Steadily increasing levels of antimicrobial resistance (AMR) are a continuous threat to our global public health. Antimicrobial polymers (APs) offer a promising solution, as their mechanism of action – the permeabilization of bacterial membranes – is unsusceptible toward AMR. However, their selectivity between is still insufficient for clinical applications.
Amphiphilicity is a central parameter determining APs activity and selectivity. Overly amphiphilic systems are usually unselective and toxic to mammalian cells. This property can be modulated by designing the polymeric architecture leading to highly selective bottle brush APs with specific aspect ratios. Too amphiphilic recipes result in irreversible unimolecular self-assembly and undesirable properties. The introduction of sugar moieties into APs sparked our curiosity as the addition of hydrophilic pendants did not have a negative influence on overall performance. Hence we questioned the necessity of amphiphilicity in APs. Advanced photo-mediated RAFT polymerization was used to create a library of APs with varying amphiphilicity and hydrogen bonding properties. Intrestingly, we found that non-amphiphilic APs can have excellent properties if cationic monomers are combined with repeats capable of strong hydrogen bonding. The absence of hydrophobic unit in turn leads to low unspecific toxicity. Non-amphiphilic APs have the unique ability to cluster on membranes, creating a supramolecular multivalence that enhances their membrane activity and aggregates bacterial cells. This effect, which only unfolds in the absence of hydrophobicity, opens new possibilities in the design of antimicrobial materials.