Department of Materials Science and Engineering, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York 12180, United States.
Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213-2617, United States.
ACS Macro Lett. 2023 Feb 21;12(2):215-220. doi: 10.1021/acsmacrolett.2c00726. Epub 2023 Jan 26.
The performance of antimicrobial polymers depends sensitively on the type of cationic species, charge density, and spatial arrangement of cations. Here we report antimicrobial polymers bearing unusually bulky tetraaminophosphonium groups as the source of highly delocalized cationic charge. The bulky cations drastically enhanced the biocidal activity of amphiphilic polymers, leading to remarkably potent activity in the submicromolar range. The cationic polynorbornenes with pendent tetraaminophosphonium groups killed over 98% at a concentration of 0.1 μg/mL and caused a 4-log reduction of within 2 h at a concentration of 2 μg/mL, showing very rapid and potent bactericidal activity. The polymers are also highly hemolytic at similar concentrations, indicating a biocidal activity profile. Polymers of a similar chemical structure but with more flexible backbones were made to examine the effects of the flexibility of polymer chains on their activity, which turned out to be marginal. We also explore variants with different spacer arm groups separating the cations from the backbone main chain. The antibacterial activity was comparably potent in all cases, but the polymers with shorter spacer arm groups showed more rapid bactericidal kinetics. Interestingly, pronounced counterion effects were observed. Tightly bound PF counteranions showed poor activity at high concentrations due to gross aggregate formation and precipitation from the assay media, whereas loosely bound Cl counterions resulted in very potent activity that monotonically increased with increasing concentration. In this paper, we reveal that bulky phosphonium cations are associated with markedly enhanced biocidal activity, which provides an innovative strategy to develop more effective self-disinfecting materials.
抗菌聚合物的性能对阳离子种类、电荷密度和阳离子的空间排列非常敏感。在这里，我们报告了一种含有异常庞大的四氨基鏻基团的抗菌聚合物，这些基团是高度离域正电荷的来源。庞大的阳离子极大地增强了两亲聚合物的杀菌活性，使其在亚微摩尔范围内具有显著的活性。带有侧挂四氨基鏻基团的阳离子型聚降冰片烯在 0.1μg/mL 的浓度下杀死了超过 98%的细菌，并在 2μg/mL 的浓度下在 2 小时内导致了 4 个对数的减少，表现出非常快速和有效的杀菌活性。这些聚合物在类似的浓度下也具有很高的溶血活性，表明其具有杀菌活性。我们还制备了具有类似化学结构但具有更灵活骨架的聚合物，以研究聚合物链的灵活性对其活性的影响，结果发现影响很小。我们还探索了不同间隔臂基团的变体，以分离阳离子和主链。在所有情况下，抗菌活性都相当强烈，但具有较短间隔臂基团的聚合物表现出更快的杀菌动力学。有趣的是，观察到明显的抗衡离子效应。紧密结合的 PF 抗衡离子由于聚集和沉淀而在高浓度下表现出较差的活性，而松散结合的 Cl 抗衡离子则导致非常强烈的活性，其活性随着浓度的增加而单调增加。在本文中，我们揭示了庞大的鏻阳离子与显著增强的杀菌活性有关，这为开发更有效的自消毒材料提供了一种创新策略。
