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尺寸可控的铵基均聚物作为广谱抗菌剂

Size-Controlled Ammonium-Based Homopolymers as Broad-Spectrum Antibacterials.

作者信息

Haktaniyan Meltem, Sharma Richa, Bradley Mark

机构信息

EaStCHEM, School of Chemistry, University of Edinburgh, Joseph Black Building, West Mains Road, Edinburgh EH9 3FJ, UK.

Precision Healthcare University Research Institute, Queen Mary University of London, Whitechapel, Empire House, London E1 1HH, UK.

出版信息

Antibiotics (Basel). 2023 Aug 16;12(8):1320. doi: 10.3390/antibiotics12081320.

Abstract

Ammonium group containing polymers possess inherent antimicrobial properties, effectively eliminating or preventing infections caused by harmful microorganisms. Here, homopolymers based on monomers containing ammonium groups were synthesized via Reversible Addition Fragmentation Chain Transfer Polymerization (RAFT) and evaluated as potential antibacterial agents. The antimicrobial activity was evaluated against Gram-positive ( and ) and Gram-negative bacteria ( and ). Three polymers, poly(diallyl dimethyl ammonium chloride), poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride), and poly(vinyl benzyl trimethylammonium chloride), were examined to explore the effect of molecular weight (10 kDa, 20 kDa, and 40 kDa) on their antimicrobial activity and toxicity to mammalian cells. The mechanisms of action of the polymers were investigated with dye-based assays, while Scanning Electron Microscopy (SEM) showed collapsed and fused bacterial morphologies due to the interactions between the polymers and components of the bacterial cell envelope, with some polymers proving to be bactericidal and others bacteriostatic, while being non-hemolytic. Among all the homopolymers, the most active, non-Gram-specific polymer was poly([2-(methacryloyloxy)ethyl]trimethylammonium chloride), with a molecular weight of 40 kDa, with minimum inhibitory concentrations between 16 and 64 µg/mL, showing a bactericidal mode of action mediated by disruption of the cytoplasmic membrane. This homopolymer could be useful in biomedical applications such as surface dressings and in areas such as eye infections.

摘要

含铵基团的聚合物具有固有的抗菌特性,能有效消除或预防有害微生物引起的感染。在此,通过可逆加成-断裂链转移聚合(RAFT)合成了基于含铵基团单体的均聚物,并将其评估为潜在的抗菌剂。针对革兰氏阳性菌( 和 )和革兰氏阴性菌( 和 )评估了抗菌活性。研究了三种聚合物,即聚二烯丙基二甲基氯化铵、聚[2-(甲基丙烯酰氧基)乙基]三甲基氯化铵和聚乙烯苄基三甲基氯化铵,以探讨分子量(10 kDa、20 kDa和40 kDa)对其抗菌活性及对哺乳动物细胞毒性的影响。通过基于染料的试验研究了聚合物的作用机制,而扫描电子显微镜(SEM)显示,由于聚合物与细菌细胞膜成分之间的相互作用,细菌形态出现塌陷和融合,一些聚合物被证明具有杀菌作用,另一些具有抑菌作用,且无溶血作用。在所有均聚物中,活性最强、非革兰氏特异性的聚合物是分子量为40 kDa的聚[2-(甲基丙烯酰氧基)乙基]三甲基氯化铵,其最低抑菌浓度在16至64 µg/mL之间,显示出通过破坏细胞质膜介导的杀菌作用模式。这种均聚物可用于生物医学应用,如表面敷料以及眼部感染等领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1225/10452032/9e7cbb542a2b/antibiotics-12-01320-g001.jpg

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