Estimation of Nanoparticle's Surface Electrostatic Potential in Solution Using Acid-Base Molecular Probes I: In Silico Implementation for Surfactant Micelles.

Surface electrostatic potential Ψ is a key characteristic of colloid particles. Since the surface of the particles adsorbs various compounds and facilitates chemical reactions between them, Ψ largely affects the properties of adsorbed reactants and governs the flow of chemical reactions occurring between them. One of the most popular methods for estimating Ψ in hydrophilic colloids, such as micellar surfactant solutions and related systems, is the application of molecular probes, predominantly acid-base indicator dyes. The Ψ value is calculated from the difference of the probe's indices of the apparent acidity constant between the examined colloid solution and, usually, some other colloid solution with noncharged particles. Here, we show how to implement this method in silico using alchemical free energy calculations within the framework of molecular dynamics simulations. The proposed implementation is tested on surfactant micelles and is shown to predict experimental Ψ values with quantitative accuracy depending on the kind of surfactant. The sources of errors in the method are discussed, and recommendations for its application are given.

Estimation of Nanoparticle's Surface Electrostatic Potential in Solution Using Acid-Base Molecular Probes II: Insight from Atomistic Simulations of Micelles.

Exploiting acid-base indicators as molecular probes is one of the most popular methods for determining the surface electrostatic potential Ψ in hydrophilic colloids like micellar surfactant solutions and related systems. Specifically, the indicator's apparent acidity constant index is measured in the colloid solution of interest and, as a rule, in a nonionic surfactant solution; the difference between the two is proportional to Ψ. Despite the widespread use of this approach, a major problem remains unresolved, namely, the dissimilarity of Ψ values obtained with different indicators for the same system. The common point of view recognizes the effect of several factors (the choice of the nonionic surfactant, the probe's localization, and the degree of hydration of micellar pseudophase) but does not allow to quantitatively assess their impact and decide which indicator reports the most correct Ψ value. Here, based on the ability to predict the reported Ψ values in silico, we examined the role of these factors using molecular dynamics simulations for five probes and two surfactants. The probe's hydration in the Stern layer was found responsible for approximately half of the dissimilarity range. The probe's localization is found important but hard to quantify because of the irregular structure of the Stern layer. The most accurate indicators among the examined set were identified. Supplementing experiments on measuring Ψ with molecular dynamics simulation is proposed as a way of improving the efficacy of the indicator method: the simulations can guide the choice of the most suitable probe and nonionic surfactant for the given nanoparticles.

Computing pKa Shifts Using Traditional Molecular Dynamics: Example of Acid-Base Indicator Dyes in Organized Solutions.

A compound's acidity constant (Ka) in a given medium determines its protonation state and, thus, its behavior and physicochemical properties. Therefore, it is among the key characteristics considered during the design of new compounds for the needs of advanced technology, medicine, and biological research, a notable example being pH sensors. The computational prediction of Ka for weak acids and bases in homogeneous solvents is presently rather well developed. However, it is not the case for more complex media, such as microheterogeneous solutions. The constant-pH molecular dynamics (MD) method is a notable contribution to the solution of the problem, but it is not commonly used. Here, we develop an approach for predicting Ka changes of weak small-molecule acids upon transfer from water to colloid solutions by means of traditional classical molecular dynamics. The approach is based on free energy (ΔG) computations and requires limited experiment data input during calibration. It was successfully tested on a series of pH-sensitive acid-base indicator dyes in micellar solutions of surfactants. The difficulty of finite-size effects affecting ΔG computation between states with different total charges is taken into account by evaluating relevant corrections; their impact on the results is discussed, and it is found non-negligible (0.1-0.4 pKa units). A marked bias is found in the ΔG values of acid deprotonation, as computed from MD, which is apparently caused by force-field issues. It is hypothesized to affect the constant-pH MD and reaction ensemble MD methods as well. Consequently, for these methods, a preliminary calibration is suggested.

Character of Localization and Microenvironment of Solvatochromic Reichardt's Betaine Dye in Sodium n-Dodecyl Sulfate and Cetyltrimethylammonium Bromide Micelles: Molecular Dynamics Simulation Study.

The problem of using surfactant micellar aqueous solutions as reaction media centers on estimating the polarity of the micellar pseudophase. The most popular approach is the utilization of solvatochromic dyes. Among the last, the strongest ones are the dipolar pyridinium N-phenolate dyes. The complication of such approach, however, consists in the nonuniform character of the environment of the indicator fixed in the micellar pseudophase. The aim of this study is to reveal the character of localization and orientation of the standard solvatochromic pyridinium N-phenolate dye, 4-(2,4,6-triphenylpyridinium-1-yl)-2,6-diphenylphenolate, the so-called Reichardt's dye, within the micellar pseudophase of an anionic (sodium n-dodecyl sulfate, SDS) and cationic (cetyltrimethylammonium bromide, CTAB) surfactants using MD simulations. The locus and hydration of the dye are found to be dependent on the surfactant nature. New approaches are proposed to quantitatively describe the state of the dye within the pseudophase. The results confirm the experimental data, which indicate the higher polarity of the interfacial region in the case of the SDS micelles. Because this dye is also used as an interfacial acid-base probe, the corresponding study is simultaneously performed for its protonated, i.e., cationic form. The neutral and protonated forms of the dye are found to be localized and hydrated in a different way in both SDS and CTAB micelles. This should be taken into account when using the Reichardt's dye as an acid-base indicator for estimating the electrical surface potential of micelles. The presented approach may be recommended to shed light upon the locus of other solvatochromic and acid-base indicators in micelles and micellar-like aggregates.

Developing and Validating a Set of All-Atom Potential Models for Sodium Dodecyl Sulfate.

We present a set of novel all-atom potential models for sodium dodecyl sulfate (SDS), developed within the framework of the widely used OPLS-AA and General AMBER force fields. The choice of the parameters for the models is made by rigorously following the methodology of the used force fields to ensure full compatibility with the models for other compounds. For the GAFF model, extensive quantum-chemical computations are performed to obtain reliable Boltzmann-averaged atomic point charges, and the latter are compared with the single-conformation charges. For representation of the hydrocarbon tail, we use recently published improved parameters that correctly reproduce the properties of lipids and long alkanes. The models are validated on the basis of correct reproduction of the main properties of micelles (size, degree of counterion binding) as well as diffusion coefficient of the SDS monomer. As an extended test, a simulation of a micelle with a high aggregation number (382) and unnatural initial shape is performed, and a restructuring to the correct shape is observed. This proves the suitability of the developed models for simulations of concentrated SDS solutions containing large micelles and also emphasizes importance of hydrocarbon tail parameters for the micelle properties. Finally, the developed DS- models are tested in combination with several common Na+ and water models. Their effect on the properties of SDS micelles is discussed, and suitable combinations are determined.

The influence of beta-cyclodextrin on acid-base and tautomeric equilibrium of fluorescein dyes in aqueous solution.

The protolytic equilibrium of fluorescein in aqueous solutions was studied in the presence of cycloheptaamylose (beta-cyclodextrin, or beta-CD). The constants of stepwise ionization of the dye (H(3)R(+)left arrow over right arrowH(2)Rleft arrow over right arrow HR(-)left arrow over right arrowR(2-)), K(a0), K(a1), and K(a2) were determined using vis-spectroscopy at ionic strength 0.05 M (NaCl+buffer) and 25 degrees C. In the presence of 0.0086 M beta-CD, the indices of ionization constants are as follows: pK(a0)=1.21+/-0.12, pK(a1)=5.08+/-0.03, pK(a2)=6.35+/-0.02. The changes in these pK(a)s, as compared with the values determined without cyclodextrin, are unequal. Namely, the pK(a0) value decreases by 1.0, while the pK(a1) value increases by 0.7. Thus, the introduction of beta-CD allows to govern the ratios K(a0)/K(a1) and K(a1)/K(a2), which are equal to, respectively, 141 and 151 in water, and 7.4 x 10(3) and 18.6 with cyclodextrin added. Rationalization of the observed phenomenon is possible taking into account the detailed scheme of protolytic equilibrium. Conclusions concerning tautomerism of dye molecules were deduced from absorption spectra; the fractions of tautomers, tautomerization constants, and microscopic ionization constants were evaluated. These data allow concluding that the main reason for the aforementioned pK(a) alterations is the binding of H(2)R by the cyclodextrin cavity accompanied by turning these neutral species into the colorless lactone. The host-guest interaction of neutral species of fluorescein isothiocyanate, 2,7-dichlorofluorescein, and 3',4',5',6'-tetrachlorofluorescein also results in the cyclodextrin-assisted shift of tautomeric equilibrium. Such nature of interactions is proved by the addition of competing agents, camphor-4-carboxylic acid and sodium n-nonylsulfonate, which results in the removing of neutral dye species from the cycloheptaamylose cavity.