The interplay of multivalence and amphiphilicity in antimicrobial bottle brush copolymers

Antimicrobial resistance is an increasingly serious problem causing a large burden on global public health. A fundamental solution would be the development of antimicrobial drugs that, unlike conventional antibiotics, do not cause resistances. Antimicrobial polymers (APs), which mimic natural host defense peptides kill bacteria via membrane disruption, a mechanism that is sufficiently unspecific to not cause resistances. While the amphiphilic balance is a key parameter determining the activity of APs, it is strongly connected to polymer topology as well. While APs featuring a bottle brush architecture in combination with moderate amphiphilicity proved to be highly effective, we wanted to probe if bottle brushes with increased amphiphilicity follow the same trend. To our surprise, when the more hydrophobic tert-butyl acrylamide is used as a comonomer, this trend is reversed with linear copolymers being highly selective and bottle brush copolymers showing limited activity and selectivity. Our data suggests that the reason for this is to be found in the differing self-assembly behavior of both topologies, with bottle brushes forming strong intramolecular associations, which limits membrane activity.