Conformational Energy Landscapes of Amphiphiles Are Modulated by Polar Co-solutes – a Markov Analysis

Microemulsions are increasingly employed within industrial processes in the pharmaceutical, food, cosmetics and petroleum industries, as well as in fundamental technologies like chemical separations. Molecular level details of microemulsion structure is a growing area of interest, as more evidence is demonstrating that intermolecular interactions between the assembled amphiphiles tune the size, shape and inter-micelle interactions within the solution. A number of features influence intermolecular interactions, including the molecular conformation of amphiphiles (through modulation of the dipole moment and molecular packing). The conformational potential energy landscape (PEL) for amphiphiles has a topology that is dictated not only by intramolecular degrees of freedom and interactions (e.g., internal hydrogen bonds) but also by how different conformations are influenced by direct solvent-solute interactions. Atomistic molecular simulations can sample the conformational ensemble, yet when monomeric units have high degrees of freedom they generate a huge amount of high-dimensional complex data. Under these circumstances, Markov state models (MSMs) are an as yet under-utilized tool to analyze simulation trajectories and provide a way to understand the conformational free energy landscape and its dependence upon solution conditions. Here, polar solute...amphiphile interactions are hypothesized to collectively control the amphiphile conformational distribution and modulate the underlying PEL. A workflow is developed for Markov state modelling that investigates the large pool of conformations that arise from the breadth of amphiphiles present in MD simulation; the MSM is used to explain the important changes to the topology of the PEL that results from solute-solvent interactions.