Releasing bioactive molecules in specific subcellular
locations
from the corresponding caged precursors offers great potential in
photopharmacology, especially when using biologically compatible visible
light. By taking advantage of the intrinsic preference of COUPY coumarins
for mitochondria and their long wavelength absorption in the visible
region, we have synthesized and fully characterized a series of COUPY-caged
model compounds to investigate how the structure of the coumarin caging
group affects the rate and efficiency of the photolysis process. Uncaging
studies using yellow (560 nm) and red light (620 nm) in phosphate-buffered
saline medium have demonstrated that the incorporation of a methyl
group in a position adjacent to the photocleavable bond is particularly
important to fine-tune the photochemical properties of the caging
group. Additionally, the use of a COUPY-caged version of the protonophore
2,4-dinitrophenol allowed us to confirm by confocal microscopy that
photoactivation can occur within mitochondria of living HeLa cells
upon irradiation with low doses of yellow light. The new photolabile
protecting groups presented here complement the photochemical toolbox
in therapeutic applications since they will facilitate the delivery
of photocages of biologically active compounds into mitochondria.