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

Abstract

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, UPy-functionalized 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.

Biological Stimuli-Induced Phase Transition of a Synthesized Block Copolymer: Preferential Interactions between PNIPAM-b-PNVCL and Heme Proteins

“…Synthesis, fabrication, and development of novel polymers, copolymers, polymeric materials, and copolymeric materials with specific and significant stimulating properties are indeed necessary to anticipate new avenues and advancements in the science, engineering, and technological process. Moreover, these will act as the main driving forces for the development of smart polymeric materials and biomaterials with foreseeable applications. − Among the diversified range of polymers, thermoresponsive polymers (TRPs) have made a specified and significant contribution to the scientific fields. TRPs belong to the class of stimuli-responsive polymers (SRPs).…”

“…The exceptional behavior of the SRPs is that they will self-assemble into the supramolecular structures/systems concerning the external physical, chemical, and biological stimuli. Among all of the SRPs, TRPs are studied well and reported extensively by various researchers and scientists due to their tunability and noninvasive nature. − Substantially, thermoresponsive block copolymers have also attracted considerable attention in various fields of science, engineering, and technology. − Understanding the molecular interactions, conformational changes, aggregation behavior, and optimization of phase-transition behavior of TRPs and block copolymers is of utmost importance for the design and development of smart materials and biomaterials for various applications. Thermoresponsive diblock copolymers have attained the ever-increasing scientific demand and attention over the decades concerning their ease of synthesis, structural modularity, synthetic versatility design, and development.…”

“…Synthesis and development of new thermoresponsive copolymeric systems using apparent polymerization and copolymerization methods along with comprehensive behavioral motifs will be useful for the extensive range of applications. − The copolymerization process of the diblock copolymers can enhance the functional properties of polymers, which in turn broadens the scope of their utilization and concerned applications. In the modern era, scientists and researchers intend to develop novel “smart” functional polymer surface systems that can be used for more than one purpose and application. − …”

Tuning the properties of hydrogen-bonded block copolymer worm gels prepared via polymerization-induced self-assembly

“…[6][7][8][9][10] For example, 2-ureido-4[1H]-pyrimidone (UPy) motifs have been used to introduce highly cooperative hydrogen bonding interactions in either aqueous or nonaqueous media. 6,9,[11][12][13][14] Thus, Meijer and co-workers 9 prepared poly(ethylene glycol)-based hydrogels by introducing UPy groups into amphiphilic copolymers in order to form strong hydrogen bonds that act as physical cross-links. Leibler's group 7,8 reported the design of hydrogen-bonded synthetic rubbers using renewable starting materials that exhibit both self-healing and thermoreversible behavior.…”

Novel Temperature/Reduction Dual-Stimulus Responsive Triblock Copolymer [P(MEO2MA-co- OEGMA)-b-PLLA-SS-PLLA-b-P(MEO2MA-co-OEGMA)] via a Combination of ROP and ATRP: Synthesis, Characterization and Application of Self-Assembled Micelles

“…Lei's team synthesized an inner-layer crosslinked tetrablock copolymer with temperature, pH, and reduction triple-stimuli-response as nanocarriers for drug delivery and release, which could self-assemble into non-crosslinked lamellar micelles in acidic aqueous solution to load the drug doxorubicin (DOX) [14]. Among all stimulus responses, temperature stimulation has unique advantages and can be easily applied to research [15,16]. It is well know that the widely studied thermo-responsive hydrophilic copolymers include poly(N-vinylcaprolactam) (PNVCL) [17,18], poly (N-isopropylacrylamide) (PNIPAAm) [19,20], poly(2-(2-methoxy ethoxy) ethylmethacrylate) (PMEO 2 MA) and poly(oligo (ethylene glycol) methacrylate) (POEGMA) [21][22][23], and poly[tri(ethylene glycol) methyl ether methacrylate] (PM3) [24][25][26].…”