Visible Light Absorbing Photoremovable Protecting Groups

M. Juetten
Iowa State University Research Foundation,
United States

Keywords: photocage, protecting group, fluorescent sensor, drug delivery


Photoremovable protecting groups (or “photocages” or “phototriggers”) are light-sensitive chemical moieties that provide control over the release of any number of reagents in a variety of environments. While photocages have important applications in areas such as organic synthesis, photolithography, and light-responsive organic materials, these structures are particularly prized for their ability to trigger in biological systems with high spatial and temporal resolution. The most popular photocages have a common limitation, however, in that they absorb light mostly in the ultraviolent range (UV-light). A photocage designed to use visible light provides several distinct advantages over the currently available UV-light absorbing photocages, including penetration of Pyrex glassware, activation with cheap lamps, greater depth of penetration in biological tissues, limited damage to biological tissue, increased researcher safety, and potential for use of multiple photocage-reagent combinations responsive to different light wavelengths in experimental design. Acting on a recently developed hypothesis, Iowa State researches intelligently designed a class of photocages derived from meso-substituted BODIPY dyes to activate upon irradiation under visible to near IR light (~500-1000 nm). The BODIPY scaffold affords the advantage of simple syntheses, a compact structure with known biological compatibility, and remarkably high extinction coefficients. The photocages have been further functionalized to have high quantum yields of release with irradiation >500 nm and have shown stability in a number of environments, including biological. Typically, the BODIPY dyes are fluorescent, but the fluorescence can be turned off with a quencher, providing an easy way to track the release of a target substrate. With a quencher as a leaving group (thus the BODIPY is fluorescent silent when caged, with turn-on activity after release), photorelease has been demonstrated in cultured Drosophila S2 cells. A variety of other leaving groups have also been demonstrated, showing broad utility of the photocages. Given the visible light absorptivity, these dyes are a clearly superior alternative to currently commercially available photocaging systems, and are applicable to a wide variety of market applications.