McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Pittsburgh, PA 15219, USA.
Biomaterials. 2010 May;31(15):4417-25. doi: 10.1016/j.biomaterials.2010.02.004. Epub 2010 Mar 2.
We report the synthesis of new polymers based on a dimethylacrylamide-methacrylate (DMAA-MA) co-polymer backbone that support both chemical and biological agent decontamination. Polyurethanes containing the redox enzymes glucose oxidase and horseradish peroxidase can convert halide ions into active halogens and exert striking bactericidal activity against gram positive and gram negative bacteria. New materials combining those biopolymers with a family of N-alkyl 4-pyridinium aldoxime (4-PAM) halide-acrylate co-polymers offer both nucleophilic activity for the detoxification of organophosphorus nerve agents and internal sources of halide ions for generation of biocidal activity. Generation of free bromine and iodine was observed in the combined material resulting in bactericidal activity of the enzymatically formed free halogens that caused complete kill of E. coli (>6 log units reduction) within 1 h at 37 degrees C. Detoxification of diisopropylfluorophosphate (DFP) by the polyDMAA MA-4-PAM iodide component was dose-dependent reaching 85% within 30 min. A subset of 4-PAM-halide co-polymers was designed to serve as a controlled release reservoir for N-hydroxyethyl 4-PAM (HE 4-PAM) molecules that reactivate nerve agent-inhibited acetylcholinesterase (AChE). Release rates for HE 4-PAM were consistent with hydrolysis of the HE 4-PAM from the polymer backbone. The HE 4-PAM that was released from the polymer reactivated DFP-inhibited AChE at a similar rate to the oxime antidote 4-PAM.
我们报告了一种新的聚合物的合成,该聚合物基于二甲基丙烯酰胺-甲基丙烯酸(DMAA-MA)共聚物骨架,支持化学和生物制剂的去污。含有氧化还原酶葡萄糖氧化酶和辣根过氧化物酶的聚氨酯可以将卤化物离子转化为活性卤素,并对革兰氏阳性菌和革兰氏阴性菌表现出显著的杀菌活性。将这些生物聚合物与一系列 N-烷基 4-吡啶基醛肟(4-PAM)卤代丙烯酸酯共聚物结合的新材料,既提供了亲核性,用于解毒有机磷神经毒剂,又提供了内部卤化物离子源,以产生杀菌活性。在组合材料中观察到游离溴和碘的生成,导致酶形成的游离卤化物的杀菌活性,在 37°C 下 1 小时内使大肠杆菌完全失活(>6 个对数单位减少)。聚二甲基丙烯酰胺-4-PAM 碘化物成分对二异丙基氟膦(DFP)的解毒作用呈剂量依赖性,在 30 分钟内达到 85%。一组 4-PAM-卤化物共聚物被设计为 N-羟乙基 4-PAM(HE 4-PAM)分子的控制释放储库,该分子可以使神经毒剂抑制的乙酰胆碱酯酶(AChE)重新激活。HE 4-PAM 的释放速率与聚合物主链上从 HE 4-PAM 的水解一致。从聚合物中释放的 HE 4-PAM 以与肟解毒剂 4-PAM 相似的速率重新激活 DFP 抑制的 AChE。