The interaction of ILs with polar or apolar groups can be modulated by the choice of cation and anion . Ions with long alkyl chains (most commonly found in the cations) increase the hydrophobicity of the ionic liquid. The composition of the IL is also crucial to modulate its aqueous solubility and its competition with water for the interactions with the protein . Water can form hydrogen bonds with most common anions; however, it is typically not as effective at solvating the, typically more hydrophobic, cations . Water molecules can effectively solvate the anions, while the interactions with the cations are of greater complexity, and become less favorable with the increase of the cation alkyl chain . Aromatic cations, like those present in imidazolium and pyridinium-based ILs, typically exhibit greater water solubility compared to aliphatic cations, which can be seen in pyrrolidinium and piperidinium-based ILs . The balance between water-protein, water-IL, and IL-protein interactions determines if the net effect of the aqueous IL solution is to denature or protect the protein structure .