The Role of Residual Hydrogen Peroxide for Biological Applications of Polymeric <i>N</i> ‐Oxides

ABSTRACT Polymers with N ‐oxide groups find applications in the biomedical field because they are highly hydrated in water, are considered to be nontoxic, and have stealth properties. Additional antimicrobial activity of polymeric N ‐oxides has also been reported, and it is currently unclear if this activity is a general feature of polymeric N ‐oxides or a special property of selected derivatives. N ‐Oxides are often prepared by oxidation of tertiary amines with hydrogen peroxide, which is notoriously difficult to remove from the resulting polymeric N ‐oxides. This study analyzes the role of residual oxidant in polymeric N ‐oxides for antimicrobial activity. Sensitive quantification reveals a significant release of hydrogen peroxide from oxidized polymers in solution and grafted on polyethylene or polyamide. The release of hydrogen peroxide from these polymers can lead to concentrations exceeding the minimum inhibitory concentrations (MICs) for Staphylococcus aureus and Escherichia coli . It can thus compromise microbiological assays. Rigorous removal of hydrogen peroxide leads to polymeric N ‐oxides with no antibacterial activity. Antibacterial effects of polymeric N ‐oxides against planktonic bacteria are primarily attributed to residual hydrogen peroxide, rather than to the intrinsic activity of the N ‐oxide functionality. Poly( N ‐oxide)‐modified surfaces are therefore inert low‐fouling materials with tunable, transient antibacterial functionality through controlled hydrogen peroxide release.