Physics-Informed Site-Specific Molecular Interaction Learning Framework for Liquid-Liquid Phase Diagram Reconstruction and Extraction Process Design

Liquid-liquid phase behavior is governed by the collective balance of intermolecular interactions and is central to predicting component partitioning and designing extraction-based separation processes. Existing thermodynamic and data-driven approaches can predict phase-equilibrium properties, but provide limited resolution of the molecular-interaction-to-phase-topology relationship underlying coupled binodal boundaries and tie-line families. Here, PSMI is proposed as a physics-informed site-specific molecular interaction learning framework that reconstructs ternary liquid-liquid phase diagrams directly from molecular structures. PSMI learns chemically meaningful intermolecular interaction sites through molecular representation learning and integrates chemical-potential consistency regularization to guide thermodynamically reliable phase reconstruction. The framework predicts coexisting extract and raffinate compositions along continuous phase paths and enables reconstruction of binodal boundaries and tie-line families. Across benchmark tests, PSMI accurately predicts coexisting extract and raffinate compositions and recovers phase-diagram topology, including both binodal shapes and tie-line directions. Interpretability analysis shows that PSMI identifies transferable molecular drivers underlying liquid-liquid phase separation, including chemically meaningful interaction patterns. Industrial case studies, together with a locally deployable web application, further demonstrate the practical utility and accessibility of PSMI for solvent screening and extraction process design. By resolving site-specific intermolecular interactions together with their macroscopic phase-partitioning consequences, PSMI provides a molecular-level perspective on how local chemical environments contribute to liquid-liquid phase behavior. This connection between localized molecular interactions and continuous phase-diagram topology provides a framework for understanding and designing complex liquid-liquid separation systems.