Amphiphilic Motif Triggers Microheterogeneity in Low‐Melting Mixtures

Microheterogeneity in low‐melting mixtures of ethylene glycol and chemically modified choline derivatives synthesized on purpose is here proposed. Novel cholinium ions with one or two N ‐butyl substituents or an N ‐hydroxybutyl chain are synthesized for the first time. Synthesis of both protiated and deuterated analogs enables the experimental exploration of a chemical space previously accessible only in silico. Visible and UV‐Raman spectroscopy, small‐angle neutron scattering, X‐ray scattering, and computational methods are used to probe intermolecular interactions from molecular to nanometric scale. The progressive shielding of the quaternary ammonium head from ethylene glycol upon mono‐ and di‐butyl substitution is observed, while elongation of the hydroxyalkyl chain alone produces negligible effects. Scattering experiments and simulations demonstrate that hydrophobic substitution at the ammonium center triggers nanoscale segregation into interpenetrating charge‐rich and charge‐poor domains, yielding a bicontinuous morphology analogous to that of amphiphilic fluids, including ionic liquids. In contrast, reference systems lacking headgroup alkylation remain structurally homogeneous. Iodide counterion weakens classical Coulombic and hydrogen‐bond interactions, enhancing the relative importance of the dispersive forces and thereby facilitating mesoscale organization. The results establish amphiphilicity‐driven dispersion as a decisive, tunable factor controlling microsegregation in low‐melting mixtures mimicking deep‐eutectic‐like liquids, expanding the design principles for structured hydrogen‐bonded solvents.