Fabrication And Functionalization Of Responsive Supramolecular Polymeric Assemblies

Supramolecular assemblies have attracted considerable interests in the past decedes due to their promising applications in diverse fields, such as catalysis, material preparation, and biomedicine, which renders this interdisciplinary research subject as one of the promising scientific issues in the 21st century. This dissertation mainly focuses on the fabrication and functionalization of supramolecular assemblies from stimuli-responsive double hydrophilic block copolymers. A series of well-defined specific functionalized polymers with varying chemical architectures were prepared in the combination of controlled/living radical polymerizations and click chemistry, include multiple thermo-responsive double hydrophilic triblock copolymers, end-functionalized polymers which can be used to construct multi-responsive supramolecular double hydrophilic block copolymers, and thermo-responsive double hydrophilic diblock copolymers functionalized by fluorescent turn-on probes. Besides the construction of the assemblies, novel approache in the surface modification of self-assembled micelles was also investigated. The dissertation includes the following four parts:1. Well-defined double thermo-responsive triblock copolymer poly(propylene glycol)-b-poly(N-isopropylacrylamide)-b-poly(N,N-dimethylacrylamide), PPO-b-PNIPAM-b-PDMA, was synthesized via sequential atom transfer radical polymerization (ATRP) technique using a PPO-based macroinitiator. The double thermo-responsive ABC triblock copolymer contains PDMA as one permanently hydrophilic block, with PPO and PNIPAM as two different thermo-responsive blocks.Thermo-responsive micellization behavior of the PPO-b-PNIPAM-b-PDMA triblock copolymer was then investigated by a combination of spectroscopic techniques and dynamic light scattering (DSL). A thermally induced two-step association is observed when heating beyond the first and second cloud points of the thermo-responsive blocks. The critical micellization temperature (CMT) and critical micellization concentration (CMC) values at different temperatures of the PPO-b-PNIPAM-b-PDMA triblock copolymer were determined. Moreover, a triply thermo-responsive biocompatible ABC triblock copolymer poly(propylene glycol)-b-poly(di(ethylene glycol) methyl ether methacrylate)-b-poly(tri(ethylene glycol) methyl ether methacrylate), PPO-b- PMEO2MA-b-PMEO3MA, was also synthesized via sequential ATRP. The thermo-responsive characteristics of the aqueous solution of the triblock copolymer have been studied in comparison with the corresponding mono-and diblocks by spectroscopic techniques and DSL. The hydrophilicity of the blocks influences each other, rendering each block a phase transition temperature different from that of the corresponding homopolymers. The cloud points of the three steps of the phase separations were determined to be 10,41, and 49℃for steps one to three, respectively, while heating the aqueous solution of the triblock copolymer.2. Supramolecular double hydrophilic block copolymer (DHBC) with multi-responsive self-assembling behavior was fabricated fromβ-CD-terminated PNIPAM (β-CD-PNIPAM) and adamantyl-terminated poly(2-(diethylamino)ethyl methacrylate) (Ad-PDEAEMA). Two alternate strategies, direct ATRP of NIPAM usingβ-CD-based initiator (β-CD-Br) and click reaction of mono-6-deoxy-6-azido-β-cyclodextrin (β-CD-N3) with alkynyl-terminated PNIPAM, were employed for the preparation ofβ-CD-PNIPAM. The latter strategy afforded well-definedβ-CD-PNIPAM with narrow polydispersity. Ad-PDEAEMA was synthesized via ATRP technique using adamantane-based initiator. Host-guest inclusion complexation betweenβ-CD and adamantyl moieties spontaneously drives the formation of supramolecular DHBC fromβ-CD-PNIPAM and Ad-PDEAEMA. Possessing well-known thermoresponsive PNIPAM and pH-responsive PDEAEMA sequences, the obtained supramolecular PNIPAM-b-PDEAEMA diblock copolymer exhibits intriguing multi-responsive and reversible micelle-to-vesicle transition behavior in aqueous solution by dually playing with solution pH and temperatures.3. Two approaches were attempted for the syntheses of a-aldehyde terminally functionalized double hydrophilic diblock or triblock copolymers of 2-(dimethyl-amino)ethyl methacrylate (DMAEMA), DEAEMA, and oligo(ethylene glycol) methyl ether methacrylate (OEGMA) via ATRP. The first approach employed 2-(2,2-dimethoxyethoxy)ethyl a-bromoisobutyrate as the ATRP initiator for the sequential polymerization of DMAEMA and DEAEMA monomers. However, after deprotection of the terminal acetal into aldehyde groups, the obtained Ald-PDMAEMA-b-PDEAEMA diblock copolymer was prone to aldol condensation at alkaline pH, leading to the extensive formation of dimmers. Directly using 4-aldehydephenyl a-bromoisobutyrate as the ATRP initiator, the sequential polymerization of OEGMA, DMAEMA, and DEAEMA resulted in the successful preparation of a-aldehyde terminally functionalized triblock copolymer, Ald-POEGMA-b-PDMAEMA-b-PDEAEMA. This triblock copolymer molecularly dissolves in acidic media, and self-assembles into three-layer "onion-like" micelles consisting of PDEAEMA cores, PDMAEMA inner shells, and POEGMA outer coronas at alkaline pH. Selective cross-linking of the PDMAEMA inner shell with 2-bis(2-iodoethoxy)ethane leads to structurally stabilized shell cross-linked (SCL) micelles surface functionalized with aldehyde groups. Possessing the PDEAEMA cores, the obtained SCL micelles exhibit reversible pH-responsive swelling/deswelling behavior, as revealed by LLS. The surface aldehyde groups enable the facile conjugation of SCL micelles with a model protein, lysozyme, via the formation of Schiff base.4. Novel DHBC-based multifunctional chemosensor to thiol and temperature was designed and synthesized. A new coumarin-based fluorescent thiol probe was constructed on the basis of the conjugate 1,4-addition of thiols toα,β-unsaturated ketones. Well-defined DHBC bearing the thiol-reactive moieties in the thermo-responsive block were synthesized by chemical modification of poly(ethylene glycol)-b-poly(di(ethylene glycol) methyl ether methacrylate-co-oligo(ethylene glycol) methyl ether methacrylate-co-2-succinyloxyethyl methacrylate) (PEG-b-P(MEO2MA-co-OEGMA-co-SEMA)), which was obtained via reversible addition-fragmentation chain transfer (RAFT) polymerization. The nonfluorescent probe moieties are subjected to selective Michael addition reaction upon addition of thiol, producing highly fluorescent species, and there is a linear relationship between temperatures and the fluorescence intensity. Thus, the thermo-responsive DHBC can serve as water-soluble multifunctional and efficient fluorescent chemosensors to thiol and temperature.