Unexpected Acid‐Triggered Formation of Reversibly Photoswitchable Stenhouse Salts from Donor‐Acceptor Stenhouse Adducts

Abstract

Donor-acceptor Stenhouse adducts (DASAs) are reversibly photoswitchable dyes, which are able to interconvert between a red/NIR absorbing triene-like state and a colorless cyclic state. Although optically attractive for multiple applications, their low solubility and lack of photoswitching in water impede their use in aqueous environments. We developed water-soluble DASAs based on indoline as donor and methyl, or trifluoromethyl, pyrazolone-based acceptors. In acetonitrile, photophysical analysis and photochemical studies, accounted with a three-state kinetic model, con-firmed the reversible photoswitching mechanism previously proposed. In water, the colorless cyclic state is a thermodynamic sink at neutral pH values. In contrast, in acidic conditions, we observed a fast scrambling of DASAs' endgroup resulting in the in situ formation of Stenhouse salts (StS), which are in turn capable of reversible photoswitching. We believe that this unexpected result is of interest not only for the future design of DASAs with improved stability, but also for further development and applications of StS as photoswitchable probes.

First-in-Class Selective Inhibitors of the Lysine Acetyltransferase KAT8

“…Each compound containing the exocyclic double bond was obtained as a single geometric isomer, except for compound 20, obtained as a 3:1 (Z/E) mixture, in line with a previous report. 36 We assigned the geometry of the double bond for each compound to Z based on NMR experiments, which are in line with earlier studies executed on numerous 4-arylidene Nphenyl-3-substituted-5-pyrazolones indicating the Z geometry as the favored one for this type of compounds. 30,36,37,39,41 Chemical−physical data and elemental analyses for all newly synthesized final compounds 1−17 and 19−43 are reported in Tables S1 and S2 (Supporting Information), respectively.…”

“…36 We assigned the geometry of the double bond for each compound to Z based on NMR experiments, which are in line with earlier studies executed on numerous 4-arylidene Nphenyl-3-substituted-5-pyrazolones indicating the Z geometry as the favored one for this type of compounds. 30,36,37,39,41 Chemical−physical data and elemental analyses for all newly synthesized final compounds 1−17 and 19−43 are reported in Tables S1 and S2 (Supporting Information), respectively. Highperformance liquid chromatography (HPLC) traces for the final…”

“…Moreover, we investigated the influence of bulkier substitutions on the C3 of the 5-pyrazolone ring by replacing the methyl group with isopropyl (33), phenyl (34), and benzyl (35) moieties. Finally, we applied various modifications to the benzoic acid portion, by either changing the position of the carboxylic group from para to meta (36) or replacing it with various amides (37−41), sulfonic acid (42), or sulfonamide (43) functions.…”

“…In contrast, the introduction of a benzyl group at the C3 position of the 5pyrazolone ring provided compound 35 that retained the selectivity over KAT3B and KAT2B but decreased the potency toward KAT8 (Table 2). Finally, moving the carboxyl group from para to meta position led to a slight decrease in KAT8 inhibitory potency (36), while replacing it with amides (37− 41), sulfonic acid (42) or suldfonamide (43) groups led to a more significant potency decrease, especially in the cases of derivatives 39 and 41 (Table 2).…”

Acidochromism of donor–acceptor Stenhouse adducts in organic solvent

“…These data suggest that, upon addition of acid, cyclization of the DASAs occurs similarly to changing the polarity of the medium. However, the presence of resonance H 8 indicates that the keto tautomer is formed, rather than the enol tautomer, 17 commonly observed upon photoisomerization in other media.…”