Surface phase behavior, not hydrogen bonding, governs hydrophobic attraction between extended solutes

Abstract: Hydrophobic interactions are central to biological self-assembly and soft matter organization, yet their microscopic origins remain debated. Traditional explanations often attribute the increase in attraction between hydrophobic solutes with increasing temperature to entropy changes resulting from disrupted hydrogen bonding in water. Here, we present a different perspective based on the physics of surface phase transitions, supported by extensive molecular dynamics simulations. Using well-tempered metadynamics, we quantify the solvent-mediated potential of mean force between nanometer-scale hydrophobic solutes in the monatomic water model (mW), the SPC/E water model, and a Lennard-Jones solvent. We develop a morphometric model grounded in a scaling theory of critical drying, linking the range and strength of hydrophobic attraction to interfacial thermodynamics and deviations from vapor-liquid coexistence, rather than specific hydrogen-bonding effects. Our results reproduce the characteristic inverse temperature dependence of hydrophobicity and demonstrate that such behavior arises generically due to a rapid thermal expansion of the solvation shell, independent of hydrogen bonding. This work reframes hydrophobic interactions between extended solutes as a universal solvophobic phenomenon governed by surface phase behavior.