Role of Cation Hydrophobicity in Protein Solvation by Ionic Liquids

Ionic liquids (ILs) are molten salts extensively used as solvents and catalysts in various systems. Optimizing IL applications requires a thorough understanding of their behavior in different chemical environments. In this study, we examine the solvation of the protein Ubiquitin in solutions of ILs, focusing on the effect of cation alkyl chain length on protein solvation. We employ molecular dynamics simulations to characterize the solvation structure and dynamics of proteins interacting with ILs composed of 1-butyl-3-methylimidazolium (BMIM), 1-ethyl-3-methylimidazolium (EMIM), dicyanamide (DCA), chloride (Cl), nitrate (NO₃), and tetrafluoroborate (BF₄). The solvation structure is analyzed using minimum-distance distribution functions and the Kirkwood-Buff theory, while time-correlation functions are used to investigate the dynamic behavior of the ions. Our results indicate that at a concentration of 0.5 mol/L, IL systems with BMIM exhibit higher ion densities compared to systems with EMIM. Consequently, the Kirkwood-Buff integrals for ions in BMIM systems converge to greater values than those in EMIM systems, suggesting a preferential accumulation of BMIM ions around Ubiquitin. Anions capable of forming hydrogen bonds with protein surface atoms play a significant role in these interactions. Among the anions studied, dicyanamide showed the highest local domain accumulation, influencing the overall ion distribution in the system. Additionally, time-correlation functions reveal that dicyanamide significantly affects the residence time of ions within 3.5 Å of the protein surface. These findings suggest that ions with high affinity for the protein's local environment drive the accumulation behavior of the ions and that this behavior is also impacted by the hydrophobicity of the cations. Detailed molecular insights into the solvation of proteins by ILs will be provided in the conference poster.