LAUSR

Poly 2-vinyl-4,4-dimethylazlactone (PVDMA) has received much attention as a "reactive platform" to prepare charge-shifting polycations via post-polymerization modification with tertiary amines that possess primary amine or hydroxyl reactive handles. Upon hydrolysis of the resulting amide or ester linkages, the polymers can undergo a gradual transition in net charge from cationic to anionic. Herein, a systematic investigation of the hydrolysis rate of PVDMA-derived charge-shifting polymers is described. PVDMA was modified with tertiary amines bearing either primary amine, hydroxyl, or thiol reactive handles. The resulting polymers possessed tertiary amine side chains connected to the backbone via amide, ester, or thioester linkages. The hydrolysis rates of each PVDMA derivative were monitored at 25 °C and 50 °C at pH values of 5.5, 7.5, and 8.5. While the hydrolysis rate of the amide-functionalized PVDMA was negligible over the period investigated, the hydrolysis rates of the ester- and thioester-functionalized PVDMA increased with increasing temperature and pH. Interestingly, the hydrolysis rate of the thioester-functionalized PVDMA appears to be more rapid than the ester-functionalized PVDMA at all pH values and temperatures investigated. We believe these results can be utilized to inform the future preparation of PVDMA-based charge-shifting polymers for biomedical applications. This article is protected by copyright. All rights reserved.