Peter H. Koenig

Asymmetric Electrostatic and Hydrophobic–Hydrophilic Interaction Forces between Mica Surfaces and Silicone Polymer Thin Films

We have synthesized model hydrophobic silicone thin films on gold surfaces by a two-step covalent grafting procedure. An amino-functionalized gold surface reacts with monoepoxy-terminated polydimethylsiloxane (PDMS) via a click reaction, resulting in a covalently attached nanoscale thin film of PDMS, and the click chemistry synthesis route provides great selectivity, reproducibility, and stability in the resulting model hydrophobic silicone thin films. The asymmetric interaction forces between the PDMS thin films and mica surfaces were measured with the surface forces apparatus in aqueous sodium chloride solutions. At an acidic pH of 3, attractive interactions are measured, resulting in instabilities during both approach (jump-in) and separation (jump-out from adhesive contact). Quantitative analysis of the results indicates that the Derjaguin-Landau-Verwey-Overbeek theory alone, i.e., the combination of electrostatic repulsion and van der Waals attraction, cannot fully describe the measured forces and that the additional measured adhesion is likely due to hydrophobic interactions. The surface interactions are highly pH-dependent, and a basic pH of 10 results in fully repulsive interactions at all distances, due to repulsive electrostatic and steric-hydration interactions, indicating that the PDMS is negatively charged at high pH. We describe an interaction potential with a parameter, known as the Hydra parameter, that can account for the extra attraction (low pH) due to hydrophobicity as well as the extra repulsion (high pH) due to hydrophilic (steric-hydration) interactions. The interaction potential is general and provides a quantitative measure of interfacial hydrophobicity/hydrophilicity for any set of interacting surfaces in aqueous solution.

Self-assembly and bilayer-micelle transition of fatty acids studied by replica-exchange constant pH molecular dynamics.

Recent interest in the development of surfactant-based nanodelivery systems targeting tumor sites has sparked our curiosity in understanding the detailed mechanism of the self-assembly and phase transitions of pH-sensitive surfactants. Toward this goal, we applied a state-of-the-art simulation technique, continuous constant pH molecular dynamics (CpHMD) with the hybrid-solvent scheme and pH-based replica-exchange protocol, to study the de novo self-assembly of 30 and 40 lauric acids, a simple model titratable surfactant. We observed the formation of a gel-state bilayer at low and intermediate pH and a spherical micelle at high pH, with the phase transition starting at 20-30% ionization and being completed at 50%. The degree of cooperativity for the transition increases from the 30-mer to the 40-mer. The calculated apparent or bulk pKa value is 7.0 for the 30-mer and 7.5 for the 40-mer. Congruent with experiment, these data demonstrate that CpHMD is capable of accurately modeling large conformational transitions of surfactant systems while allowing the simultaneous proton titration of constituent molecules. We suggest that CpHMD simulations may become a useful tool in aiding in the design and development of pH-sensitive nanocarriers for a variety of biomedical and technological applications.

Atomistic simulations of pH-dependent self-assembly of micelle and bilayer from fatty acids

Detailed knowledge of the self-assembly and phase behavior of pH-sensitive surfactants has implications in areas such as targeted drug delivery. Here we present a study of the formation of micelle and bilayer from lauric acids using a state-of-the-art simulation technique, continuous constant pH molecular dynamics (CpHMD) with conformational sampling in explicit solvent and the pH-based replica-exchange protocol. We find that at high pH conditions a spherical micelle is formed, while at low pH conditions a bilayer is formed with a considerable degree of interdigitation. The mid-point of the phase transition is in good agreement with experiment. Preliminary investigation also reveals that the effect of counterions and salt screening shifts the transition mid-point and does not change the structure of the surfactant assembly. Based on these data we suggest that CpHMD simulations may be applied to computational design of surfactant-based nano devices in the future.

Simulating pH titration of a single surfactant in ionic and nonionic surfactant micelles.

Calculation of surfactant pK(a)s in micelles is a challenging task using traditional electrostatic methods due to the lack of structural data and information regarding the effective dielectric constant. Here we test the implicit- and hybrid-solvent-based continuous constant pH molecular dynamics (CpHMD) methods for predicting the pK(a) shift of a lauric acid solubilized in three micelles: dodecyl sulfate (DS), dodecyltrimethylammonium (DTA), and dodecyltriethylene glycol ether (DE3). Both types of simulations are able to reproduce the observed positive pK(a) shifts for the anionic DS and nonionic DE3 micelles. However, for the cationic DTA micelle, the implicit-solvent simulation fails to predict the direction of the pK(a) shift, while the hybrid-solvent simulation, where conformational sampling is conducted in explicit solvent, is consistent with experiment, although the specific-ion effects remain to be accurately determined. Comparison between the implicit- and hybrid-solvent data shows that the latter gives a more realistic description of the conformational environment of the titrating probe. Surprisingly, in the DTA micelle, surfactants are only slightly attracted to the laurate ion, which diminishes the magnitude of the electrostatic stabilization, resulting in a positive pK(a) shift that cannot be explained by chemical intuition or other theoretical models. Our data underscores the importance of microscopic models and ionization-coupled conformational dynamics in quantitative prediction of the pK(a) shifts in micelles.

Establishing Effective Simulation Protocols for β-and α/β-Peptides. II. Molecular Mechanical (MM) Model for a Cyclic β-Residue

All-atom molecular mechanical (MM) force field parameters are developed for a cyclic beta-amino acid, amino-cyclo-pentane-carboxylic acid (ACPC), using a multi-objective evolutionary algorithm. The MM model is benchmarked using several short, ACPC-containing alpha/beta-peptides in water and methanol with SCC-DFTB (self consistent charge-density functional tight binding)/MM simulations as the reference. Satisfactory agreements are found between the MM and SCC-DFTB/MM results regarding the distribution of key dihedral angles for the tetra-alpha/beta-peptide in water. For the octa-alpha/beta-peptide in methanol, the MM and SCC-DFTB/MM simulations predict the 11- and 14/15-helical form as the more stable conformation, respectively; however, the two helical forms are very close in energy (2-4 kcal/mol) at both theoretical levels, which is also the conclusion from recent NMR experiments. As the first application, the MM model is applied to an alpha/beta-pentadeca-peptide in water with both explicit and implicit solvent models. The stability of the peptide is sensitive to the starting configuration in the explicit solvent simulations due to their limited length ( approximately 10-40 ns). Multiple ( approximately 20 x 20 ns) implicit solvent simulations consistently show that the 14/15-helix is the predominant conformation of this peptide, although substantially different conformations are also accessible. The calculated nuclear Overhauser effect (NOE) values averaged over different trajectories are consistent with experimental data, which emphasizes the importance of considering conformational heterogeneity in such comparisons for highly dynamical peptides.

Molecular dynamics simulations of ionic and nonionic surfactant micelles with a generalized born implicit‐solvent model

In recent years, all‐atom and coarse‐grained models have been developed andapplied to simulations of micelles and biological membranes. Here, we explorethe question of whether a combined all‐atom representation of surfactantmolecules and continuum description of solvent based on the generalized Bornmodel can be used to study surfactant micelles. Specifically, we report theparameterization of the GBSW model with a surface‐area dependent nonpolarsolvation energy term for dodecyl sulfate, dodecyl tetramethylammonium, anddodecyl triethyleneglycol ether molecules. In the parameterization procedure,the atomic Born radii were derived from the radial distribution functions ofsolvent charge and refined targeting the potential of mean force of dimerinteractions from explicit‐solvent simulations. The optimized radii were thenapplied in molecular dynamics simulations of the ionic and nonionic micelles.We found that the micelles are stable but more compact and rigid than inexplicit solvent as a consequence of the drastic reduction in solvation andmobility of surfactant monomers within the micelle. Based on these data and ourprevious work, we suggest that in addition to a more accurate description ofthe nonpolar solvation energy, the ruggedness in the short‐range interactionsdue to solvent granularity is a critical feature that needs to be taken intoaccount to accurately model processes such as micelle formation and proteinfolding in implicit solvent. Finally, the explicit‐solvent data presented hereoffers new insights into different conformational behavior of ionic andnonionic micelles which is valuable for understanding hydrophobic assembliesand of interest to the detergent industry.

Liquid–liquid equilibria for soft-repulsive particles: Improved equation of state and methodology for representing molecules of different sizes and chemistry in dissipative particle dynamics

Three developments are presented that significantly expand the applicability of dissipative particle dynamics (DPD) simulations for symmetric and non-symmetric mixtures, where the former contain particles with equal repulsive parameter for self-interactions but a different repulsive parameter for cross-interactions, and the latter contain particles with different repulsive parameters also for the self-interactions. Monte Carlo and molecular dynamics simulations for unary phases covering a wide range of repulsive parameters and of densities for single-bead DPD particles point to deficiencies of the Groot and Warren equation of state (GW-EOS) [J. Chem. Phys. 107, 4423 (1997)]. A revised version, called rGW-EOS, is proposed here that is significantly more accurate over a wider range of parameters/densities. The second development is the generalization of the relationship between the Flory-Huggins χ parameter and the repulsive cross-interaction parameter when the two particles involved have different molecular volumes. The third aspect is an investigation of Gibbs ensemble Monte Carlo simulation protocols, which demonstrates the importance of volume fluctuations and excess volumes of mixing even for equimolar symmetric mixtures of DPD particles. As an illustrative example, the novel DPD methodology is applied to the prediction of the liquid-liquid equilibria for acetic anhydride/(n-hexane or n-octane) binary mixtures.

Determination of characteristic lengths and times for wormlike micelle solutions from rheology using a mesoscopic simulation method

We apply our recently developed mesoscopic simulation method for entangled wormlike micelle (WLM) solutions to extract multiple micellar characteristic lengths and time constants: i.e., average micelle length, breakage rate, and entanglement and persistence lengths, from linear rheological measurements on commercial surfactant solutions, one containing sodium lauryl one ether sulfate (SLE1S), and the other containing both SLE1S and cocamidopropyl betaine, as well as a perfume mixture, in both cases with a sample salt (NaCl) added. Measurements include both mechanical rheometry and diffusing wave spectroscopy, the latter providing the high-frequency data needed to determine micelle persistence length accurately. By fitting the experimental data ( G′ and G″) across the entire frequency range through our iteration procedure, the method is of practical use in predicting micellar parameters, which are difficult to obtain from other theoretical or experimental methods. The dependence of micellar parameters on a...

Predicting proton titration in cationic micelle and bilayer environments.

Knowledge of the protonation behavior of pH-sensitive molecules in micelles and bilayers has significant implications in consumer product development and biomedical applications. However, the calculation of pKas in such environments proves challenging using traditional structure-based calculations. Here we apply all-atom constant pH molecular dynamics with explicit ions and titratable water to calculate the pKa of a fatty acid molecule in a micelle of dodecyl trimethylammonium chloride and liquid as well as gel-phase bilayers of diethyl ester dimethylammonium chloride. Interestingly, the pKa of the fatty acid in the gel bilayer is 5.4, 0.4 units lower than that in the analogous liquid bilayer or micelle, despite the fact that the protonated carboxylic group is significantly more desolvated in the gel bilayer. This work illustrates the capability of all-atom constant pH molecular dynamics in capturing the delicate balance in the free energies of desolvation and Coulombic interactions. It also shows the importance of the explicit treatment of ions in sampling the protonation states. The ability to model dynamics of pH-responsive substrates in a bilayer environment is useful for improving fabric care products as well as our understanding of the side effects of anti-inflammatory drugs.

Effects of Surfactants and Polyelectrolytes on the Interaction between a Negatively Charged Surface and a Hydrophobic Polymer Surface

We have measured and characterized how three classes of surface-active molecules self-assemble at, and modulate the interfacial forces between, a negatively charged mica surface and a hydrophobic end-grafted polydimethylsiloxane (PDMS) polymer surface in solution. We provide a broad overview of how chemical and structural properties of surfactant molecules result in different self-assembled structures at polymer and mineral surfaces, by studying three characteristic surfactants: (1) an anionic aliphatic surfactant, sodium dodecyl sulfate (SDS), (2) a cationic aliphatic surfactant, myristyltrimethylammonium bromide (MTAB), and (3) a silicone polyelectrolyte with a long-chain PDMS midblock and multiple cationic end groups. Through surface forces apparatus measurements, we show that the separate addition of three surfactants can result in interaction energies ranging from fully attractive to fully repulsive. Specifically, SDS adsorbs at the PDMS surface as a monolayer and modifies the monotonic electrostatic repulsion to a mica surface. MTAB adsorbs at both the PDMS (as a monolayer) and the mica surface (as a monolayer or bilayer), resulting in concentration-dependent interactions, including a long-range electrostatic repulsion, a short-range steric hydration repulsion, and a short-range hydrophobic attraction. The cationic polyelectrolyte adsorbs as a monolayer on the PDMS and causes a long-range electrostatic attraction to mica, which can be modulated to a monotonic repulsion upon further addition of SDS. Therefore, through judicious selection of surfactants, we show how to modify the magnitude and sign of the interaction energy at different separation distances between hydrophobic and hydrophilic surfaces, which govern the static and kinetic stability of colloidal dispersions. Additionally, we demonstrate how the charge density of silicone polyelectrolytes modifies both their self-assembly at polymer interfaces and the robust adhesion of thin PDMS films to target surfaces.