From l -Amino Acid Polymers to Nanozymes: Free-Radical Polymerization and Self-Assembled Nanostructure Formation

Artificial enzymes that marry synthetic simplicity with enzyme-like function remain elusive. We report water-soluble acrylamide random copolymers obtained by aqueous free-radical copolymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA, M n ≈ 500) with acryloyl- l -amino acids (histidine, serine, arginine, aspartic acid; 30–50 mol %). In water, these polymers self-assemble into catalytic polymeric nanoparticles, as visualized by transmission electron microscope (TEM). 1 H nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FTIR) confirm amino-acid incorporation; TEM reveals dynamic reorganization and fusion-driven growth, indicative of dynamic micellar-like assembly behavior. The nanoparticles catalyze both (i) the direct aldol of cyclohexanone with p -nitrobenzaldehyde and (ii) hydrolysis of p -nitrophenyl benzoate (PNB). Aldol conversions are quantitative under basic conditions but enantioselectivity remains modest (syn/anti ≈ 1:2–1:3; ee up to 17.8% with Zn 2+ ), reflecting flexible, weakly organized chiral environments within the dynamic aggregates. In PNB hydrolysis, histidine/serine increase k cat (3–4 h –1 ) relative to arginine (∼0.5 h –1 ), while Zn 2+ coordination modestly improves efficiency, indicating metal-residue cooperativity. These results establish a minimalist route to aqueous nanozymes and delineate how residue identity, polymer self-assembly, and Zn 2+ coordination govern reactivity and selectivity in polymeric catalysts.