Synthesis And Properties Of Novel Toothbrush-like And Graft Copolymers

In polymer science, the progress in “living”/controlled polymerization techniques and coupling chemistry has efficiently promoted the development of complex macromolecular architectures including block, star and graft copolymers. As well known, the structural complexity and special functionality are crucial for advanced polymer materials. In recent years, synthesis of sequence-regulated and stimuli-responsive polymers has attracted much attention due to the possibility to imitate the complexity of structure and function of biological macromolecules. These functional polymers have a great potential in biomedical materials for loading and release of drugs, and they are expected to exhibit biofunctions such as biological data storage, structure control and self-replicating in future. In sequence-defined polymers, linear polymers have been extensively studied, whilst nonlinear polymers such as graft polymers are scarcely investigated although they favor to reveal the structure-property correlations. This study aimed at synthesis and properties of sequence-regulated and stimuli-responsive toothbrush-like and graft copolymers, in which the combinations of “living”/controlled polymerization, quaternization and click reaction were used for synthesis, and the dependence of physicochemical properties and potential applications of various copolymers on macromolecular parameters was preliminarily investigated. The main contents are listed as follows.The study in Part 1 aimed at synthesis and properties of(A-g-D)(B-alt-C)mD-type heterografted toothbrush-like copolymers with multicomponent grafts and two kinds of grafting densities. The target copolymers had three types of building blocks involving terminal comblike block with quaternization bridging poly(N,N-dimethylaminoethyl methacrylate)(PDMA, A) substrate and D grafts, middle comblike block with poly(styrene-alt-maleimide) backbone and alternating PEG(B) and PCL(C) grafts, and terminal D segment involving poly(N-isopropylacrylamide)(PNIPAM), poly(methyl methacrylate)(PMMA), polystyrene(PSt), and poly(methyl acrylate)(PMA). 2-(2-Cyanopropyl) dithiobenzoate(CPDB) mediated RAFT polymerization of N,N-dimethylaminoethyl methacrylate(DMA) afforded couplable PDMA(A), and followed by RAFT copolymerization of α-methoxy-ω-vinylbenzyl poly(ethylene glycol)(St-PEG) and maleimidic poly(ε-caprolactone)(MI-PCL) to generate A(B-alt-C)m toothbrushlike copolymer. After introducing variable CTA functionality via quaternization between DMA unit and 3-bromopropyl 4-(benzodithioyl)-4-cyanopentanoate(BBCP), the third RAFT process was performed to synthesize the target toothbrushlike copolymers with various D segments. The synthesized amphiphilic copolymers possessed rich compositions, variable chain lengths, and versatile building blocks comprising terminal quaternized comblike block with tunable grafting density, middle block with alternating PEG and PCL grafts, and terminal D segment as the handle. The resultant copolymers and their precursors had well-controlled molecular weight and relatively low polydispersity(PDI = 1.08-1.35), as evident form 1H NMR and GPC-MALLS analyses. The introduction of chemical heterogeneity into non-responsive toothbrushlike copolymers could endow polymer films with notable thermo-dependent wettability due to accelerated surface penetration and reconstruction, in which PSt-bearing polymer films could exhibit enhanced water contact angle up to 29.6o as the temperature increased from 25 oC to 40 oC. In addition, PNIPAM-based copolymer acted as a model sample to load doxorubicin(DOX) into polymeric aggregates and perform drug delivery. As compared with drug release lacking external stimuli, the increment of cumulative release(ICR, defined as the enhanced percent as compared with the lowest cumulative release amount) varied in the range of 34.1-113% via changing the temperature(T = 25 or 37 oC) or adding DL-dithiothreitol(DTT) or α-CD. As a result, the sequence-regulated toothbrush-like copolymers have a great potential in stimuli-sensitive surface and biomedical materials.The study in Part 2 aimed at facile synthesis and properties of PNIPAM-g-PCL copolymers. Three step reactions comprising RAFT polymerization, ring-opening polymerization(ROP) and thio-bromo click reaction were used for synthesis of the target graft copolymers. First, 4-cyano-4-phenylcarbonothioylthiopentyl-2-(2-bromo-2-methyl propanoyl)methyl-2-hydroxylmethylpropanoate(CBHP) mediated RAFT polymerization of NIPAM gave PNIPAM(H1, Mn,GPC = 4580 g mol–1, PDI = 1.10). Second, multiblock PNIPAM with reactive hydroxyl moieties(H2, FOH ≈ 6) was synthesized via thio-bromo "click" reaction, in which Mn,GPC and PDI were 27900 and 1.40. Last, ROP of ε-caprolactone(CL) initiated with H2 afforded four PNIPAM-g-PCL samples G1-G4 with controlled molecular weight and relatively low polydispersity(PDI = 1.12-1.29). Meanwhile, two PNIPAM-b-PCL samples(B1 and B2) were synthesized and acted as linear analogues of G3. These samples had similar weight compositions of PNIPAM and PCL, and the molecular weights of B1 and B2 were similar to those of minimum and total building blocks of G3. On this basis, the physicochemical properties of graft copolymer and its linear counterparts were investigated. The differences in glass transition temperature, melting temperature and degree of crystallinity revealed the influence of topology on chain relaxation, melting and crystallization behaviors. With increasing PCL content, the LCST of PNIPAM-g-PCL gradually increased from 36.8 oC to 48.9 oC, and critical aggregation concentration(CAC) decreased from 8.34 to 3.72 mg L–1. As compared with their linear analogues, G3 was liable to exhibit enhanced LCST(41.8 oC) and reduced CAC(4.76 mg L–1). The presence of PCL grafts was liable to partly confine the chain mobility of PNIPAM backbone, and PNIPAM may adopt folding or interpenetration conformations to attain hydrophobic-hydrophilic equilibria, resulting in weakened hydrophilic properties than its linear analogues. The graft copolymers could self-assemble into micelles, compound micelles and vesicles as the PCL content was different. Meanwhile, the graft copolymer could act as nanocarrier to encapsulate DOX, and the release process was affected by temperature and additives such as β-CD and glutathione(GSH). These results indicated that the change in weight composition and topology could adjust the physicochemical properties of graft copolymers due to their influence on hydrophobic/hydrophilic ratio, chain stacking and strength and types of macromolecular interactions.In summary, we have designed and synthesized two types of novel topological polymers and investigated their dependence of physicochemical properties on macromolecular parameters. Our study enriches the methodology of sequence-regulated graft polymers and their derivatives, in which controlled polymerization and highly linking reactions were combined to construct toothbrush-like and graft copolymers. In addition, with the introduction of stimuli-sensitive polymer segments, the target copolymers had physicochemical properties different from their linear counterparts, and they had a great potential in smart surface and biomedical materials.