Easily Accessible, Highly Potent, Photocontrolled Modulators of Bacterial Communication

External control of bacterial communication quorum sensing allows for the regulation of a multitude of biological processes. Herein, we describe the development of a new synthetic methodology, as well as the characterization, photoisomerization, and biological evaluation of a privileged series of novel photoswitchable quorum-sensing agonists and antagonists. The presented method allows for the rapid and convenient synthesis of previously unknown photoswitchable agonists with up to 70% quorum-sensing induction and inhibitors reaching up to 40% inhibition, which significantly extends the level of photocontrol over bacterial communication achieved before, Remarkably, for the lead photoswitchable agonist, a >700-fold difference in activity was observed between the irradiated and non-irradiated forms, which allows for antagonismto-agonism switching upon exposure to light, showing levels of control unprecedented in photopharmacology, Finally, utilizing this system, we were able to regulate toxin production in Pseudomonas aeruginosa with light.