Diffusion and Interaction Effects On Molecular Release Kinetics From Collapsed Microgels.

The efficient transport of small molecules through dense hydrogel networks is crucial for various applications, including drug delivery, biosensing, catalysis, nanofiltration, water purification, and desalination. In dense polymer matrices, such as collapsed microgels, molecular transport follows the solution-diffusion principle: Molecules dissolve in the polymeric matrix and subsequently diffuse due to a concentration gradient. Employing dynamical density functional theory (DDFT), we investigate the nonequilibrium release kinetics of nonionic subnanometer-sized molecules from a microgel particle, using parameters derived from prior molecular simulations of a thermoresponsive hydrogel. The kinetics is primarily governed by the microgel radius and two intensive parameters: the diffusion coefficient and solvation free energy of the molecule. Our results reveal two limiting regimes: a diffusion-limited regime for large, slowly diffusing, and poorly soluble molecules within the hydrogel; and a reaction-limited regime for small, rapidly diffusing, and highly soluble molecules. These principles allow us to derive an analytical equation for release time, demonstrating excellent quantitative agreement with the DDFT results-a valuable and straightforward tool for predicting release kinetics from microgels.

Interaction-Limited Aggregation: Fine-Tuning the Size of pNIPAM Particles by Association with Hydrophobic Ions.

We have investigated the formation of stable clusters of poly(N-isopropylacrylamide) (pNIPAM) chains in water at temperatures above the lower critical solution temperature (LCST), induced by the presence of sodium tetraphenylborate, NaPh4B. The hydrophobic Ph4B- ions interact strongly with the pNIPAM chains, providing them with a net effective negative charge, which leads to the stabilization of pNIPAM clusters for temperatures above the LCST, with a mean cluster size that depends non-monotonically on salt concentration. Combining experiments with physical modeling at the mesoscopic level and atomistic molecular dynamic simulations, we show that this effect is caused by the interplay between the hydrophobic attraction between pNIPAM chains and the electrostatic repulsion induced by the associated Ph4B- ions. These results provide insight on the significance of weak associative anion-polymer interaction driven by hydrophobic interaction and how this anionic binding can prevent macroscopic phase separation. Harvesting the competition between attractive hydrophobic and repulsive electrostatic interaction opens avenues for the dynamic control of the formation of well-calibrated polymer microparticles.

Effect of organic and inorganic ions on the lower critical solution transition and aggregation of PNIPAM.

We have studied the effect of different ions belonging to the extended Hofmeister series on the thermosensitive polymer poly(N-isopropylacrylamide) (PNIPAM), by combining Differential Scanning Calorimetry (DSC) and Dynamic Light Scattering (DLS). The variations in the lower critical solution temperature (TLCS) and enthalpy change during PNIPAM phase separation evidence the importance of considering both hydration and hydrophobicity to explain the interaction of ions with interfaces. The results obtained in the presence of inorganic ions can be explained by the tendency of water molecules to preferentially hydrate the PNIPAM chains or the ions, depending on the kosmotropic (highly hydrated) or chaotropic (poorly hydrated) character of the ions. On the contrary, tetraphenyl organic ions (Ph4B- and Ph4As+) interact with the hydrophobic moieties of PNIPAM chains, inducing a significant reduction of the TLCS. DLS results show that the aggregation state of PNIPAM above the TLCS is also strongly influenced by the presence of ions. While macroscopic phase separation (formation of a polymer-rich phase insoluble in water) was apparent in the presence of inorganic ions, we observed the formation of submicron PNIPAM aggregates at temperatures above the TLCS in the presence of the hydrophobic ions. Kinetically arrested monodisperse PNIPAM nanoparticles were formed in the presence of the Ph4B- anion, while a rather polydisperse distribution of particle sizes was observed in the presence of Ph4As+. These results show that ionic specificity influences both the static (thermodynamic) and dynamic (kinetically controlled aggregation) states of PNIPAM in an aqueous environment.

Adsorption of Milk Proteins (ß-Casein and ß-Lactoglobulin) and BSA onto Hydrophobic Surfaces.

Here, we study films of proteins over planar surfaces and protein-coated microspheres obtained from the adsorption of three different proteins ( ß -casein, ß -lactoglobulin and bovine serum albumin (BSA)). The investigation of protein films in planar surfaces is performed by combining quartz crystal microbalance (QCM) and atomic force microscopy (AFM) measurements with all-atomic molecular dynamics (MD) simulations. We found that BSA and ß -lactoglobulin form compact monolayers, almost without interstices between the proteins. However, ß -casein adsorbs forming multilayers. The study of the electrokinetic mobility of protein-coated latex microspheres shows substantial condensation of ions from the buffer over the complexes, as predicted from ion condensation theories. The electrokinetic behavior of the latex-protein complexes is dominated by the charge of the proteins and the phenomenon of ion condensation, whereas the charge of the latex colloids plays only a minor role.

Interaction of organic ions with proteins.

In this study we have investigated how different proteins interact with big organic ions. Two ions that are similar in size and chemical structure (Ph4B- anion and Ph4As+ cation) were studied. The proteins chosen are the two major allergenic proteins of cow's milk, ß-lactoglobulin and ß-casein, and bovine serum albumin, BSA, as the reference protein. First, a quantitative study to determine the hydrophobic degree of the proteins was performed. Then, electrokinetic and stability measurements on protein-coated polystyrene (PS) microspheres as a function of the tetraphenyl ion concentration were carried out. Our results show that the affinity of the organic ions depends on the hydrophobicity of the interface. Big charge inversions and re-stabilization patterns were observed at very low concentrations of tetraphenyl ions for the most hydrophobic protein studied (with ß-casein). Besides, the ionic concentrations needed to destabilize these colloidal systems were roughly one order of magnitude lower for the anion than for the cation. In addition, we studied conformational changes of the adsorbed proteins with a quartz crystal microbalance. Proteins were adsorbed onto hydrophobic flat substrates and then exposed to the tetraphenyl ions. The protein films swelled or collapsed as a function of the accumulation of tetraphenyl ions. Similarly to the electrokinetic/stability studies, the ionic concentration necessary to trigger structural changes of the protein films was one order of magnitude larger for the cation than for the anion. All the results evidence that the accumulation of these organic ions on an interface depends directly on its degree of hydrophobicity. We attribute the different interactions of the anion and the cation with these interfaces to their dissimilar hydration, which makes the anion show a more hydrophobic behaviour than the cation.

Anions make the difference: insights from the interaction of big cations and anions with poly(N-isopropylacrylamide) chains and microgels.

Minute concentrations of big hydrophobic ions have the ability to induce substantial effects in soft matter systems, including novel phases in lipid layers, giant charge inversion in colloids and nanostructuration in polymer surfaces in contact with water. The effects are so strong that the term "soft matter disruptors" was coined to describe their deep impact on interfaces, which goes far beyond that found by using the classical ions considered in lyotropic (Hofmeister) sequences. In these effects, solvation thermodynamics plays a fundamental role. Interestingly, it is possible to obtain big hydrophobic cations and anions with an almost identical size and structure (e.g. Ph4B(-), Ph4As(+)), which only differ in their central atom. Here we employ different techniques (Molecular Dynamics (MD) simulations, electrophoretic mobility and Atomic Force Microscopy (AFM)) to demonstrate the dramatic differences in the interaction of Ph4B(-) and Ph4As(+) with poly(N-isopropylacrylamide) (PNIPAM), a thermoresponsive polymer with expanded (well hydrated) and collapsed (poorly hydrated) states. Although both ions interact strongly with neutral PNIPAM chains and cationic or anionic PNIPAM microgels in the collapsed states, the effects of Ph4B(-) on PNIPAM are always substantially stronger than the effects of Ph4As(+). MD simulations predict that ion-PNIPAM free energy of interaction is four times larger for Ph4B(-) than for Ph4As(+). Electrokinetic and AFM experiments show that, acting as counter-ions, both ions are able to invert the charge of anionic or cationic PNIPAM microgels at minute concentrations, but the charge inversion due to Ph4B(-) is much larger than that obtained with Ph4As(+). Therefore, even for big ions of identical size, shape and valence, the affinity of anions and cations for interfaces is intrinsically different.

Thermally sensitive reversible microgels formed by poly(N-Isopropylacrylamide) charged chains: a Hofmeister effect study.

In this study, we present a new method to obtain anionic and cationic stable colloidal nanogels from PNIPAM charged chains. The stability of the particles formed by inter-chain aggregation stems from the charged chemical groups attached at the sides of PNIPAM polymer chains. The particle formation is fully reversible-that is, it is possible to change from stable polymer solutions to stable colloidal dispersions and vice versa simply by varying temperature. In addition, we also demonstrate that the polymer LCST (lower critical solution temperature), the final particle size and the electrokinetic behavior of the particles formed are highly dependent on the electrolyte nature and salt concentration. These latter results are related to Hofmeister effects. The analysis of these results provides more insights about the origin of this ionic specificity, confirming that the interaction of ions with interfaces is dominated by the chaotropic/kosmotropic character of the ions and the hydrophobic/hydrophilic character of the surface in solution.

Ions-induced nanostructuration: effect of specific ionic adsorption on hydrophobic polymer surfaces.

The effect of surface charges on the ionic distribution in close proximity to an interface has been extensively studied. On the contrary, the influence of ions (from dissolved salts) on deformable interfaces has been barely investigated. Ions can adsorb from aqueous solutions on hydrophobic surfaces, generating forces that can induce long-lasting deformation of glassy polymer films, a process called ion-induced polymer nanostructuration, IPN. We have found that this process is ion-specific; larger surface modifications are observed in the presence of water ions and hydrophobic and amphiphilic ions. Surface structuration is also observed in the presence of certain salts of lithium. We have used streaming potential and atomic force microscopy to study the effect of dissolved ions on the surface properties of polystyrene films, finding a good correlation between ionic adsorption and IPN. Our results also suggest that the presence of strongly hydrated lithium promotes the interaction of anions with polystyrene surfaces and more generally with hydrophobic polymer surfaces, triggering then the IPN process.

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.

Hofmeister effects on poly(NIPAM) microgel particles: macroscopic evidence of ion adsorption and changes in water structure.

The term Hofmeister effects is broadly used to refer to ionic specificities in many different physical, chemical and biological phenomena. The origin of this ionic specificity is sought in two interdependent microscopic sources: 1) the peculiarities of the solvent structure near surfaces and around the ions, and 2) specific ion adsorption-exclusion mechanisms near a surface. In this work, Hofmeister effects on poly(N-isopropylacrylamide) [poly(NIPAM)]-based microgels are examined. Poly(NIPAM) particles are thermally sensitive microgels exhibiting volume-phase transitions with temperature. This temperature-sensitive system seems to be suitable for the independent observation of the two microscopic sources of Hofmeister effects. On the one hand, volume-phase transition, evaluated by photon correlation spectroscopy (PCS), gives information about how the presence of ions changes the water structure around the poly(NIPAM) chains. On the other hand, electrokinetic studies show relevant data about ionic adsorption-exclusion phenomena at the polymer surface.

Cationic and anionic poly(N-isopropylacrylamide) based submicron gel particles: electrokinetic properties and colloidal stability.

A cationic and an anionic poly(N-isopropylacrylamide) (poly(NIPAM)) microgel latex were synthesized via batch radical polymerization under emulsifier-free conditions. The hydrodynamic properties, colloidal stability, and electrokinetic characteristics of these two samples were studied. The hydrodynamic particle size variation was discussed by considering the effect of salinity and temperature on the shrinkage of the thermally sensitive polymer domains. The colloidal stability also depended on temperature and electrolyte concentration. A stability diagram with two well-defined domains (stable and unstable) was obtained. The flow from one domain to the other was fully reversible due to the peculiar (de)hydration properties of the polymer. The electrokinetic behavior, which depends on electrical and frictional properties of the particles, was analyzed via electrophoretic mobility measurements. Results were discussed by considering both the particle structure dependence on temperature and salinity, and the electric double layer compression. In addition, the electrophoretic mobility data were analyzed using Ohshima's equations for particles covered by an ion-penetrable surface charged layer, as well as using another simpler equation for charges located on a hydrodynamic equivalent hard sphere. Differences between the properties of both latexes were justified by the presence of a hydrophilic comonomer, aminoethyl methacrylate hydrochloride (AEMH), in the cationic microgel.