Center for Polymers and Organic Solids, Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Department of Chemistry and Chemical Engineering, National University of Singapore, Singapore, 117543, Singapore.
ChemistryOpen. 2022 Feb;11(2):e202100260. doi: 10.1002/open.202100260.
Cationic conjugated oligoelectrolytes (COEs) are a class of compounds that can be tailored to achieve relevant in vitro antimicrobial properties with relatively low cytotoxicity against mammalian cells. Three distyrylbenzene-based COEs were designed containing amide functional groups on the side chains. Their properties were compared to two representative COEs with only quaternary ammonium groups. The optimal compound, COE2-3C-C3-Apropyl, has an antimicrobial efficacy against Escherichia coli with an MIC=2 μg mL , even in the presence of human serum albumin low cytotoxicity (IC =740 μg mL ) and minimal hemolytic activity. Moreover, we find that amide groups increase interactions between COEs and a bacterial lipid mimic based on calcein leakage assay and allow COEs to readily permeabilize the cytoplasmic membrane of E. coli. These findings suggest that hydrogen bond forming moieties can be further applied in the molecular design of antimicrobial COEs to further improve their selectivity towards bacteria.
阳离子共轭低聚物（COEs）是一类可以根据需要设计，以获得具有相关体外抗菌性能且对哺乳动物细胞相对低细胞毒性的化合物。本文设计了三种基于二苯乙烯的 COE，其侧链上含有酰胺官能团。将它们的性质与仅含有季铵基团的两种代表性 COE 进行了比较。最佳化合物 COE2-3C-C3-Apropyl 对大肠杆菌具有抗菌功效，MIC=2μg/mL，即使在人血清白蛋白存在的情况下也具有低细胞毒性（IC=740μg/mL）和最小的溶血活性。此外，我们发现酰胺基团增加了 COE 与基于钙黄绿素渗漏测定的细菌脂质模拟物之间的相互作用，并允许 COE 轻易地渗透大肠杆菌的细胞质膜。这些发现表明，氢键形成部分可以进一步应用于抗菌 COE 的分子设计中，以进一步提高它们对细菌的选择性。
