Molecular Hydration Tunes the Cation–π Interaction Strength in Aqueous Solution

Abstract Cation–π interactions are considered to be among the most important strong noncovalent interactions in aqueous solutions and as regulators of various biological phenomena, including biological adhesion, signal transduction, and liquid–liquid phase separation (LLPS). Despite their significant roles, cation–π interactions in aqueous environments are not systematically and experimentally understood. Here, we directly experimentally examined cation–π interactions between cationic and aromatic moieties common to biological systems using a surface forces apparatus (SFA) augmented by computational methods. Specifically, we chose cationic and aromatic moieties with different levels of hydration and observed how the molecular hydration of these moieties affects the formation and strengths of cation–π bonds. To date, the charge densities of the interacting moieties are primarily considered to modulate the interaction strength; however, it is experimentally and computationally revealed that the hydration strengths (or hydrophobic properties) of the interacting moieties are more important for controlling in underwater interactions.