高等学校化学学报

高等学校化学学报 ›› 2009, Vol. 30 ›› Issue (6): 1245.

• 研究论文 • 上一篇    下一篇

聚[(甲氧基乙氧基乙氧基)1.0(乙氧基吡咯烷酮)1.0]膦腈的合成及性能研究

殷跃凡1, 李艳梅1, 资彦楠1, 周轶平2, 毕韵梅1   

  1. 1. 云南师范大学化学化工学院, 昆明 650092;
    2. 昆明医学院云南省天然药物药理重点实验室, 昆明 650031
  • 收稿日期:2008-08-25 出版日期:2009-06-10 发布日期:2009-06-10
  • 通讯作者: 毕韵梅, 女, 博士, 教授, 从事功能高分子合成和性能研究. E-mail: yunmeibi@hotmail.com
  • 基金资助:

    国家自然科学基金(批准号: 20364002)和云南省自然科学基金(批准号: 2005B0027M)资助.

Synthesis, Characterization, in Vitro Degradation and Cytotoxicity of Poly{[2-(2-oxy-1-pyrrolidiny) ethoxy]1.0(methoxyethoxyethoxy)1.0] phosphazene}

YIN Yue-Fan1,2, LI Yan-Mei1, ZI Yan-Nan1, Zhou Yi-Ping3, BI Yun-Mei1*   

  1. 1. College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming 650092, China;
    2. Yunnan Pharmacological Laboratories of Natural Products, Kunming Medical College, Kunming 650031, China
  • Received:2008-08-25 Online:2009-06-10 Published:2009-06-10
  • Contact: BI Yun-Mei, E-mail: yunmeibi@hotmail.com
  • Supported by:

    国家自然科学基金(批准号: 20364002)和云南省自然科学基金(批准号: 2005B0027M)资助.

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摘要：

用三氯化铝催化六氯三聚膦腈开环聚合制得线性聚二氯膦腈(PDCP), 通过PDCP磷原子上的亲核取代反应, 合成了新的水溶性高分子聚[(甲氧基乙氧基乙氧基)1.0(乙氧基吡咯烷酮)1.0]膦腈(P3), 用31P NMR, 1H NMR, 13C NMR和IR对其结构进行了确证, 用DSC测定了其玻璃化转变温度Tg和熔融温度Tm, 用蒸汽压渗透法(VPO)测定了其数均分子量. 改进了聚二(乙氧基吡咯烷酮)膦腈(P2)的合成方法. 体外降解实验表明, P3具有和P2类似的pH响应性降解行为, 降解速率在pH=5.0时最快, 而在pH=7.4和8.0时较慢. P3在所测试的3个pH缓冲溶液中均比P2降解慢. 用31P NMR、薄层色谱(TLC)和滴定法对降解产物进行了检测, 初步推断了P3在不同pH介质中的水解机理, 其在pH=5.0的缓冲溶液中的降解, 除侧链断裂外, 聚膦腈的骨架也裂解; 而在pH=7.4和8.0时的降解仅为侧链的断裂. 用噻唑蓝(MTT)比色法进行的体外细胞毒性评价实验表明, P3及其在pH=5.0的缓冲溶液中降解49 d后的产物均对细胞表现出了很好的生物相容性, 而且其降解产物在浓度为800 μg/mL时还表现出一定的促进细胞增殖作用.

关键词: 聚膦腈, 乙氧基吡咯烷酮, 甲氧基乙氧基乙氧基, pH响应性降解, 水解机理, 体外细胞毒性

Abstract:

Polydichlophosphazene(PDCP) was prepared by the ring-opening polymerization of hexachlorocyclotriphosphazene in the presence of 2%AlCl3. A new mixed substituent poly(organophosphazene) bearing 2-(2-oxy-1-pyrrolidiny) ethoxy and methoxyethoxyethoxy side groups was synthesized via the macromolecular substitution reactions of poly(dichlorophosphazene) with the sodium salt of 1-(2-hydroxyethyl)-2-pyrrolidone and sodium methoxyethoxyethoxide. Its structure was verified by 31P NMR, 1H NMR, 13C NMR, IR and DSC. Its molecular weight was determined by vapor pressure osmometry(VPO). 18-Crown-6 was used in the synthesis of poly[di(2-oxy-1-pyrrolidiny)ethoxyphophazene](PYRP) as phase transfer catalysis in order to improve its synthetic method. The new polymer and PYRP were water-soluble and their in vitro degradation behavior was studied at varied pH conditions. The results indicate that the degradation of poly(organophosphazenes) with (2-oxy-1-pyrrolidiny)ethoxy side groups is dependent on pH of the buffer solution. The rate of hydrolysis was more rapid at pH=5.0 than at pH=7.4 and pH=8.0. It was shown that addition of methoxyethoxyethoxy side group to PYRP structure resulted in a decrease in the rate of hydrolysis. The hydrolysis products of the poly(organophosphazenes) were analyzed by 31P NMR, thin layer chromatography(TLC) and titration methods. A hydrolysis pathway of the new polymer in buffer solutions with pH=5.0, 7.4 and 8.0 was proposed. The degradation of the polymers at pH=5.0 involved a hydrolytic cleavage of (2-oxy-1-pyrrolidiny)ethoxy from the chain followed by the degradation of the phosphorus-nitrogen backbone to form phosphate and ammonium. However, the degradation of the polymers at pH=7.4 and pH=8.0 was only cleavage of the side group. The MTT test for the new polymer and its hydrolysis products at pH=5.0 in HepG2 cell revealed that an increase in polymer concentration from 1.3 to 800 μg/mL was not harmful for the cell survival. The hydrolysis products of the new polymer at 800 μg/mL were able to promote cell proliferation.

Key words: Polyphosphazene, 2-(2-Oxy-1-pyrrolidiny)ethoxy, Methoxyethoxyethoxy, pH-sensitive hydrolytic degradation property, Hydrolysis pathway, In vitro cytotoxicity

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