Temperature induced self-assembly of amino acid-derived vinyl block copolymers via dual phase transitions

The unique thermoresponsive phase behaviors of diblock copolymers from amino acid-derived vinyl monomers have been demonstrated in view of variation in the aggregation state in water. Amino acid-based block copolymers composed of N-acryloyl-Ala-methylester (NAAMe) and N-acryloyl-βAla-methylester (NAβAMe) are successfully synthesized by RAFT polymerization. The resultant block copolymers poly(NAAMe₄₈-b-NAβAMe_m) contain a constant degree of polymerization (DP=48) of the poly(NAAMe) block, but the DP of the poly(NAβAMe) block varies (m=80-122). The turbidimetry subjected to these copolymer aqueous solutions exhibits two LCST transitions upon heating. In the 1st LCST region, the block copolymer forms a relatively loose-molecular packing, while large aggregates due to partial dehydration of polymer molecules, which subsequently transform into a stable micelle structure in a region of 30-39°C. Finally, a tight aggregate composed of the dehydrated micelles is formed. Temperature-dependent ¹H NMR spectroscopy of the diblock copolymers also supports such a postulation for the dual phase transitions and stable micelle structure formation. In addition, a typical salting-out effect is observed in the thermal behavior of the polymer, but a serious cytotoxic effect is not observed in NIH/3T3 cells, suggesting that the novel diblock copolymers are relevant for biomedical applications.