Zhang Shiyi, Wang Hai, Shen Yuefei, Zhang Fuwu, Seetho Kellie, Zou Jiong, Taylor John-Stephen A, Dove Andrew P, Wooley Karen L
Department of Chemistry, Department of Chemical Engineering, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, P.O. BOX 30012, 3255 TAMU, College Station, Texas, 77842, USA ; Department of Chemistry, Washington University in St. Louis, St. Louis, Missouri, 63130, USA.
Macromolecules. 2013 Jul 9;46(13):5141-5149. doi: 10.1021/ma400675m.
The direct synthesis of an acid-labile polyphosphoramidate by organobase-catalyzed ring-opening polymerization and an overall two-step preparation of polyphosphodiester ionomers (PPEI) by acid-assisted cleavage of the phosphoramidate bonds along the backbone of the polyphosphoramidate were developed in this study. The ultrafast organobase-catalyzed ring-opening polymerization of a cyclic phospholane methoxyethyl amidate monomer initiated by benzyl alcohol allowed for the preparation of well-defined polyphosphoramidates (PPA) with predictable molecular weights, narrow molecular weight distributions (PDI<1.10), and well-defined chain ends. Cleavage of the acid-labile phosphoramidate bonds on the polyphosphoramidate repeat units was evaluated under acidic conditions over a pH range of 1-5, and the complete hydrolysis produced polyphosphodiesters. The thermal properties of the resulting polyphosphoester ionomer acid and polyphosphoester ionomer sodium salt exhibited significant thermal stability. The parent PPA and both forms of the PPEIs showed low cytotoxicities toward HeLa cells and RAW 264.7 mouse macrophage cells. The synthetic methodology developed here has enriched the family of water-soluble polymers prepared by rapid and convenient organobase-catalyzed ring-opening polymerizations and straightforward chemical medication reactions, which are designed to be hydrolytically degradable and have promise for numerous biomedical and other applications.
本研究开发了通过有机碱催化的开环聚合直接合成酸不稳定的聚磷酰胺，以及通过酸辅助裂解聚磷酰胺主链上的磷酰胺键来两步制备聚磷酸二酯离聚物（PPEI）的方法。由苄醇引发的环磷烷甲氧基乙酯单体的超快有机碱催化开环聚合，能够制备出具有可预测分子量、窄分子量分布（PDI<1.10）和明确链端的聚磷酰胺（PPA）。在1-5的pH范围内的酸性条件下评估了聚磷酰胺重复单元上酸不稳定的磷酰胺键的裂解，完全水解产生聚磷酸二酯。所得聚磷酸酯离聚物酸和聚磷酸酯离聚物钠盐的热性能表现出显著的热稳定性。母体PPA以及两种形式的PPEIs对HeLa细胞和RAW 264.7小鼠巨噬细胞均表现出低细胞毒性。这里开发的合成方法丰富了通过快速便捷的有机碱催化开环聚合和直接化学修饰反应制备的水溶性聚合物家族，这些聚合物被设计为可水解降解的，并且在众多生物医学和其他应用中具有前景。
