Bioinspired Autocatalysis for Polymer Nanoparticle Synthesis: Monomer Preassembly through Liquid–Liquid Phase Separation

Biomimetic synthesis represents a cutting-edge topic in chemical and materials sciences. Herein, we present an approach to bioinspired polymerization autocatalysis using a single amino acid monomer in water. Similar to biomolecular condensates, this monomer undergoes an entropically driven liquid–liquid phase separation (LLPS)-mode self-assembly involving densely charged molecular clusters formation, LLPS of charged monomer clusters leading to submicron-scale droplets, crystallization of charged monomer clusters within droplet crowding environments resulting in dynamic nanocrystals@droplets and finally less dynamic aged-lamellae. Supramolecular chirality inversion and nanocrystal disassembly into charged monomer clusters occur upon doping of a minor RAFT agent. Autocatalysis with solvent-tuned H+-feedback and covalent-driven chirality inversion is achieved using extremely dynamic nanocrystals@droplets. Decelerated kinetics upon deionization/ion-pairing underscore the vital importance of LLPS for the “higher charge repulsion leads to more rapid polymerization”, yielding polymer nanoparticles with protein-like structural complexity up to >98% conversion in 2-min-propagation period. This autocatalysis provides new insights into bioinspired efficient synthesis of polymer nanoparticles.