Coumarinylmethyl Caging Groups with Redshifted Absorption

Abstract

The small and synthetically easily accessible coumarinylmethyl backbone has been modified to generate a family of photolabile protecting groups with redshifted absorption. We relied on introducing electron‐donating groups in the 7 position and electron‐withdrawing groups in the 2‐, and 2‐ and 3 positions. In particular, we showed that the diethylamino‐thiocoumarylmethyl and the diethylamino‐coumarylidenemalononitrilemethyl are relevant for uncaging with cyan light. They both exhibit a significant action cross section for uncaging in the 470–500 nm wavelength range and a low light absorption between 350 and 400 nm. These attractive features are favorable to perform chromatic orthogonal photoactivation with UV and blue‐cyan light sources, respectively.

Optochemical Control of Biological Processes in Cells and Animals

“…[1e,214] Notable examples for red-shifted nitrobenzene derivatives are bisstyrylthiophene (see Figure 13), ANBP (see Figure 29), and nitrodibenzofuran (NDBF). [215] Long-wavelength activated coumarin groups include thiocoumarin, [45] dicyanocoumarin, [216] and 3-acrylamide-modified aminocoumarin, for example, 32 (see Figure 32). [217] …”

π-Expanded coumarins: synthesis, optical properties and applications

“…124,125 Coumarins, particularly those of 4-hydroxymethyl derivatives are known to undergo photolysis (Scheme 56). A molecule of biological interest is "caged" by the covalent attachment of a photo-labile protecting group onto a functional group of the molecule.…”

Development of Green/Red-Absorbing Chromophores Based on a Coumarin Scaffold That Are Useful as Caging Groups

“…10 This coumarinylmethyl platform is easy to synthesize and amenable to structural modifications allowing the attachment of the molecule to be caged through a variety of bonds, including esters, amides, carbamates or carbonates. 1bc In recent years, thionation of the carbonyl group of the lactone has been used to shift the absorption maximum, which allowed to trigger uncaging with blue-light in different systems, as reported by Jullien, 8,11 and Costa 12 groups.…”

“…8,13 This modification has also been incorporated in coumarin-caged cyclic morpholino oligonucleotides by Deiters, Chen and collaborators for sequential gene silencing, 14 as well as by us in a caged cyclic RGD peptide for applications in photocontrolled targeted therapies.…”

“…With this idea in mind, we decided to choose the N,N-diethylamino(coumarin 4-yl)methyl moiety as a starting point since the diethylamino electron-donating group (EDG) at position 7 causes larger red shifts in the absorption spectrum than other EDG substituents such as alkoxy. 8 Moreover, polar groups such as carboxylates could be eventually appended to the aniline moiety to increase, if necessary, the aqueous solubility of the caged compound without significantly compromise the spectral properties of the chromophore. 9 Recent studies have also demonstrated that modification of N,N-dialkyamino substituents at the coumarin's 7-position can be used to improve the photophysical properties of fluorescent dyes such as brightness, photostability and quantum yield.…”