Cationic Poly(benzyl ether)s as Self-Immolative Antimicrobial Polymers
Cationic Poly(benzyl ether)s as Self-Immolative Antimicrobial Polymers
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DOI：
10.1021/acs.biomac.7b01062
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发表时间：
2017-10-01
影响因子：
6.2
通讯作者：
Palermo, Edmund F.
中科院分区：
文献类型：
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作者：
Ergene, Cansu;Palermo, Edmund F.
自降解聚合物（Self-immolative polymers，SIMPs）是一类在外界刺激下自发解聚成小分子的高分子聚合物。我们在这里报告的第一个例子，抗菌SIMPs具有强大的，快速的，广谱的杀菌活性。它们的抗菌和溶血活性作为阳离子官能度的函数进行了检查。带有伯铵阳离子基团的聚合物对大肠杆菌显示出更有效的杀菌活性，相对于叔铵和季铵对应物，而季铵聚合物显示出最低的溶血毒性。当由外部施加的刺激触发时，这些抗菌聚阳离子经历端对端解聚。具体地，使用半胱胺HCl通过光引发的硫醇-烯自由基加成将用甲硅烷基醚基团封端并带有侧链烯丙基侧链的聚（苄基醚）转化为聚阳离子。完整的聚阳离子在溶液中是稳定的，但它们在暴露于氟离子时自发地解压缩成它们的组分单体，具有优异的灵敏度和选择性。在引发解聚后，抗菌效力在很大程度上得以保留，但溶血毒性大幅降低。因此，我们揭示了自分解抗菌聚合物平台的第一个例子，该平台将使抗菌材料在引入专门设计的刺激物后自发地解压缩成生物活性小分子。
Self-immolative polymers (SIMPs) are macromolecules that spontaneously undergo depolymerization into small molecules when triggered by specific external stimuli. We report here the first examples of antimicrobial SIMPs with potent, rapid, and broad-spectrum bactericidal activity. Their antibacterial and hemolytic activities were examined as a function of cationic functionality. Polymers bearing primary ammonium cationic groups showed more potent bactericidal activity against Escherichia coli, relative to tertiary and quaternary ammonium counterparts, whereas the quaternary ammonium polymers showed the lowest hemolytic toxicity. These antibacterial polycations undergo end-to-end depolymerization when triggered by an externally applied stimulus. Specifically, poly(benzyl ether)s end-capped with a silyl ether group and bearing pendant allyl side chains were converted to polycations by photoinitiated thiol-ene radical addition using cysteamine HCl. The intact polycations are stable in solution, but they spontaneously unzip into their component monomers upon exposure to fluoride ions, with excellent sensitivity and selectivity. Upon triggered depolymerization, the antibacterial potency was largely retained but the hemolytic toxicity was substantially reduced. Thus, we reveal the first example of a self-immolative antibacterial polymer platform that will enable antibacterial materials to spontaneously unzip into biologically active small molecules upon the introduction of a specifically designed stimulus.