Family of BODIPY Photocages Cleaved by Single Photons of Visible/Near-Infrared Light.

Photocages are light-sensitive chemical protecting groups that provide external control over when, where, and how much of a biological substrate is activated in cells using targeted light irradiation. Regrettably, most popular photocages (e.g., o-nitrobenzyl groups) absorb cell-damaging ultraviolet wavelengths. A challenge with achieving longer wavelength bond-breaking photochemistry is that long-wavelength-absorbing chromophores have shorter excited-state lifetimes and diminished excited-state energies. However, here we report the synthesis of a family of BODIPY-derived photocages with tunable absorptions across the visible/near-infrared that release chemical cargo under irradiation. Derivatives with appended styryl groups feature absorptions above 700 nm, yielding photocages cleaved with the highest known wavelengths of light via a direct single-photon-release mechanism. Photorelease with red light is demonstrated in living HeLa cells, Drosophila S2 cells, and bovine GM07373 cells upon ∼5 min irradiation. No cytotoxicity is observed at 20 µM photocage concentration using the trypan blue exclusion assay. Improved B-alkylated derivatives feature improved quantum efficiencies of photorelease ∼20-fold larger, on par with the popular o-nitrobenzyl photocages (ÎµΦ = 50-100 M-1 cm-1), but absorbing red/near-IR light in the biological window instead of UV light.

BODIPY-derived photoremovable protecting groups unmasked with green light.

Photoremovable protecting groups derived from meso-substituted BODIPY dyes release acetic acid with green wavelengths >500 nm. Photorelease is demonstrated in cultured S2 cells. The photocaging structures were identified by our previously proposed strategy of computationally searching for carbocations with low-energy diradical states as a possible indicator of a nearby productive conical intersection. The superior optical properties of these photocages make them promising alternatives to the popular o-nitrobenzyl photocage systems.

Self-immolative phthalate esters sensitive to hydrogen peroxide and light.

Self-immolative aryl phthalate esters were conjugated with cleavable masking groups sensitive to light and hydrogen peroxide. The phthalate linker releases the fluorescent dye 7-hydroxycoumarin upon exposure to light or H2O2, respectively, leading to an increase in fluorescence. The light-sensitive aryl phthalate ester is demonstrated as a pro-fluorophore in cultured S2 cells.

Self-immolative aryl phthalate esters.

We report that aryl phthalate esters are robust self-immolative linkers. This linker is easy to conjugate and releases output phenols upon cleaving a fluoride-sensitive mask to yield a benign phthalic acid byproduct, making these linkers potentially useful as fluoride sensors and promising for use in biological and materials applications.