Cationic Molecular Umbrellas as Antibacterial Agents with Remarkable Cell-Type Selectivity

• DOI: 10.1021/acsami.9b19076
• Publication Date: 2020-01-09T17:33:03Z
• Authors: Ao Chen; Apostolos Karanas...; Kaitlyn R. Casey; Matthew Necelis; Benjamin R. Carone; Gregory A. Caputo; Edmund F. Palermo
• Keywords: Cationic polymerization

We synthesized a combinatorial library of dendrons that display cluster cationic charges juxtaposed with hydrophobic alkyl chain, using the so-called "molecular umbrella" design approach. Systematically tuning generation number and chain length enabled detailed study structure–activity relationships in terms both content charges. These discrete, unimolecular compounds rapid broad-spectrum bactericidal activity comparable to antibacterial peptides. Micellization was examined by pyrene emission dynamic light scattering, which revealed monomeric, individually solvated are present aqueous media. The mechanism action is putatively driven membrane-disrupting nature these surfactants, we confirmed enzymatic assays on E. coli cells. hemolytic dendritic macromolecules sensitively dependent dendron length. Via structural optimization two key features, identified leading candidate potent (4–8 μg/mL) combined outstanding hemocompatibility (up 5000 μg/mL). This selected compound >1000-fold more active against bacteria as compared red blood cells, represents one highest selectivity index values ever reported for agent. Thus, from this initial screen holds great potential future applications nontoxic, degradable disinfectant.