Multi-Hydrogen Bonding on Quaternized-Oligourea Receptor Facilitated Its Interaction with Bacterial Cell Membranes and DNA for Broad-Spectrum Bacteria Killing

Herein, we report a new strategy for the design of antibiotic agents based on the electrostatic interaction and hydrogen bonding, highlighting the significance of hydrogen bonding and the increased recognition sites in facilitating the interaction with bacterial cell membranes and DNA. A series of quaternary ammonium functionalized urea-based anion receptors were studied. While the monodentate mono-urea <b>M1</b>, bisurea <b>M2</b>, and trisurea <b>M3</b> failed to break through the cell membrane barrier and thus could not kill bacteria, the extended bidentate dimers <b>D1</b>-<b>D3</b> presented gradually increased membrane penetrating capabilities, DNA conformation perturbation abilities, and broad-spectrum antibacterial activities against <i>E. coli</i>, <i>P. aeruginosa</i>, <i>S. aureus</i>, <i>E. faecalis</i>, and <i>S. epidermidis</i>.