Effect of Extended π-Bridges and Molecular Charge on the Photodynamic Activity of Aggregation-Induced Emission Photosensitizers against Multidrug-Resistant Bacteria

Multidrug resistant (MDR) bacterial infections are a major challenge encountered in global healthcare today. We have designed and synthesized three aggregation-induced emission (AIE) photosensitizers with different positive charges, named ((E)-N,N-diphenyl-4-(7-(2-(pyridin-4-yl)vinyl)benzo[c][1,2,5]thiadiazol-4-yl)aniline, TPA–S-N), ((E)-4-(2-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)vinyl)-1-ethylpyridin-1-ium bromide, TPA–S-N⁺), and ((E)-4-(2-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)vinyl)-1-(3-(trimethylammonio)propyl)pyridin-1-ium bromide, TPA–S-N⁺⁺), through the extended π-bridge strategy and the introduction of a C═C double bond. We have investigated the effects of the extended π-bridges and differences in molecular charge on the activity of the photosensitizers against multidrug-resistant bacteria. The results showed that they efficiently produced reactive oxygen species under white light irradiation due to the extended π-bridges. After white light irradiation (40 mW cm^–2), TPA–S-N⁺ was 1.75 times more effective than TPA–S-N⁺⁺ in killing methicillin-resistant Staphylococcus aureus (MRSA) at a concentration of only 0.10 μM (0.06 μg/mL). With the increase of positive charge, the enhancement of electrostatic interaction and the decrease of hydrophobicity, TPA–S-N⁺⁺ inactivated 80.30% of MDR E. coli at a concentration of 5.00 μM (3.72 μg/mL), and the antimicrobial effect was 3.12 times higher than that of TPA–S-N⁺. The photosensitizers all provide clear fluorescent imaging of bacterial cell membranes and act primarily on bacterial membranes to kill bacteria. In vivo experiments showed that TPA–S-N⁺ and TPA–S-N⁺⁺ successfully promoted wound healing in MRSA-infected mice. In addition, we coincubated the two bacteria and added photosensitizers for costaining and found that photosensitizers fluoresced red on the membranes of MRSA while MDR E. coli did not, which provided a means of visualizing the tracing of MRSA.