Investigating Antibacterial Efficiency and Mechanism of Oligo-thiophenes under White Light and Specific Biocidal Activity against E. coli in Dark.

More strategies are required to develop better photosensitizers for photodynamic therapy (PDT). As oligo(phenylene-ethynylene) electrolytes (OPE), oligo(thiophene)s with primary amine as pendant groups (P-OT), and oligo(thiophene ethynylene) (OTE) exhibit excellent light-induced biocidal activity, we desire to converge the molecular design principles of these three kinds of antibacterial agents to combine their advantages to obtain high efficiency and economic biocides. Thus, four oligo(thiophene)s (OTs) were designed and synthesized in this study. The light-induced and dark antibacterial efficacy of the four OTs against Gram-positive Staphylococcus aureus ( S. aureus ) and Gram-negative Escherichia coli (E. coli) were both evaluated. Notably, all the OTs present high biocidal efficacy in the broad spectrum at low (micromolar) concentrations after white-light irradiation. In particular, the low cell cytotoxicity of OTs exhibits their good biocompatibility. These results illustrate that the OTs could work as promising PDT biocides. Interestingly, OT-3 shows a strong and specific dark killing activity against E. coli . The higher biocidal efficacy of T-OTs compared with that of Q-OTs confirms the tertiary amine is a better pendant group for π-conjugated antibacterial agents against E. coli . Mechanistic investigation proves ROS is the necessary element for antibiosis under white light. The interacting efficacy of the OT to the cell membrane, involving synergistic effects between hydrophilic-hydrophobic interactions and electrostatic attractions, is also critical in the killing process. The membrane intercalating activity plays a more essential role, as indicated by the antibacterial activity of OTs. The results provide a unique insight into the relationship between molecular structure and antibacterial activities of this class of antibacterial agents.