The 16th Mini-Symposium on Liquids 2023

Abstract

Drug and materials discovery is a complex, expensive, and time-consuming process vital for global health and industrial progress. A common nominator for these problems is their connection to molecules’ behavior and affinity for the aqueous phase. While many solutes possess great properties of interest, they may not dissolve well or are aggregation-prone rendering an otherwise great drug useless. To remedy this issue ions and co-solvents are commonly utilized to modulate the activity, function, and binding of the solute. The effect of ions that cannot be attributed to ion valency is manifested in the well-known Hofmeister series, asserting ions can be ranked in their ability to perturb solute equilibria. Despite the discovery by Hofmeister more than a century ago, the molecular mechanism(s) are still under much investigation. To provide further insight into ion-specific effects we have employed a combination of molecular dynamics and free energy computations to obtain a total understanding of small molecule solvation. Utilizing the novel Energy-Representation Theory of Solvation we illustrate the fundamental contrast in anions and cations role to either favor or disfavor the solvation of the solute. We also decompose the contributions arising from the solute–solvent and solute-ions interactions and that from the excluded volume, enabling us to pinpoint the mechanism of the salt particles individually as well as water. In the case of caffeine being the solute, we find the cations salting-in caffeine via binding to the polar ketone groups, while the anions were found to be salting-out via perturbations of water. In agreement with previous findings, the perturbation by salt is mostly anion dependent, with the magnitude of the excluded-volume effect found to be the governing mechanism. The broader implication of our work allows us also to address the existence of the kosmotropic and chaotropic properties of salt and quantify their implication in solute solvation. This is an interesting development due to water ordering and disordering by co-solvent being an old theory that has fallen into increasing obscurity in recent years with instead the theory of preferential accumulation or exclusion becoming more dominant.

Stefan Hervø-Hansen

Specially Appointed Researcher

My research interests include molecular simulation methods, free energy calculations, and rational macromolecular design.