Salting out the polar polymorph: analysis by alchemical solvent transformation.

We computationally examine how adding NaCl to an aqueous solution with α- and γ-glycine nuclei alters the structure and interfacial energy of the nuclei. The polar γ-glycine nucleus in pure aqueous solution develops a melted layer of amorphous glycine around the nucleus. When NaCl is added, a double layer is formed that stabilizes the polar glycine polymorph and eliminates the surface melted layer. In contrast, the non-polar α-glycine nucleus is largely unaffected by the addition of NaCl. To quantify the stabilizing effect of NaCl on γ-glycine nuclei, we alchemically transform the aqueous glycine solution into a brine solution of glycine. The alchemical transformation is performed both with and without a nucleus in solution and for nuclei of α-glycine and γ-glycine polymorphs. The calculations show that adding 80 mg/ml NaCl reduces the interfacial free energy of a γ-glycine nucleus by 7.7 mJ/m(2) and increases the interfacial free energy of an α-glycine nucleus by 3.1 mJ/m(2). Both results are consistent with experimental reports on nucleation rates which suggest: J(α, brine) < J(γ, brine) < J(α, water). For γ-glycine nuclei, Debye-Hückel theory qualitatively, but not quantitatively, captures the effect of salt addition. Only the alchemical solvent transformation approach can predict the results for both polar and non-polar polymorphs. The results suggest a general "salting out" strategy for obtaining polar polymorphs and also a general approach to computationally estimate the effects of solvent additives on interfacial free energies for nucleation.

Size-Dependent Surface Free Energy and Tolman-Corrected Droplet Nucleation of TIP4P/2005 Water.

Classical nucleation theory is notoriously inaccurate when using the macroscopic surface free energy for a planar interface. We examine the size dependence of the surface free energy for TIP4P/2005 water nanodroplets (radii ranging from 0.7 to 1.6 nm) at 300 K with the mitosis method, that is, by reversibly splitting the droplets into two subclusters. We calculate the Tolman length to be -0.56 ± 0.09 Å, which indicates that the surface free energy of water droplets that we investigated is 5-11 mJ/m(2) greater than the planar surface free energy. We incorporate the computed Tolman length into a modified classical nucleation theory (δ-CNT) and obtain modified expressions for the critical nucleus size and barrier height. δ-CNT leads to excellent agreement with independently measured nucleation kinetics.

Polymorph specific RMSD local order parameters for molecular crystals and nuclei: α-, ß-, and γ-glycine.

Crystal nucleation is important for many processes including pharmaceutical crystallization, biomineralization, and material synthesis. The progression of structural changes which occur during crystal nucleation are often described using order parameters. Polymorph specific order parameters have been developed for crystallization of spherically symmetric particles; however, polymorph specific order parameters for molecular crystals remain a challenge. We introduce template based polymorph specific order parameters for molecular crystals. For each molecule in a simulation, we compute the root mean squared deviation (RMSD) between the local environment around the molecule and a template of the perfect crystal structure for each polymorph. The RMSD order parameters can clearly distinguish the α-, ß-, and γ-glycine polymorph crystal structures in the bulk crystal and also in solvated crystallites. Surface melting of glycine crystallites in supersaturated aqueous solution is explored using the newly developed order parameters. The solvated α-glycine crystallite has a thinner surface melted layer than the γ-glycine crystallite. α-glycine forms first out of aqueous solution, so surface melted layer thickness may provide insight into interfacial energy and polymorph selection.

Estimating diffusivity along a reaction coordinate in the high friction limit: Insights on pulse times in laser-induced nucleation.

In the high friction limit of Kramers' theory, the diffusion coefficient for motion along the reaction coordinate is a crucial parameter in determining reaction rates from mean first passage times. The Einstein relation between mean squared displacement, time, and diffusivity is inaccurate at short times because of ballistic motion and inaccurate at long times because trajectories drift away from maxima in the potential of mean force. Starting from the Smoluchowski equation for a downward parabolic barrier, we show how drift induced by the potential of mean force can be included in estimating the diffusivity. A modified relation between mean squared displacement, time, and diffusivity now also includes a dependence on the barrier curvature. The new relation provides the diffusivity at the top of the barrier from a linear regression that is analogous to the procedure commonly used with Einstein's relation. The new approach has particular advantages over previous approaches when evaluations of the reaction coordinate are costly or when the reaction coordinate cannot be differentiated to compute restraining forces or velocities. We use the new method to study the dynamics of barrier crossing in a Potts lattice gas model of nucleation from solution. Our analysis shows that some current hypotheses about laser-induced nucleation mechanisms lead to a nonzero threshold laser pulse duration below which a laser pulse will not affect nucleation. We therefore propose experiments that might be used to test these hypotheses.

Nucleation in a Potts lattice gas model of crystallization from solution.

Nucleation from solution is important in many pharmaceutical crystallization, biomineralization, material synthesis, and self-assembly processes. Simulation methodology has progressed rapidly for studies of nucleation in pure component and implicit solvent systems; however little progress has been made in the simulation of explicit solvent systems. The impasse stems from the inability of rare events simulation methodology to be combined with simulation techniques which maintain a constant chemical potential driving force (supersaturation) for nucleation. We present a Potts lattice gas (PLG) to aid in the development of new simulation strategies for nucleation from solution. The PLG captures common crystallization phase diagram features such as a eutectic point and solute/solvent melting points. Simulations of the PLG below the bulk solute melting temperature reveal a competition between amorphous and crystalline nuclei. As the temperature is increased toward the bulk melting temperature, the nucleation pathway changes from a one step crystalline nucleation pathway to a two step pathway, where an amorphous nucleus forms and then crystallizes. We explain these results in terms of classical nucleation theory with different size-dependant chemical potentials for the amorphous and crystalline nucleation pathways. The two step pathway may be particularly important when crystallization is favored only at postcritical sizes.

Nonequilibrium accumulation of surface species and triboelectric charging in single component particulate systems.

Triboelectric charging occurs in granular systems composed of chemically identical particles even though there is no apparent driving force for charge transfer. We show that such charging can result from nonequilibrium dynamics in which collision-induced electron transfer generates electron accumulation on a particle-size-dependent subset of the system. This idea rationalizes experimental results that suggest that smaller particles charge negatively while the large ones charge positively. This effect occurs generally when there are high energy electrons on a surface that cannot equilibrate to lower energy states on the same surface, but can transfer to lower energy states on other particles during collisions.

Molecular dynamics investigation of the effects of a water surface on the aggregation of bent-core molecules.

Molecular dynamics simulations are used to determine how the presence of a water surface affects the way that bent-core surfactant molecules interact with one another. The simulations are carried out for isolated pairs of bent-core molecules, and for pairs of bent-core molecules on a water surface. The results show that the water surface fundamentally alters the nature of the interaction between the bent-core molecules: a stable complex is formed when the two molecules are on the water surface, but not for an isolated pair of molecules. This difference occurs because the water surface constrains the internal structure and orientation of the molecules, which makes the packing of the molecules into a stable complex more thermodynamically favorable.

Shear-induced crystallization in jammed systems.

Simulations are used to address the effects of oscillating shear strain on jammed systems composed of spherical particles. The simulations show that shear oscillations with amplitudes of more than a few percent lead to substantial crystallization of the system. To ensure that the conclusions are independent of the simulation methodology, a range of simulations are carried out that use both molecular dynamics and athermal dynamics methods, soft and hard potentials, potentials with and without attractive forces, and systems with and without surrounding walls. The extent of crystallization is monitored primarily by the Q(6) order parameter, but also in some simulations by the potential energy and the radial distribution function, and by direct visual inspection. A mechanism is proposed for shear-induced crystallization of jammed systems, based on fold catastrophes of the free-energy landscape.

Molecular dynamics investigation of bent-core molecules on a water surface.

Molecular dynamics simulations are carried out for bent-core molecules at water surfaces. The water surface is shown to alter the equilibrium molecular structure significantly by causing a different class of torsional states to become more favorable. The equilibrium structure is also altered by the substitution of chlorine atoms for hydrogen atoms on the central phenyl ring in that this substitution forces the bent core to remain in a single torsional state rather than be delocalized among several torsional states. The consequences of these structural changes on the chirality and packing of these molecules on water surfaces are discussed.

Stretching the immunoglobulin 27 domain of the titin protein: the dynamic energy landscape.

Molecular simulations are carried out on the Immunoglobulin 27 domain of the titin protein. The energy landscape is mapped out using an implicit solvent model, and molecular dynamics simulations are run with the solvent explicitly modeled. Stretching a protein is shown to produce a dynamic energy landscape in which the energy minima move in configuration space, change in depth, and are created and destroyed. The connections of these landscape changes to the mechanical unfolding of the Immunoglobulin 27 domain are addressed. Hydrogen bonds break upon stretching by either intrabasin processes associated with the movement of energy minima, or interbasin processes associated with transitions between energy minima. Intrabasin changes are reversible and dominate for flexible interactions, whereas interbasin changes are irreversible and dominate for stiff interactions. The most flexible interactions are Glu-Lys salt bridges, which can act like tethers to bind strands even after all backbone interactions between the strands have been broken. As the protein is stretched, different types of structures become the lowest energy structures, including structures that incorporate nonnative hydrogen bonds. Structures that have flat energy versus elongation profiles become the lowest energy structures at elongations of several Angstroms, and are associated with the unfolding intermediate state observed experimentally.