Synthesis, Assembling Kinetics And Applications Of Responsive Polymers

Stimuli-responsive polymers have attracted increasing interest due to their ability to undergo reversible or irreversible changes in physical properties and/or chemical structures to an external stimulus including pH, temperature, ionic strength, light irradiation, mechanical forces, electric and magnetic fields, as well as specific analytes and external additives, to name a few, which make them particularly suitable in areas such as drug and gene delivery, tissue engineering, biosensors and separation processes. In this dissertation, applications in sensor based on stimuli-responsive polymers and the kinetics processes for stimuli-responsive polymers self-assembling were investigated in detail. The dissertation includes the following six parts:1. The amphiphilic diblock copolymers poly(glycidyl methacrylate)-b-poly(N- isopropyl acrylamide) (PGMA-b-PNIPAM) with three different block ratio were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Their self-assembly behavior in mix solution was studied in detail. Experimental results indicate that the amphiphilic diblock copolymer could assemble to form different aggregates due to the block ratio: when the hydrophilic block was long, it would form micelle; while the hydrophilic block was short, it would form vesicle.2. Reported the fabrication of thermoresponsive double hydrophilic block copolymer (DHBC)-based highly sensitive ratiometric fluorescent probe for pH and temperature. This type of fluorescent and responsive DHBC, poly(N-isopropylacrylamide)-b-poly(oligo(ethylene glycol) monomethyl ether methacrylate) (PNIPAM-b-POEGMA) was synthesized via RAFT polymerization with the thermoresponsive PNIPAM block and hydrophilic POEGMA block labeled with fluorescein isothiocyanate (FITC) and rhodamine B-based moieties (RhBAM) possessing pH-switchable emission characteristics, respectively. Since the fluorescence intensity of FITC is increased with the increasing pH value, while the influence of pH on RhBAM is quite in opposition, this type DHBC is highly-sensitive to pH exhibiting multicolor-switch when the pH is changed. Moreover, the pH sensitivity can also be enhanced at elevated temperature.3. Two types of diblock copolymers containing phenylboronic acid and glucose moieties, respectively, poly(N-isopropylacrylamide)-b-poly(N-acryloyl-3- aminophenylboronic acid) (PNIPAM-b-PAPBA) and poly(N- isopropylacrylamide)-b-poly(acryloyl glucosamine) (PNIPAM-b-PAGA) were synthesized via RAFT polymerization. Due to the formation of borate ester functionalities between phenylboronic acid and glucose moieties under slightly alkaline conditions (pH 9.3), mixed solution of PNIPAM-b-PAPBA and PNIPAM-b-PAGA diblock copolymers can spontaneously form interpolymer complex micelles consisting of PAPBA/PAGA complex cores and PNIPAM coronas. Since the formation/cleavage of borate ester linkages is highly reversible upon the variation of solution pH and glucose concentrations, and the PNIPAM-shell has temperature sensitivity, the obtained interpolymer complex micelles via reversible covalent bond formation between PAPBA and PAGA exhibit multi-responsiveness to pH, glucose, and temperature.4. Multifunctional ratiometric probes for glucose and temperatures based on thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) microgels covalently incorporated with glucose-recognizing moieties, N-acryloyl-3- aminophenylboronic acid (APBA), fluorescence resonance energy transfer (FRET) donor dyes, 4-(2-acryloyloxyethylamino)-7-nitro-2,1,3-benzoxadiazole (NBDAE), and rhodamine B-based FRET acceptors (RhBEA) were prepared. P(NIPAM-APBA-NBDAE-RhBEA) microgels containing FRET pairs and APBA were synthesized via free radical emulsion copolymerization. The spatial proximity of FRET donors and acceptors within microgels can be tuned via thermo-induced microgel collapse or glucose-induced microgel swelling at appropriate pH and temperatures, leading to the facile modulation of FRET efficiencies. APBA moieties within P(NIPAM-APBA-NBDAE-RhBEA) microgels can bind with glucose at appropriate pH to form cyclic boronate moieties, which can decrease the pKa of APBA residues and increase the volume phase transition (VPT) temperature of microgels. The gradual addition of glucose into fluorescent microgel dispersions at intermediate temperatures, i.e., between microgel VPT temperatures in the absence and presence of glucose, respectively, can lead to the re-swelling of initially collapsed microgels. Thus, P(NIPAM-APBA-NBDAE-RhBEA) microgels can serve as dual ratiometric fluorescent probes for glucose and temperatures by monitoring the changes in fluorescence emission intensity ratios. Moreover, P(NIPAM-APBA-NBDAE- RhBEA) microgels at pH 8 and 37 oC can serve as a ratiometric fluorescent glucose sensor with improved detection sensitivity as compared to that at 25 oC. MTT assays further revealed that thermoresponsive microgels are almost non-cytotoxic up to a concentration of 1.6 g/L. These results augur well for the application of P(NIPAM-APBA-NBDAE-RhBEA) microgels for multifunctional purposes such as sensing, imaging, and triggered-release nanocarriers under in vivo conditions.5. A zwitterionic poly(4-vinylbenzoic acid-b-N-(morpholino)ethyl methacrylate) (PVBA-b-PMEMA) diblock copolymer was prepared. This diblock copolymer exhibit interesting'schizophrenic'micellization behavior in aqueous solutions. At a low pH value, PVBA-core micelles are formed, while at a high pH value, the diblock copolymer can be dissolved as unimers. In the presence of sufficient Na2SO4, PVBA-core micelles are formed in acidic media and well-defined PMEMA-core micelles are formed in alkaline one. Thus, if dissolved in the presence of 0.8 M Na2SO4, the zwitterionic diblock copolymer can be switched from PVBA-core micelles to PMEMA-core micelles (and vice versa) simply by manipulating the solution pH. The micelle formation and micelle reversion kinetics of this PVBA-b-PMEMA diblock copolymer was studied by making use of a stopped-flow light scattering technique.6. A novel sulfobetaine block copolymer, poly(N-(morpholino)ethyl methacrylate)-b-poly(4-(2-sulfoethyl)-1-(4-vinylbenzyl) pyridinium betaine) (PMEMA-b-PSVBP), was synthesized via RAFT polymerization. It exhibits intriguing'schizophrenic'micellization behavior in aqueous solution, taking advantage of the fact that the PMEMA block gets insoluble at >0.6 M Na2SO4, and the PSVBP block is only molecularly soluble in the presence of >0.2 M NaBr. Thus, PMEMA-core and PSVBP-core micelles can respectively form in aqueous solution due to the selective water solubility of both blocks, depending on the concentration and type of added salts. 1H NMR and laser light scattering (LLS) were employed to characterize the equilibrium structures of the two types of purely salt-induced micelles. Furthermore, the kinetics of the salt-induced formation/dissociation of PMEMA-core and PSVBP-core micelles, and the structural inversion between these two types of micelles were investigated by using stopped-flow apparatus equipped with a light scattering detection.