The Discovery, Development and Demonstration of Three Caged Compounds

An overview of the history, mechanistic aspects and applications is provided for p-hydroxyphenacyl (pHP) and benzoin photoremovable protecting groups, which release biologically important leaving groups upon photolysis with UV light. Also discussed is (7-diethylaminocoumarin-4-yl)methyl (DEACM), a photoremovable protecting group that absorbs visible light. These are followed by the α-keto amides and naphtho- and benzothiophene-2-carboxanilides as caging groups, which eliminate leaving groups via photochemically produced zwitterionic intermediates. Also covered are amino-1,4-benzoquinones, which upon exposure to green and red wavelengths of light photorearrange to an unstable photoproduct that subsequently eliminates leaving groups in aqueous media. Selected examples are given that use these photoremovable protecting (caging) groups for the light-activated release of biologically important substrates under physiological conditions in cells and tissue as practical applications in biology, biochemistry and physiology. These caging groups have found significant applications because their photochemistry is efficient and a single coproduct is formed in addition to the photoreleased substrate.