Abstract 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.

中文翻译：

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多磷酸盐水解降解机理研究

摘要 环状磷酸酯的开环聚合提供了一种快速获得定义明确、水溶性和（生物）可降解的聚磷酸酯 (PPE) 的途径。特别是，聚（烷基亚乙基磷酸酯）已被用作纳米载体或水凝胶的构建块。然而，它们降解的分子机制尚不清楚。在此，我们研究了两种最常用的 PPE，聚（磷酸甲酯）（PMEP）和聚（磷酸乙酯）（PEEP）的水解降解。降解过程通过 NMR 光谱分析，可识别和量化中间体和降解产物。我们证明主要的降解途径是反咬合，导致一种主要的水解产物，乙基或甲基亚乙基磷酸酯（一种二磷酸酯）。加速水解，在碱性和酸性条件下进行，显示 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-基团被氨基甲酸乙酯封闭，则降解动力学的降低进一步支持了反咬合机制。我们的发现有助于开发具有可调水解动力学的可降解纳米器件。