Amphiphilic Polyoxazoline‐block‐Polypeptoid Copolymers by Sequential One‐Pot Ring‐Opening Polymerizations

Amphiphilic block copolymers possess great potential as biomaterials in drug delivery and gene therapy. Herein, pseudopeptidic‐type diblock copolymer of poly(2‐oxazoline)‐block‐polypeptoid (POx‐b‐POI) is presented and synthesized. Poly[2‐(3‐butenyl)‐2‐oxazoline]‐block‐poly(sarcosine) (PBuOx‐b‐PSar) comprising hydrophobic POx segment bearing alkenyl side chain and hydrophilic POI segment of N‐methyl glycine, viz., sarcosine, is prepared by ring‐opening polymerization (ROP) through a one‐pot and three‐step route. Diphenyl phosphate initiates ROP of BuOx, and then the living chain end of PBuOx is quenched by ammonia to obtain PBuOx‐ammonium phosphate in situ, the active ammonium group initiates ROP of sarcosine N‐carboxy anhydride. PBuOx‐b‐PSar with controlled molecular weights (4.7–10.8 kg mol⁻¹) and narrow dispersities (Ð _M 1.15–1.21) are characterized by ¹H NMR, ¹³C NMR, and size‐exclusion chromatography. Dynamic light scattering and transmission electron microscopy analysis reveal that PBuOx‐b‐PSar self‐assembles into nanostructures of average diameter D _H of 37–109 nm in aqueous solution. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide test demonstrates the cytocompatibility (relative cell viability > 80%) of the PBuOx‐b‐PSar. In view of the self‐assembly and biocompatibility, the readily prepared diblock copolymers may hopefully be used in biomedical applications.