Photoswitchable ligands as biological tools provide an opportunity to explore the kinetics and dynamics of the clinically relevant µ-opioid receptor. These ligands can potentially activate and deactivate the receptor when desired, using light. Spatial and temporal control of biological activity allows for application in a diverse range of biological investigations. Photoswitchable ligands have been developed in this work, modeled on the known agonist fentanyl, with the aim of expanding the current 'toolbox' of fentanyl photoswitchable ligands. In doing so, ligands have been developed that change geometry (isomerize) upon exposure to light, with varying photophysical and biochemical properties. This variation in properties may be valuable in further studying the functional significance of the µ-opioid receptor.

With high spatiotemporal control, the conformation, rigidity and electronics of photoresponsive bioactive molecules can be altered. This, in turn, allows for control over the biological properties of these molecules. Incorporation of a photoswitchable moiety into a number of reported inhibitors, ligands and modulators has demonstrated the ability to modulate enzyme, receptor and ion channel responses using light. To date, the major classes of photoswitches explored in biological applications have been the azobenzenes and diarylethenes. Even though the use of these photoswitches has established the value of photoresponsive molecules as biological tools, several limitations have become apparent. Fulgimides represent a promising class of photoswitches that are not widely used for such biological purposes. Their properties are similar to that of diarylethenes, as their photochromism is based on a 6π‐electrocyclic rearrangement, however, fulgimides have the added advantage of thermal stability for both isomers. Fulgimides exhibit high photostationary states and fatigue resistance, with the ability to switch in aqueous buffer solutions. In this minireview, these advantageous photophysical properties will be discussed, as well as the use of fulgimides in biological investigations.

The Cover Feature shows fulgimides as light‐activated biological tools. Upon exposure to certain wavelengths of light, fulgimides undergo a reversible change in structure and properties. This allows access to a closed and open isomer when desired. These isomers may have significant differences in target interactions, thus resulting in compounds that have a biologically active and inactive state. Such behaviour has been documented, as summarized in our review paper. The ability for light to switch fulgimides, which in turn activates and inactivates biological systems, is depicted in this figure both literally and figuratively. More information can be found in the Minireview by B.König et al.