Hydrophobic (deep) eutectic solvents: from characterization and modeling to rational design and applications

(Deep) eutectic solvents (DESs) have emerged as versatile designer solvents because of their simple preparation, broad compositional flexibility, and highly tunable physicochemical properties. Hydrophobic (deep) eutectic solvents (HDESs), first reported in 2015, further extend the potential of eutectic solvents to aqueous and multiphase systems by exhibiting limited affinity toward water. This feature has generated growing interest in HDESs for separation, resource recovery, pollutant removal, gas capture, and reaction processes. Despite their rapid development, HDES research remains relatively young, and fundamental questions regarding HDES definition, characterization, and rational design remain unresolved. Moreover, while most previous reviews have largely focused on specific HDES formulations or applications, the experimental and computational tools required to systematically characterize, understand, and design these solvents have received comparatively limited attention. This review addresses this gap by providing a practical framework connecting HDES fundamentals, experimental characterization, computational modeling, rational design, and applications. Key physicochemical properties, including density, viscosity, thermal stability, phase behavior, and hydrophobicity/water stability, are discussed together with the information provided by different characterization methods, their advantages, limitations, and recommended uses. Computational approaches, including quantum chemical calculations, COSMO-RS, molecular dynamics simulations, and machine learning, are further reviewed as complementary tools for elucidating molecular interactions, predicting solvent behavior, and guiding solvent design. HDES applications are discussed according to the phase configuration and physical role of the solvent, including liquid-liquid extraction, solid-liquid extraction, gas-liquid absorption, and reaction media. Finally, key challenges and future research needs are discussed to support the advancement of HDESs toward rationally designed and practically viable solvent systems.