Photoactivation of Molecular Function

For billions of years, nature has made use of light in a variety of ways. In recent decades, chemists have sought ways in which they also could use light to activate certain molecular functions. Using light as a stimulus for activating a molecular function offers many advantages. Most importantly, it offers the ability to regulate where the molecular function is activated simply through positioning of the light source. For example, photopharmacology aims to locally activate a drug with light only at the required site (such as a tumor), leaving it off in the rest of the body and preventing side effects.
Photo-activation of molecular function can be achieved through the use of photocleavable protecting groups (PPGs). PPGs are molecules that - once attached to the structure of a certain molecular cargo - can silence the ‘natural’ activity of that molecule. Then, upon light irradiation, the cargo molecule (for example a drug) is freed and its natural function is restored.
Crucial to the successful application of PPGs is their efficiency, as it determines how much light is required before a PPG releases its cargo. In this thesis, we delve deep into this parameter; we build an understanding of what determines this efficiency and discover new strategies to improve it. Also, we discover new types of PPGs with unique properties that teach us more about their mechanism of action. Furthermore, we design photo-activatable antibiotics and a photo-activatable variant of the natural compound Amygdalin that releases toxic cyanide. Our ‘Photo-Amygdalin’ is able to release cyanide upon light irradiation and kill human cells. Through providing fundamental understanding, this work paves the way for the future development of superior photoactivatable molecular tools.