Competitive Interfacial Partitioning in Cetyltrimethylammonium Bromide Self‐Assembly: A Coarse‐Grained Study Across Deep Eutectic Solvents

Understanding surfactant self‐assembly in deep eutectic solvents (DES) is fundamentally challenging, and computational efforts for in silico screening are frequently hampered by the computational expense of all‐atom simulations. To circumvent these limitations, we present newly parameterized and rigorously validated coarse‐grained Martini 3 models for the cetyltrimethylammonium (CTA) cation and glycerol. We deploy these models to unravel the anomalous phase behavior of cetyltrimethylammonium bromide (CTAB), which forms stable micelles in Glyceline (2:1 mixture of glycerol and choline chloride) but is macroscopically insoluble in the urea‐based DES, Reline (2:1 mixture of urea and choline chloride). By simulating surfactant titration across a mixed Glyceline‐to‐Reline gradient, we analyze solvent–component interactions with the micelles. Thermodynamic and spatial distribution analyses (MDDF, RDF, , and SDF) reveal that this solvophobic effect is not electrostatically driven by the static choline cations. Rather, it is dictated by the competitive interfacial partitioning of the hydrogen‐bond donors. While dilute urea acts as an aggressive cosurfactant, increasing bulk urea concentrations trigger a thermodynamic bulk reclamation mechanism: the highly cohesive urea‐choline chloride network pulls urea away from the CTA headgroups, stripping the primary solvation shell and driving macroscopic precipitation. Ultimately, this demonstrates coarse‐grained molecular dynamics as a powerful, predictive in silico screening tool for solvent‐directed assembly.