Origin of the inverse temperature dependence of hydrophobic attraction

Using enhanced sampling techniques, we have precisely characterized the water-mediated interactions between nanometer-sized spherical hydrophobic solutes. The interaction potential is captured with remarkable accuracy by a tailored morphometric theory that distills and integrates essential physical properties of the solvation shell. Notably, our simulations successfully replicate a previously poorly understood phenomenon: the anomalous strengthening of hydrophobic attraction with rising temperature. Our theory pinpoints the origin of this “inverse temperature” effect in the rapid thermal expansion of the solvation shell, a process driven by a critical drying transition. Intriguingly, this effect becomes increasingly pronounced with stronger solute-water van der Waals attraction, i.e., decreasing hydrophobicity—a subtle yet significant feature accounted for by our theory.