Facile synthesis of thermosensitive functional polyaspartamide derivatives by click chemistry

Biodegradable and thermosensitive polyaspartamide derivatives containing pendant azide groups P(Asp‐Az)_X‐HPAs were synthesized from poly(l ‐succinimide) via the ring‐opening reaction with 2‐azidoethylamine (Az) and 5‐hydroxypentylamine (HPA). Then hydrophobic phenethyl (PEA) and imidazole (IMZ) moieties were introduced successfully with very high reaction efficiency above 90% to the side chains of P(Asp‐Az)_X‐HPA by click reaction to obtain thermoresponsive polyaspartamide derivatives containing pendant aromatic rings P(Asp‐Az)_X‐HPA‐PEAs and the thermo/pH‐responsive polyaspartamide derivatives containing pendant imidazole rings P(Asp‐Az)_X‐HPA‐IMZs, respectively. The thermoresponsive behaviors of P(Asp‐Az)_X‐HPA‐PEAs and P(Asp‐Az)_X‐HPA‐IMZs were confirmed by dynamic light scattering (DLS) and transmittance measurements, and the cloud point can be tuned by designed amounts of azide groups and can be further adjusted by the grafting molar percentage of hydrophobic phenethyl or imidazole moieties to the side chains of P(Asp‐Az)_X‐HPA via click chemistry. The pH‐responsive behavior of P(Asp‐Az)_X‐HPA‐IMZs can also be tuned. These results indicate that the obtained polyaspartamide‐based functional polymers can be further functionalized with hydrophilic long PEG chain and/or targeted moieties via click chemistry for drug delivery. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1296–1303