Photocleavable Protecting Groups Using a Sulfite Self-Immolative Linker for High Uncaging Quantum Yield and Aqueous Solubility.

Using light as an external stimulus to control (bio)chemical processes offers many distinct advantages. Most importantly, it allows for spatiotemporal control simply through operating the light source. Photocleavable protecting groups (PPGs) are a cornerstone class of compounds that are used to achieve photocontrol over (bio)chemical processes.

The fate of the contact ion pair determines the photochemistry of coumarin-based photocleavable protecting groups.

Photocleavable protecting groups (PPGs) enable the precise spatiotemporal control over the release of a payload of interest, in particular a bioactive substance, through light irradiation. A crucial parameter that determines the practical applicability of PPGs is the efficiency of payload release, largely governed by the quantum yield of photolysis (QY). Understanding which parameters determine the QY will prove crucial for engineering improved PPGs and their effective future applications, especially in the emerging field of photopharmacology.

Cation delocalization and photo-isomerization enhance the uncaging quantum yield of a photocleavable protecting group.

Photocleavable protecting groups (PPGs) enable the light-induced, spatiotemporal control over the release of a payload of interest. Two fundamental challenges in the design of new, effective PPGs are increasing the quantum yield (QY) of photolysis and red-shifting the absorption spectrum. Here we describe the combination of two photochemical strategies for PPG optimization in one molecule, resulting in significant improvements in both these crucial parameters.