Increasing applications of ionic liquids and their analogues, namely Deep Eutectic Solvents (DESs), requires further investigation into the effect of moisture content on the physico-chemical characteristics of these fluids. Although it is common practice to synthesize these fluids in a moisture-controlled environment, as moisture is generally considered to have an impact on their properties, there are no systematic studies on this. We herein examine the effects of water on Reline, a Type-III DES composed of urea and choline chloride. Experiments were performed to obtain the physical properties of aqueous Reline solution. We observed moderate changes in density, speed of sound, refractive index, and pH with increasing water fraction; however, the change in viscosity and conductivity was strong and exponential. In addition, molecular dynamics simulations were performed to analyze the intermolecular interactions of Reline and aqueous Reline solutions. The simulations primarily present the significance of urea–anion interaction to explain the low melting point of the DES. In the presence of water, the anion is preferentially hydrated as compared to urea or the cation. More interestingly, simulations help to classify the effects of water into different regimes. At low water fractions (<5%) the urea–urea interactions are enhanced, as is revealed through the hydrogen bond analysis. Beyond 25% water fractions, the components of Reline are individually hydrated and have high diffusivity, which is further reflected in the change in transport properties. The results presented herein provide valuable information on aqueous Reline solutions both in terms of experimental data and molecular insights, which in turn, we believe, might assist in developing further applications of Reline and other related DESs.

Experiments hold intriguing, circumstantial clues to the mechanisms behind arginine-mediated solubilization of small organic drugs and suppression of protein aggregation driven by hydrophobic or aromatic associations, but how exactly arginine’s molecular structure and interactions contribute to its function remains unclear since attention has focused so far on the thermodynamics of the preferential exclusion or binding of arginine. Here, we examine, through molecular dynamics simulations, how arginine solubilizes nanoscale particles with hydrophobic surfaces or aromatic-ring-type surface interactions. We show that preferential, hydrophobic, and dispersion interactions of arginine’s guanidinium group with the particles lead to a surfactant-like behavior of arginine around the particles and to a solvation layer with a protective polar mask creating a hydrophilic shell. Additionally, arginine-arginine association around the solvation layer further prevents aggregative contacts. The results shed some light on the mechanistic basis of arginine’s function as a suppressant of protein aggregation, although the complex energy landscapes and kinetic pathways of aggregation are protein-dependent and pose formidable challenges to developing comprehensive mechanistic pictures. Our results suggest arginine’s mode of interaction with hydrophobic patches and aromatic residues could reduce aggregation-prone intermediate states of proteins and shield protein-protein aggregative contacts. The approach used here offers a systematic way of exploring implications of other amino acid/excipient interactions by studying interactions of the excipient with particles grafted with amino acids.