Structural Transformation of the 2‐(p‐Aminophenyl)‐1‐hydroxyinden‐3‐ylmethyl Chromophore as a Photoremovable Protecting Group

Abstract

Photoremovable protecting groups (PPGs) have attracted much attention not only in the field of organic synthesis but also in biology and materials science because of the spatiotemporally controlled release of various functional molecules upon photolysis. In this study, a new PPG, the 2-(p-aminophenyl)-1hydroxyinden-3-ylmethyl (pAPHi) chromophore, is designed and synthesized for the efficient and fast release of functional molecules with high conversion yields. The photolysis of caged benzoic acid with the pAPHi chromophore in dimethyl sulfoxide released benzoic acid in 96 % yield, with a decomposition quantum yield of 13 %. A high quantum yield of 51 % was observed with the clean formation of benzoic acid (94 % yield) in methanol. Transient absorption spectroscopic analyses clarified the generation of an intermediate carbocation as well as its reactivity.

Two-photon uncaging of bioactive compounds: Starter guide to an efficient IR light switch

“…[196] Pyridinium moieties were also reported to undergo photochemical cleavage, [197] and were used in an antenna-sensitized 2PU system. [198] It is worth highlighting that several more photocleavable structures [1] including BODIPY, [140,141] fluorenes, [142] bimanes, [199] hydroxyinden-3ylmethyls, [200] xanthenes [201] and methylene blue derivatives [202] have been reported in literature, but have neither been developed for nor tested under 2PE, which opens more avenues in terms of molecular engineering of 2P cages.…”

Development of a Two-Photon-Responsive Chromophore, 2-(p-Aminophenyl)-5,6-dimethoxy-1-(hydroxyinden-3-yl)methyl Derivative, as a Photoremovable Protecting Group

“…20 The pAPI chromophore, however, showed a very small 2P absorption cross section in the NIR region with the uncaging efficiency of δ 2 < 0.5 GM at 680 nm, which prevents its application to biological studies. 15,20,26 Therefore, a higher 2P cross section in the biological window is required because pAPI-PPG shows high uncaging quantum yields. In this study, we synthesized and characterized new caged benzoic acids 12a,b, in which electron-donating groups (EDG) such as methoxy groups were introduced at the C5 and C6 positions of the pAPI structure.…”

“…Notably, the photochemical quantum yields of decomposition of 12a and 12b were 0.73 and 0.74, respectively, which were significantly higher than those reported previously for caged compound A (entry 1 in Table 2). 20 Products derived from the chromophore moiety were not identified because of the complex mixtures. After 30% conversion, a slight decrease in photoreactions of 12a and 12b was observed (Figures S3c and 3d).…”

“…The quenching of carbocation by DMSO is reported to form the corresponding sulfonium ion. 44 Similarly, the transient absorption spectrum of 12b showed a positive absorption S8) (18 GM at 720 nm), 45 was used as a reference to determine the 2P cross section of compounds 12a,b. Figure 7a,c shows the time profiles of the photoreactions of 12a,b, respectively, at wavelengths of 690−720 nm.…”

“…An emerging approach to achieve NIR light-induced reactions is the use of simultaneous two-photon (2P) excitation. Using the 2P excitation, the release of bioactive molecules can not only be triggered by light (650–1350 nm), which provides deeper penetration and less toxicity to cells but can also be controlled with high three-dimensional spatial resolution. − A crucial parameter for evaluating the 2P excitation process is the 2P uncaging efficiency (δ 2 ), which is defined as the multiplication of the 2P cross section (σ 2 in GM, 1 GM = 10 –50 cm 4 s photon –1 molecule –1 ) and photochemical quantum yield (Φ u ) for the uncaging reaction. An ideal caged compound for biological studies should possess a 2P uncaging efficiency greater than 0.5 GM. ,− Examples of 2P-responsive caged compounds are listed in Figure b. ,− …”