Sequential Uncaging with Green Light can be Achieved by Fine‐Tuning the Structure of a Dicyanocoumarin Chromophore

Abstract

We report the synthesis and photochemical properties of a series of dicyanocoumarinylmethyl (DEAdcCM)‐ and dicyanocoumarinylethyl (DEAdcCE)‐based photocages of carboxylic acids and amines with absorption maximum around 500 nm. Photolysis studies with green light have demonstrated that the structure of the coumarin chromophore as well as the nature of the leaving group and the type of bond to be photocleaved (ester or carbamate) have a strong influence on the rate and efficiency of the uncaging process. These experimental observations were also supported by DFT calculations. Such differences in deprotection kinetics have been exploited to sequentially photolyze two dicyanocoumarin‐caged model compounds (e.g., benzoic acid and ethylamine), and open the way to increasing the number of functional levels that can be addressed with light in a single system, particularly when combining dicyanocoumarin caging groups with other photocleavable protecting groups, which remain intact under green light irradiation.

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

“…Recently, we have demonstrated that both the structure of the coumarin chromophore and the nature of the leaving group have a strong influence on the rate and efficiency of the uncaging process. 21 Indeed, the incorporation of a methyl group at the 4-position of dicyanocoumarinylmethyl (DEAdcCM) derivatives led to new dicyanocoumarinylethyl (DEAdcCE)-photocleavable protecting groups that can be removed upon green light irradiation more efficiently from the corresponding caged carboxylic acids and amines. 21 This result can be attributed to the higher stability of the secondary carbocation intermediate generated upon photoheterolysis of the C-O bond in the corresponding caged compounds.…”

“…21 Indeed, the incorporation of a methyl group at the 4-position of dicyanocoumarinylmethyl (DEAdcCM) derivatives led to new dicyanocoumarinylethyl (DEAdcCE)-photocleavable protecting groups that can be removed upon green light irradiation more efficiently from the corresponding caged carboxylic acids and amines. 21 This result can be attributed to the higher stability of the secondary carbocation intermediate generated upon photoheterolysis of the C-O bond in the corresponding caged compounds. Taking into account these precedents, we decided to synthesize the caged model compound 28 (Scheme 4) with the aim of comparing its photolysis with that of the non-methylated analogue (25) at reflux, 69% (2 steps i + j); k) first, 10 + NEt 3 in anhydrous ACN/DCM 1:1 2 h RT, then…”

“…A solution of HCl in 1,4-dioxane (4 M, 2.5 mL, 10 mmol) was added to 22 21 (1.5 g, 4.92 mmol) in absolute ethanol (120 mL). The reaction mixture was heated at 90ºC for 20 h and evaporated under vacuum.…”

“…The uncaging quantum yield for coumarin derivatives 25 and 28 was estimated as previously described. 21 Briefly, 1.7 mL of 20 M solutions of the compounds were irradiated in a 1 x 1 cm quarz cuvette at 505 nm using a LED lamp. The irradiance was determined as 1.05 x 10 -7 Einstein/s by actinometry with Aberchrome 540.…”

Coumarin Photocaging Groups Modified with an Electron‐Rich Styryl Moiety at the 3‐Position: Long‐Wavelength Excitation, Rapid Photolysis, and Photobleaching

“…[10] In the development of new PPGs,t hey are expected to have long-wavelength absorption that leads to deeper tissue penetration and matches the common laser wavelengths. [19] In addition, it is worth mentioning that besides the absorption wavelength and uncaging efficiency,t he competitive absorption by the photolysis byproducts also affects the application of PPGs,e specially for high-concentration or thick samples because of the inner filtering of light rapidly attenuates the valid light intensity, [20] which significantly prolongs the uncaging time and decreases the overall conversion. Among them, the coumarin-based photocaging groups attract much attention because of the rapid photolysis and large two-photon (TP) absorption cross-section.…”