Synthesis And Properties Of Comblike-Linear Block Copolymers With Linear And V-shaped Grafts

Controlled synthesis and properties of graft polymers and their derivatives are important topics in polymer science,and the integration of precise microstructure and multiple stimulation can further enrich physicochemical properties and applications of polymer materials.Design of topological polymers with predetermined structures and functions favors revealing structure-property-application correlations.Although some graft polymers with linear,V-and Y-shaped side chains have been synthesized,densely graft copolymers with linear and V-shaped grafts have not been reported thus far.Such brush terpolymers possess asymmetric structures and two different types of grafting modes,and the reduced entanglement of distinct side chains favors overcoming the kinetic barrier for self-assembly,according the possibility to form complex microphase-separated nanostructures.Moreover,with the introduction of stimuli-responsive segments and stimuli-labile linkages,more interesting transitions in topology and morphology may be achieved,and thus the functions and applications were further extended.As well documented,styrene and maleimide-based comonomers are liable to form alternating copolymers as the copolymerization is performed in equimolar ratio.In this study,such alternating copolymerization system was adopted to synthesize alternating copolymers with two types of initiating moieties,followed by controlled polymerization to generate multicomponent linear-comblike-linear and comblike-linear block copolymers,where the comblike block was constructed by combination of“grafting through”and“grafting from”methods,and the linear handle was formed by RAFT chain extension polymerization.On this basis,the thermoresponsive and self-assembly behaviors were investigated,and drug-loading and release properties were revealed to explore the potential in biomedical materials.Main contents of this thesis are listed below.The research in part one aimed at synthesis,self-assembly and drug release behaviors of reduction-labile multi-responsive linear-comblike-linear block quaterpolymers with linear and V-shaped grafts.Bis(2-hydroxyethyl)disulfide di(4-(benzodithioyl)-4-cyanopentanoate)(S-CPDB)was used to mediate reversible addition-fragmentation chain transfer(RAFT)copolymerization of?-methoxy-?-vinylbenzyl poly(ethylene glycol)(St-PEG)and 3-hydroxyl-2-maleimidylpropyl2-bromo-2-methylpropanoate(HMBP),followed by multistep reactions involving RAFT chain extension polymerization of N-isopropylacrylamide(NIPAM),ring-opening polymerization(ROP)of?-caprolactone(CL),atom transfer radical polymerization(ATRP)of tert-butyl acrylate(t BA),and hydrolysis to generate three examples of PNIPAM-b-P((St-PEG)-alt-(HMBP-g-PCL/PAA))-SS-P((St-PEG)-alt-(HMBP-g-PCL/PAA))-b-PNIPAM(B4a-B4c)bearing poly(acrylic acid)(PAA)segments.The molecular weights of the target polymers and their precursors were well controlled,and the dispersity(?)ranged between 1.12 and 1.35.With increasing chain length of PAA grafts,the LCST of B4a-B4c gradually increased from 37.3 to42.9 ^oC(c_p=1.0 mg m L^–1).As external stimuli were adopted,the copolymer assemblies could be subjected to topological and morphological transformations due to stimuli-triggered destabilization and reassembly,and rich morphologies involving large compound micelles,sea cucumber-like micelles,hyperbranched micelles,and vesicles were obtained under different conditions.The polymer materials have good biocompatibility and relatively high drug loading efficiency.DOX-loaded copolymer aggregates were prone to perform sustained release with prolonging time,and the release kinetics could be efficiently tuned by adopting a single stimulus or combined stimuli.The research in part two aimed at synthesis,self-assembly and drug release behaviors of thermo-and p H-responsive comblike-linear diblock quaterpolymers with linear and V-shaped grafts.2-(2-cyanopropyl)dithiobenzoate(CPDB)was used to mediate RAFT copolymerization of St-PEG and HMBP,followed by multistep reactions involving RAFT chain extension polymerization of NIPAM,ROP of CL,and ATRP of 2-(diisopropylamino)ethyl methacrylate(DPA)or 2-(hexamethyl-leneimino)ethyl methacrylate(C7A)to generate the desired comblike-linear diblock quaterpolymers B3 and B4.¹H NMR and GPC analyses revealed that various copolymers had well-controlled molecular weights and relatively low dispersity indices(?=1.15-1.28).For PDPA-based B3 and PC7A-based B4,the LCST values were 35.2 and 36.6 ^oC(c_p=1.0 mg m L^–1),and the p K_a values were 6.3 and 7.1,respectively.As solution p H and temperature changed,the variable degree of tertiary amine groups and dehydration of PNIPAM segment led to distinct amphiphilicity and macromolecular interactions,resulting in reassembly and formation of copolymer aggregates with different sizes and morphologies.Under different conditions,B3aggregates were mixtures of micelles and vesicles(25 ^oC,p H 7.4),compound micelles(25 ^oC,p H 5.3),vesicles(37 ^oC,p H 7.4)and spherical micelles(37 ^oC,p H5.3),and B4 aggregates formed at p H 7.4 and 5.3 were spherical micelles with different sizes(T=25 ^oC)and vesicles with distinct thickness of membrane(T=37^oC).In vitro drug release revealed the sustained release of DOX upon a single stimulus or dual stimuli,and the release rate and cumulative release at 37 ^oC were liable to decrease in the order p H 7.4<p H 5.3<saturated CO₂(p H 4.4).B3 and B4-based nanocarriers had good biocompatibility and storage stability,and flow cytometry and confocal laser scanning microscopy measurements confirmed the efficient cellular uptake and endocytosis of drug-loaded aggregates,where B4aggregates were more sensitive to microenvironment of tumors than B3 aggregates.In summary,stimuli-responsive comblike-linear block copolymers bearing densely heterografted block involving linear and V-shaped grafts were controllably synthesized,and the influence of external stimuli on aggregation behaviors and drug release properties was investigated.The application of external stimuli could be efficiently used to tune drug release kinetics,and the change in p K_a could lead to different p H responsiveness in microenvironment of tumors,and thus the resultant block quaterpolymers may hold great potential in smart drug-loading nanocarriers.A general route to synthesize multi-responsive block miktobrush copolymers with linear and V-shaped grafts is developed in this study,and the progress favors enriching the types of nonlinear architectural polymers and revealing the structure-stimuli-property correlations.The success of this study further paves way for exploring the unique properties and multipurpose applications of multicomponent brushlike copolymers and their derivatives.