Specific Counterion Research Articles

Aluminum-Catalyzed Intramolecular Vinylation of Arenes by Vinyl Cations.

This study addresses the challenges associated with vinyl cation generation, a process that traditionally requires quite specific counterions. Described herein is a novel intramolecular vinylation of arenes catalyzed by aluminum(III) chloride, utilizing practical conditions and readily available vinyl triflates derived from 2-aceto-3-arylpropionates. Comprehensive experimental data support diverse carbocycle synthesis, exemplified by indenes and higher analogues. Control experiments verify the applicability of the vinylation protocol, and synthetic applications showcase a potent tubulin polymerization inhibitor with anticancer properties. Density functional theory computations reveal a Lewis-acid-driven mechanism involving triflate moiety abstraction to generate a reactive vinyl cation.

Asymptotic analysis on charging dynamics for stack-electrode model of supercapacitors

Supercapacitors are promising electrochemical energy storage devices due to their prominent performance in rapid charging/discharging rates, long cycle life, stability, etc. Experimental measurement and theoretical prediction on charging timescale for supercapacitors often have large differences. This work develops a matched asymptotic expansion method to derive the charging dynamics of supercapacitors with porous electrodes, in which the supercapacitors are described by the stack-electrode model. Coupling leading-order solutions between every two stacks by continuity of ionic concentration and fluxes leads to an ODE system, which is a generalized equivalent circuit model for zeta potentials, with the potential-dependent nonlinear capacitance and resistance determined by physical parameters of electrolytes, e.g. specific counterion valences for asymmetric electrolytes. Linearized stability analysis on the ODE system after projection is developed to theoretically characterize the charging timescale. The derived asymptotic solutions are numerically verified. Further numerical investigations on the biexponential charging timescales demonstrate that the proposed generalized equivalent circuit model, as well as companion linearized stability analysis, can faithfully capture the charging dynamics of symmetric/asymmetric electrolytes in supercapacitors with porous electrodes.

Lipid exchange among electroneutral Sulfo-DIBMA nanodiscs is independent of ion concentration.

Polymer-encapsulated nanodiscs enable membrane proteins to be investigated within a native-like lipid-bilayer environment. Unlike other bilayer-based membrane mimetics, these nanodiscs are equilibrium structures that permit lipid exchange on experimentally relevant timescales. Therefore, examining the kinetics and mechanisms of lipid exchange is of great interest. Since the high charge densities of existing anionic polymers can interfere with protein-protein and protein-lipid interactions as well as charge-sensitive analysis techniques, electroneutral nanodisc-forming polymers have been recently introduced. However, it has remained unclear how the electroneutrality of these polymers affects the lipid-exchange behavior of the nanodiscs. Here, we use time-resolved Förster resonance energy transfer to study the kinetics and the mechanisms of lipid exchange among nanodiscs formed by the electroneutral polymer Sulfo-DIBMA. We also examine the role of coulombic repulsion and specific counterion association in lipid exchange. Our results show that Sulfo-DIBMA nanodiscs exchange lipids on a similar timescale as DIBMA nanodiscs. In contrast with nanodiscs made from polyanionic DIBMA, however, the presence of mono- and divalent cations does not influence lipid exchange among Sulfo-DIBMA nanodiscs, as expected from their electroneutrality. The robustness of Sulfo-DIBMA nanodiscs against varying ion concentrations opens new possibilities for investigating charge-sensitive processes involving membrane proteins.

Chloride Ions Are Required for Thermosipho africanus MurJ Function.

Most bacteria have a peptidoglycan cell wall that determines their cell shape and helps them resist osmotic lysis. Peptidoglycan synthesis depends on the translocation of the lipid-linked precursor lipid II across the cytoplasmic membrane by the MurJ flippase. Structure-function analyses of MurJ from Thermosipho africanus (MurJTa) and Escherichia coli (MurJEc) have revealed that MurJ adopts multiple conformations and utilizes an alternating-access mechanism to flip lipid II. MurJEc activity relies on membrane potential, but the specific counterion has not been identified. Crystal structures of MurJTa revealed a chloride ion bound to the N-lobe of the flippase and a sodium ion in its C-lobe, but the role of these ions in transport is unknown. Here, we investigated the effect of various ions on the function of MurJTa and MurJEc in vivo. We found that chloride, and not sodium, ions are necessary for MurJTa function, but neither ion is required for MurJEc function. We also showed that murJTa alleles encoding changes at the crystallographically identified sodium-binding site still complement the loss of native murJEc, although they decreased protein stability and/or function. Based on our data and previous work, we propose that chloride ions are necessary for the conformational change that resets MurJTa after lipid II translocation and suggest that MurJ orthologs may function similarly but differ in their requirements for counterions. IMPORTANCE The biosynthetic pathway of the peptidoglycan cell wall is one of the most favorable targets for antibiotic development. Lipid II, the lipid-linked PG precursor, is made in the inner leaflet of the cytoplasmic membrane and then transported by the MurJ flippase so that it can be used to build the peptidoglycan cell wall. MurJ functions using an alternating-access mechanism thought to depend on a yet-to-be-identified counterion. This study fills a gap in our understanding of MurJ's energy-coupling mechanism by showing that chloride ions are required for MurJ in some, but not all, organisms. Based on our data and prior studies, we propose that, while the general transport mechanism of MurJ may be conserved, its specific mechanistic details may differ across bacteria, as is common in transporters. These findings are important to understand MurJ function and its development as an antibiotic target.

Nanoscale chemomechanical variations of montmorillonite induced by the specificity of counterions—An in situ XRD and AFM study

The variable structural characteristics of montmorillonite (Mnt) in salt solutions depend not only on the quantity and distribution of the Mnt layer charge, but also on the specificity of counterions, including their radius, valence, concentration, and hydratability. In order to determine the nanoscale chemomechanical processes in a clay mineral–water–salt system, in situ X-ray diffraction (XRD) and atomic force microscopy (AFM) methods were used to investigate the structural variations of Mnt caused by different counterion species (e.g., Li+, Na+, K+, Rb+, Cs+, Mg2+, Ca2+, and Sr2+) at different concentrations (0.2–3.0 M). With an increasing concentration of counterions, separation of water molecules from the interlayer space of more weakly hydrated cations (Cs+, Rb+, and K+) is faster than for the more strongly hydrated cations (Li+, Na+, Mg2+, Ca2+, and Sr2+), water molecules are lost more slowly from the hydration shell, which remains stable even at high counterion concentrations. The sequential ion exchange in a monolayer Mnt observed by in situ AFM is consistent with the d(001) results from the real-time XRD analysis. Moreover, various defects on Mnt surfaces were visible in the high-resolution AFM images, which restrict the spatial arrangement of adsorbed cations. The water molecule partitioning between the interlayers in Mnt is controlled by the specificity of the counterions, and the cations can spontaneously form ordered structures on the surface of Mnt. These nonclassical interfacial phenomena occurred in the electric double layer (EDL) is controlled by the hydration of counterions, the surface structure and the charge distribution of Mnt.

Specific Counterion Effects on the Swelling Behavior of Strong Polyelectrolyte Brushes

Specific Counterion Effects on the Swelling Behavior of Strong Polyelectrolyte Brushes

Long-Range Electrostatic Colloidal Interactions and Specific Ion Effects in Deep Eutectic Solvents.

While the traditional consensus dictates that high ion concentrations lead to negligible long-range electrostatic interactions, we demonstrate that electrostatic correlations prevail in deep eutectic solvents where intrinsic ion concentrations often surpass 2.5 M. Here we present an investigation of intermicellar interactions in 1:2 choline chloride:glycerol and 1:2 choline bromide:glycerol using small-angle neutron scattering. Our results show that long-range electrostatic repulsions between charged colloidal particles occur in these solvents. Interestingly, micelle morphology and electrostatic interactions are modulated by specific counterion condensation at the micelle interface despite the exceedingly high concentration of the native halide from the solvent. This modulation follows the trends described by the Hofmeister series for specific ion effects. The results are rationalized in terms of predominant ion–ion correlations, which explain the reduction in the effective ionic strength of the continuum and the observed specific ion effects.

Mathematical Modeling of the Effect of Pulsed Electric Field on the Specific Permselectivity of Ion-Exchange Membranes.

The application of pulsed electric field (PEF) in electrodialysis has been proven to be efficient for a number of effects: increasing mass transfer rate, mitigation of scaling and fouling, reducing water splitting. Recently, the improvement of the membrane permselectivity for specific counterions was discovered experimentally by the group of Laurent Bazinet (N. Lemay et al. J. Memb. Sci. 604, 117878 (2020)). To better understanding the effect of PEF in electrodialysis, simulations were performed using a non-stationary mathematical model based on the Nernst–Planck and Poisson equations. For the first time, it was not only the condition used when the current density is specified but also the condition when the voltage is set. A membrane and two adjacent diffusion layers are considered. It is shown that when applying the regime used by Lemay et al. (the same current density in conventional continuous current (CC) mode and during the pulses in PEF mode), there is a significant gain in specific permselectivity. It is explained by a reduction in the membrane concentration polarization in PEF mode. In the CC mode of electrodialysis, increasing current density leads to a loss in specific permselectivity: concentration profiles in the diffusion layers and membrane are formed in such a way that ion diffusion reduces the migration flux of the preferentially transferred ion and increases that of the poorly transferred ion. In PEF mode, the concentration profiles are partially restored during the pauses when the current is zero. However, if a different condition is used than the condition applied by Lemay et al., that is, when the same average current density is applied in both the PEF and CC modes, there is no gain in specific permeability. It is shown that within the framework of the applied mathematical model, the specific selectivity depends only on the average current density and does not depend on the mode of its application (CC or PEF mode).

Quantifying the Counterion-Specific Effect on Surfactant Adsorption Using Modeling, Simulation, and Experiments.

Ionic surfactants behave differently in the presence of various counterions, which plays an important role in many scientific and engineering processes. Previous work has shown that the counterion-specific surface tension can be reproduced with classical adsorption models, but the underlying origin of this effect has not been explained. In this paper, we extend our previously developed adsorption model to account for the specific counterion adsorption. This model can accurately predict the surface tension of surfactant solutions like sodium dodecyl sulfate (SDS) in the presence of the monovalent salts LiCl, NaCl, KCl, and CsCl. The predicted surface excess and surface potential are validated by corresponding sum-frequency generation (SFG) spectroscopy experiments. We also used molecular dynamic (MD) simulation to explain the origin of the counterion-specific effect for surfactant behavior. Our study shows that for SDS, binding of the counterion to both the headgroup and a few CH2 fragments close to the surfactant head contributes to the counterion-specific effect. In general, SDS behaves like a large ion, and it prefers to bind with large counterions such as Cs+, which is consistent with Collins's law of matching water affinity. Therefore, large counterions enhance the surface adsorption and lower the surface tension the most.

Aqueous solubility of beryllium(II) at physiological pH: effects of buffer composition and counterions

Beryllium ion elicits p53-mediated cell cycle arrest in some types of human cancer cells, and it is a potent inhibitor of GSK3 kinase activity. Paradoxically, Be2+ is regarded to have almost negligible aqueous solubility at physiological pH, due to precipitation as Be(OH)2. This study demonstrates that the interaction of Be2+ with serum proteins greatly increases its effective solubility. In typical serum-supplemented mammalian cell culture medium, Be2+ was soluble up to about 0.5 mM, which greatly exceeds the concentration needed for biological activity. Some biochemical studies require protein-free Be2+ solutions. In such cases, the inclusion of a specific inorganic counterion, sulfate, increased solubility considerably. The role of sulfate as a solubility-enhancing factor became evident during preparation of buffered solutions, as the apparent solubility of Be2+ depended on whether H2SO4 or a different strong acid was used for pH adjustment. The binding behavior of Be2+ observed via isothermal titration calorimetry was affected by the inclusion of sodium sulfate. The data reflect a “Diverse Ion Effect” consistent with ion pair formation between solvated Be2+ and sulfate. These insights into the solubility behavior of Be2+ at physiological and near-physiological pH will provide guidance to assist sample preparation for biochemical studies.

Attraction between Like-Charged Macroions Mediated by Specific Counterion Configurations.

Attraction between like-charged macroions is fundamental to many processes in biology, chemistry, and physics. It also plays an important role in industrial applications such as ion-extraction processes or catalysis. In this work, we report a novel mechanism by which attraction can be realized between spherical macroions at high ionic strength. It consists of specific configurations of two, three, and more counterions that appear between macroions with high statistical probability. The attraction is manifested in a minimum in the potential of mean force between the macroions at short distances. Its depth increases with increasing charge of the macroion, demonstrating that the attraction is electrostatic in nature. It is shown that the implicit solvent model with a distance-dependent dielectric constant can capture both the geometry and thermodynamics of charge-stabilized macroion dimers on the qualitative level. The results obtained for a model colloid with a smooth surface are extrapolated to more realistic systems. Evidence is found that the reported mechanism can be observed in small chemical compounds with encapsulated ions such as fullerenes.

Mesoporous Silica Colloids: Wetting, Surface Diffusion, and Cationic Surfactant Adsorption

We have investigated the wetting and surface diffusion of mesoporous colloidal silica particles at the water surface and the adsorption of cationic cetyltrimethylammonium (CTA+) surfactant on these particles. Porous silica colloids diffuse at the surface of water and in the volume, interacting with cationic surfactants that can adsorb inside the pores of the particles. We observed that surfactant adsorption on mesoporous silica depends dramatically not only on the particle pore size but also on specific counterion effects. We measured striking differences both on a macroscopic property of the interface, i.e., surface tension, and also at a single particle level by evaluating the translational diffusion of partially wetted particles at the fluid interface. We varied the pore size from 2 to 7 nm and explored the effects of ions possessing different hydration number and kosmotropic/chaotropic character. At concentrations lower than the critical micellar concentration, we evidence that cationic surfactants adsorb on silica as surface micelles and surfactant adsorption inside the pores occurs only if the pore diameter is larger than the size of surface micelles. With a view to understand the surprising different adsorption behavior of CTA+OH– and CTA+Br– on porous silica particles, we investigated the effect of counterions on the surfactant adsorption on porous silica colloids by tuning the pH and the counterion properties.

Advances in Conducting, Biodegradable and Biocompatible Copolymers for Biomedical Applications

Electroactive biomaterials are a new generation of “smart” biomaterials based on intrinsically conducting polymers (ICP). Among them, poly(3,4-ethylenedioxythiophene) (PEDOT), polypyrrole (PPy) and polyaniline (PANI) are well known conducting polymers that present excellent electrical and optical properties emerging as main candidates for potential biomedical applications. Additionally, the biodegradability of biomaterials is very useful and desirable. In this context, biodegradable polymers based on polyesters, such as poly(D,L-lactic acid) (PDLLA), polycaprolactone (PCL) and poly(glycolic acid) (PGA) appear to be promising candidates because of their good biocompatibility and, as a consequence, they have been attracting attention as sustainable alternatives for applications in medicine. Weak molecular interaction with cells, biocompatibility, biodegradability, mechanics and topography are some of the main challenges for the use of conducting polymers as biomaterials. In order to improve their own biocompatibility, the main strategies are whether by doping with specific counter ions (biodopants) or chemically modifying the monomers with different molecules. Although conventional ICPs still present low or none biodegradability, there are relatively few examples of biodegradable electroactive polymers in the literature. Recently, novel approaches have been applied to solve the problem of lack of biodegradability of conducting polymers, mainly through (1) synthesis of a modified electroactive oligomers connected via degradable ester linkages creating block copolymers and (2) synthesis of modified electroactive and biodegradable macromonomers based on polyesters used in a second step copolymerization with conductive monomers. This mini-review focuses on developing trends, challenges and summarizes the recent advances on synthesis of conducting, biodegradable and biocompatible copolymers in terms of optimizing the chemical properties to improved response towards different cells, aiming biomedical applications.

Counterion Effect on Vibrational Relaxation and the Rotational Dynamics of Interfacial Water and an Anionic Vibrational Probe in the Confined Reverse Micelles Environment

Vibrational relaxation and the rotational dynamics of water molecules encapsulated in reverse micelles (RMs) have been investigated by ultrafast infrared (IR) spectroscopy and two-dimensional IR (2D IR) spectroscopy. By changing the counterion of the hydrophilic headgroup in the RMs formed by Aerosol-OT (AOT) from Na+ to K+, Cs+ and Ca2+, we could determine the specific counterion effects on the rotational dynamics of water molecules. The orientational relaxation time constant of water decreases in the order Ca2+ > Na+ > K+ > Cs+. The SCN- anionic probe and counterion can form ion pairs at the interfacial region of the RMs. The rotational dynamics of SCN- anion significantly decreases because of the synergistic effects of confinement and the surface interactions in the interfacial region of the RMs. The results can provide a new understanding of the cationic Hofmeister effect at the molecular level observed in biological studies.

Coacervation of Interfacial Adhesive Proteins for Initial Mussel Adhesion to a Wet Surface.

Coacervation of mussel adhesive proteins (MAPs) is proposed as a potential strategy that mussels may use during secretion due to their high concentration density, lack of dispersion into seawater, and low interfacial tension. Particularly, coacervations of interfacial MAPs, foot protein type-3 fast variant (fp-3F) and type-5 (fp-5), are important in the initial mussel adhesion process due to the relationship between the easy secretion/surface wetting properties of the coacervate and primer-like surface adhesive role of interfacial MAPs, which directly contact the marine surface. To the best of the authors' knowledge, this is the first report on coacervate formation of major recombinant interfacial MAPs with high charge densities and the highest 3,4-dihydroxyphenylalanine (Dopa) contents. Specifically, salt-induced coacervation of fp-3F is observed at low pH values corresponding to the acidified environment of the distal depression during mussel secretion. In addition, it shows enthalpy driven upper critical solution temperature behavior, possibly relying on bridging interactions between like-charged cationic fp-3Fs including salt-bridge and cation-π/π-π interactions in the presence of specific counterions, supported by Raman spectroscopy. It is believed that this study has broadened the scope of the understanding of coacervation of MAPs and may provide new insight for responsive biomaterial design.

Salt-Induced Colloidal Destabilization, Separation, Drying, and Redispersion in Aqueous Phase of Cationic and Anionic Nanochitins.

This study is aimed at facilitating the use of ocean biomass for the isolation and use of derived nanostructures. Specifically, cationic and anionic nanochitins were produced from never-dried crab shells that underwent partial deacetylation (PD-NCh) or TEMPO-oxidization (TO-NCh). The effects of different electrolyte types (NaCl, CH3COONa, Na2CO3, CaCl2, AlCl3, and NH4Cl) were investigated with regards to fractionation (via colloidal destabilization and precipitation), drying, and ultimate redispersion of the nanochitins. Sodium carbonate was most effective in the case of PD-NCh processing, whereas no significant effect of salt type was noted for TO-NCh. The results are rationalized in terms of the dispersion stability that resulted from specific counterion adsorption and nanoparticle association as well as electrostatic-charge development at a given solution pH. These effects were used to limit hydrogen bonding and nonspecific interactions upon drying of the nanochitins. The weak interactions between nanochitin and monovalent Na+ and NH4+ explain the experimental observations. Aqueous dispersions reconstituted from dried PD-NCh and TO-NCh were colloidally stable and yielded highly viscous, gel-like nanochitin dispersions at mass concentrations as low as 1.5 and 3.0%, respectively. Our findings are expected to greatly facilitate green processing of nanochitin, an emerging type of biobased nanomaterial.

Corrigendum: Counterion Specificity of Polyelectrolyte Brushes: Role of Specific Ion‐Pairing Interactions

In the above paper, the y-axis label of Figure 1 was incorrect. The y-axis label should read “Δf / Hz”and the corrected figure is shown below as Figure 1. Salt-concentration (Csalt) dependence of the frequency shift (Δf) of PMETAC brushes in the presence of different types of counterions with Na+ as the common cation. Here, the overtone number (n) is 3. The authors apologize for this oversight.

Counterion Specificity of Polyelectrolyte Brushes: Role of Specific Ion-Pairing Interactions.

We demonstrate here that the properties of poly (2-(methacryloyloxy) ethyl trimethylammonium chloride) brushes can be tuned by counterion species. When the brushes are exposed to external chloride (Cl- ) counterions, obvious dehydration and collapse are only observed at high salt concentrations. In the presence of very strongly chaotropic perchlorate (ClO4- ), the brushes strongly dehydrate and collapse at a very low salt concentration. For the strongly chaotropic thiocyanate ion (SCN- ), the changes in hydration and conformation of the brushes are similar to those observed for ClO4- but at a smaller extent at very low salt concentrations. With the addition of kosmotropic acetate (Ac- ), hydration of the brushes increases, accompanied by a swelling of the brushes in the low-salt-concentration regime. In contrast, the brushes dehydrate and collapse with increasing concentration of Ac- in the high-salt-concentration regime. The counterion specificity of the brushes demonstrated here is determined by specific ion-pairing interactions through modulating the osmotic pressure within the brushes and the hydrophobicity of the ion pairs.

Dual Effect of Histidine on Polysorbate 20 Stability: Mechanistic Studies.

L-Histidine (L-His) and polysorbate 20 (PS20) are two excipients frequently included in parenteral products to stabilize biotherapeutics. The objective of the current work was to investigate the impact of L-His on PS20 stability in aqueous solutions when subjected to forced oxidation and accelerated stability testing. The stability of PS20 in L-His buffer was compared with that in acetate buffer. Forced oxidation of PS20 in these two buffer systems was initiated by a free radical generator, 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH), while accelerated stability tests were carried out at 40°C. Ultra-performance liquid chromatography mass spectrometry was utilized to monitor intact PS20 and to analyze degradation products. Our results demonstrate a dual effect of L-His on PS20 stability. During exposure to AAPH, L-His protects PS20 from oxidation. Stable isotope labeling of L-His with 13C was employed for mechanistic investigations. The protection of L-His was abrogated when acetate was added to L-His buffer, implying that the anti-oxidative activity of L-His may be compromised by specific counter ions. The replacement of L-His by various His derivatives led to significant changes in the protection of PS20 against AAPH-induced degradation. In contrast to forced degradation, the addition of L-His promoted oxidative PS20 degradation during accelerated storage at 40°C in solution, generating mainly short chain POE-laurates. L-His exhibits a dual effect on the stability profile of PS20, protecting against AAPH-induced oxidation but promoting oxidative degradation during accelerated stability testing.

Colloid chemical characteristics of nanoporous glasses with different compositions in solutions of simple and organic electrolytes. 3. Calculation of electrochemical characteristics of membranes in terms of a homogeneous model

The electrosurface characteristics of nanoporous glass membranes–ion concentrations in pores with taking into account the specificity of counterions, electrokinetically mobile charge, the convective component of pore solution electrical conductivity, electroosmotic mobility of a liquid in the field of streaming potential and ion mobilities in pore space–were calculated within the homogeneous model. The effects of the type of counterion (sodium, potassium, ammonium, tetramethylammonium, and tetraethylammonium ions), solution concentration, glass composition, and pore size on the equilibrium and transport characteristics of membrane systems have been analyzed. A method for the determining of electrolyte activity coefficients in the membranes has been proposed.