【作者】 徐友翠；

【导师】 董常明；

【作者基本信息】 上海交通大学 ， 化学工程， 2012， 硕士

【摘要】 本论文以扇型/线型结构的聚赖氨酸Dm-PZLys为前聚体,通过与PEO结合,得到了一系列扇型/线型-线型的可降解及具有生物相容性的嵌段聚合物,并通过脱除赖氨酸侧链氨基的保护基团得到聚阳离子共聚物。(1)点击化学和开环聚合方法制备扇型-线型Dm-PZLys-b-PEO嵌段共聚物及其表征利用具有“点击”功能化的端炔基化聚酰胺-胺,采用“点击”化学(Click Chemistry)和开环聚合(ROP)的方法,设计合成了扇型/线型-线型聚( -苄氧羰基-L-赖氨酸)嵌段共聚物,通过利用红外光谱、核磁氢谱、凝胶渗透色谱、差示扫描量热仪、偏光显微镜、广角X射线衍射等对嵌段共聚物的化学结构与物理性能进行了详细的表征;PZLys链段在聚赖氨酸均聚物和共聚物中均出现了液晶相的转变,并且这种转变是不可逆的。同时,随着PZLys链段组成的增加,PEO链段在线性共聚物中的结晶度从96.2 %降至20.4 %,而扇型-线型共聚物中的PEO链段的结晶完全受到了抑制;随着链长的增加,PZLys链段的二级结构从?-折叠构象向?-螺旋构象转变。这一系列的共聚物可在水溶液中组装成球形纳米粒子,阿霉素作为模型药物,负载后对共聚物组装形成纳米粒子的形貌几乎没有影响;所有的阿霉素载药纳米粒子在pH 7.4及pH 5.5条件下表现三相释放模式,释放周期长达两个月。(2)扇型-线型共聚物Dm-PLys-b-PEO的合成、性能表征,以及超分子水凝胶的制备在前面合成的Dm-PZLys-b-PEO基础上,利用脱保护化学,得到了聚阳离子共聚物Dm-PLys-b-PEO,利用红外光谱、核磁氢谱、广角X射线衍射、偏光显微镜、动态光散射等对共聚物的化学结构、物化性能及自组装性能进行了表征。运用主-客体化学和聚氨基酸链段之间的氢键相互作用,初步探索利用同一种聚赖氨酸基两嵌段共聚物来构筑“普通胶束水凝胶”和“反胶束水凝胶”,这种超分子水凝胶是通过聚(L-赖氨酸)链段之间的氢键相互作用以及聚乙二醇与-环糊精间的包络作用而共同形成的,并利用广角X射线衍射、差示扫描量热仪等表征手段对超分子水凝胶的物化性能和成胶机理进行了初步的探索。更多还原

【Abstract】 Dendronlike poly(?-benzyloxycarbonyl-L-lysine)/linear poly(ethylene oxide) block copolymers (i.e., Dm-PZLys-b-PEO, m = 0 and 3; Dm are the propargyl focal point poly(amido amine) dendrons having 2m primary amine groups) were for the first time synthesized by combining ring-opening polymerization (ROP) of ?-benzyloxycarbonyl-L-lysine N-carboxyanhydride (Z-Lys-NCA) and click chemistry, where Dm-PZLys homopolypeptides were click conjugated with azide-terminated PEO.Then through the deprotection of benzyloxycarbonyl group on the PZLys block, Dm-PLys-b-PEO were achieved.(1) Synthesis and Characterization of Dendron-like/Linear Dm-PZLys-b-PEO Copolymers via ROP and Click Chemistry A new class of dendron-like/linear Dm-PZLys-b-PEO block copolymers was synthesized via controlled ring-opening polymerization (ROP) of Z-Lys-NCA followed by a click conjugation with azide-terminated poly(ethylene oxide) (PEO-N3). Their molecular structures and physical properties were characterized in detail by FT-IR, 1H NMR, gel permeation chromatography, differential scanning calorimetry, polarized optical microscopy, and wide angle X-ray diffraction. Both homopolypeptides and copolymers presented a liquid crystalline phase transition for PZLys block, and the transition was irreversible. Moreover, the degree of crystallinity of PEO block within linear copolymers decreased from 96.2 % to 20.4 % with increasing PZLys composition, while that within dendritic copolymers decreased to zero. The secondary conformation of PZLys progressively changed from -sheet to -helix with increasing the chain length. These copolymers self-assembled into spherical nanoparticles in aqueous solution, and the anticancer drug doxorubicin-loaded nanoparticles gave a similar morphology compared to their blank counterparts. The drug-loaded nanoparticles showed a triphasic drug-release profile at aqueous pH 7.4 or 5.5 and 37℃, and sustained a longer drug-release period for about two months.(2)Synthesis and Hydrogelation of Dendronlike/Linear Dm-PLys-b-PEO Copolymers Dm-PLys-b-PEO copolymers were synthesized through the deprotection of benzyloxycarbonyl group on the PZLys block,their molecular structures and physical properties were characterized in detail by FT-IR, 1H NMR, polarized optical microscopy, and wide angle X-ray diffraction. The self-assembly behavior of Dm-PLys-b-PEO copolymers was investigated by means of dynamic light scattering (DLS), and the corresponding normal and reverse micellar hydrogel from the same polypeptide-based copolymer were prepared via the cooperation of host-guest chemistry and hydrogen-bonding interactions.更多还原