Bicephalic amphiphile architecture affects antibacterial activity

A series of cationic amphiphiles, each with an aromatic core, was prepared and investigated for antimicrobial properties. The synthesized amphiphiles in this study are bicephalic (double-headed) in that they each possess two trimethylammonium head groups and a single linear alkoxy tail. Minimum inhibitory and minimum bactericidal concentrations of these amphiphiles were in the low micromolar range. Antimicrobial activities are highly sensitive to the chain length of the hydrophobic region, and modestly reliant on the relative positioning of the head groups on the aromatic core. These trends were more pronounced in time kill assays, wherein longer chain compounds required significantly shorter times to completely kill bacteria. Microscopy suggested that the mode of cell death was lysis. Strong inhibition was observed with both biscationic compounds and monocationic comparisons against Gram-positive bacteria; only biscationic amphiphiles maintained good activity versus the Gram-negative bacteria tested. These observations provide direction for future antimicrobial structural investigations.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of biscationic bicephalic (double-headed) amphiphiles was prepared. ► Amphiphiles were evaluated for antimicrobial activity. ► Inhibition was observed for both Gram-positive and Gram-negative bacteria. ► Activity was highly sensitive to hydrophobic chain length. ► Activity was modestly reliant on polar head-group architecture.