Easily Accessible, Highly Potent, Photocontrolled Modulators of Bacterial Communication

Abstract

By applying the photopharmacological approach, bacterial communication can be controlled with light through the application of photoswitchable modulators. Interestingly, one of the lead photoswitchable modulators of bacterial communication, presented herein, shows a remarkable (>700-fold) difference in activity between the non-irradiated and irradiated states. The photoresponsive quorum-sensing modulators can be used to control toxin production in Pseudomonas aeruginosa and have a promising outlook as next-generation research tools.

General Principles for the Design of Visible‐Light‐Responsive Photoswitches: Tetra‐ortho‐Chloro‐Azobenzenes

“…Photostationary state distributions (PSDs) that can be achieved under irradiation with visible light are of crucial importance for applications,e specially in biological context where the two isomers are expected to have different potency in, for example,binding to the cellular target. [11] Only in very rare cases [55,56] it is possible to design molecules in which the stable isomer is almost inactive at agiven concentration, while the irradiation leads to the metastable isomer which is orders of magnitude more potent, thereby making the application virtually independent from PSD.Inthe majority of cases, [9,57] the difference in potencyismuch less pronounced, requiring high efficiencyfor switching in both directions.…”

“…In photopharmacology,afew azobenzene-based bioactive molecules have been described in which the cis isomer shows potencyseveral orders of magnitude higher than trans. [55,56] In such cases,the photostationary state distribution that one can achieve is of less importance,aseven low concertation of the metastable state will result in localized activation. Here,t he use of tetra-ortho-chloro-azobenzenes with strong electrondonating groups (for example,compound 1)isrecommended, as it offers the most efficient activation with visible light.…”

General Principles for the Design of Visible‐Light‐Responsive Photoswitches: Tetra‐ortho‐Chloro‐Azobenzenes

“…Photostationary state distributions (PSDs) that can be achieved under irradiation with visible light are of crucial importance for applications, especially in biological context where the two isomers are expected to have different potency in, for example, binding to the cellular target [11] . Only in very rare cases [55, 56] it is possible to design molecules in which the stable isomer is almost inactive at a given concentration, while the irradiation leads to the metastable isomer which is orders of magnitude more potent, thereby making the application virtually independent from PSD. In the majority of cases, [9, 57] the difference in potency is much less pronounced, requiring high efficiency for switching in both directions.…”

Photoinduced, Direct C(sp2)−H Bond Azo Coupling of Imidazoheteroarenes and Imidazoanilines with Aryl Diazonium Salts Catalyzed by Eosin Y

“…Analogously, arylazo compounds are widely used in several areas, including the chemical industry, pharmaceuticals, chemosensors, electronics, and liquid crystals ( 1 a – d , Figure ) . In this way, very recently, Feringa described the photoisomerization and biological evaluation of a diazo‐based privileged series of novel photoswitchable quorum‐sensing agonists and antagonists …”