Molecular Dynamics Investigation of Giant Clustering in Small-Molecule Solutions: The Case of Aqueous PEHA.

The importance of the formation of giant clusters in solution, in nature and industry, is increasingly recognized. However, relatively little attention has been paid to the formation of giant clusters in solutions of small, relatively soluble but nonamphiphilic molecules. In this work, we present a general methodology based on molecular dynamics that can be used to investigate such systems. As a case study, we focus on the formation of apparently stable clusters of pentaethylenehexamine (PEHA) in water. These clusters have been used as templates for the construction of bioinspired silica nanoparticles. To better understand clustering in this system, we study the effect of PEHA protonation state (neutral, +1, and +2) and counterion type (chloride or acetate) on PEHA clustering in dilute aqueous solutions (200 and 400 mM) using large-scale classical molecular dynamics. We find that large stable clusters are formed by singly charged PEHA with chloride or acetate as the counterion, although it is not clear for the case with acetate whether bulk phase separation, that might lead to precipitation, would eventually occur. Large clusters also appear to be stable for doubly charged PEHA with acetate, the less soluble counterion. We attribute this behavior to a form of complex coacervation, observed here for relatively small and highly soluble molecules (PEHA + counterion) rather than the large polyions usually found to form such coacervates. We discuss whether this behavior might also be described by an effective SALR (short-range attraction, long-range repulsion) interaction. This work might help future studies of additives for the design of novel bioinspired templated nanomaterials and of giant clustering in small-molecule solutions more generally.

Molecular Dynamics Investigation of Clustering in Aqueous Glycine Solutions.

Recent experiments with undersaturated aqueous glycine solutions have repeatedly exhibited the presence of giant liquid-like clusters or nanodroplets around 100 nm in diameter. These nanodroplets re-appear even after careful efforts for their removal and purification of the glycine solution. The composition of these clusters is not clear, although it has been suggested that they are mainly composed of glycine, a small and very soluble amino acid. To gain insights into this phenomenon, we study the aggregation of glycine in aqueous solutions at concentrations below the experimental solubility limit using large-scale molecular dynamics simulations under ambient conditions. Three protonation states of glycine (zwitterion = GLZ, anion = GLA, and cation = GLC) are simulated using molecular force fields based on the 1.14*CM1A partial charge scheme, which incorporates the OPLS all-atom force field and TIP3P water. When initiated from dispersed states, we find that giant clusters do not form in our simulations unless salt impurities are present. Moreover, if simulations are initiated from giant cluster states, we find that they tend to dissolve in the absence of salt impurities. Therefore, the simulation results provide little support for the possibility that the giant clusters seen in experiments are composed purely of glycine (and water). Considering that strenuous efforts are made in experiments to remove impurities such as salt, we propose that the giant clusters observed might instead result from the aggregation of reaction products of aqueous glycine, such as diketopiperazine or other oligoglycines which may be difficult to separate from glycine using conventional methods, or their co-aggregation with glycine.

Cluster formation in symmetric binary SALR mixtures.

The equilibrium cluster fluid state of a symmetric binary mixture of particles interacting through short-ranged attractive and long-ranged repulsive interactions is investigated through Monte Carlo simulations. We find that the clustering behavior of this system is controlled by the cross-interaction between the two types of particles. For a weak cross-attraction, the system displays a behavior that is a composite of the behavior of individual components, i.e., the two components can both form giant clusters independently and the clusters distribute evenly in the system. For a strong cross-attraction, we instead find that the resulting clusters are mixtures of both components. Between these limits, both components can form relatively pure clusters, but unlike clusters can join at their surfaces to form composite clusters. These insights should help to understand the mechanisms for clustering in experimental binary mixture systems and help tailor the properties of novel nanomaterials.