Polymerization-Induced Self-Coacervation of Alternating Poly(disulfide)s via Ring-Opening Reaction-Mediated Polycondensation of Cyclic Thiosulfinate and Dithiol

Polymerization-induced self-assembly (PISA) has been extensively studied for the preparation of a wide range of morphologies. However, most of the current research in PISA has focused on ordered solid assemblies; using PISA to produce membraneless coacervates imposes challenges. Inspired by the recent sticker–spacer model for protein phase separation, we here demonstrate that the amphiphilic poly(disulfide)s, prepared through an alternating ring-opening reaction-mediated polycondensation (ROMPOC) strategy, can in situ self-coacervation into microsized liquid droplets. The ROMPOC relies on thiolate's reversible SN2-type engagement with a cyclic thiosulfate, promptly generating a disulfide bond's terminal sulfenic acid, which functions as a difunctional monomer, rapidly condenses proximate dithiols, and allows rapid polymer chain extension, ultimately yielding alternative poly(disulfide)s. In addition, we found one representative cyclic thiosulfinate, 1,2-dithiane-1-oxide, which serves as a modular sticker monomer, facilitating polymer-induced self-coacervation when paired with suitable spacer monomers. The resultant coacervates' physicochemical properties, including coalescence, mobility, and molecular partitioning ability, can be tailored by adjusting the spacer monomer. Furthermore, the introduction of a short, positively charged CRGGC peptide into the coacervates greatly enhances their ability to concentrate for biomacromolecules, making the resultant coacervates highly promising in nucleic acid biosensing and biomacromolecular delivery.