Highly Effective, Water-Soluble, Hemocompatible 1,3-Propylene Oxide-Based Antimicrobials: Poly[(3,3-quaternary/PEG)-copolyoxetanes]

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• 作者：Souvik Chakrabarty ; Allison King ; Pinar Kurt ; Wei Zhang ; Dennis E. Ohman ; Lynn F. Wood ; C. Lovelace ; Raj Rao ; Kenneth J. Wynne
• 刊名：Biomacromolecules
• 出版年：2011
• 出版时间：March 14, 2011
• 年：2011
• 卷：12
• 期：3
• 页码：757-769
• 全文大小：1084K
• 年卷期：v.12,no.3(March 14, 2011)
• ISSN：1526-4602

文摘

This study focuses on the solution antimicrobial effectiveness of a novel class of copolyoxetanes with quaternary ammonium and PEG-like side chains. A precursor P[(BBOx-m)(ME2Ox)] copolyoxetane was prepared by cationic ring-opening copolymerization of 3-((4-bromobutoxy)methyl)-3-methyloxetane (BBOx) and 3-((2-(2-methoxyethoxy)ethoxy)methyl)-3-methyloxetane (ME2Ox) to give random copolymers with 14鈭?00 (m) mol % BBOx. Reaction of P[(BBOx-m)(ME2Ox)] with dodecyl dimethylamine gave the corresponding quaternary P[(C12-m)(ME2Ox)] polycation salts, designated C12-m, as viscous liquids in 100% yield. BBOx/ME2Ox and C12/ME2Ox ratios were obtained by ¹H NMR spectroscopy. C12-m molecular weights (M_n, 3.5鈭?1.9 kDa) were obtained from ¹H NMR end group analysis. DSC studies up to 150 掳C showed only thermal transitions between 鈭?9 and 鈭?4 掳C assigned to T_g values. Antibacterial activity for the C12-m copolyoxetanes was tested by determining minimum inhibitory concentrations (MICs) against Gram(+) Staphylococcus aureus and Gram(鈭? Escherichia coli and Pseudomonas aeruginosa. MIC decreased with increasing C12 mol percent, reaching a minimum in the range C12鈭?3 to C12鈭?0. Overall, the antimicrobial with consistently low MICs for the three tested pathogenic bacteria was C12鈭?3: (bacteria, MIC, 渭g/mL) E. coli (6), S. aureus (5), and P. aeruginosa (33). For C12鈭?3, minimum biocidal concentration (MBC) to reach 99.99% kill in 24 h required 1.5脳 MIC for S. aureus and 2脳 MIC for E. coli and P. aeruginosa. At 5脳 MIC against a challenge of 10⁸ cfu/mL, C12鈭?3 kills 鈮?9% S. aureus, E. coli, and P. aeruginosa within 1 h. C12-m copolyoxetane cytotoxicity toward human red blood cells was low, indicating good prospects for biocompatibility. The tunability of C12-m copolyoxetane compositions, effective antimicrobial behavior against Gram(+) and Gram(鈭? bacteria, and promising biocompatibility offer opportunities for further modification and potential applications as therapeutic agents.