Bulk Chloroform Membrane Research Articles

Utilizing an Amino Acid Scaffold to Construct Heteroditopic Receptors Capable of Interacting with Salts under Interfacial Conditions.

A 4-nitro-L-phenylalanine scaffold was used to construct effective ion pair receptors capable of binding anions in an enhanced manner with the assistance of alkali metal cations. A benzocrown ether was linked to a receptor platform via the amide function so as to support the squaramide function in anion binding and to allow all three NHs to act simultaneously. The binding properties of the receptors were determined using UV-vis, 1H NMR, 2D NMR, and DOSY spectroscopy in MeCN and in the solid state by X-ray measurements. Ion pair receptor 2 was found to interact with the most strongly with salts, and the removal of its key structural elements was shown to hinder the receptor action. The amide proton was recognized to switch from having involvement in an intramolecular hydrogen bond to interacting with anions upon complexation. Apart from carboxylates, which promote deprotonation, and other monovalent salts creating 1:1 complexes with the receptor, more complex equilibria were established upon the complexation of 2 with sulfates. Receptor 2 was shown to be capable of the extraction of ion pairs from the aqueous to organic phase and of the cation-enhanced transport chloride and sulfate anions across a bulk chloroform membrane. These features may open the door for its use in regulating ion concertation under interfacial conditions and acting as a potential drug to treat channelopathies.

Complexation and transport of amino acid esters and their salts with synthesised chiral novel aza crown ether derivatives

The syntheses of four aza-15-crown-5 ethers bearing phenyl and phenoxymethyl moieties attached to a stereogenic centre on the crown ring were achieved. Macrocycles have exhibited strong binding ability (Ka = 5364–12,969 M− 1) and modest enantiomeric discrimination towards the enantiomers of amino acid methyl ester salts by UV titration method in CHCl3 at 25°C. Computer modelling results supported experimental data providing a detailed understanding of the molecular recognition mode between hosts and guests and the likely binding sites involved. Macrocycles were used for chiral discrimination of amino acids in their zwitterionic forms or as potassium and sodium salts in transport experiments across a bulk chloroform membrane with satisfactory selectivity.

Anion transport across phospholipid bilayers promoted by a guanidinium calix[4]arene conjugate

The ionophoric activity of a calix[4]arene guanidinium conjugate (4G4Oct) has been investigated in bulk chloroform membrane and mainly in liposomes. In both membrane models 4G4Oct shows high activity in the transport of chloride. The mechanistic evidence suggests a carrier mechanism in which the calixarene binds the anions through electrostatic interactions and hydrogen bonds with the guanidinium moieties. Studies on anion transport in liposomes indicate a peculiar selectivity sequence inverse to the most commonly observed lyotropic series with chloride transported faster than bromide and iodide virtually non-transported. This selectivity sequence together with competitive inhibition of chloride transport by the non-transported ions suggests a strong anion binding to the guanidinium moieties in the membrane environment. The complex formed is lipophilic and is able to shuttle the ion across the membrane. The origin of the observed anion selectivity is suggested to be related to a less favourable ion exchange at the membrane interface of iodide with respect to chloride with OH− , which is the antiported ion in the transport process in liposome. These studies complement the reported ability of 4G4Oct to condensate plasmid DNA and to transfect cells, showing that the calixarene derivative is also able to efficiently transport chloride across a phospholipid bilayer.

Synthesis of New N,N′-bis(2-aminothiophenol)-α,α′-bis(5-bromocarboxylidene phenoxy)xylene and their Liquid Membrane Transport of Copper Cations

New Schiff base (H2L) containing nitrogen-sulfur-oxygen atoms was synthesized by reaction of α,α′-bis(5-bromo-2-carboxyaldehyde phenoxy)-1.4-xylene with aminothiophenol. Transport of copper ion across a bulk chloroform membrane containing Schiff base ligand (H2L) as carrier has been studied. The parameters influencing the transport efficiency such as composition of receiving phase, pH of the feed phase, carrier concentration in the membrane, EDTA concentration in the receiving phase, and the effect of temperature and time dependency of the process were studied and discussed.

The synthesis of N2O2-Schiff base ligand and bulk liquid membrane transport of Cu2+

New Schiff base (N2O2) containing nitrogen–oxygen atoms was designed and synthesized by the reaction of 5-amino-2-methoxy-phenol with terephthaldialdehyde. Transport of copper ion across bulk chloroform membrane containing (N2O2) as carrier has been studied. The parameters influencing the transport efficiency such as composition of receiving phase, pH of the feed phase, carrier concentration in the membrane, EDTA concentration in the receiving phase, effect of stirring speed, effect of temperature and time dependency of the process were studied and discussed. The selectivity of the processes toward copper ions were tested by performing the competitive transport experiments on the mixture containing Pb2+, Ni2+, Cd2+, Zn2+ and Co2+ ions. The amount of copper transport through the liquid membrane after 90min was 99% at 25°C.

Synthetic polyion-counterion transport systems in polymersomes and gels

Transport across the membranes of polymersomes remains difficult in part due to the great thickness of the polymer bilayers. Here, we report that dynamic polyion-counterion transport systems are active in fluorogenic polymersomes composed of poly(dimethylsiloxane)-b-poly(2-methyloxazoline) (PDMS-PMOXA). These results suggest that counterion-activated calf-thymus DNA can act as cation carrier that moves not only across lipid bilayer and bulk chloroform membranes but also across the "plastic" membranes of polymersomes. Compared to egg yolk phosophatidylcholine (EYPC) lipsosomes, activities and activator scope in PDMS-PMOXA polymersomes are clearly reduced. Embedded in agar gel matrices, fluorogenic PDMS-PMOXA polymersomes respond reliably to polyion-counterion transporters, with high contrast, high stability and preserved selectivity. Compared to standard EYPC liposomes, it cannot be said that PDMS-PMOXA polymersomes are better. However, they are different, and this difference could be interesting for the development of sensing devices.

Amphiphilic Counterion Activators for DNA: Stimuli‐Responsive Cation Transporters and Biosensors in Bulk and Lipid Bilayer Membranes

We report that amphiphilic counterions can enable DNA to act as cation carrier, enzyme detector and biosensor. Calf thymus DNA is used as example throughout the study. Evaluation of a series of counterion activators suggests that strong amphiphilicity, alkyl or calix[4]arene tails and guanidinium cations give best results, whereas weak amphiphilicity, bola-amphiphilicity, planar aryl tails and ammonium cations are less satisfactory for various reasons. In the U-tube, DNA-counterion complexes can carry cations such as safranin O or p-xylene-bis-pyridinium bromide (DPX) across bulk chloroform membranes, whereas anions such as carboxyfluorescein (CF) and (8-Hydroxy-1,3,6-pyrenetrisulfonate (HPTS) are not transported. Uptake of DNA-counterion complexes into intact vesicles is demonstrated by DNA trapping experiments with internal polylysine. Comparison of results from different assays suggests that DNA-counterion complexes act as cation carriers under mild conditions, whereas pore formation and lysis dominate at higher concentrations. Applicability of DNA-counterion transporters for the detection of enzyme activity is demonstrated with phytate as an inactivating substrate and phytase as a reactivating enzyme. Compatibility with biosensing is exemplified with the fluorometric monitoring of phytate levels in almond extracts. The conceptual significance of these findings is briefly discussed, as are promising perspectives such as the application of DNA chemistry to multianalyte sensing in fluorogenic vesicles.

Copper(II) Interaction with Mono-, Bis- and Tris-Ring N3O2 Macrocycles: Synthetic, X-ray, Competitive Membrane Transport, and Hypochromic Shift Studies

New N-phenyl (L(1)), azo-coupled (L(2)), and tri-linked (L(3)) substituted derivatives of a parent dibenzo-N(3)O(2) macrocycle, 1,12,15-triaza-3,4:9,10-dibenzo-5,8-dioxacycloheptadecane (L(4)), have been synthesized. Competitive seven-metal transport studies across a bulk chloroform membrane employing an aqueous source phase containing equal molar concentrations of Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Ag(I), and Pb(II) as their nitrate salts have been performed using both L(1) and L(3) as the ionophore, with the results discussed in terms of those obtained previously for related mono-ring (L(5)) and di-linked (L(6)) macrocyclic systems. Sole transport selectivity for Cu(II) was observed in each case. On a per macrocyclic cavity basis the tri-linked analogue L(3) gave less efficient Cu(II) transport than its monomeric or di-linked analogues. At least in part, this may reflect the tendency of tri-linked derivative L(3) to form a 2:1 complex (metal/ligand) with Cu(II) under the conditions employed; such a stoichiometry was demonstrated to occur in acetonitrile using both spectrophotometric titration and Job plot procedures. The azo-coupled derivative (L(2)) yields a red solution (lambda(max) = 495 nm, epsilon(max) = 23000 M(-1) cm(-1)) and undergoes significant hypochromic metal-induced shifts (Delta lambda(max) = 54-174 nm) on metal addition. Cu(II) induces the largest shift (Delta lambda(max) = 174 nm), corresponding to a color change from red to pale-yellow. The X-ray structures of red L(2) x HNO(3) together with its Cu(II) complexes, [Cu(L(2))NO(3)]NO(3) x CH(2)Cl(2) (6) (pale-yellow) and [{Cu(L(2))}(2)(mu-OH)(2)](ClO(4))(2) x 2 CH(2)Cl(2) x 2 H(2)O (7) (dark-red), are reported. The structural determinations have allowed insight into the structure-function relationships governing the observed color variation between these species.

Chiral lariat ethers as membrane carriers for chiral amino acids and their sodium and potassium salts

Four chiral lariat ethers 8– 11 containing a ( p-methoxyphenoxy) methyl side arm were used for chiral discrimination of amino acids in their zwitterionic form or as potassium and sodium salts in transport across a bulk chloroform membrane with satisfactory selectivity. The carriers that were employed exhibited different transport selectivity relative to the amino acids and their salts under study. The d/ l selectivity strongly depends on the amino acids or their salts, and in some cases reverse selectivity has been obtained. The best selectivity was obtained in the case of tyrosine and its potassium salts for all carriers. The transport rates of amino acids and their salts were found to be controlled by factors such as the structure of the carriers and amino acids or their salts. Among these factors, it was also found that the side arm of the lariat ethers plays an important role in the transport process. As a consequence, the main goal of our investigation was to separate the chiral amino acids through liquid membranes.

Efficient and selective transport of ω-amino acids across a bulk chloroform membrane by a macrocyclic dicopper(II) complex

The Cu(II) complex of a ditopic macrocyclic ligand efficiently transports ω-amino acids of different length across a bulk chloroform membrane with promising selectivity.

Metal ion recognition via 'selective detuning'. The interaction of selected transition and post-transition metal ions with a mono-N-benzylated O2N3-donor macrocycle and its xylyl-bridged ring analogue.

The interaction of cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II), silver(I) and lead(II) with symmetrical mono-N-benzylated and xylyl-linked macrocyclic ligands derived from the O2N3-macrocycle, 1,12,15-triaza-3,4:9,10-dibenzo-5,8-dioxacycloheptadecane, has been investigated. The log K values for the respective 1 : 1 complexes in 95% methanol (I= 0.1; Et4NClO4, 25 degrees C) of the mono-benzylated derivative have been determined potentiometrically and the results compared with the values obtained previously for the parent (non-benzylated) ring system as well as for related di- and tri-benzylated macrocyclic species. Mono-benzylation results in slightly enhanced stability for the 1 : 1 silver(I) complex while the values for the corresponding complexes of the other six ions are in each case decreased even though the highest stability is still maintained for the 1 : 1 copper(II) complex. The log K results are in accord with a previous proposal that N-benzylation of amine-containing macrocyclic rings of the present type will normally have only a minor (positive or negative) influence on the affinity towards silver(I) while the corresponding binding strengths towards the remaining six metal ions are significantly reduced-behaviour we term 'selective detuning'. Competitive seven-metal transport experiments across a bulk chloroform membrane have been performed using both ligand systems as ionophores. In parallel to the log K results, transport selectivity for copper(II) was exhibited by both systems, with similar transport efficiencies being evident when compared on a 'per macrocyclic cavity' basis.

Anion-mediated transfer of polyarginine across liquid and bilayer membranes.

The accumulation of reports on the puzzling behavior of guanidinium-rich oligo/polymers in bilayer membranes, reaching from HIV-Tat-like (HIV Tat is the human immunodeficiency virus transactivator of transcription) translocation to selectivity and voltage-gating of ion channels, prompted us to investigate possible contributions from counteranions to these phenomena. We report that anion-mediated variability of charge and solubility makes guanidinium-rich oligo/polymers adaptable to many environments. For example, poly- and hexaarginine but not polylysine phase transferred from water into chloroform in the presence of amphiphilic anions such as monomeric sodium dodecyl sulfate (SDS), egg yolk phosphatidylglycerol (EYPG), cholesterol sulfate, pyrenebutyrate, and stearate. Hydrophilic anions with high affinity inhibited phase transfer of 5(6)-carboxyfluorescein (CF)-polyarginine complexes into bulk membranes (sulfate, adenosine 5'-triphosphate, adenosine 5'-monophosphate, heparin, and micellar SDS). At least binary anion cocktails were necessary to activate polyarginine as a carrier in bulk chloroform membranes. Refined combinations of EYPG, phosphate, and azide or TFA were found to maximize translocation of CF across bulk membranes by polyarginine. Polyarginine-mediated CF efflux from large unilamellar vesicles was best in the presence of EYPG in the bilayer as well as phosphate and TFA in the medium. Similar regulatory activities of several anions were in support of a common carrier mechanism for guanidinium-rich oligo/polymers in bulk and bilayer membranes. The identified activities of polyarginine in bulk and lipid membranes suggested that anion-mediated adaptability of the solubility of guanidinium-rich oligo/polymers cannot be ignored in studies on biological function. The infinite variability and dynamic nature of available regulatory anion cocktails may contribute to the elusive character of guanidinium-rich oligo/polymer function in biomembranes.

3-(4-Tolylazo)phenylboronic acid as the active component of polyhydroxy compounds-selective electrodes

Ionophoric, extraction, acidic and hydrophobic properties of 3-(4-tolylazo)phenylboronic acid (TAPBA) were studied. Determined K d value equals to 36±2, p K a equals to 8.6±0.5. TAPBA extracts dobutamine from water into chloroform and transports it across a bulk chloroform membrane. The recovery is 83% (pH=7.5), the transport rate – (6.5±0.5)×10 −7 mol/h. 1 H and 13 C NMR data confirm the formation of an 1:1 complex between arylboronic acid and catecholamine. TAPBA was used as electrode-active component of plasticized membrane electrodes with cationic and anionic responses to catecholamines and phenolic acids, respectively. For the diethyl sebacate-plasticized membrane, a slope of electrode function to dobutamine is 56±2 mV/decade; the detection limit is 1.3×10 −5 mol/l; the linear range – 5×10 −5–1×10 −2 mol/l; the working pH-range – 4.8–7.6; the response time – 5–10 s. ISE gives incomplete cationic function to less lipophilic catecholamines. The membrane with cationic additive shows an anionic response to caffeic acid in wide pH range.

Metal ion recognition. The interaction of cobalt(ii), nickel(ii), copper(ii), zinc(ii), cadmium(ii), silver(i) and lead(ii) with N-benzylated macrocycles incorporating O2N2-, O3N2- and O2N3-donor sets

The interaction of cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II), silver(I) and lead(II) with a series of mixed-donor, N-benzylated macrocyclic ligands incorporating O2N2-, O3N2- and O2N3-donor sets has been investigated. The log K values for the respective 1 ∶ 1 complexes in 95% methanol (I = 0.1 mol dm−3; Et4NClO4, 25 °C) have been determined potentiometrically and the results compared with the values obtained previously for the parent (non-benzylated) macrocyclic systems. Examples of N-benzylation of individual parent macrocycles leading to enhanced discrimination for silver(I) are presented. In the case of a dibenzylated O3N2-ring and a tribenzylated O2N3-ring, both 17-membered, high selectivity for this ion was observed relative to the other metal ions investigated. Competitive mixed-metal transport experiments across a bulk chloroform membrane have been performed using the benzylated derivatives as ionophores. For each experiment the source contained equimolar concentrations of the above metal ions and transport was performed against a pH gradient; the aqueous source and receiving phases were buffered at pH 4.9 and 3.0, respectively. In parallel to the log K results, transport selectivity for silver(I) was exhibited by the di- and tri-benzylated ligands mentioned above. The remaining ligands proved to be poor ionophores, showing no significant metal ion transport under the conditions employed. In a further study, high silver ion (transport) selectivity was maintained when the above tribenzylated ligand was incorporated as the ionophore in a polymer inclusion membrane system. Single metal and mixed (seven-metal) solvent extraction experiments employing similar aqueous source and chloroform phases to those used in the bulk membrane transport runs have also been performed for the tribenzylated ligand derivative; significant selectivity for silver was again maintained in these solvent extraction experiments. An X-ray study of [AgL]ClO4 (where L is the above-mentioned dibenzylated derivative) confirms that all donor atoms of the macrocycle coordinate to the silver ion; the latter is five-coordinate with the complex cation exhibiting a highly distorted trigonal bipyramidal geometry.

Structural and Dynamic Evidence for C−H···O Hydrogen Bonding in Lariat Ethers: Implications for Protein Structure

Seven diaza-18-crown-6 ethers having aromatic sidearms were studied: benzyl (1), 2-hydroxybenzyl (2), dansyl (3), 1-naphthylmethyl (4), 2-naphthylmethyl (5), 9-anthrylmethyl (6), and 1-pyrenylmethyl (7). Solution studies of these compounds included homogeneous binding constant determination, picrate extraction efficiency, and/or bulk chloroform membrane transport rate experiments. Compounds 2, 3, 4, 6, and 7 exhibited binding affinities for alkali metal cations that were surprisingly low. Fifteen crystal structures have been used to understand the conformations of 1−7 and their alkali metal complexes. Unusually weak cation binding in solution was found to correlate with intramolecular interactions observed between the crown's macroring and both sidearms. For one of the five weakly binding crowns (2) the low binding affinity is attributed to an intramolecular O−H···N hydrogen bond, confirmed by the solid-state structure and IR studies. The weak cation binding abilities of 3, 4, 6, and 7 are ascribed to in...

Macrocyclic ligand design. Interaction of selected transition and post-transition metal ions with a new N2O2-donor macrocycle incorporating a pyridylmethyl pendant arm

A pyridylmethyl derivative of a 14-membered, N2O2-donor macrocycle (L) and its complexes with cobalt(II), copper(II), zinc(II), silver(I), cadmium(II) and lead(II) have been prepared. Thermodynamic stabilities of the 1∶1 (metal∶ligand) complexes in 95% methanol (I = 0.1 mol dm−3, NEt4ClO4; 25 °C) and crystal structures of the 1∶1 complexes of copper(II), silver(I) and lead(II) with L were determined. The structure of the copper complex shows the presence of a cation of type [CuL(NO3)]+; it has a distorted octahedral geometry in which one co-ordination site is occupied by a unidentate nitrate ligand. In contrast, the cationic silver complex is of type [AgL]+ with the two pyridine ring nitrogen atoms of L dominating the co-ordination environment, which may be regarded as essentially two-co-ordinate. On the other hand, the lead complex, [PbL(NO3)(ClO4)], is eight-co-ordinate and incorporates bidentate nitrate and unidentate perchlorate ligands. A competitive mixed-metal transport experiment across a bulk chloroform membrane incorporating L as ionophore was performed. The aqueous source phase contained equimolar concentrations of cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II), silver(I), and lead(II) as their nitrate salts. Under the influence of a back proton gradient, silver and copper were preferentially transported to the aqueous receiving phase.

Transport of carbohydrates across a bulk liquid membrane with substituted calyx[8]arenes and phosphoryl-containing podand

Adamantyl- andtert-butyl-substituted calyx[8]arene esters and tripodal podand containing diphenylphosphoryl terminal groups are capable of transporting monosaccharides, but not disaccharides, across a bulk chloroform membrane. Both stoichiometry of complex formation and transport selectivity, in particular, glucose-fructose selectivity, are sensitive to the structure of a carrier.

Efficient and Highly Selective Copper(II) Transport across a Bulk Liquid Chloroform Membrane Mediated by Lipophilic Dipeptides

Several structurally simple N-monoalkylated and -dialkylated dipeptides made of α-amino acids Gly, Phe, and Leu, 1−11, were synthesized and investigated as carriers for the transport of Cu(II), Zn(II), and Ni(II) from an aqueous pH = 5.6 buffer source to a 0.1 M HCl receiving phase across a bulk chloroform membrane. The proton-driven translocation was followed during the process by analyzing the metal ion concentrations in the three phases. The transport efficiency depends on the ease of formation of a neutral complex with Cu(II) (the peptide group and carboxylic acid being deprotonated) at the source−chloroform interface and on that of its disruption by protonation at the receiving phase: the carrier's lipophilicity favors the metal ion uptake and not the release. By modulating the length of the N-alkyl chains and the hydrophobicity of the dipeptide moiety, a quite remarkable transport efficiency was observed for Cu(II), in most cases superior to that of the industrial extractant Kelex 100. Moreover, using l,l- and l,d-N-octyl-PheLeu as carriers, remarkable diastereomeric effects were observed in the rate of uptake and release of Cu(II) ion although the differences mutually compensate in the overall transport rate. Under the conditions used the carriers are much less effective in the translocation of Zn(II) and Ni(II) and their transport efficiency drops dramatically in the presence of Cu(II), the latter being favored by factors of 1.2 × 103 and >104, respectively. Such very high selectivities depend on the fact that only Cu(II) among other transition metal ions can form neutral complexes at the pH value of the source phase.

Selective Liquid Membrane Transport of Lead(II) by an Acyclic Polyether Dicarboxylic Acid Ionophore

The effects of the chain structure and substitutents in six acyclic polyether dicarboxylic acids and one acyclic polyether carboxylic acid upon the efficiency and selectivity of pH-driven Pb(2+) transport in a bulk chloroform membrane system have been assessed. Among the carriers, 1,2-bis[2-(o-carboxyphenoxy)ethoxy]-4-tert-butylbenzene (1) is found to exhibit high selectivity for transport of Pb(2+) compared with alkali metal cations and a variety of other divalent metal ion species. Ionophore 1 also extracts Pb(2+) from aqueous solution into chloroform with the loss of two protons. A 1:1 complex of Pb(2+) with di-ionized 1 was isolated.

Syntheses of bis- and tetra-crowned clefts and studies of their selectivities in metal ion complexation

A novel “tetra[benzo(18-crown-6)]-crowned cleft” ( 2) and two new “bis[benzo(15-crown-5)]-crowned clefts” ( 3 and 4) have been synthesized. Their respective selectivities in (i) alkali metal picrate extraction into chloroform and (ii) alkali metal perchlorate transport across bulk chloroform membranes have been determined relative to those of appropriate model compounds in each case. The observed picrate extraction selectivity order for 2, i. e. Cs + > Rb + > K + > Na + > Li +, strongly suggests the existence of “sandwich” complexes which result from extraction cooperativity between two spatially proximate benzo(18-crown-6) units in 2 and a guest alkali metal cation. Interestingly, the corresponding selectivity order for 3 and 4 suggests that only 1: 1 metal ion-crown ether complexes are formed. For bulk chloroform membranes, bis- and tetra-crowned clefts exhibit much more efficient transport of certain alkali metal perchlorates than do model mono-crown ether compounds.