Structural Design And Property Study Of Functional Polypeptoids

Polypeptoids can be described as mimics of aliphatic polyamides in which the side chain is attached to the backbone amide nitrogen instead of the α-carbon.Since the side group replaces the hydrogen on the nitrogen atom of the amide bond of the polypeptide backbone and eliminates the hydrogen bond donor,the intramolecular and intermolecular hydrogen bond interactions inherent to the polypeptide do not exist in the polypeptoid backbone structure.Such a structure enables it to exhibit many advantageous properties different from polypeptides,such as good solubility and thermal processing properties,better resistance to protease hydrolysis.In addition,the properties of polypeptoids are mainly determined by the types and physicochemical properties of side groups,and this structural feature plays a positive role in polymer structure design and performance regulation,effective regulation of physicochemical properties.The unique structures and properties of polypeptoids make them of great application value in functional coatings,drug delivery,biomineralization,and energy storage.The synthesis methods of polypeptoids mainly include solid-phase synthesis and ringopening polymerization of N-substituted N-carboxyanhydrides(NNCA).Among them,NNC A ring-opening polymerization has the advantages of simple operation and high yield,and can prepare polymers with relatively narrow distribution and high molecular weight on a large scale.However,most of the polypeptoids prepared by NNCA ring-opening polymerization are limited to the side groups with inactive alkyl groups.These substituents cannot be functionalized,which limits the application scope of polypeptoids.Therefore,it is of great significance to find an efficient and feasible synthetic strategy to prepare functional polypeptoids.Focusing on this key issue,our design idea is to use a variety of methods to directly synthesize functional peptoid monomers,and realize their controlled polymerization to prepare functional polypeptoids with controllable structure,and expand this new type of degradable polymer.The research content of this thesis includes the synthesis and properties of photo-responsive polypeptoids bearing azobenzene side-chains and dual-responsive polypeptoids bearing OEGylated azobenzene side-chains,as well as the synthesis and controlled polymerization of functional peptoid monomers based on Schmidt reaction.The specific research contents and conclusions are summarized as follows:1.Synthesis and properties of photo-responsive polypeptoid-based copolymers bearing azobenzene side-chainsIn order to prepare a reversible photo-responsive polypeptoid,we designed and synthesized a novel peptoid monomer Azo-NNC A with an azobenzene side group,and then obtained the corresponding photo-respinsive polymer through ring-opening polymerization initiated by mPEG-NH2,the responsive polypeptoid mPEG-b-PAzon,and explored the photo-responsive property and self-assembly behavior of this diblock polypeptoids.The response process was tracked by 1H NMR and UV-Vis spectroscopy,and it was found that polyeptoids exhibited reversible photo-responsive behavior in both organic solvents and water.Depending on the length of the PAzo segment,the diblock polypeptoids assemble into a variety of nanostructures,such as spherical or short rod-like micelles,and the above assemblies can undergo a series of reversible morphological changes under continuous UV and visible light irradiation.At the same time,the diblock polypeptoids also have a certain temperature responsiveness,which can lead to irreversible morphological transformation of the assembly.In addition,the polypeptoids showed lower cytotoxicity to L929 cells.Therefore,the successful preparation of the polypeptoids with azobenzene side chain not only introduces reversible photo-responsiveness,but also provides a certain feasibility for its potential biological application.2.Synthesis and properties of photo-and thermal-responsive polypeptoids bearing OEGylated azobenzene side-chainsIn view of the good performance of photo-responsive polypeptoids containing azobenzene side groups,in order to prepare a functional polypeptoid system with better applicability,we introduced water-soluble ethylene glycol at the end of the azobenzene side chain.We designed and synthesized three peptoid monomers OEGm-Azo-NNCA(m=2,4,6)with different unit lengths,and then carried out ring-opening polymerization with nhexylamine as the initiator to prepare a series of theoretical degrees of polymerization.The homopolymer P(OEGm-Azo)n was used to study its dual responsiveness and self-assembly behaviors.The results show that the series of polypeptoids exhibit reversible temperature/photo-responsive behavior,and due to the difference in the hydrophilicity of the side chains,the series of homopolymers can be assembled into various morphologies in aqueous solution.Furthermore,based on the supramolecular interaction of azobenzene and cyclodextrins,we fabricated hydrogels with reversible responsiveness,which can achieve rapid sol-gel transition under UV/Vis irradiation.3.Synthesis and properties of oxidation-responsive polypeptoid-based copolymers bearing thioether side-chainsDiblock copolymers with pendant thioether side-chains(mPEG-b-PMeSn)were synthesized through the ring-opening polymerization initiated by mPEG-NH2,the selfassembly behavior and H2O2-responsive property of the copolymers were explored.These amphiphilic diblock polypeptoids could self-assemble into spherical micelles with an average diameter of about 266 nm in the aqueous solution,and the pendant hydrophobic thioether groups were transformed to hydrophilic sulfoxide groups in PMeS block in the presence of H2O2,which resulted in the dissociation of the nanoparticles.The entire oxidant dissociation process of micelles were characterized by dynamic light scattering and transmission electron microscopy.In addition,modifiable groups were introduced into the side-chains of the diblock copolymers by methionine click reaction to afford polypeptoids with a range of functionality.In vitro cell cytotoxicity assay indicated that mPEG-b-PMeSn exhibited good biocompatibility,which could be used as drug carriers for controlled release.4.Preparation of functional polypeptoids based on Schmidt reactionThe process of preparing functional polypeptoids by NNCA method is divided into the preparation of NNCA monomer and the ring-opening polymerization.In terms of monomer preparation,since active groups(hydroxyl or thiol group,etc.)cannot exist stably during the cyclization reaction,conventional methods cannot prepare functional peptoid monomers.In this study,we propose a new method for the rapid and efficient synthesis of functional peptoid monomers,that is,using succinic anhydride as a raw material and undergoing Schmidt reaction with azide compounds with different functional groups,which can be prepared in one step.The reaction mechanism is very mature,the reaction conditions are relatively mild,and a variety of active groups can exist stably.Then,by adjusting the nitrogen substituent structure of peptoid monomers and optimizing the polymerization reaction conditions,the controllable synthesis of various functional polypeptoids can be realized.The addition reaction and the click reaction were used to modify the fluorescent molecules FITC and sulfhydryl compounds respectively,which not only verified the postmodification ability,but also enriched the types of functional polypeptoids,providing a theoretical basis for subsequent application research.