Development of new Photocages
Photocages are protecting groups that cleave from a molecule of interest when exposed to light, thereby liberating the molecule of interest in its active form. This is shown pictorally below:
Photocages are particularly useful for the release of biomolecules into tissues. Using brief flashes of light, large concentrations of the biomolecule can be released very rapidly. This allows biochemists to study the rates of very fast biological responses (such as muscle contraction and neural signaling) to the 'concentration jump' of the biomolecule.
The most widely used photocages suffer from serious drawbacks that complicate the studies in which they are employed. These limitations include the photogeneration of highly reactive and absorbing by-products, relatively slow release of the bioagent on exposure to light, and poor solubility in water.
A major thrust in our laboratory is the development of new photocages that do not possess these drawbacks. Our first success in this area came with the development of the 'ketoprofenate' photocage (reference 12 on the publication page). This photocage works by photochemical decarboxylation of 1 to give a benzylic carbanion (2), which then eliminates the leaving group.
We have successfully released of a variety of leaving groups from the ketoprofenate cage including carboxylic acids, alcohols, and drug molecules. The release rates are 3 to 7 orders of magnitude greater for our photocage than for the most widely used photocages in current use. These molecules have excellent solubity in water, which is important if they are to be used in biological systems.