Competitive Interfacial Partitioning in Cetyltrimethylammonium Bromide Self-Assembly: A Coarse-Grained Study Across...

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, $C\left(N\right)$ , 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.