Water-soluble Azobenzene Photoswitches for Controlling Biological Systems

Photoswitches are small molecules that reversibly change their shape and properties upon irradiation with light of different colors. Since these molecules can be manipulated with nonharmful light from the outside at any given location and time, photoswitches are a powerful tool to study different biological targets and for the development of novel light-responsive therapeutics. The major challenges for the application of photoswitches in biological settingare their insolubility in water as well as the fact that the aqueous environment often has a negative impact on the properties of the photoswitch. In addition, many known photoswitches respond to UV light which is damaging to tissue. Those challenges have inspired great efforts to redesign the photoswitch molecules to fully respond to exclusively visible light while also featuring water solubility. In my thesis I focused on developing water-soluble photoswitchesand applying them to manipulate biological systems. The synthesized photoswitches were used to harness the cell-destroying activity of a biological toxin resulting, in a system which could destroy cancer cells upon illumination with light of a specific color. Furthermore, a photoswitch was incorporated into a peptide known to play a crucial role in neurodegenerative diseases, such as Huntington’s disease, to shed light on the mechanism of the disease. Furthermore, this thesis reports several photoswitches which are both watersoluble and completely responsive to visible light thus bringing them one step closer towards applications in living organisms