Specific anion and cation binding to lipid membranes investigated on a solid supported membrane

Ion binding to a lipid membrane is studied by application of a rapid solution exchange on a solid supported membrane. The resulting charge displacement is analyzed in terms of the affinity of the applied ions to the lipid surface. We find that chaotropic anions and kosmotropic cations are attracted to the membrane independent of the membrane composition. In particular, the same behavior is found for lipid headgroups bearing no charge, like monoolein. This general trend is modulated by electrostatic interaction of the ions with the lipid headgroup charge. These results cannot be explained with the current models of specific ion interactions.     

Interaction of monovalent ions with hydrophobic and hydrophilic colloids: charge inversion and ionic specificity

Here we study experimentally and by simulations the interaction of monovalent organic and inorganic anions with hydrophobic and hydrophilic colloids. In the case of hydrophobic colloids, our experiments show that charge inversion is induced by chaotropic inorganic monovalent ions but it is not induced by kosmotropic inorganic anions. For organic anions, giant charge inversion is observed at very low electrolyte concentrations. In addition, charge inversion disappears for both organic and inorganic ions when turning to hydrophilic colloids. These results provide an experimental evidence for the hydrophobic effect as the driving force for both ion specific effects and charge inversion. In the case of organic anions, our molecular dynamics (MD) simulations with full atomic detail show explicitly how the large adsorption free energies found for hydrophobic colloids are transformed into large repulsive barriers for hydrophilic colloids. Simulations confirm that solvation free energy (and hence the hydrophobic effect) is responsible for the build up of a Stern layer of adsorbed ions and charge inversion in hydrophobic colloids and it is also the mechanism preventing charge inversion in hydrophilic colloids. Overall, our experimental and simulation results suggest that the interaction of monovalent ions with interfaces is dominated by solvation thermodynamics, that is, the chaotropic/kosmotropic character of ions and the hydrophobic/hydrophilic character of surfaces.     

Dynamical Dimension to the Hofmeister Series: Insights from First‐Principles Simulations

A systematic characterization of the competing kosmotropic and chaotropic effects of a series of divalent salts on the aqueous H‐bonding structure by means of first‐principles molecular dynamics simulations is presented. The structural properties are quantified by means of experimental and computed ¹H NMR chemical shifts, whereby the local environments of cations and anions can be discriminated. Complementary to the well‐established structural features, a dynamical aspect is added to the concept of kosmotropes and chaotropes. The H‐bond dynamics, quantified in terms of the H‐bonding autocorrelation functions, shows a good correlation with the structural kosmotropic and chaotropic modifications, which are commonly referred to as the Hofmeister series. The considerably enhanced (reduced) fluctuations of the H‐bonding network in the hydration shells around the anions (cations) are a complementary dynamical dimension to the concept of kosmotropic/chaotropic behavior of solvated ions.     

Is “Water in Salt” Electrolytes the Ultimate Solution? Achieving High Stability of Organic Anodes in Diluted Electrolyte Solutions Via a Wise Anions Selection

The introduction of the water-in-salt (WIS) electrolytes concept to prevent water splitting and widen the electrochemical stability window, has spurred extensive research efforts toward development of improved aqueous batteries. The successful implementation of these electrolyte solutions in many electrochemical systems shifts the focus from diluted to WIS electrolyte solutions. Considering the high costs and the tendency of these nearly saturated solutions to crystallize, this trend can be carefully re-evaluated. Herein we show that the stability of organic electrodes comprising the active material perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA), is strongly influenced by the solvation character of the anions rather than the concentration of the electrolyte solution. Even though the charging process of PTCDA involves solely insertion of cations (i.e., principal counter-ions), surprisingly, the dominant factor influencing its electrochemical performance, including long-term electrode stability, is the type of the co-ions (i.e., electrolytic anions). Using systematic electrochemical analysis combined with theoretical simulations, we show that the selection of kosmotropic anions results in fast fading of the PTCDA anodes, while a selection of chaotropic anions leads to excellent stability, even at electrolytes concentrations as low as 0.2 M. These findings provide a new conceptual approach for designing advanced electrolyte solutions for aqueous batteries.     

Improving the Enzyme Catalytic Efficiency Using Ionic Liquids with Kosmotropic Anions

The kosmotropicity of cations and anions in ionic liquids has a strong influence on the enzyme catalytic efficiency in aqueous environments. The kosmotropic anion CF3COO^- seemed to activate the protease, and the chaotropic anions tended to destabilize the enzyme.     

Sulfonium and phosphonium, new ion-pairing agents with unique selectivity towards polarizable anions

Ion-pair chromatography (IPC) almost universally relies upon ammonium-based ion-pairing agents (IPAs) for anion separations. This work compares tetrabutylammonium (TBA) with tetrabutylphosphonium (TBP) and tributylsulfonium (TBS). To best understand the retention behavior analytes used for characterization of the IPAs spanned the Hofmeister series; from kosmotropic monoanions (iodate, chloride, nitrite) and intermediate anions (nitrate, bromide) to chaotropic ions (perchlorate, thiocyanate, iodide). The studies demonstrate that tetrabutylphosphonium is the most chaotropic IPA, followed by tetrabutylammonium and finally tributylsulfonium is the least chaotropic. In the case of the chaotropic anions, the retention of perchlorate was least with tributylsulfonium, and greatest for tetrabutylphosphonium, with tetrabutylammonium being intermediate. The multivalent kosmotropic anions (sulfate, chromate, thiosulfate) demonstrated unique selectivity changes depending on the kosmotropic/chaotropic nature of the IPA. Demonstrating increases in retention with increasing IPA concentration only with tributylsulfonium, whereas the more chaotropic IPAs universally decreased the retention of the multivalent anions.     

Effects of antidepressants on the conformation of phospholipid headgroups studied by solid-state NMR

The effect of tricyclic antidepressants (TCA) on phospholipid bilayer structure and dynamics was studied to provide insight into the mechanism of TCA-induced intracellular accumulation of lipids (known as lipidosis). Specifically we asked if the lipid-TCA interaction was TCA or lipid specific and if such physical interactions could contribute to lipidosis. These interactions were probed in multilamellar vesicles and mechanically oriented bilayers of mixed phosphatidylcholine-phosphatidylglycerol (PC-PG) phospholipids using (31)P and (14)N solid-state NMR techniques. Changes in bilayer architecture in the presence of TCAs were observed to be dependent on the TCA's effective charge and steric constraints. The results further show that desipramine and imipramine evoke distinguishable changes on the membrane surface, particularly on the headgroup order, conformation and dynamics of phospholipids. Desipramine increases the disorder of the choline site at the phosphatidylcholine headgroup while leaving the conformation and dynamics of the phosphate region largely unchanged. Incorporation of imipramine changes both lipid headgroup conformation and dynamics. Our results suggest that a correlation between TCA-induced changes in bilayer architecture and the ability of these compounds to induce lipidosis is, however, not straightforward as imipramine was shown to induce more dramatic changes in bilayer conformation and dynamics than desipramine. The use of (14)N as a probe was instrumental in arriving at the presented conclusions.     

Phospholipid Bilayer-Perturbing Properties Underlying Lysis Induced by pH-Sensitive Cationic Lysine-Based Surfactants in Biomembranes

Amino acid-based surfactants constitute an important class of natural surface-active biomolecules with an unpredictable number of industrial applications. To gain a better mechanistic understanding of surfactant-induced membrane destabilization, we assessed the phospholipid bilayer-perturbing properties of new cationic lysine-based surfactants. We used erythrocytes as biomembrane models to study the hemolytic activity of surfactants and their effects on cells' osmotic resistance and morphology, as well as on membrane fluidity and membrane protein profile with varying pH. The antihemolytic capacity of amphiphiles correlated negatively with the length of the alkyl chain. Anisotropy measurements showed that the pH-sensitive surfactants, with the positive charge on the α-amino group of lysine, significantly increased membrane fluidity at acidic conditions. SDS-PAGE analysis revealed that surfactants induced significant degradation of membrane proteins in hypo-osmotic medium and at pH 5.4. By scanning electron microscopy examinations, we corroborated the interaction of surfactants with lipid bilayer. We found that varying the surfactant chemical structure is a way to modulate the positioning of the molecule inside bilayer and, thus, the overall effect on the membrane. Our work showed that pH-sensitive lysine-based surfactants significantly disturb the lipid bilayer of biomembranes especially at acidic conditions, which suggests that these compounds are promising as a new class of multifunctional bioactive excipients for active intracellular drug delivery.     

Self-assembled multilayers of gold nanoparticles: nitrate-induced rectification of quantized capacitance charging and effects of alkaline (earth) ions in aqueous solutions

Gold nanoparticle multilayers were self-assembled onto an electrode surface by using a dipping method. The particle assemblies exhibited quantized capacitance charging characteristics in aqueous media that were rectified by hydrophobic anions such as PF6-, BF4- and ClO4-, similar to the behavior with the monolayer counterparts. More interestingly, even in the presence of less hydrophobic anions such as NO3-, very well-defined single electron transfers were observed voltammetrically with these particle multilayers, a response unseen previously with particle monolayers. This was ascribed, in part, to the enhanced interactions between the particle multilayers and the electrolyte anions as well as the minimization of the structural defects within the particle thin films as compared to the monolayer counterparts. Further studies showed that with particles functionalized with oligo(ethylene oxide) moieties, the particle charge transfer properties were also found to be affected by electrolyte cations, reflected by the variation of the particle molecular capacitance and formal potentials with the nature of the alkaline (earth) metal ions.     

Cholesterol slows down the lateral mobility of an oxidized phospholipid in a supported lipid bilayer

We investigated the mobility and phase-partitioning of the fluorescent oxidized phospholipid analogue 1-palmitoyl-2-glutaroyl-sn-glycero-3-phospho-N-Alexa647-ethanolamine (PGPE-Alexa647) in supported lipid bilayers. Compared to the conventional phospholipid dihexadecanoylphosphoethanolamine (DHPE)-Bodipy we found consistently higher diffusion constants. The effect became dramatic when immobile obstacles were inserted into the bilayer, which essentially blocked the diffusion of DHPE-Bodipy but hardly influenced the movements of PGPE-Alexa647. In a supported lipid bilayer made of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), the differences in probe mobility leveled off with increasing cholesterol content. Using coarse-grained molecular dynamics simulations, we could ascribe this effect to increased interactions between the oxidized phospholipid and the membrane matrix, concomitant with a translation in the headgroup position of the oxidized phospholipid: at zero cholesterol content, its headgroup is shifted to the outside of the DOPC headgroup region, whereas increasing cholesterol concentrations pulls the headgroup into the bilayer plane.     

Mechanistic studies on the separation of cations in zwitterionic ion chromatography

Electrostatic ion chromatography, also known as zwitterionic ion chromatography, has been predominantly used for the analysis of anions. Consequently, separation mechanisms proposed for this technique have been based on anion retention data obtained using a sulfobetaine-type surfactant-coated column. A comprehensive cation retention data set has been obtained on a C18 column coated with the zwitterionic surfactant N-tetradecylphosphocholine (which has the negatively and positively charged functional groups reversed in comparison to the sulfobetaine surfactants), with mobile phases being varied systematically in the concentration and species of both the mobile-phase anion and cation. A retention mechanism based on both an ion exclusion effect and a direct (chaotropic) interaction with the inner negative charge on the zwitterion is proposed for the retention of cations. Despite the relatively low chaotropic nature of cations compared with anions, the retention data shows that cations are retained in this system predominantly due to a chaotropic interaction with the inner charge, analogous to anions in a system where the C18 column is coated with a sulfobetaine-type surfactant. The retention of an analyte cation, and the effect of the mobile-phase anion and cation, can be predicted by the relative positions of these species on the Hofmeister (chaotropic) series.     

Effects of Hofmeister anions on the phase transition temperature of elastin-like polypeptides

The modulation of the lower critical solution temperature (LCST) of two elastin-like polypeptides (ELPs) was investigated in the presence of 11 sodium salts that span the Hofmeister series for anions. It was found that the hydrophobic collapse/aggregation of these ELPs generally followed the series. Specifically, kosmotropic anions decreased the LCST by polarizing interfacial water molecules involved in hydrating amide groups on the ELPs. On the other hand, chaotropic anions lowered the LCST through a surface tension effect. Additionally, chaotropic anions showed salting-in properties at low salt concentrations that were related to the saturation binding of anions with the biopolymers. These overall mechanistic effects were similar to those previously found for the hydrophobic collapse and aggregation of poly(N-isopropylacrylamide), PNIPAM. There is, however, a crucial difference between PNIPAM and ELPs. Namely, PNIPAM undergoes a two-step collapse process as a function of temperature in the presence of sufficient concentrations of kosmotropic salts. By contrast, ELPs undergo collapse in a single step in all cases studied herein. This suggests that the removal of water molecules from around the amide moieties triggers the removal of hydrophobic hydration waters in a highly coupled process. There are also some key differences between the LCST behavior of the two ELPs. Specifically, the more hydrophilic ELP V5A2G(3)-120 construct displays collapse/aggregation behavior that is consistent with a higher concentration of anions partitioning to polymer/aqueous interface as compared to the more hydrophobic ELP V(5)-120. It was also found that larger anions could bind with ELP V5A2G(3)-120 more readily in comparison with ELP V(5)-120. These latter results were interpreted in terms of relative binding site accessibility of the anion for the ELP.     

Chaotropic Monovalent Anion‐Induced Rectification Inversion at Nanopipettes Modified by Polyimidazolium Brushes

A nonintuitive observation of monovalent anion‐induced ion current rectification inversion at polyimidazolium brush (PimB)‐modified nanopipettes is presented. The rectification inversion degree is strongly dependent on the concentration and species of monovalent anions. For chaotropic anions (for example, ClO₄^?), the rectification inversion is easily observed at a low concentration (5 mm ), while there is no rectification inversion observed for kosmotropic anions (Cl^?) even at a high concentration (1 m ). Moreover, at the specific concentration (for example, 10 mm ), the variation of rectification ratio on the type of anions is ranged by Hofmeister series (Cl^?≥NO₃^?>BF₄^?>ClO₄^?>PF₆^?>Tf₂N^?). Estimation of the electrokinetic charge density (σ^ek) demonstrates that rectification inversion originates from the charge inversion owing to the over‐adsorption of chaotropic monovalent anion. To qualitatively understand this phenomenon, a concentration‐dependent adsorption mechanism is proposed.     

Hofmeister effects on the colloidal stability of an IgG-coated polystyrene latex

The effect of various ions related to the Hofmeister series (HS) on different properties of a cationic latex covered with a protein (IgG) is analyzed in this study. NaNO3, NH4NO3, and Ca(NO3)2 were used to compare the specificity of the cations, and NaCl, NaSCN, NaNO3, and Na2SO4, to compare the specificity of the anions. Two pH values, 4 and 10, were chosen to analyze the behavior of these ions acting as counter- and co-ions. At pH 4, the total surface charge is positive, whereas at pH 10 it is negative. Three different phenomena have been studied in the presence of these Hofmeister ions: (1) colloidal aggregation, (2) electrophoretic mobility, and (3) colloidal restabilization. The specific effect of the ions was clearly observed in all experiments, obtaining ion sequences ordered according to their specificity. The most important parameter for ion ordering was the sign of the charge of the colloidal particle. Positively charged particles displayed an ion order opposite that observed for negatively charged surfaces. Another influential factor was the hydrophobic/hydrophilic character of the particle surface. IgG-latex particle surfaces at pH 10 were more hydrophilic than those at pH 4. The SCN- ion had a peculiar specific effect on the phenomena studied (1)-(3) at pH 10. With respect to the restabilization studies at high ionic strengths, new interesting results were obtained. Whereas it is commonly known that cations may provoke colloidal restabilization in negative particles when they act as counterions, our experiments demonstrated that such restabilization is also possible with positively charged particles. Likewise, restabilization of negative surfaces induced by the specific effect of chaotropic anions (acting as co-ions) was also observed.     

Specific ion effects on the electrochemical properties of cytochrome c

The range of salts used as supporting electrolytes in electrochemical studies of redox proteins and enzymes varies widely, with the choice of an electrolyte relying on the assumption that the electrolyte used does not affect the electrochemical properties of the proteins and enzymes under investigation. Examination of the electrochemical properties of the redox protein cytochrome c (cyt c) at a 4,4'-bipyridyl modified gold electrode demonstrates that both the redox potential (E(o')) and the faradaic current are influenced by the nature of the electrolyte used, in a manner explained primarily by Hofmeister effects. The faradaic peak currents display an atypical trend on switching from kosmotropic to chaotropic anions, with a maximum current observed in the presence of Cl(-). For a series of cations, the peak current increased in the sequence: Li(+) (0.34 μA) < guanidinium(+) (0.36 μA) < Na(+) (0.37 μA) < K(+) (0.38 μA) < Cs(+) (0.40 μA) and for anions it decreased in the sequence: Cl(-) (0.37 μA) > Br(-) (0.35 μA) > ClO(4)(-) (0.35 μA) > SCN(-) (0.31 μA) > F(-) (0.30 μA). E(o') decreased by a total of 24 mV across the series F(-) > Cl(-) > Br(-) > ClO(4)(-) > SCN(-) whereas no specific ion effect on E(o') was observed for cations. Factorisation of E(o') into its enthalpic and entropic components showed that while no specific trends were observed, large changes in ΔH(o') and ΔS(o') occurred with individual ions. The effect of anions on the faradaic peak current can be qualitatively explained by considering Collins' empirical rule of 'matching water affinities'. The effect of cations cannot be explained by this rule. However, both anion and cation effects can be understood by taking into account the cooperative action of electrostatic and ion dispersion forces. The results demonstrate that the choice of a supporting electrolyte in electrochemical investigations of redox proteins is important and emphasize that care needs to be taken in the determination and comparison of E(o'), ΔH(o') and ΔS(o') in different solutions.     

Electrochemical quartz crystal microbalance studies of the rectified quantized charging of gold nanoparticle multilayers

Electrochemical quartz crystal microbalance (EQCM) was employed to investigate the dynamics of rectified quantized charging of gold nanoparticle multilayers by in situ monitoring of the interfacial mass changes in aqueous solutions with varied electrolytes. EQCM measurements showed that interfacial mass changes only occurred at potentials more positive than the potential of zero charge (PZC), where nanoparticle quantized charging was well-defined, whereas in the negative potential regime where only featureless voltammetric responses were observed, the QCM frequency remained virtually invariant. This was ascribed to the fact that nanoparticle quantized charging was induced by the formation of ion-pairs between hydrophobic electrolyte anions (PF6-, ClO4-, BF4-, and NO3-) and positively charged gold nanoparticles. Based on the total frequency changes and the number of electrolyte anions adsorbed onto the particle layers, the number of water molecules that were involved in the ion-pairing processes was then quantitatively estimated at varied particle charge states, which was found to increase with increasing hydrophobicity of the anions. Additionally, the electron-transfer dynamics of the gold particle multilayers were also evaluated by electrochemical impedance measurements. It was found that the particle electron-transfer rate was about an order of magnitude slower than that of the ion diffusion and binding.     

Donnan permselectivity in layer-by-layer self-assembled redox polyelectrolye thin films

Redox polyelectrolyte multilayers have been assembled with use of the layer-by-layer (LBL) deposition technique with cationic poly(allylamine) modified with Os(bpy)(2)ClPyCHO (PAH-Os) and anionic poly(styrene)sulfonate (PSS) or poly(vinyl)sulfonate (PVS). Different behavior has been observed in the formal redox potential of the Os(II)/Os(III) couple in the polymer film with cyclic voltammetry depending on the charge of the outermost layer and the electrolyte concentration and pH. The electrochemical quartz crystal microbalance (EQCM) has been used to monitor the exchange of ions and solvent with the external electrolyte during redox switching. At low ionic strength Donnan permselectivity of anions or cations is apparent and the nature of the ion exclusion from the film is determined by the charge of the topmost layer and solution pH. At high electrolyte concentration Donnan breakdown is observed and the osmium redox potential approaches the value for the redox couple in solution. Exchange of anions and water with the external electrolyte under permselective conditions and salt and water under Donnan breakdown have been observed upon oxidation of the film at low pH for the PAH-Os terminating layer. Moreover, at high pH values and with PVS as the terminating layer EQCM mass measurements have shown that cation release was masked by water exchange.     

Understanding the Hofmeister effect in interactions between chaotropic anions and lipid bilayers: molecular dynamics simulations

A set of all-atom molecular dynamics simulations have been performed to better understand critical phenomena regarding a Hofmeister series of anions and lipid bilayers. The simulations isolate the effect of anion size and show clear differences in the interactions with the dipolar phoshpatidylcholine headgroup. Cl- anions penetrate into the headgroup region of the bilayer, but the simulations confirm theories which predict that larger anions penetrate more deeply, into a more heterogeneous and hydrophobic molecular region. That anion size leads to such differences in partitioning in the bilayer provides atomic-level support to hypotheses inspired by several experimental studies. The ability of larger anions to bury deep within the bilayer is correlated with a less well-structured hydration shell, shedding of which upon penetration incurs a smaller penalty for the larger anions than for Cl-.     

Hofmeister离子对水溶液中热响应聚合物的局域环境的影响

The Hofmeister ion effect is a very interesting but elusive phenomenon, the importance of which is revealed in self-assembly, ion recognition, and protein folding regulation. With an increasing number of studies suggesting that interactions between ions and solutes play a role in the Hofmeister ion effect, the nature of the Hofmeister phenomenon becomes more debatable. Yet, it is not clear whether the Hofmeister ion effect is a local effect or bulk effect that can reach beyond many hydration shells, where specific interactions between ions and solutes play key roles. In order to further explore this, we applied proton nuclear magnetic resonance (¹H-NMR) spectroscopy to study the effects of specific ions on the local environment around N, N-dimethylpropionamide (NDA) and N-isopropylisobutyramide (NPA), which are the model compounds for poly(2-ethyl-2-oxazoline) and poly(N-isopropylacrylamide), respectively. These polymers are important bio-engineering materials that possess thermoresponsive properties and are also subject to specific ion effects. By correlating the changes in chemical shifts of the two methyl groups on either side of the amide bond, it was found that the Hofmeister ion effects on NPA were more anisotropic than on NDA, and that the cationic effects were more anisotropic than the anionic effects on NPA. These results indicated that the effects of specific ions were almost identical for all methyl groups of NDA. On the other hand, NPA is a larger molecule; thus, not all of its methyl groups were subjected to the specific ion effects to the same extent. The calculation of the electrostatic potential surfaces of NDA and NPA suggested that these observations on the Hofmeister ion effects might be due to steric hindrance, and that the observations on the cationic effects might be due to the interactions between cations and NPA being stronger than the interactions between anions and NPA. This would explain why the highly charged cations caused a significant anisotropicity. Additionally, we found that the chemical shift of the water protons (Δδ_H2O) of conventional kosmotropic anions was larger than zero, which suggested a stronger HB and more charge transfer between water and these anions. The Δδ_H2O of conventional chaotropic anions was less than zero. Despite the different solutes, the results were indifferent in both NDA and NPA solutions. Surprisingly, the Δδ_H2O of Cl^- at concentrations lower than 1 mol∙L^-1 was zero, thus becoming the benchmark between chaotropes and kosmotropes. These results suggested a quantitative measurement of kosmotropicity/chaotropicity, where the anion would be kosmotropic if its Δδ_H2O were higher than that of Cl^- and chaotropic for the opposing condition. Moreover, the results showed that the effects of the cations on the water structure were minimal, which was consistent with minimal charge transfer between the cations and water. The overall results of this study suggest that the Hofmeister ion effect is a global effect, while local interactions of ions with solutes also play a key role.     

Mechanisms of passive ion permeation through lipid bilayers: insights from simulations

Multistate empirical valence bond and classical molecular dynamics simulations were used to explore mechanisms for passive ion leakage through a dimyristoyl phosphatidylcholine lipid bilayer. In accordance with a previous study on proton leakage (Biophys. J. 2005, 88, 3095), it was found that the permeation mechanism must be a highly concerted one, in which ion, solvent, and membrane coordinates are coupled. The presence of the ion itself significantly alters the response of those coordinates, suggesting that simulations of transmembrane water structures without explicit inclusion of the ionic solute are insufficient for elucidating transition mechanisms. The properties of H(+), Na(+), OH(-), and bare water molecules in the membrane interior were compared, both by biased sampling techniques and by constructing complete and unbiased transition paths. It was found that the anomalous difference in leakage rates between protons and other cations can be largely explained by charge delocalization effects rather than the usual kinetic picture (Grotthuss hopping of the proton). Permeability differences between anions and cations through phosphatidylcholine bilayers are correlated with suppression of favorable membrane breathing modes by cations.