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 ((<i>E</i>)-N,N-diphenyl-4-(7-(2-(pyridin-4-yl)vinyl)benzo[<i>c</i>][1,2,5]thiadiazol-4-yl)aniline, <b>TPA-S-N</b>), ((<i>E</i>)-4-(2-(7-(4-(diphenylamino)phenyl)benzo[<i>c</i>][1,2,5]thiadiazol-4-yl)vinyl)-1-ethylpyridin-1-ium bromide, <b>TPA-S-N</b>^<b>+</b>), and ((<i>E</i>)-4-(2-(7-(4-(diphenylamino)phenyl)benzo[<i>c</i>][1,2,5]thiadiazol-4-yl)vinyl)-1-(3-(trimethylammonio)propyl)pyridin-1-ium bromide, <b>TPA-S-N</b>^<b>++</b>), 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), <b>TPA-S-N</b>^<b>+</b> was 1.75 times more effective than <b>TPA-S-N</b>^<b>++</b> in killing methicillin-resistant <i>Staphylococcus aureus</i> (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, <b>TPA-S-N</b>^<b>++</b> inactivated 80.30% of MDR <i>E. coli</i> at a concentration of 5.00 μM (3.72 μg/mL), and the antimicrobial effect was 3.12 times higher than that of <b>TPA-S-N</b>^<b>+</b>. The photosensitizers all provide clear fluorescent imaging of bacterial cell membranes and act primarily on bacterial membranes to kill bacteria. <i>In vivo</i> experiments showed that <b>TPA-S-N</b>^<b>+</b> and <b>TPA-S-N</b>^<b>++</b> 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 <i>E. coli</i> did not, which provided a means of visualizing the tracing of MRSA.