The interplay between hydrophobic and solute–solute interactions: Implications for Hofmeister Effects

• A sequential relationship is found between hydrophobicity and solute–solute forces. • The interactions between solutes are classified as global or local. • Global and local solute concentration profiles are expected at external surface. • This study offers a framework to understand the mechanism of Hofmeister effects. Various forces are found between dissolved solutes, and the final thermodynamic equilibrium state is due to the combined effects of them. They may be categorized into water–mediated hydrophobic interactions and direct solute–solute forces. This work is devoted to investigate the interplay between hydrophobic and solute–solute interactions. Driven by hydrophobic interactions, solutes tend to approach one another so as to maximize the hydrogen bonding of water. As the separation between solutes decreases, the direct solute–solute interactions become dominant, particularly upon direct contact in water. Therefore, a temporal and spatial sequence may be expected between hydrophobic interactions and direct solute–solute forces. Additionally, these are demonstrated by the calculated potential of mean forces (PMFs) from molecular dynamics (MD) simulations. Furthermore, these interactions can be classified as global and local, potentially influencing global and local solute distributions in solution. These findings may be applied to understand the mechanism underlying Hofmeister effects.