Water-Catalyzed Excited-State Proton-Transfer Reactions in 7‑Azaindole and Its Analogues

Abstract

The mechanism of the water-catalyzed excited-state proton-transfer (ESPT) reaction for 7-azaindole (<b>7AI</b>) has long been investigated, but there are some controversial viewpoints. Recently, owing to the superiority of sensing biowaters in proteins by a <b>7AI</b> analogue, 2,7-diazatryptophan, it is timely to reinvestigate water-catalyzed ESPT in <b>7AI</b> and its analogues in an attempt to unify the mechanism. Herein, a series of <b>7AI</b> analogues and their methylated derivatives were synthesized to carry out a systematic study on p<i>K</i>_a, p<i>K</i>_a*, and the associated fluorescence spectroscopy and dynamics. The results conclude that all <b>7AI</b> derivatives undergo water-catalyzed ESPT in neutral water. However, for those derivatives with −H (<b>7AI</b>) and a electron-donating substituent at C(3), they follow water-catalyzed ESPT to form an excited N(7)–H proton-transfer tautomer, T*. T* is rapidly protonated to generate an excited cationic (TC*) species. TC* then undergoes a fast deactivation to the N(1)–H normal species in the ground state. Conversely, protonation in T* is prohibited for those derivatives with an electron-withdrawing group at the C(2) or C(3) or with the C(2) atom replaced by an electron-withdrawing nitrogen atom (N(2) in, e.g., 2,7-diazatryptophan), giving a prominent green T* emission. Additional support is given by the synthesis of the corresponding N(7)–CH₃ tautomer species, for which p<i>K</i>_a* of the cationic form, that is, the N(7)–CH₃N­(1)–H⁺ species, is measured to be much greater than 7.0 for those with electron-donating C(3) substituents, whereas it is lower than 7.0 upon anchoring electron-withdrawing groups. For <b>7AI</b>, the previously missing T* emission is clearly resolved with a peak wavelength at 530 nm in the pH interval of 13.0–14.3 (<i>H</i>_– 14.2)