Biscationic Tartaric Acid-Based Amphiphiles: Charge Location Impacts Antimicrobial Activity.
Cationic amphiphiles have received increasing attention as antimicrobials given their unique ability to disrupt bacteria cell membranes. While extensive research has demonstrated that amphiphiles' 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' antibacterial and membrane activity.
Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey 08854, United States.
Allison
A
Faig
Timothy D
TD
Arthur
Patrick O
PO
Fitzgerald
Center for Digestive Health, New Jersey Institute for Food, Nutrition and Health , New Brunswick, New Jersey 08901, United States.
Michael
M
Chikindas
Lander College of Arts and Sciences, Touro College , 1602 Avenue J, Brooklyn, New York 11230, United States.|Department of Chemistry and Biochemistry, Stern College , 245 Lexington Ave., Room 552, New York, New York 10016, United States.
Evan
E
Mintzer
Department of Chemistry and Chemical Biology, Rutgers University , Piscataway, New Jersey 08854, United States.
Kathryn E
KE
Uhrich
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002412:Cations / Q000737:chemistry*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013644:Tartrates / Q000737:chemistry* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002412:Cations; D013644:Tartrates; C029768:tartaric acid