Supramolecularly assisted chlorhexidine-bacterial membrane interaction with enhanced antibacterial activity and reduced side effects

Bacterial infection has emerged as a grievous threat to public health, and lots of antibacterial agents were developed to solve this issue. However, enhancing the antibacterial activity of antibacterial agents while reducing their side effects remains a challenge. Herein, a supramolecular antibacterial agent based on the host–guest interaction between cucurbit[7]uril (CB[7]) and chlorhexidine (CHX) was designed. CHX can be encapsulated in the cavity of CB[7] to form a 1:3 host–guest complex (CHX-3CB[7]). It was amazingly found that this supramolecular complex could display higher antibacterial activity than CHX alone. Electrospray mass spectrometry and UV–vis spectra revealed that the introduction of CB[7] promoted the protonation of N-atoms on CHX, resulting in stronger ion interaction with phospholipids and thus enhancing the destruction of the bacterial membrane. Scanning electron microscopy (SEM), surface ζ-potentials and outer/inner membrane integrity assays also reveal that the introduction of CB[7] aggravates the rupture of membrane. What is more, the cytotoxicity and irritation of CHX were decreased by forming the host–guest complex with CB[7]. This work provides a paradigm for enhancing antibacterial activity and reducing side effects of drugs through supramolecular chemistry.