Coumarin‐4‐ylmethyl‐ and p‐Hydroxyphenacyl‐Based Photoacid Generators with High Solubility in Aqueous Media: Synthesis, Stability and Photolysis

Abstract

(Coumarin‐4‐yl)methyl (c4m) and p‐hydroxyphenacyl (pHP)‐based compounds are well known for their highly efficient photoreactions, but often show limited solubility in aqueous media. To circumvent this, we synthesized and characterized the two new c4m and pHP‐based photoacid generators (PAGs), 7‐[bis(carboxymethyl)amino]‐4‐(acetoxymethyl)coumarin (c4m‐ac) and p‐hydroxyphenacyl‐2,5,8,11‐tetraoxatridecan‐13‐oate (pHP‐t), and determined their solubilities, stabilities and photolysis in aqueous media. The two compounds showed high solubilities in water of 2.77 mmol L−1±0.07 mmol L−1 (c4m‐ac) and 124.66 mmol L−1±2.1 mmol L−1 (pHP‐t). In basic conditions at pH 9, solubility increased for c4m‐ac to 646.46 mmol L−1±0.63 mmol L−1, for pHP‐t it decreased to 34.68 mmol L−1±0.62 mmol L−1. Photochemical properties of the two PAGs, such as the absorption maxima, the maximum molar absorption coefficients and the quantum yields, were found to be strongly pH‐dependent. Both PAGs showed high stabilities s24h ≥95 % in water for 24 h, but decreasing stability with increasing pH value due to hydrolysis. The present study contributes to a clearer insight into the synthesis, solubilities, stabilities, and photolysis of c4m and pHP‐based PAGs for further photochemical applications when high PAG concentrations are required, such as in polymeric foaming.

Conditionally Activatable Visible-Light Photocages

“…These processes became possible by the development of photoresponsive materials that efficiently convert light into chemical energy. Among photoresponsive materials, photolabile protecting groups (PPGs) or photocages (PCs) play an increasing role in both chemical biology studies and in therapeutic applications. − These photosensitive groups may be used to mask the biological function of small-molecular effectors, − proteins, , nucleotides, , or drugs, − rendering them inactive. Upon light induced removal of these photolabile moieties by irradiation with a suitable wavelength, the activity of the caged substrate is restored.…”

pH dependency of photolabile protection groups used for applications in dynamic structural biology

“…1 is not affected as discussed, while the differences between 3 and 4 are relatively big despite the small structural difference of the hydroxyl group position. Comparing the extinction coefficients of 3 for λmax in pH 3 and 9 conditions an increase can be observed 27 . In Figure 5 an overview of used PPGs is shown to highlight the influences of different pH in the solution to the main absorption wavelength.…”

“…7-Diethylamino-4-methylcoumarin (DEACM) is often chosen in application due to its highly configurable main scaffold. Derivatives with variations of substituents on the ring systems or the nitrogen atom offer flexibility in compound design 27,28 . The DEACM main scaffold is highly sensitive to variations of the pH as it is very prone to hydrogen bonding and protonation.…”

Choose your leaving group: selective photodeprotection in a mixture of pHP-caged compounds by VIPER excitation

“…27 The applications of pHP as a PPG encompass neurobiology, 17,[28][29][30][31][32][33][34][35] enzyme catalysis, where fast uncaging is essential, 17,27,34,[36][37][38] biochemistry, such as in drug-delivery or the release of nucleobases, amines and NAD + , [39][40][41][42] supramolecular chemistry, 43 controlled etching of surfaces, 44 and tissue engineering via hydrogel foams that can be used as scaffolds. 45 There are currently ongoing efforts to increase the quantum yield of release of phenolic LGs such as the amino acid tyrosine. 46 Extending the already vast application range for pHP further, it is shown here that even multiple simultaneously present pHP-SCN isotopologues can be used, which, in conjunction with VIPER, makes product release on demand from a desired pHP-LG combination feasible.…”