Synthesis, Enzymatic Degradation, and Polymer-Miscibility Evaluation of Nonionic Antimicrobial Hyperbranched Polyesters with Indole or Isatin Functionalities

Most macromolecular antimicrobials are ionic and thus lack miscibility/compatibility with nonionic substrate materials. In this context, nonionic hyperbranched polyesters (HBPs) with indole or isatin functionality were rationally designed, synthesized, and characterized. Antimicrobial disk diffusion assay indicated that these HBPs showed significant antibacterial activity against 8 human pathogenic bacteria compared to small molecules with indole or isatin groups. According to DSC measurements, up to 20% indole-based HBP is miscible with biodegradable polyesters (polyhydroxybutyrate or polycaprolactone), which can be attributed to the favorable hydrogen bonding between the N-H moiety of indole and the C=O of polyesters. HBPs with isatin or methylindole were completely immiscible with the same matrices. None of the HBPs leaked out from plastic matrix after being immersed in water for 5 days. The incorporation of indole into HBPs as well as small molecules facilitated their enzymatic degradation with PETase from Ideonella sakaiensis, while isatin had a complex impact. Molecular docking simulations of monomeric molecules with PETase revealed different orientations of the molecules at the active site due to the presence of indole or isatin groups, which could be related to the observed different enzymatic degradation behavior. Finally, biocompatibility analysis with a mammalian cell line showed the negligible cytotoxic effect of the fabricated HBPs.

Automated summary

Nonionic hyperbranched polyesters (HBPs) with indole functionality exhibited significant antibacterial activity and were miscible with biodegradable polyesters, while HBPs with isatin or methylindole were completely immiscible with the same matrices. Molecular docking simulations revealed different orientations of molecules at the active site of PETase due to the presence of indole or isatin groups, which could explain the observed enzymatic degradation behavior. Biocompatibility analysis showed negligible cytotoxic effects of the fabricated HBPs on a mammalian cell line.