Search Results (46)

Specific ion effects are widespread and have been studied for over a century, yet they remain poorly understood. Terms like “kosmotropes” and “chaotropes” are convenient rules of thumb but the frequent reversal of the Hofmeister series implies their limitations. Polarizability is often used to classify ions, with kosmotropes considered low in polarizability and chaotropes high. However, for polyatomic ions, this framework becomes misleading. The anisotropic nature of polarizability in polyatomic ions plays a decisive role in shaping their behavior. In this work, we study pseudohalides (KOCN, KSCN, and KSeCN) aqueous solutions to explore these effects. We evaluate properties of these anions through experimental measurements of conductivity, density, viscosity, infrared spectra, and polarizability. Our results demonstrate that, even for linear isoelectronic polyatomic ions, the anisotropy of polarizability governs their hydration behavior. Full article

The interactions and structural organization of water molecules play a crucial role in a wide range of physical, chemical, and biological processes. The ability of water to form hydrogen bonds (H-bonds) underpins its unique properties and enables it to respond dynamically to various environmental factors. These interactions at the molecular level may affect vital processes like protein folding, enzyme activity, and cellular organization. The presence of solutes and spatial constraints can alter the H-bonding network of water, and these effects are ubiquitous in the biological environment. In this study, we analyzed the fluorescence of 2-acetyl-6-(dimethylamino)naphthalene (ACDAN) fluorescence emission in water solutions containing kosmotropic and chaotropic salts and in agar hydrogels. Recently, this dye has proven invaluable in studying water network structure and dynamics, as its fluorescence signal changes based on the local dielectric environment, revealing variations in the dipolar relaxation of water. Our results show that ACDAN spectral response correlates with the degree of water ordering, providing important insights into solute–water interactions and water dynamics in free and confined environments. Full article

The Hofmeister series categorizes ions based on their effects on protein stability, yet the microscopic mechanism remains a mystery. In this series, NaCl is neutral, Na₂SO₄ and Na₂HPO₄ are kosmotropic, while GdmCl and NaSCN are chaotropic. This study employs CD and NMR to investigate the effects of NaCl, Na₂SO₄, and Na₂HPO₄ on the conformation, stability, binding, and backbone dynamics (ps-ns and µs-ms time scales) of the WW4 domain with a high stability and accessible side chains at concentrations ≤ 200 mM. The results indicated that none of the three salts altered the conformation of WW4 or showed significant binding to the four aliphatic hydrophobic side chains. NaCl had no effect on its thermal stability, while Na₂SO₄ and Na₂HPO₄ enhanced the stability by ~5 °C. Interestingly, NaCl only weakly interacted with the Arg27 amide proton, whereas Na₂SO₄ bound to Arg27 and Phe31 amide protons with Kd of 32.7 and 41.6 mM, respectively. Na₂HPO₄, however, bound in a non-saturable manner to Trp9, His24, and Asn36 amide protons. While the three salts had negligible effects on ps-ns backbone dynamics, NaCl and Na₂SO₄ displayed no effect while Na₂HPO₄ significantly increased the µs-ms backbone dynamics. These findings, combined with our recent results with GdmCl and NaSCN, suggest a microscopic mechanism for the Hofmeister series. Additionally, the data revealed a lack of simple correlation between thermodynamic stability and backbone dynamics, most likely due to enthalpy–entropy compensation. Our study rationalizes the selection of chloride and phosphate as the primary anions in extracellular and intracellular spaces, as well as polyphosphate as a primitive chaperone in certain single-cell organisms. Full article

The ability of thermoresponsive polymers to respond to temperature with a reversible conformational change makes them promising ‘smart’ materials for solutions in medical and biotechnological applications. In this work, two such polymers and structural isomers were studied: poly(N-isopropyl acrylamide) (PNiPAm) and poly(2-isopropyl-2-oxazoline) (PiPOx). We compare the critical solution temperatures (CST) of these polymers in D₂O and H₂O in the presence of Hofmeister series salts, as results obtained under these different solvent conditions are often compared. D₂O has a higher dipole moment and electronegativity than H₂O, which could significantly alter the CST transition. We used two complementary methods to measure the CST, dynamic light scattering (DLS) and differential scanning calorimetry (DSC) and found that the CST decreased significantly in D₂O compared to H₂O. In the presence of highly concentrated kosmotropes, the CST of both polymers decreased in both solvents. The influence of the kosmotropic anions was smaller than the water isotope effect at low ionic strengths but considerably higher at physiological ionic strengths. However, the Hofmeister anion effect was quantitatively different in H₂O than in D₂O, with the largest relative differences observed for Cl⁻, where the CSTs in D₂O decreased more than in H₂O measured by DLS but less by DSC. PiPOx was more sensitive than PNiPAm to the presence of chaotropes. It exhibited much higher transition enthalpies and multistep transitions, especially in aqueous solutions. Our results highlight that measurements of thermoresponsive polymer properties in D₂O cannot be compared directly or quantitatively to application conditions or even measurements performed in H₂O. Full article

GdmCl and NaSCN are two strong chaotropic salts commonly used in protein folding and stability studies, but their microscopic mechanisms remain enigmatic. Here, by CD and NMR, we investigated their effects on conformations, stability, binding and backbone dynamics on ps-ns and µs-ms time scales of a 39-residue but well-folded WW4 domain at salt concentrations ≤200 mM. Up to 200 mM, both denaturants did not alter the tertiary packing of WW4, but GdmCl exerted more severe destabilization than NaSCN. Intriguingly, GdmCl had only weak binding to amide protons, while NaSCN showed extensive binding to both hydrophobic side chains and amide protons. Neither denaturant significantly affected the overall ps-ns backbone dynamics, but they distinctively altered µs-ms backbone dynamics. This study unveils that GdmCl and NaSCN destabilize a protein before the global unfolding occurs with differential binding properties and µs-ms backbone dynamics, implying the absence of a simple correlation between thermodynamic stability and backbone dynamics of WW4 at both ps-ns and µs-ms time scales. Full article

Agarose is a natural polysaccharide known for its ability to form thermoreversible hydrogels. While the effects of curing temperature and polysaccharide concentration on mechanical properties have been discussed in the literature, the role of ionic strength has been less studied. In the present manuscript, we investigate the effects of supporting salt concentration and the role of cation (i.e. Na⁺ or Li⁺, neighbors in the Hofmeister series), on the setting and performance of agarose hydrogels. Compressive and rheological measurements show that the supporting salts reduce the immediate elastic response of agarose hydrogels, with Li⁺ showing a stronger effect than Na⁺ at high ionic strength, while they significantly increase the extent of linear stress-strain response (i.e., linear elasticity). The presence of increasing amounts of added supporting salt also leads to a reduction in hysteresis during mechanical deformation due to loading and unloading cycles, which is more pronounced with Li⁺ than with Na⁺. The combination of rheological measurements and NMR relaxometry shows a mesh size in agarose hydrogels in the order of 6–17 nm, with a thickness of the water layer bound to the biopolymer of about 3 nm. Of note, the different structuring of the water within the hydrogel network due to the different alkali seems to play a role for the final performance of the hydrogels. Full article

Ion channels exhibit gating behavior, fluctuating between open and closed states, with the transmembrane voltage serving as one of the essential regulators of this process. Voltage gating is a fundamental functional aspect underlying the regulation of ion-selective, mostly α-helical, channels primarily found in excitable cell membranes. In contrast, there exists another group of larger, and less selective, β-barrel channels of a different origin, which are not directly associated with cell excitability. Remarkably, these channels can also undergo closing, or “gating”, induced by sufficiently strong electric fields. Once the field is removed, the channels reopen, preserving a memory of the gating process. In this study, we explored the hypothesis that the voltage-induced closure of the β-barrel channels can be seen as a form of reversible protein denaturation by the high electric fields applied in model membranes experiments—typically exceeding twenty million volts per meter—rather than a manifestation of functional gating. Here, we focused on the bacterial outer membrane channel OmpF reconstituted into planar lipid bilayers and analyzed various characteristics of the closing-opening process that support this idea. Specifically, we considered the nearly symmetric response to voltages of both polarities, the presence of multiple closed states, the stabilization of the open conformation in channel clusters, the long-term gating memory, and the Hofmeister effects in closing kinetics. Furthermore, we contemplate the evolutionary aspect of the phenomenon, proposing that the field-induced denaturation of membrane proteins might have served as a starting point for their development into amazing molecular machines such as voltage-gated channels of nerve and muscle cells. Full article

Currently, taste sensors utilizing lipid polymer membranes are utilized to assess the taste of food products quantitatively. During this process, it is crucial to identify and quantify basic tastes, e.g., sourness and sweetness, while ensuring that there is no response to tasteless substances. For instance, suppression of responses to anions, like tasteless NO₃⁻ ions contained in vegetables, is essential. However, systematic electrochemical investigations have not been made to achieve this goal. In this study, we fabricated three positively charged lipid polymer membranes containing oleylamine (OAm), trioctylemethylammonium chloride (TOMACl), or tetradodecylammonium bromide (TDAB) as lipids, and sensors that consist of these membranes to investigate the potential change characteristics of these sensors in solutions containing different anions (F⁻, Cl⁻, Br⁻, NO₃⁻, I⁻). The ability of each anion solution to reduce the positive charge on membranes and shift the membrane potential in the negative direction was in the following order: I⁻ > NO₃⁻ > Br⁻ > Cl⁻ > F⁻. This order well reflected the order of size of the hydrated ions, related to their hydration energy. Additionally, the OAm sensor displayed low ion selectivity, whereas the TOMACl and TDAB sensors showed high ion selectivity related to the OAm sensor. Such features in ion selectivity are suggested to be due to the variation in positive charge with the pH of the environment and packing density of the OAm molecule in the case of the OAm sensor and due to the strong and constant positive charge created by complete ionization of lipids in the case of TOMACl and TDAB sensors. Furthermore, it was revealed that the ion selectivity varies by changing the lipid concentration in each membrane. These results contribute to developing sensor membranes that respond to different anion species selectively and creating taste sensors capable of suppressing responses to tasteless anions. Full article

Amyloid fibrils have immense potential to become the basis of modern biomaterials. The formation of amyloid fibrils in vitro strongly depends on the solvent properties. Ionic liquids (ILs), alternative solvents with tunable properties, have been shown to modulate amyloid fibrillization. In this work, we studied the impact of five ILs with 1-ethyl-3-methylimidazolium cation [EMIM⁺] and anions of Hofmeisterseries hydrogen sulfate [HSO₄⁻], acetate [AC⁻], chloride [Cl⁻], nitrate [NO₃⁻], and tetrafluoroborate [BF₄⁻] on the kinetics of insulin fibrillization and morphology, and the structure of insulin fibrils when applying fluorescence spectroscopy, AFM and ATR-FTIR spectroscopy. We found that the studied ILs were able to speed up the fibrillization process in an anion- and IL-concentration-dependent manner. At an IL concentration of 100 mM, the efficiency of the anions at promoting insulin amyloid fibrillization followed the reverse Hofmeister series, indicating the direct binding of ions with the protein surface. At a concentration of 25 mM, fibrils with different morphologies were formed, yet with similar secondary structure content. Moreover, no correlation with the Hofmeister ranking was detected for kinetics parameters. IL with the kosmotropic strongly hydrated [HSO₄⁻] anion induced the formation of large amyloid fibril clusters, while the other kosmotropic anion [AC⁻] along with [Cl⁻] led to the formation of fibrils with similar needle-like morphologies to those formed in the IL-free solvent. The presence of the ILs with the chaotropic anions [NO₃⁻] and [BF₄⁻] resulted in longer laterally associated fibrils. The effect of the selected ILs was driven by a sensitive balance and interplay between specific protein–ion and ion–water interactions and non-specific long-range electrostatic shielding. Full article

Poly-3,4-ethylenedioxythiophene:polystyrene sulfonate (PEDOT:PSS) is a widely used conducting polymer with versatile applications in organic electronics. The addition of various salts during the preparation of PEDOT:PSS films can significantly influence their electrochemical properties. In this study, we systematically investigated the effects of different salt additives on the electrochemical properties, morphology, and structure of PEDOT:PSS films using a variety of experimental techniques, including cyclic voltammetry, electrochemical impedance spectroscopy, operando conductance measurements and in situ UV-VIS spectroelectrochemistry. Our results showed that the electrochemical properties of the films are closely related to the nature of the additives used and allowed us to establish a probable relationship with the Hofmeister series. The correlation coefficients obtained for the capacitance and Hofmeister series descriptors indicate a strong relationship between the salt additives and the electrochemical activity of PEDOT:PSS films. The work allows us to better understand the processes occurring within PEDOT:PSS films during modification with different salts. It also demonstrates the potential for fine-tuning the properties of PEDOT:PSS films by selecting appropriate salt additives. Our findings can contribute to the development of more efficient and tailored PEDOT:PSS-based devices for a wide range of applications, including supercapacitors, batteries, electrochemical transistors, and sensors. Full article

Unlike halides, where the kosmotropicity decreases from fluoride to iodide, the kosmotropic nature of halates apparently increases from chlorate to iodate, in spite of the lowering in the static ionic polarizability. In this paper, we present an experimental study that confirms the results of previous simulations. The lyotropic nature of aqueous solutions of sodium halates, i.e., NaClO₃, NaBrO₃, and NaIO₃, is investigated through density, conductivity, viscosity, and refractive index measurements as a function of temperature and salt concentration. From the experimental data, we evaluate the activity coefficients and the salt polarizability and assess the anions’ nature in terms of kosmotropicity/chaotropicity. The results clearly indicate that iodate behaves as a kosmotrope, while chlorate is a chaotrope, and bromate shows an intermediate nature. This experimental study confirms that, in the case of halates XO₃⁻, the kosmotropic–chaotropic ranking reverses with respect to halides. We also discuss and revisit the role of the anion’s polarizability in the interpretation of Hofmeister phenomena. Full article

Membrane chromatography is a modern, high-throughput separation method that finds important applications in therapeutic protein purification. Multimodal, salt-tolerant membranes are the most recent innovation in chromatographic membrane adsorbents. Due to the complex structure of their ligands and the bimodal texture of their carriers, their adsorption properties have not been sufficiently investigated. This work deals with the equilibrium and kinetic properties of a multimodal anion-exchange chromatography membrane, Sartobind STIC. Single- and two-component adsorption experiments were carried out with bovine serum albumin (BSA) and salmon DNA as model target and impurity components. The effect of the Hofmeister series ions and ionic strength on the BSA/DNA adsorption was investigated in micromembrane flow experiments. A significant difference was observed between the effects of monovalent and polyvalent ions when strong kosmotropic salts with polyvalent anions acted as strong displacers of BSA. On the contrary, DNA binding was rather high at elevated ionic strength, independent of the salt type. Two-component micromembrane experiments confirmed very high selectivity of DNA binding at a rather low sodium sulfate feed content and at pH 8. The strength of binding was examined in more than a dozen different desorption experiments. While BSA was desorbed relatively easily using high salt concentrations independent of buffer type and pH, while DNA was desorbed only in a very limited measure under any conditions. Separation experiments in a laboratory membrane module were carried out for the feed containing 1 g/L of BSA, 0.3 g/L of DNA, and 0.15 M of sodium sulfate. The negative flow-through mode was found to be more advantageous than the bind-elute mode, as BSA was obtained with 99% purity and a 97% yield. Membrane reuse was investigated in three adsorption-desorption-regeneration cycles. Full article

Steric exclusion chromatography (SXC) is a promising purification method for biological macromolecules such as the Orf virus (ORFV) vector. The method’s principle is closely related to conventional polyethylene glycol (PEG) precipitation, repeatedly implementing membranes as porous chromatographic media. In the past decade, several purification tasks with SXC showed exceptionally high yields and a high impurity removal. However, the effect of varying process parameters, on the precipitation success and its limitations to SXC, is not yet well understood. For this reason, the precipitation behavior and SXC adaptation for ORFV were investigated for the PEG/ORFV contact time, the membranes pore size, and the type and concentration of ions. All three parameters influenced the ORFV recoveries significantly. A small pore size and a long contact time induced filtration effects and inhibited a full virus recovery. The application of salts had complex concentration-dependent effects on precipitation and SXC yields, and ranged from a complete prevention of precipitation in the presence of kosmotropic substances to increased efficiencies with Mg²⁺ ions. The latter finding might be useful to reduce PEG concentrations while maintaining high yields. With this knowledge, we hope to clarify several limitations of SXC operations and improve the tool-set for a successful process adaptation. Full article

Cloud point extraction is a versatile method aimed at separating compounds from complex mixtures and arouses great technological interest, particularly among the biochemical industries. However, one must have deep knowledge of the liquid–liquid equilibrium behavior of systems to properly use the method. Thus, we used thermodynamic parameters to evaluate the effect of citrate, sulfate, and tartrate anions on the phase separation of water + Triton X-114^® mixtures at 283.2 K, 293.2 K, and 303.2 K. In these systems, increasing the temperature and the anion molar fraction expanded the biphasic region in the following order: ${\mathrm{C}}_6{\mathrm{H}}_5{\mathrm{O}}_7^{3-}$> ${\mathrm{SO}}_4^{2-}$ > ${ \mathrm{C}}_4{\mathrm{H}}_4{\mathrm{O}}_6^{2-}$. Unlike other studies based on the Hofmeister series, the Gibbs free energy of micellization correlated the anion effect on the biphasic region with the spontaneity of the micelle formation. The water molecules structured around these anions were evaluated according to the shell volume of the immobilized water by electrostriction, volume of water around the hydration shell, Gibbs free energy of hydration, and Gibbs free energy of electrostriction ($\Delta {\mathrm{G}}_{\mathrm{el}12}$). The citrate anion presented a higher $\Delta {\mathrm{G}}_{\mathrm{el}12}$ of −1781.49 kJ mol⁻¹, due to the larger number of electrons around it. In addition, the partition coefficient of the surfactant in the two liquid phases revealed a linear dependence upon the anion mole fractions by following the previous anion sequence and temperature in the phase separation. Full article

Sulfate groups on cellulose particles such as cellulose nanocrystals (CNCs) provide colloidal stability credit to electrostatic repulsion between the like-charged particles. The introduction of sodium counter cations on the sulfate groups enables drying of the CNC suspensions without irreversible aggregation. Less is known about the effect of other counter cations than sodium on extending the properties of the CNC particles. Here, we introduce the alkali metal counter cations, Li⁺, Na⁺, K⁺, Rb⁺, and Cs⁺, on sulfated CNCs without an ion exchange resin, which, so far, has been a common practice. We demonstrate that the facile ion exchange is an efficient method to exchange to any alkali metal cation of sulfate half esters, with exchange rates between 76 and 89%. The ability to form liquid crystalline order in rest was observed by the presence of birefringence patterns and followed the Hofmeister series prediction of a decreasing ability to form anisotropy with an increasing element number. However, we observed the K-CNC rheology and birefringence as a stand-out case within the series of alkali metal modifications, with dynamic moduli and loss tangent indicating a network disruptive effect compared to the other counter cations, whereas observation of the development of birefringence patterns in flow showed the absence of self- or dynamically-assembled liquid crystalline order. Full article