Thermoresponsivity, Micelle Structure, and Thermal-Induced Structural Transition of an Amphiphilic Block Copolymer Tuned by Terminal Multiple H-Bonding Units

Constructing noncovalent interactions has been a benign method to tune the stimuli responsivity and assembled structure of polymers in solution; this is essential for controlling the functions and properties of stimuli-responsive materials. Herein, we demonstrate a novel supramolecular strategy to manipulate the cloud point (T-cp) and assembled structure of thermoresponsive polymers in solution by using H-bonding interactions. We use poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b- poly(lactide-co-glycolide) (PLGA-PEG-PLGA) as a model thermoresponsive polymer and functionalize its chain terminals by the self-complementary quadruple H-bonding motif, 2-ureido-4[1H]-pyrimidinone (UPy). UPy end functionalization and increasing PLGA block length decrease the T-cp of copolymer. Both UPy- and nonfunctionalized copolymers form the spherical micelles at low temperature. They undergo the intermicellar aggregation and form large compound micelles during heating; this thermally induced structural transition causes the presence of T-cp. Due to the UPy-UPy H-bonding interactions, UPy end functionalization leads to more copolymer chains to associate in one micelle, thus, enhancing the hydrodynamic, gyration radii, core size, as well as the packing density of PLGA in micelle core and grafting density of PEG on core-shell interface. The decreased T-cp of UPy-functionalized copolymer stemmed from the stronger intermicellar attractions at high temperature. Furthermore, UPyfunctionalized copolymers exhibit higher drug loading content, slower drug release rate, and better separation efficiency in removing the hydrophobic substances from water than PLGA-PEG-PLGA precursors.