Supramolecules have been drawing increasing attention recently in addressing healthcare challenges caused by infectious pathogens. We herein report a novel class of guanidinium-perfunctionalized polyhedral oligomeric silsesquioxane (Gua-POSS) supramolecules with highly potent antimicrobial activities. The modular structure of Gua-POSS Tm-Cn consists of an inorganic T10 or T8 core (m = 10 or 8), flexible linear linkers of varying lengths (n = 1 or 3), and peripherally aligned cationic guanidinium groups as the membrane-binding units. Such Gua-POSS supramolecules with spherically arrayed guanidinium cations display high antimicrobial potency against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, as well as fungus (Candida albicans), with the best showing excellently low minimal inhibitory concentrations (MICs) of 1.7-6.8 μM in media, yet with negligible hemolytic activity and low in vitro cytotoxicity to mammalian cells. More significantly, they can inhibit biofilm formation at around their MICs and near-completely break down preestablished difficult-to-break biofilms at 250 μg mL-1 (∼50 μM). Their strong antiviral efficacy was also experimentally demonstrated against the enveloped murine hepatitis coronavirus as a surrogate of the SARS-CoV species. Overall, this study provides a new design approach to novel classes of sphere-shaped organic-inorganic hybrid supramolecular materials, especially for potent antimicrobial, anti-biofilm, and antiviral applications.
Keywords: antimicrobial; antiviral agents; biofilm; guanidinium; supramolecular chemistry.