Hydrogen-Bond Network Collapse and Molecular Confinement in Ethanol–Water Mixtures at the Azeotrope

Azeotropic behavior in hydrogen-bonded mixtures raises the question of whether the azeotropic composition represents a unique microscopic structure or a continuous evolution of hydrogen bonding. Here, by integrating cavity-enhanced Raman spectroscopy with molecular dynamics (MD) simulations and density functional theory (DFT) calculations, we resolve the compositional evolution of ethanol-water mixtures with high sensitivity at the azeotropic concentration. We reveal two key signatures: the complete collapse of the tetrahedral water network with a high-frequency shift of the free OH stretch indicates dispersion of water as microclusters and isolated states, and ethanol spectra reveal a gauche-to-trans conformational change. MD simulations, supported by DFT calculations, indicate that these spectroscopic features reflect a microscopic reorganization of hydrogen-bond structure, characterized by the fragmentation of extended water-water connectivity and the spatial confinement of water molecules by surrounding ethanol. Our results provide direct experimental evidence of a structural transition in hydrogen-bond topology and molecular confinement occurring at the azeotropic composition.