Solubilizing Nonpolar Substances in Polar Solvents: Strategies, Molecular Mechanisms, and Applications

Efficient solubilization of nonpolar substances in polar solvents represents a fundamental challenge in environmental remediation, green chemistry, and separation processes. This limitation stems from the hydrophobic effect, which creates thermodynamic barriers, resulting in low intrinsic solubility and strong phase separation. This review examines the thermodynamic basis of solubilization, focusing on free-energy changes and molecular interaction mechanisms. It discusses various strategies, including surface and interface engineering, host–guest inclusion, solvent engineering, and nanostructure encapsulation, along with their practical applications. Future research directions include smart responsive materials, green solvent design theories, and precise construction of solubilization systems through multi-scale simulations.