Synthesis of Thermo-Responsive Monofunctionalized Diblock Copolymer Worms

Poly(glycerol monomethacrylate)-block-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA) with worm-like morphology is a typical example of reversible addition–fragmentation chain transfer (RAFT) dispersion polymerized thermo-responsive copolymer via polymerization-induced self-assembly (PISA) in aqueous solution. Chain transfer agents (CTAs) are the key component in controlling RAFT, the structures of which determine the end functional groups of the polymer chain. It is therefore of interest to monofunctionalize the polymers via CTA moiety, for bioactive functionality conjugation and in the meantime maintain the precisely controlled morphology of the copolymers and the related property. In this work, a newly designed CTA 5-(2-(tert-butoxycarbonylamino) ethylamino)-2-cyano-5-oxopentan-2-yl benzodithioate(t-BocCPDB) was synthesized and used for the RAFT polymerization of PGMA45-PHPMA120. Subsequently, PGMA45-PHPMA120copolymers with primary amine, maleimide, and reduced L-glutathione (a tripeptide) monofunctionalized terminals were synthesized via deprotection and conjugation reactions. These monofunctionalized copolymers maintain worm-like morphology and thermo-responsive property in aqueous solution (10%w/v), as confirmed by the transmission electron microscopy (TEM) images, and the observation of the phase transition behavior in between 4 °C and room temperature (~20 °C), respectively. Summarily, a range of thermo-responsive monofunctionalized PGMA45-PHPMA120diblock copolymer worms were successfully synthesized, which are expected to offer potential biomedical applications, such as in polymer therapeutics, drug delivery, and diagnostics.Keywords:PGMA-PHPMA;diblock copolymer worm;worm gel;thermo-responsive hydrogel;post-modification;monofunctionalization;RAFT;PISA;bioconjugation