Site-Specific Recruitment, Localization of Ionized Monomer to Macromolecular Crowded Droplet Compartments Can Lead to Catalytic Coacervates for Photo-RAFT in Dilution

Catalytic coacervates, or droplet reactors, represent a forefront research area in chemistry and materials science. Despite advancements in this field, challenges persist in achieving liquid-liquid phase separation (LLPS) droplet compartmentalization and site-specific reactant recruitment/localization for reaction catalysis, similar to those within biological systems. Herein, we describe the catalytic coacervates for aqueous photo-RAFT in dilution, focusing on the site-specific recruitment/localization of ionized monomer with the aid of <i>macromolecular crowding and confinement</i>. Cooperative hydrogen-bonded interpolymer complexation (IPC) of imidazolium-copolymers initiates the ion-cluster formation. Further hierarchical inter-cluster complexation (ICC) leads to the LLPS droplet compartmentalization into charged <i>dense-phase</i> and neutral <i>dilute-phase</i> compartments. Site-specific recruitment and localization of the oppositely charged monomer into <i>dense-phase</i> compartments are achieved by salt-bridging molecular recognition. "Substantial DMA-dilution" (that is, macromolecular crowding) results in sustainable <i>dense-phase</i> catalytic sites within <i>dilute-phase</i> crowding surroundings, enabling reaction catalysis in dilution (<2% <i>w</i>/<i>w</i> monomer) to 97% conversion in 12 min. These findings underscore the key roles of <i>macromolecular crowding and confinement</i> in the tailorable LLPS droplet compartmentalization and also the site-specific reactant recruitment/localization essential for enzyme reaction catalysis, and provide practical guidelines for creating catalytic coacervates towards lifelike reaction functions.