A Blue-Absorbing Photolabile Protecting Group for in Vivo Chromatically Orthogonal Photoactivation

Abstract

The small and synthetically easily accessible 7-diethylamino-4-thiocoumarinylmethyl photolabile protecting group has been validated for uncaging with blue light. It exhibits 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 have been implemented in living zebrafish embryos to perform chromatic orthogonal photoactivation of two biologically active species controlling biological development with UV and blue-cyan light sources, respectively.

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

“…Taking into account these results and the spectroscopic properties of 4 (see below), we selected the 4-nitrophenyl moiety for exploring the incorporation of different substituents at the ortho positions of the aromatic ring (CN,F and NO 2 ) with the aim of tuning the photophysical properties of the coumarin chromophore. All the required arylacetonitrile compounds (11)(12)(13)(14)(15) were synthesized, except 2-(2,4,6-trinitrophenyl)acetonitrile (13), which was commercially available.…”

“…After hydrolysis of the ester and decarboxylation by reaction with HCl in a H 2 O/AcOH mixture, the desired arylacetonitrile derivatives were obtained in moderate yields 14 (32%) and 15 (39%). Coumarins 5-9 (Scheme 2) were synthesized in a similar way that compound 4 by reacting 2 with the corresponding arylacetonitrile derivatives (11)(12)(13)(14)(15). All the compounds were isolated by silica column chromatography with moderate to good yields and their purity was assessed by reversed-phase HPLC analysis, revealing a single peak in all cases ( Figure S4).…”

“…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.…”

How to control proteins with light in living systems

“…Clearly, improvements are needed if one wants to precisely monitor expression and stoichiometry in any cellular context. Except for the control of different photosensitive ion channels 72,73 , we are not aware of many examples of multiplexing in the photocontrol of cellular processes [74][75][76] , but this will certainly be one of the future challenges of that nascent field.…”

Ultraviolet light-mediated drug delivery: Principles, applications, and challenges

“…[50] NB derivatives are A C C E P T E D M A N U S C R I P T easy to synthesize. Most of the NB derivatives absorb light between 260 and 380nm[51] while some of the coumarin derivatives absorb light wavelengths as long as 530 nm, which may be more attractive for some biomedical applications [52]. Over…”