Mechanistic study on the hydrolytic degradation of polyphosphates
Mechanistic study on the hydrolytic degradation of polyphosphates
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DOI：
10.1016/j.eurpolymj.2018.08.058
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发表时间：
2018-11-01
影响因子：
6
通讯作者：
Wurm, Frederik R.
中科院分区：
文献类型：
--
作者：
Bauer, Kristin N.;Liu, Lei;Wurm, Frederik R.
环状磷酸酯的开环聚合提供了一种快速获得定义明确的、水溶性和（生物）可降解的聚磷酸酯（PPE）的方法。特别地，聚（烷基亚乙基磷酸酯）已被用作纳米载体或水凝胶的结构单元。然而，其降解的分子机制还不清楚。在此，我们研究了两种最常用的PPE，聚（甲基乙烯磷酸酯）（PMEP）和聚（乙基乙烯磷酸酯）（PEEP）的水解降解。通过NMR光谱法分析降解过程，鉴别并定量中间体和降解产物。我们证明，主要的降解途径是反咬，导致一个主要的水解产物，乙基或甲基亚乙基磷酸（二磷酸）。在碱性和酸性条件下进行的加速水解显示出PEE在酸性条件下的高稳定性，而它们在碱性条件下容易降解。如果末端OH-基团被氨基甲酸酯阻断，则降解动力学的降低进一步支持了反咬机制。我们的发现有助于开发具有可调节水解动力学的可降解纳米器件。
Ring-opening polymerization of cyclic phosphates offers a fast access to well-defined, water soluble and (bio)degradable polyphosphoesters (PPEs). In particular, poly (alkyl ethylene phosphate)s have been used as building blocks for nanocarriers or hydrogels. The molecular mechanism of their degradation is, however, not well understood. Herein, we study the hydrolytic degradation of two most frequently used PPEs, poly(methyl ethylene phosphate) (PMEP) and poly(ethyl ethylene phosphate) (PEEP). The degradation process is analyzed by NMR spectroscopy, which identifies and quantifies intermediates and degradation product(s). We prove that the major degradation pathway is backbiting, leading to one dominating hydrolysis product, ethyl or methyl ethylene phosphate (a diphosphate). Accelerated hydrolysis, performed in basic and acidic conditions, shows the high stability of PEEs under acidic conditions, while they readily degrade under basic conditions. The backbiting mechanism is further supported by the reduction of the degradation kinetics if the terminal OH-group is blocked by a urethane. Our findings help to develop degradable nanodevices with adjustable hydrolysis kinetics.