Dynamic Covalent Polymerization through Liquid–Liquid Phase Separation

Abstract Liquid–liquid phase separation (LLPS) is a ubiquitous phenomenon in living systems wherein membraneless organelles form through the spontaneous compartmentalization of small molecules or biopolymers. Synthetic (supra)molecular systems─including small molecules, oligomers, and polymers─have each been shown to undergo LLPS independently. However, creating synthetic polymeric systems that, like living systems, exhibit constitutional dynamics across multiple length scales─from small molecules to macromolecules─remains a formidable challenge. Here, we report an artificial dynamic polymeric LLPS system constructed from biologically relevant building blocks, such as amino acids and disulfides, in which the constitutional dynamics between small molecules and polymers can be engineered within condensed microenvironments that involve multiple weak yet reversible chemical bonds. Compartmentalization within disordered droplets not only elevates the thermodynamic driving force for disulfide-mediated ring-opening polymerization but also kinetically activates the dynamics of disulfide bonds, enabling the spontaneous, catalyst-free synthesis of high-molecular-weight poly(disulfide)s in water. The resulting polymers form thermodynamically stable, self-entangled hydrogels, and upon dehydration, they undergo quantitative photochemical depolymerization to regenerate virgin-quality monomers. These findings provide a model for constructing a biological system that integrates LLPS with intrinsic dynamic behavior and may open new opportunities for supramolecular biomaterials.