The Influence Of Structure On Properties And Self-Assembly Behaviors Of Hyperbranched Multiarm Copolymers

Hyperbranched polymers are a novel kind of three dimensional torispherical irregularmacromolecules possessing highly branched architectures, many inner cavities and a largeamount of terminal functional groups. Due to their unique molecular structures andproperties, hyperbranched polymers have become the hot topics in many research fields.Up to now, great progresses have been made in the synthesis, characterization,modification, and application of hyperbranched polymers. At the same time, due to thecombination of hyperbranched polymers and linear polymers, hyperbranched multiarmcopolymers which possess a hyperbranched core and many linear arms have attractedmore and more attentions recently. Scientists could endow hyperbranched multiarmcopolymers with different kinds of properties by choosing different blocks. However,many problems still need to be resolved, such as the exploration of the unknown features,the explanation of new phenomena and the spread of the application fields. In thisdissertation, based on the summarization of previous research works of hyperbranchedmultiarm copolymers, multiple kinds of hyperbranched multiarm copolymers with thecontrollable molecular topology were synthesized. Subsequently, the influence ofmolecular topology on self-assembly behaviors、thermoresponsive behaviors and genedelivery was investigated. In addition, the packing parameter theory was proposed toexplain such the molecular topology-dependent self-assembly behaviors. The main resultsare shown as follows.1. Effect of degree of branching (DB) on the self-assembly behaviors of amphiphilichyperbranched multiarm copolymers PEHO-star-PEOs; The work reported for the first time the influence of DB of precursor polymer on theself-assembly behaviors of amphiphilic hyperbranched multiarm copolymers. A series ofamphiphilic copolyethers of PEHO-star-PEOs with a hydrophobic DB-variablehyperbranched PEHO core and many hydrophilic PEO short arms were synthesizedthrough cationic ring-opening polymerization at different temperature. TEM, SEM,CTEM and AFM are used to directly detect the morphology of the self-assembly objects.The results indicate that the copolymers with different DB can self-assemble into differentmorphologies in water. The copolymer with a relatively high DB of44%can formvesicles in water, and that with a mid DB of33%can form wormlike micelles, while thatwith a relatively low DB of20%or5%can form spherical micelles. The sphericalmicelles are a kind of the multimicelle aggregate (MMAs) with the basic building units ofsmall micelles. Molecular packing model based on the packing parameter theory wasproposed to explain such the DB-dependent self-assembly behaviors. For thePEHO-star-PEO copolymers with a high DB like44%, the packing parameter ρ is close to1, thus the highly branched copolymers spontaneously segregate into a cylinder shape andself-assemble into vesicles. When the DB decreases, the ρ decreases close to1/2. Themolecular geometry is thus altered from a cylinder to a trapezoidal cylinder, leading to theformation of cylindrical micelles. Further decrease of DB and thus the ρ cause a conemolecular geometry, leading to the formation of spherical micelles.2. Effect of DB on the thermoresponsive phase transition behaviors of hyperbranchedmultiarm copolymers;This work reports for the first time the influence of DB on the thermoresponsive phasetransition behaviors of hyperbranched multiarm copolymers. A series ofPEHO-star-PDMAEMAs with the hydrophobic DB-variable PEHO core andstimuli-responsive linear PDMAEMA short arms were synthesized by graft-from method,through atom transfer radical polymerization. The thermoresponsive phase transitionbehaviors of both of two series PEHO-star-PEOs (series A, in chapter1) andPEHO-star-PDMAEMAs (series B) presented here were evaluated. It was found these twoseries demonstrate thermoresponsive phase transitions with the lower critical solutiontemperature (LCST). The studies on the LCST transition mechanism indicate that series Abelongs to the thermoresponsive polymer system with LCST transition based onhydrophilic-hydrophobic balance, while series B belongs to the thermoresponsive polymer system with LCST transition based on coil-to-globule transition. Correspondingly, there is abig difference in the DB dependence of LCST transition between series A and series B. Forseries A, the LCST phase transition is highly dependent on the DB of the PEHO core incopolymers. For series B, the LCST phase transition is independent of the DB but dependenton solution pH. Such results may extend the knowledge on the structure-activity relationshipof thermoresponsive highly branched polymers.3. Gene delivery of hyperbranched multiarm copolymers PEHO-star-PDMAEMAs;In vitro gene delivery experiments were performed using PEHO-star-PDMAEMAs aspolycationic vectors. Firstly, self-assembly behaviors of PEHO-star-PDMAEMAs werestudied, all the samples can form into spherical micelles less than500nm. The resultsindicated that the size of micelles self-assembled from copolymer with highly branchedPEHO core are much smaller than copolymer with linear PEHO core when arm length is4;when arm length increases to7, the size of micelles self-assembled from copolymer withhighly branched PEHO core are slightly smaller than copolymer with linear PEHO core.Then, the biological experiments were carried out. The gene delivery results indicated thatthe transfection efficiency of D0.48-4increases dramatically compared to PDMAEMAhomopolymer, even reaches the same level with PEI; the transfection efficiency ofcopolymers is independent of PDMAEMA short arm length but dependent of PEHO DB,the larger the DB, the higher the transfection efficiency is. MTT cytotoxicity studiesindicated that D0.48-4exhibits much less toxicity in COS-7cell than PDMAEMAhomopolymer, and also exhibit less toxicity than PEI control. In addition, the cytotoxicityof copolymer is independent on both of PEHO DB and PDMAEMA arm length.4. Synthesis and self-assembly of amphiphilic hyperbranched polyglycerols (HPG)modified with palmitoyl chloride;Firstly, a series of HPG were synthesized through cationic ring-openingpolymerization at different temperature (-80oC~0oC) and different monomer-to-catalystratio (8/1,200/1). The results indicated that DB of HPG keeps approximately60%and canhardly be controlled by changing reaction-temperature and monomer-to-catalyst ratio.Secondly, a series of palmitoyl chloride-grafted hyperbranched polyglycerols (HPG-C16)were synthesized through the end-group modification. The obtained grafted copolymer ofHPG-C16possesses a hydrophilic hyperbranched polyether core and many hydrophobicalkyl arms, which shows interesting self-assembly behavior in THF and water. When in a selective solvent of the grafted alkyl arms like THF, the copolymers with a relatively highgrafting ratio can form regular unimolecular micelles; however, the copolymers with a lowgrafting ratio will self-assemble into vesicles around200nm. When in a selective solvent ofHPG cores like water, the copolymers with a relatively high grafting ratio will self-assembleinto giant vesicles around1~10μm; however, the copolymers with a low grafting ratio willself-assemble into multimolecular spherical micelles around200nm. Such a specialself-assembly rule is certainly related to the inverted polymer structure, and can be wellexplained by the packing parameter theory.5. The construction of hyperbranched polymer vesicles and reverse vesicles based onphosphate structure and their self-assembly behaviors;Based on C16-HPG in chapter4, hyperbranched miktoarm copolymers ofC16-HPG-HEP and C16-HPG-PC were synthesized by the further end-group modificationof residual hydroxyl in HPG. C16-HPG-HEP can form reverse vesicles in acetone. Thesize of reverse vesicles can be readily controlled from nanosize to microsize through theadjustment of polymer concentration. Meanwhile, the size of reverse vesicles can also becontrolled by ambient temperature. The higher the temperature, the smaller the size ofreverse vesicles is. DSC measurement proved that the influence of ambient temperature onthe size of reverse vesicles is caused by the gel-to-fluid transition of vesicles. In addition,microporous films can be prepared by using C16-HPG-HEP reverse vesicles solution ofacetone. Then, the self-assembly behaviors of phospholipid-analogous C16-HPG-PC wereinvestigated. The results indicated that C16-HPG-PC can form vesicles with the size of700nm in water, which show almost no cytotoxicity.