Charge regulation of nanoparticles in the presence of multivalent electrolytes.

We explore the charge regulation (CR) of spherical nanoparticles immersed in an asymmetric electrolyte of a specified pH. Using a recently developed reactive canonical Monte Carlo (MC) simulation method, titration isotherms are obtained for suspensions containing monovalent, divalent, and trivalent coions. A theory based on the modified Poisson-Boltzmann approximation, which incorporates the electrostatic ion solvation free energy and discrete surface charge effects, is used to compare with the simulation results. A remarkably good agreement is found without any fitting parameters, both for the ion distributions and titration curves, suggesting that ionic correlations between coions and hydronium ions at the nanoparticle surface play only a minor role in determining the association equilibrium between hydroniums and the functional sites on the nanoparticle surface. On the other hand, if suspension contains multivalent counterions, we observe a large deviation between theory and simulations, showing that the electrostatic correlations between counterions and hydronium ions at the nanoparticle surface are very significant and must be properly taken into account to correctly describe CR for such solutions.

On the Validity of Constant pH Simulations.

Constant pH (cpH) simulations are now a standard tool for investigating charge regulation in coarse-grained models of polyelectrolytes and colloidal systems. Originally developed for studying solutions with implicit ions, extending this method to systems with explicit ions or solvents presents several challenges. Ensuring proper charge neutrality within the simulation cell requires performing titration moves in sync with the insertion or deletion of ions, a crucial aspect often overlooked in the literature. Contrary to the prevailing views, cpH simulations are inherently grand-canonical, meaning that the controlled pH is that of the reservoir. The presence of the Donnan potential between the implicit reservoir and the simulation cell introduces significant differences between titration curves calculated for open and closed systems; the pH of an isolated (closed) system is different from the pH of the reservoir for the same protonation state of the polyelectrolyte. To underscore this point, in this paper, we will compare the titration curves calculated using the usual cpH algorithm with those from the exact canonical simulation algorithm. In the latter case, titration moves adhere to the correct detailed balance condition, and pH is calculated using the recently introduced surface Widom insertion algorithm. Our findings reveal a very significant difference between the titration isotherms obtained using the standard cpH algorithm and the canonical titration algorithm, emphasizing the importance of using the correct simulation approach when studying charge regulation of polyelectrolytes, proteins, and colloidal particles.

Canonical titration simulations.

We present a Monte Carlo approach for performing titration simulations in the canonical ensemble. The standard constant pH (cpH) simulation methods are intrinsically grand canonical, allowing us to study the protonation state of molecules only as a function of pH in the reservoir. Due to the Donnan potential between a system and an (implicit) reservoir of a semi-grand canonical simulation, the pH of the reservoir can be significantly different from that of an isolated system, for an identical protonation state. The new titration method avoids this difficulty by using the canonical reactive Monte Carlo algorithm to calculate the protonation state of macromolecules as a function of the total number of protons present inside the simulation cell. The pH of an equilibrated system is then calculated using a new surface insertion Widom algorithm, which bypasses the difficulties associated with the bulk Widom particle insertion for intermediate and high pH values. To properly treat the long range Coulomb force, we use the Ewald summation method, showing the importance of the Bethe potential for calculating the pH of canonical systems.

Titration in Canonical and Grand-Canonical Ensembles.

We discuss problems associated with the notion of pH in heterogeneous systems. For homogeneous systems, standardization protocols lead to a well-defined quantity, which, although different from Sørensen's original idea of pH, is well reproducible and has become accepted as the measure of the "hydrogen potential". On the other hand, for heterogeneous systems, pH defined in terms of the chemical part of the electrochemical activity is thermodynamically inconsistent and runs afoul of the Gibbs-Guggenheim principle that forbids splitting of the electrochemical potential into separate chemical and electrostatic parts, since only the sum of two has any thermodynamic meaning. The problem is particularly relevant for modern simulation methods which involve charge regulation of proteins, polyelectrolytes, nanoparticles, colloidal suspensions, and so forth. In this paper, we show that titration isotherms calculated using semigrand canonical simulations can be very different from the ones obtained using canonical reactive Monte Carlo simulations.

A new method for reactive constant pH simulations.

We present a simulation method that allows us to calculate the titration curves for systems undergoing protonation/deprotonation reactions-such as charged colloidal suspensions with acidic/basic surface groups, polyelectrolytes, polyampholytes, and proteins. The new approach allows us to simultaneously obtain titration curves both for systems in contact with salt and acid reservoir (semi-grand canonical ensemble) and for isolated suspensions (canonical ensemble). To treat the electrostatic interactions, we present a new method based on Ewald summation-which accounts for the existence of both Bethe and Donnan potentials within the simulation cell. We show that the Donnan potential dramatically affects the pH of a suspension. Counterintuitively, we find that in suspensions with a large volume fraction of nanoparticles and low ionic strength, the number of deprotonated groups can be 100% larger in an isolated system, compared to a system connected to a reservoir by a semi-permeable membrane-both systems being at exactly the same pH.

Interaction between two overall neutral charged microscopically patterned surfaces.

We study the interaction between heterogeneously charged surfaces in an electrolyte solution by employing classical Density Functional Theory (cDFT) and Monte Carlo simulations. We observe a consistent behavior between cDFT and Monte Carlo simulations regarding force curves and two-dimensional density profiles. Armed with the validated cDFT, we explore the system's behavior under parameters that are challenging to simulate directly. Our findings include the impacts of domain size, domain charge, domain charge configuration, and bulk electrolyte concentration on the osmotic pressure. Remarkably, the force curve is more sensitive to the domain size for an asymmetric configuration than a symmetry configuration; the bulk concentration weakly influences the force curve independent of the system configurations.

Charge fluctuations in charge-regulated systems: dependence on statistical ensemble.

We investigate charge regulation of nanoparticles in concentrated suspensions, focusing on the effect of different statistical ensembles. We find that the choice of ensemble does not affect the mean charge of nanoparticles, but significantly alters the magnitude of its fluctuation. Specifically, we compared the behaviors of colloidal charge fluctuations in the semi-grand canonical and canonical ensembles and identified significant differences between the two. The choice of ensemble-whether the system is isolated or is in contact with a reservoir of acid and salt-will, therefore, affect the Kirkwood-Shumaker fluctuation-induced force inside concentrated suspensions. Our results emphasize the importance of selecting an appropriate ensemble that accurately reflects the experimental conditions when studying fluctuation-induced forces between polyelectrolytes, proteins, and colloidal particles in concentrated suspensions.

Comment on "Simulations of ionization equilibria in weak polyelectrolyte solutions and gels" by J. Landsgesell, L. Nová, O. Rud, F. Uhlík, D. Sean, P. Hebbeker, C. Holm and P. Kosovan, Soft Matter, 2019, 15, 1155-1185.

In a recent review Landsgesell et al., Soft Matter 2019, 15, 1155 stated that pH - pKa is a "universal parameter" for titrating systems. We show that this is not the case. This broken symmetry has important implications for constant pH (cpH) simulations. In particular, we show that for concentrated suspensions the error resulting from the use of cpH algorithm described by Landsgesell et al. is very significant, even for suspension containing 1 : 1 electrolyte. We show how to modify the cpH algorithm to account for the grand-canonical nature of the cpH simulations and for the charge neutrality requirement.

Theory of Charge Regulation of Colloidal Particles in Electrolyte Solutions.

We present a theory that enables us to (i) calculate the effective surface charge of colloidal particles and (ii) efficiently obtain titration curves for different salt concentrations. The theory accounts for the shift of pH of solution due to the presence of 1:1 electrolyte. It also accounts self-consistently for the electrostatic potential produced by the deprotonated surface groups. To examine the accuracy of the theory, we have performed extensive reactive Monte Carlo simulations, which show excellent agreement between theory and simulations without any adjustable parameters.

Widom insertion method in simulations with Ewald summation.

We discuss the application of the Widom insertion method for calculation of the chemical potential of individual ions in computer simulations with Ewald summation. Two approaches are considered. In the first approach, an individual ion is inserted into a periodically replicated overall charge neutral system representing an electrolyte solution. In the second approach, an inserted ion is also periodically replicated, leading to the violation of the overall charge neutrality. This requires the introduction of an additional neutralizing background. We find that the second approach leads to a much better agreement with the results of grand canonical Monte Carlo simulation for the total chemical potential of a neutral ionic cluster.

Reactive Monte Carlo simulations for charge regulation of colloidal particles.

We use a reactive Monte Carlo simulation method and the primitive model of electrolyte to study acid-base equilibrium that controls charge regulation in colloidal systems. The simulations are performed in a semi-grand canonical ensemble in which colloidal suspension is in contact with a reservoir of salt and strong acid. The interior of colloidal particles is modeled as a low dielectric medium, different from the surrounding water. The effective colloidal charge is calculated for different numbers of surface acidic groups, pH, salt concentrations, and types of electrolyte. In the case of potassium chloride, the titration curves are compared with the experimental measurements obtained using potentiometric titration. A good agreement is found between simulations and experiments. In the case of lithium chloride, the specific ionic adsorption is taken into account through the partial dehydration of lithium ion.

Interaction between Charge-Regulated Metal Nanoparticles in an Electrolyte Solution.

We present a theory which allows us to calculate the interaction potential between charge-regulated metal nanoparticles inside an acid-electrolyte solution. The approach is based on the recently introduced model of charge regulation which permits us to explicitly-within a specific microscopic model-relate the bulk association constant of a weak acid to the surface association constant for the same weak acid adsorption sites. When considering metal nanoparticles we explicitly account for the effect of the induced surface charge in the conducting core. To explore the accuracy of the approximations, we compare the ionic density profiles of an isolated charge-regulated metal nanoparticle with explicit Monte Carlo simulations of the same model. Once the accuracy of the theoretical approach is established, we proceed to calculate the interaction force between two charge-regulated metal nanoparticles by numerically solving the Poisson-Boltzmann equation with charge regulation boundary condition. The force is then calculated by integrating the electroosmotic stress tensor. We find that for metal nanoparticles the charge regulation boundary condition can be well approximated by the constant surface charge boundary condition, for which a very accurate Derjaguin-like approximation was recently introduced. On the other hand, a constant surface potential boundary condition often used in colloidal literature, shows a significant deviation from the charge regulation boundary condition for particles with large charge asymmetry.

Electrolytes in regimes of strong confinement: surface charge modulations, osmotic equilibrium and electroneutrality.

In the present work, we study an electrolyte solution confined between planar surfaces with nanopatterned charged domains, which has been connected to a bulk ionic reservoir. The system is investigated through an improved Monte Carlo (MC) simulation method, suitable for simulation of electrolytes in the presence of modulated surface charge distributions. We also employ a linear approach in the spirit of the classical Debye-Hückel approximation, which allows one to obtain explicit expressions for the averaged potentials, ionic profiles, effective surface interactions and the net ionic charge confined between the walls. Emphasis is placed on the limit of strongly confined electrolytes, in which case local electroneutrality in the inter-surface space might not be fulfilled. In order to access the effects of such a lack of local charge neutrality on the ion-induced interactions between surfaces with modulated charge domains, we consider two distinct model systems for the confined electrolyte: one in which a salt reservoir is explicitly taken into account via the osmotic equilibrium with an electrolyte of fixed bulk concentration, and a second one in which the equilibrium with a charge neutral ionic reservoir is implicitly considered. While in the former case the osmotic ion exchange might lead to non-vanishing net charges, in the latter model charge neutrality is enforced through the appearance of an implicit Donnan potential across the charged interfaces. A strong dependence of the ion-induced surface interactions on the employed model system is observed at all surface separations. These findings strongly suggest that due care is to be taken while choosing among different scenarios to describe the ion exchange in electrolytes confined between charged surfaces, even in cases when the monopole (non zero net charge) surface contributions are absent.

Charge regulation of colloidal particles in aqueous solutions.

We study the charge regulation of colloidal particles inside aqueous electrolyte solutions. To stabilize a colloidal suspension against precipitation, colloidal particles are synthesized with either acidic or basic groups on their surface. On contact with water, these surface groups undergo proton transfer reactions, resulting in colloidal surface charge. The charge is determined by the condition of local chemical equilibrium between hydronium ions inside the solution and at the colloidal surface. We use a model of Baxter sticky spheres to explicitly calculate the equilibrium dissociation constants and to construct a theory which is able to quantitatively predict the effective charge of colloidal particles with either acidic or basic surface groups. The predictions of the theory for the model are found to be in excellent agreement with the results of Monte Carlo simulations. This theory is further extended to treat colloidal particles with a mixture of both acidic and basic surface groups.

Osmotic stress and pore nucleation in charged biological nanoshells and capsids.

A model system is proposed to investigate the chemical equilibrium and mechanical stability of biological spherical-like nanoshells in contact with an aqueous solution with added dissociated electrolyte of a given concentration. The ionic chemical equilibrium across the permeable shell is investigated in the framework of an accurate Density Functional Theory (DFT) that incorporates electrostatic and hardcore correlations beyond the traditional mean-field (e.g., Poisson-Boltzmann) limit. The accuracy of the theory is tested by a direct comparison with Monte Carlo (MC) simulations. A simple analytical expression is then deduced which clearly highlights the entropic, electrostatic, and self-energy contributions to the osmotic stress over the shell in terms of the calculated ionic profiles. By invoking a continuum mean-field elastic approach to account for the shell surface stress upon osmotic stretching, the mechanical equilibrium properties of the shell under a wide variety of ionic strengths and surface charges are investigated. The model is further coupled to a continuum mechanical approach similar in structure to a Classical Nucleation Theory (CNT) to address the question of mechanical stability of the shells against a pore nucleation. This allows us to construct a phase diagram which delimits the mechanical stability of capsids for different ionic strengths and shell surface charges.

Charge Regulation of Colloidal Particles: Theory and Simulations.

To explore charge regulation (CR) in physicochemical and biophysical systems, we present a model of colloidal particles with sticky adsorption sites which account for the formation of covalent bonds between the hydronium ions and the surface functional groups. Using this model and Monte Carlo simulations, we find that the standard Ninham and Parsegian (NP) theory of CR leads to results which deviate significantly from computer simulations. The problem with the NP approach is traced back to the use of a bulk equilibrium constant to account for surface chemical reactions. To resolve this difficulty we present a new theory of CR. The fundamental ingredient of the new approach is the sticky length, which is nontrivially related to the bulk equilibrium constant. The theory is found to be in excellent agreement with computer simulations, without any adjustable parameters. As an application of the theory we calculate the effective charge of colloidal particles containing carboxyl groups, as a function of pH and salt concentration.

Isothermal adsorption of polyampholytes on charged nanopatterned surfaces.

We investigate the adsorption of neutral polyampholytes on charged nanopatterned surfaces. The surfaces have charged domains but are overall neutral. To perform efficient simulations, we use an approach which combines the explicit form of the interaction potential between the polyampholyte monomers and the surface with a 3d Ewald summation method. We observe that the amount of adsorption and the structure of the adsorbed polyampholytes depend strongly on the surface pattern, the relative size of the surface domains, and the charge distribution along the polyampholyte backbone.

Efficient simulation method for nano-patterned charged surfaces in an electrolyte solution.

We present a method to efficiently simulate nano-patterned charged surfaces inside an electrolyte solution. Simulations are performed in the grand canonical ensemble and are used to calculate the force between surfaces with various charge patterns. The electric field produced by the surfaces is calculated analytically and is used as an external potential. To treat the long range Coulomb interaction between the ions we use a modified 3d Ewald summation method. The force between the surfaces is found to depend strongly on the specific charge pattern, on the surface alignment and separation.

Adsorption isotherms of charged nanoparticles.

We present theory and simulations which allow us to quantitatively calculate the amount of surface adsorption excess of charged nanoparticles onto a charged surface. The theory is very accurate for weakly charged nanoparticles and can be used at physiological concentrations of salt. We have also developed an efficient simulation algorithm which can be used for dilute suspensions of nanoparticles of any charge, even at very large salt concentrations. With the help of the new simulation method, we are able to efficiently calculate the adsorption isotherms of highly charged nanoparticles in suspensions containing multivalent ions, for which there are no accurate theoretical methods available.

Interaction between random heterogeneously charged surfaces in an electrolyte solution.

We study, using Monte Carlo simulations, the interaction between infinite heterogeneously charged surfaces inside an electrolyte solution. The surfaces are overall neutral with quenched charged domains. An average over the quenched disorder is performed to obtain the net force. We find that the interaction between the surfaces is repulsive at short distances and is attractive for larger separations.