| The supramolecular self-assembly of small molecular and polymeric building blocks via noncovalent interactions have exhibited important roles in developing novel biomaterials,smart devices,information science,and nanotechnology,which renders this interdiscipilary research subject as one of the key scientific issues in the 21st century.This dissertation mainly focuses on the fabrication and structural tuning of stimuli-responsive supramolecular polymeric assemblies.A series of amphiphilic and double hydrophilic block copolymers with varying chain topologies including AB diblock,AB4 and A4BA4-type miktoarm star copolymers,dendritic-linear and macrocyclic block copolymers were synthesized.In aqueous solution, chain architectural effects on thier self-assembling properties under varying solution conditions were investigated.Moreover,their relevant applications in the field of catalysis,drug delivery,and clinical diaglosis(MRI) have ben explored. Stimuli-responsive supramolecular polymers with varying chain architectures were constructed via crown ether and cyclodextrin-based molecular recognition or terpyridine-based metal-ligand complexation,and their self-assembling properties in dilute solution and reversible gel formation at high concentrations were investigated. This dissertation can be further categorized into seven main parts as described below:1.Double hydrophilic block copolymers,poly(N-isopropylacrylamide)-b-poly(N-vinylimidazole )(PNIPAM-b-PVim),were successfully prepared with good control via reversible addition-fragmentation chain transfer(RAFT) using PNIPAM-based macromolecular xanthate agents(i.e.,MADIX,macromolecular design via the interchange of xanthates).This represents the first preparation of well-defined block copolymers based on N-vinylimidazole,which has been well-known to be able to catalyze esterolysis reactions.The imidazole-containing diblock copolymers molecularly dissolve at low temperatures in water.Above the phase transition temperatures of PNIPAM or in a proper mixture of methanol/water(cononsolvency),the PNIPAM block becomes hydrophobic and stable micelles form with a dense core consisting of a hydrophobic PNIPAM block and a polar PVim shell.The catalytic activities of PNIPAM-b-PVim toward the hydrolysis of p-nitrophenyl acetate(NPA) at different temperatures or methanol/water compositions were then determined and compared to that of PVim homopolymer.The Arrhenius plot for the PVim-based diblock copolymers exhibited a pronounced upward curvature above the critical micellization temperature(CMT).Moreover,in the methanol/water mixture,the catalytic activities of PNIPAM-b-PVim diblock copolymers evolved discontinuously as a function of solvent composition and exhibited a maximum in the range of volume fraction of methanol,φmethanol,between 0.3 and 0.5,corresponding to the solvent composition range where cononsolvency-induced micellization took place.For the first time,double hydrophilic block copolymer micelles of PNIPAM-b-PVim can serve as self-catalyzing nanoreactors.Most importantly, the catalytic activities can be well-tuned with external temperature or solvent compositions.In terms of potential applications of polymeric assemblies in clinical diagnosis(magnetic resonance imaging,MRI),amphiphilic block copolymers,poly(ε-caprolactone)-b-poly(oligo(ethylene glycol) methacrylate -co-3-azidopropyl methacrylate),PCL-b-P(OEGMA-co-AzPMA),were synthesized via a combination of atom transfer radical polymerization(ATRP) and ring-open polymerization(ROP).The subsequent click conjugation of PCL-b-P(OEGMA-co-AzPMA) with alkynyl-containing targeting moieties, alkynyl-folate,and MRI contrast agent,alkynyl-(DOTA)Gd afforded amphiphilic block copolymers,PCL-b-P(OEGMA-co-DOTA)Gd and PCL-b-P(OEGMA-co-folate ).In aqueous solution,mixed micelles of PCL-b-P(OEGMA-co-DOTA)Gd and PCL-b-P(OEGMA-co-folate)(1:1 w/w) were obtained via self-assembly using ethanol as the cosolvent.In vivo MRI experiments in rabbits revealed mixed micelles can serve as excellent contrast agents to the liver organs. Moreover,the dug-loading capacity and controlled release profiles were also investigated.All the results augur well for potential applications of this novel type of biocompatible hybrid micelles beating targeting and MRI contrasting moieties for combined anti-cancer treatment and in-situ therapeutic monitoring.2.Amphiphilic dendritic-linear diblock copolymers,[G-2]-PNIPAM and [G-3]-PNIPAM,were prepared by reversible addition-fragmentation transfer (RAFT) polymerizations of N-isopropylacrylamide(NIPAM) by employing [G-2]- and[G-3]-based RAFT agents,respectively.Transmission electron microscopy results indicate the presence of spherical micelles in aqueous solutions.The thermo-responsive conformational changes of PNIPAM chains located at the micellar coronas have been thoroughly investigated with a combination of laser light scattering and excimer fluorescence of pyrene.The thermo-responsive collapse of the PNIPAM shell is a two-stage process;the first one occurs gradually in the temperature range of 20-29℃,which is much lower than the lower critical solution temperature(LCST) of linear PNIPAM homopolymer,followed by the second process,in which the main collapse of PNIPAM chains takes place in the narrow temperature range of 29-31℃.In terms of dumbbell-shaped dendritic-linear-dendritic triblock copolymers, [G-3]-PNIPAM-[G-3]was facilely synthesized via RAFT polymerization for the first time using novel[G-3]-based trithiocarbonate-containing RAFT agent, [G-3]-CH2SCSSCH2-[G-3],which was prepared from third-generation dendritic poly(benzyl ether) bromide,[G-3]-CH2Br.The amphiphilic dumbbell-shaped triblock copolymer contains a thermo-responsive PNIPAM middle block.In aqueous solution,it self-assembles into spherical nanoparticles with the core consisting of hydrophobic[G-3]dendritic block and coronas of PNIPAM central blocks,which form loops surrounding the insoluble core.3.Well-defined double hydrophilic miktoarm AB4 star copolymer, PNIPAM-b-(PDEA)4,was synthesized by polymerizing 2-(diethylamino) ethyl methacrylate(DEA) via ATRP using PNIPAM-based tetrafunctional ATRP macroinitiator.For comparison,PNIPAM-b-PDEA linear diblock copolymer with comparable molecular weight and composition to that of PNIPAM-b-(PDEA)4 was also prepared via RAFT polymerization.The chain architectural effects on pH- and thermo-responsive 'schizophrenic' micellization behavior of the obtained PNIPAM65-b-(PDEA63)4 and PNIPAM70-b-PDEA260 were investigated.In acidic solution and elevated temperatures,PNIPAM-core micelles were formed;whereas at slightly alkaline conditions and room temperature,structurally inverted PDEA-core micelles were formed.The size of the PDEA-core micelles of PNIPAM65-b-(PDEA63)4 is much smaller than that of PNIPAM70-b-PDEA260.Furthermore,the pH-induced micellization kinetics of the AB4 miktoarm star and AB block copolymers were investigated upon a pH jump from 4 to 10.Typical kinetic traces for the micellization of both types of copolymers can be well fitted with double-exponential functions,yielding a fast (τ1) and a slow(τ2) relaxation processes.τ1 for both copolymers decreased with increasing polymer concentration.τ2 was independent of polymer concentration for PNIPAM65-b-(PDEA63)4,whereas it decreased with increasing polymer concentration for PNIPAM70-b-PDEA260.Following similar protocols,H-shaped A2BA2-type and A4BA4-type star copolymers possessing pH-responsive and thermoresponsive arms,(PDEA)2-PNIPAM-b-(PDEA)2 and(PDEA)4-PNIPAM -b-(PDEA)4,were also synthesized and their multi-responsive supramolecular self-assembly in aqueous solution were investigated.In another example,double hydrophilic heteroarm star copolymers of poly(methacrylic acid) (PMAA) and poly(ethylene oxide)(PEO) possessing a cross-linked microgel core of poly(divinylbenzene)(PDVB) were synthesized via ATRP using the "in-out" method.This novel type of double hydrophilic heteroarm star copolymer can be considered as unimolecular micelles with hybrid coronas.The star copolymers exhibited pH-dependent solubility in water,being soluble at high pH and insoluble at low pH,due to the formation of hydrogen-bonded complexes between the PEO and PMAA arms.A mixed solution of the heteroarm star copolymer and a PEO-b-PQDMA diblock copolymer,where PQDMA is poly(2-(dimethylamino) ethyl methacrylate) fully quatemized with methyl iodide, remained stable in the whole pH range,and exhibited an intriguing pH-switchable complexation behavior accompanied with structural rearrangement.At high pH,the PQDMA block and ionized PMAA arms formed insoluble polyelectrolyte complexes,which were co-stabilized by PEO chains from both the PEO-b-PQDMA and the(PEO)n-PDVB-(PMAA)n.At low pH,the neutral PMAA arms and PEO formed hydrogen-bonded complexes,and the colloidal particles again possessed a hydrophobic PDVB core,an inner layer of PMAA/PEO hydrogen-bonded complexes,and a stabilizing PQDMA outer corona.4.α-Alkynyl-ω-azidoheterodifunctional linear-PMEO2MA-b-POEGMA-N3 was synthesized via the azidation of alkynyl-terminated PMEO2MA-b-POEGMA-Br prepared via successive ATRP,where PMEO2M was poly(2-(2-methoxy-ethoxy)-ethylmethacrylate ).High end group functionality of linear precursors is crucial to achieve successful cyclization reaction and confirming the strategy of high-efficiency cyclization under micellar conditions.Firstly,the evolution of chain-end functionality during the preparation of heterodifunctional linear diblock copolymer was determined by ATRP of MEO2MA using benzyl 2-bromoisobutyrate(BBIB) as the initiator under the same conditions,after its transformation into benzyl-PMEO2MA-N3 and the subsequent click reaction with an excess of 1-(2-propynyloxy)benzene,the end group functionality of benzyl-PMEO2MAA -N3 was determined to be 96%.Following similar procedures,the end group functionality of benzyl-PMEO2MA-b-POEGMA-N3 was also determined to be very high(＞90%).Thus,the end functionality of linear-PMEO2MA-b-POEGMA-N3 can be determined to be＞90%.Then,the high-efficiency synthesis of water-soluble cyclic diblock copolymers, cyclic-PMEO2MA-b-POEGMA,was achieved via "selective" click reaction in aqueous micellar solutions ofα,ω-heterodifunctional linear precursors at a relatively high concentration(10 g/L),which relies on controlling the spatial accessibility between terminal reactive groups within micellar entities and the "tadpole" conformation of unimers.Moreover,it was found that macrocyclic diblock copolymers,possess higher CMC values,smaller h>,and lower average aggregation numbers(Nagg) in self-assembled micelles,as compared to their linear precursors5.DB24C8-terminated four-arm star PCL(4-arm star PCL-DB24C8) and DBAS-terminated two-arm PCL(2-arm PCL-DBAS) were synthesized by a combination of ROP and click reaction.Based on these well-defined precursors, stimuli-responsive supramolecular gels were constructed,taking advantage of the formation of pseudorotaxane linkages between terminal crown ether and ammonium moieties.The resultant supramolecular gels underwent thermo- and pH-induced reversible gel-sol transitions.Moreover,the obtained multiresponsive supramolecular networks contain cavities,the size of which are expected to be facilely adjusted by changes in the arm lengths of 4-arm star PCL-DB24C8 and 2-arm PCL-DBAS.This augurs well for their applications as smart nanocarriers for guest molecules and complicated molecular devices. Supramolecular ABA triblock copolymers based on crown ether-based molecular recognition were also fabricated.DB24C8-terminated polystyrene(PS-DB24C8) was synthesized via the ATRP of styrene and subsequent click reaction.The mixed solution of PS24-DB24C8 and DBAS-PCL-DBAS form reversible supramolecular ABA triblock copolymers via peseudorotaxane formation.With the increase of molecular weights of DBAS-PCL-DBAS,the average association constants between PS24-DB24C8 and DBAS-PCL-DBAS decreased rapidly due to the steric effect of the PCL coils with higher molecular weights.Supramolecular ABA triblock copolymer,PS24-PCL36-PS24,self-assembles into micelles in the selective solvent of PS outer blocks(cyclohexane,40℃).6.Supramolecular hybranched polymers were constructed via cyclodextrin (CD)-based molecular recognition.AB2 type macromonomer containing one adamantyl(AD) and twoβ-CD moieties,AD-PNIPAM11-(β-CD)2,was synthesized via atom transfer radical polymerization(ATRP) and consecutive "click" reactions.General synthetic routes employed for the preparation of AD-PNIPAM11-(β-CD)2 are as follows.AD-PNIPAM11-N3 was prepared via ATRP using AD-Cl as the initiator and the subsequent nucleophilic substitution reaction with NaN3.The 'click' reaction between AD-PNIPAM11-N3 and an excess of trialkynyl-containing small molecule afforded dialkynyl-terminated polymer,AD-PNIPAM11-(Alkynyl)2.The target product,AD-PNIPAM11-(β-CD)2, was prepared via click coupling reaction between AD-PNIPAM11-(Alkynyl)2 andβ-CD-N3.In aqueous solution,AD-PNIPAM11-(β-CD)2 can self-organize into supramolecular hyperbranched polymer at relatively higher concentrations, which have been evidenced by 2D NOESY spectrum and viscosity measurements.7.Terpyridine-containing double hydrophilic diblock copolymer,PMEO2MA-b-P (DEA-co-TpyMA),was successfully prepared with good control via RAFT polymerization by employing PMEO2MA-based macromolecular RAFT agent. Structurally stable core cross-linked(CCL) nanoparticles were prepared in ethanol upon addition of ruthenium(Ⅲ) and N-ethylmorpholine via the formation of bis(2,2':6',2"-terpyridine) ruthenium(Ⅱ) complexes.In aqueous solution,the nanoparticles exhibit pH-responsive core swelling/collapse and thermoresponsive corona swelling/collapse.Interestingly,the obtained metallo-supramolecular CCL nanoparticles can be disintegrated into unimers upon addition of N-(2-hydroxyethyl)ethylenediaminetriacetic acid(HEEDTA). Furthermore,metallo-supramolecular multiblock and cyclic block copolymers were fabricated from terpyridine-terminated PPO-PEO-PPO(tpy-PPO-PEO-PPO -tpy) via the formation of bis(2,2':6',2"-terpyridine)-ruthenium(Ⅱ) complexes at relatively high concentration(1 g/mL) and low concentration(0.46 mg/mL),where PPO is polyprpylene oxide.The number of repeating sequences of metallo- supramolecular multiblock copolymer was estimated to be～6 from GPC results.
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