Ludovic Jullien

Efficient tools for controlling molecular functions with exquisite spatiotemporal resolution are much in demand to investigate biological processes in living systems. Here we report an easily synthesized caged dexamethasone for photo‐activating cytoplasmic proteins fused to the glucocorticoid receptor. In the dark, it is stable in vitro as well as in vivo in both zebrafish ( Danio rerio ) and Xenopus sp , two significant models of vertebrates. In contrast, it liberates dexamethasone upon UV illumination, which has been harnessed to interfere with developmental steps in embryos of these animals. Interestingly, this new system is biologically orthogonal to the one for photo‐activating proteins fused to the estrogen ERT receptor, which brings great prospect for activating two distinct proteins down to the single cell level.

Donor‐acceptor Stenhouse adducts (DASAs) are reversibly photoswitchable dyes, which are able to interconvert between a red/NIR absorbing triene‐like state and a colorless cyclic state. Although optically attractive for multiple applications, their low solubility and lack of photoswitching in water impede their use in aqueous environments. We developed water‐soluble DASAs based on indoline as donor and methyl, or trifluoromethyl, pyrazolone‐based acceptors. In acetonitrile, photophysical analysis and photochemical studies, accounted with a three‐state kinetic model, confirmed the reversible photoswitching mechanism previously proposed. In water, the colorless cyclic state is a thermodynamic sink at neutral pH values. In contrast, in acidic conditions, we observed a fast scrambling of DASAs’ end‐group resulting in the in situ formation of Stenhouse salts (StS), which are in turn capable of reversible photoswitching. We believe that this unexpected result is of interest not only for the future design of DASAs with improved stability, but also for further development and applications of StS as photoswitchable probes.