Biscationic Tartaric Acid-Based Amphiphiles: Charge Location Impacts Antimicrobial Activity

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• 作者：Allison Faig ; Timothy D. Arthur ; Patrick O. Fitzgerald ; Michael Chikindas ; Evan Mintzer ; Kathryn E. Uhrich
• 刊名：Langmuir
• 出版年：2015
• 出版时间：November 3, 2015
• 年：2015
• 卷：31
• 期：43
• 页码：11875-11885
• 全文大小：478K
• ISSN：1520-5827

文摘

Cationic amphiphiles have received increasing attention as antimicrobials given their unique ability to disrupt bacteria cell membranes. While extensive research has demonstrated that amphiphiles鈥?hydrophobic-to-charge ratio significantly modulates antibacterial activity, less work has focused on elucidating the specific impact of charge location on amphiphile bioactivity. In this study, two series of cationic amphiphiles, termed bola-like and gemini-like, were synthesized with analogous hydrophobic-to-charge ratios yet differing charge location, and their resulting antibacterial activity was assessed. Bola-like amphiphiles exhibited preferential activity against two Gram-positive bacteria, with activity increasing with increasing hydrophobicity, whereas gemini-like amphiphiles were active against both Gram-positive and Gram-negative bacteria, with activity decreasing with increasing hydrophobicity. After identifying lead compounds from each amphiphile series (bola- and gemini-like), biophysical experiments indicated that both amphiphiles were membrane-active; notably, the lead gemini-like amphiphile exhibited a strong dependence on electrostatic interactions for membrane interaction. In contrast, the lead bola-like amphiphile exhibited a reliance on both hydrophobic and electrostatic contributions. These results demonstrate that charge location significantly impacts cationic amphiphiles鈥?antibacterial and membrane activity.