Novel pH-tunable thermoresponsive polymers displaying lower and upper critical solution temperatures

Novel pH-tunable thermoresponsive 3-azido-2-hydroxypropyl methacrylate-based polymers displaying lower critical solution temperature (LCST) and upper critical solution temperature (UCST) were successfully synthesized by a combination of atom transfer radical polymerization (ATRP) and a chemical modification reaction. Firstly, a novel monomer dimethyl 3,3'-(((1-(2-hydroxy-3-(methacryloyloxy)propyl)-1H-1,2,3-triazol-4-yl)methyl)azanediyl) dipropanoate (HPMAB) with a hydroxyl group was prepared from 3-azido-2-hydroxypropyl methacrylate (AHPMA) and N,N-bis(3-methoxycarbonyl-ethyl)-propargylamine (BMP) by click chemistry and polymerized via ATRP into a polymer bearing hydroxyl groups, P(HPMAB). Then, P(HPMAB) was subsequently reacted with excess succinic anhydride in the presence of pyridine to yield a polymer bearing carboxyl groups, P(PMAB-COOH). P(HPMAB) and P(PMAB-COOH) exhibited a soluble-insoluble-soluble transition (S-I-S) with LCST from 53.4 to 79.1°C and UCST from 79.4 to 88.3°C in phosphate buffer solutions (PBS) with pH values from 4.7 to 7.8. The pH values in PBS were found to dramatically affect their characteristic thermoresponsive behaviors. As a comparison, a similar functional polymer containing no hydroxyl or carboxyl groups, P(PMAB), was also synthesized by ATRP of the monomer dimethyl 3,3′-(((1-(3-(methacryloyloxy)propyl)-1H-1,2,3-triazol-4-yl)methyl)azanediyl) dipropanoate (PMAB), prepared from 3-azidopropyl methacrylate (APMA) and BMP by click chemistry, and only exhibited a soluble-insoluble transition (S-I) with LCST from 41 to 60°C in PBS with pH values from 4.7 to 7.8. P(HPMAB), P(PMAB-COOH) and P(PMAB) possessed excellent biocompatibility by methyl tetrazolium (MTT) assays against NIH3T3 cells and could be regarded as biomedical materials.