorporating these calix[4]arene derivatives as neutral carrier ionophores in sodium-selective poly (vinyl chloride) membrane electrodes the performance was assessed on the basis of the sensitivity and selectivity over the alkali, alkaline earth metals and hydrogen and ammonium ions. The temperature dependence, response times and lifetimes were also determined. Four ionophores in particular gave excellent sensitivity and selectivity and lifetimes of > 200 days. These electrodes were then tested without additional lipophilic additives and one ionophore was incorporated into poly (vinyl chloride) membrane electrodes with plasticizing solvents of varying polarity.     

Dithiaporphyrin derivatives as photosensitizers in membranes and cells

We synthesized a series of analogues of 5,20-diphenyl-10,15-bis(4-carboxylatomethoxy)phenyl-21,23-dithiaporphyrin (I) as potential photosensitizers for photodynamic therapy (PDT). The photosensitizers differ in the length of the side chains that bind the carboxyl to the phenol at positions 10 and 15 of the thiaporphyrin. The spectroscopic, photophysical, and biophysical properties of these photosensitizers are reported. The structural changes have almost no effect on the excitation/emission spectra with respect to I's spectra or on singlet oxygen generation in MeOH. All of the photosensitizers have a very high, close to 1.00, singlet oxygen quantum yield in MeOH. On the contrary, singlet oxygen generation in liposomes was considerably affected by the structural change in the photosensitizers. The photosensitizers possessing short side chains (one and three carbons) showed high quantum yields of around 0.7, whereas the photosensitizers possessing longer side chains showed smaller quantum yield, down to 0.14 for compound X (possessing side-chain length of 10 carbons), all at 1 microM. Moreover a self-quenching process of singlet oxygen was observed, and the quantum yield decreased as the photosensitizer's concentration increased. We measured the binding constant of I to liposomes and found Kb = 23.3 +/- 1.6 (mg/mL)-1. All the other photosensitizers with longer side chains exhibited very slow binding to liposomes, which prevented us from assessing their Kb's. We carried out fluorescence resonance energy transfer (FRET) measurements to determine the relative depth in which each photosensitizer is intercalated in the liposome bilayer. We found that the longer the side chain the deeper the photosensitizer core is embedded in the bilayer. This finding suggests that the photosensitizers are bound to the bilayer with their acid ends close to the aqueous medium interface and their core inside the bilayer. We performed PDT with the dithiaporphyrins on U937 cells and R3230AC cells. We found that the dark toxicity of the photosensitizers with the longer side chain (X, VI, V) is significantly higher than the dark toxicity of sensitizers with shorter side chains (I, III, IV). Phototoxicity measurements showed the opposite direction; the photosensitizers with shorter side chains were found to be more phototoxic than those with longer side chains. These differences are attributed to the relationship between diffusion and endocytosis in each photosensitizer, which determines the location of the photosensitizer in the cell and hence its phototoxicity.     

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     

Nitrate-selective electrodes based on meso-tetrakis[(2-arylphenylurea)-phenyl]porphyrins as neutral lipophilic ionophores

Polymeric-membrane electrodes for NO₃⁻ anion based on (α,α,α,α)-5,10,15,20-tetrakis [2-(4-methylphenylurea)phenyl]porphyrin I and similar urea-functionalized porphyrins II-IV as neutral ionophores were prepared. The effects of polymeric-membrane composition and test solution pH were tested. The electrodes revealed good selectivity coefficients for NO₃⁻ over a wide variety of other anions, and the values of eight anions were measured. Of the various electrodes prepared, the electrode based on urea-functionalized porphyrin I exhibits a linear stable response over a wide concentration range (1.0×10⁻⁵ to 1.0×10⁻¹) with a slope of −57.4 mV per decade, a detection limit of log[NO₃⁻]=−5.72, and a selectivity coefficient for nitrate against perchlorate anion ().     

Anion binding versus intramolecular hydrogen bonding in neutral macrocyclic amides

Although amide groups are important hydrogen-bond donors in natural and synthetic anion receptors, studies on structure-affinity relationships of amide-based macrocyclic receptors are still very limited. Therefore, we synthesized a series of macrocyclic tetraamides 5-8 derived from 1,3-benzenedicarboxylic (isophthalic) acid and aliphatic alpha,omega-diamines of different lengths. (1)H NMR titrations in DMSO solution show that the anion affinity of these receptors decreases with increasing size of the macrocycle irrespective of the anion, and this suggests a minor role of geometric complementarity. Comparison with their previously studied pyridine congeners reveals that the isophthalic acid based macrocycles are less potent, in contrast to what was found for simple model diamides. Combined theoretical and experimental structural studies were carried out to determine the reasons behind this behaviour. The results show that the unexpectedly low anion binding ability of the isophthalic acid-based receptors is due to the self-complementary nature of the isophthalic bis-amide fragments: when two such moieties are present within a sufficiently flexible macrocycle, they adopt syn-anti conformations and bind each other by two strong intramolecular hydrogen bonds that close the macrocyclic cavity. Nevertheless, anion binding is able to break these hydrogen bonds and switch a macrocycle into a convergent all-syn conformation. Despite the ill-preorganized conformation, 20-membered receptor 6 is better than either its open-chain analogue (macrocyclic effect) and/or its isomer having differently placed carbonyl groups. The crystal structures of four anion complexes of the macrocyclic receptors are reported. X-ray studies and solution NMR data confirmed the inclusive nature of the complexes and pointed to strong involvement of aromatic CH hydrogen atoms in anion binding.     

Anion recognition in water with use of a neutral uranyl-salophen receptor

A new water-soluble uranyl-salophen complex incorporating two glucose units has been synthesized. This neutral derivative shows noteworthy binding affinity for fluoride in water thanks to the Lewis acid-base interaction occurring between the metal and the anion. Such interaction is strong enough to overcome the high hydration enthalpy of fluoride. Moreover this complex effectively binds hydrogen phosphate and exhibits remarkably strong association for nucleotide polyanions ADP(3-) and ATP(4-).     

Hydroxy-thioxanthones as suitable neutral ionophores for the preparation of PVC-membrane potentiometric sensors for Al(III) ion.

The complexation of five recently synthesized hydroxy-thioxanthone derivatives with Al3+ ion was studied in a methanol solution spectrophotometrically, and the stepwise formation constants of the resulting 1:1 and 2:1 (ligand-to-metal) complexes were evaluated. The suitability of the thioxanthone derivatives as neutral ionophores for the preparation of a new Al3+ ion-selective PVC-membrane electrode was investigated, and 1-hydroxy-3-methyl-thiocanthone was selected as the best compound for this purpose. The prepared electrode exhibits a Nernstian response for Al3+ ions over a wide concentration range (2.0 x 10(-2) to 2.0 x 10(-6) M), with a limit of detection of 1.0 x 10(-6) M. It has a very fast response time of about 5 s and can be used for at least 3 months without any considerable divergence in the potentials. The proposed membrane sensor revealed very good selectivities for Al3+ over a wide variety of other metal ions, and could be used at a working pH range of 3.4 - 5.0. It was used as an indicator electrode in potentiometric titration of aluminum ions with EDTA, and in the determination of Al3+ in different real samples.     

The preparation and properties of neutral diamide ionophores for group IIA metal cations-II

The elaboration of a series of neutral ligands featuring vicinal ether and N,N-dialkylacetamido groups is described. Several of these ligands were prev with K_app=10³-10⁵ in methanol of the Group IIA cations for which they are sensitive. Binding constants by the Scatchard method are reported for a number of ligands mainly with Ca, Sr, Mn and Ba. The ligands in methylene chloride solution extract these cations via their picrate salts from water. The electrochemical K_ij^pot (selectivity) values for some of the ligands when they are incorporated into liquid membrane electrodes and tested with various cations as determined by Simon . (ETH Zurich) are reported. Selectivity ratios of over 100:1 for Na vs Ca were found for several piperidenyl amides of 1,2-phenylenedioxydiacetic acid. Incorporation of N-methylamino instead of ether oxygen groups into the basic structure gives a stronger cation binder which is still selective for Group IIA vs Group IA cations but with binding capacity for transition metal cations also. Limitations of the Scatchard plots for these ligands and the non-correspondance of electrochemical selectivities with the ordering of binding of cations in single liquid phase are discussed.     

Electrostatic interaction of neutral semi-permeable membranes

We consider an osmotic equilibrium between bulk solutions of polyelectrolyte bounded by semi-permeable membranes and separated by a thin film of salt-free liquid. Although the membranes are neutral, the counter-ions of the polyelectrolyte molecules permeate into the gap and lead to a steric charge separation. This gives rise to a distance-dependent membrane potential, which translates into a repulsive electrostatic disjoining pressure. From the solution of the nonlinear Poisson-Boltzmann equation, we obtain the distribution of the potential and of ions. We then derive an explicit formula for the pressure exerted on the membranes and show that it deviates from the classical van't Hoff expression for the osmotic pressure. This difference is interpreted in terms of a repulsive electrostatic disjoining pressure originating from the overlap of counterion clouds inside the gap. We also develop a simplified theory based on a linearized Poisson-Boltzmann approach. A comparison with simulation of a primitive model for the electrolyte is provided and does confirm the validity of the theoretical predictions. Beyond the fundamental result that the neutral surfaces can repel, this mechanism not only helps to control the adhesion and long-range interactions of living cells, bacteria, and vesicles, but also allows us to argue that electrostatic interactions should play enormous role in determining behavior and functions of systems bounded by semi-permeable membranes.