Synthesis of quinolyl-pyrrole derivatives as novel environment-sensitive fluorescent probes

• Published in: Journal of photochemistry and photobiology. A, Chemistry. Chemistry., 2019-09, Vol.382, p.111900, Article 111900
• Main Authors: Shinotsuka, Ryo, Oba, Toru, Mitome, Takahiro, Masuya, Takuto, Ito, Satoshi, Murakami, Yukie, Kagenishi, Tomoko, Kodama, Yutaka, Matsuda, Masaru, Yoshida, Takashi, Wakamori, Minoru, Ohkura, Masamichi, Nakai, Junichi
• Format: Article
• Language: English
• Subjects: Absorption spectra; Chemical compounds; Chloroplasts; Cross coupling; Dyes; Electric potential; Environment-sensitive; Fluorescence; Fluorescent indicators; Fluorescent probe; Fluorophores; Membranes; Permittivity; Polarity; Quinoline; Sensitivity; Solvatochromism; Synthesis; Voltage; Voltage-sensitive dye
• ISSN: 1010-6030; 1873-2666
• DOI: 10.1016/j.jphotochem.2019.111900

[Display omitted] •Environment-sensitive fluorescent probes were synthesized.•These dyes possessed a quinolyl-pyrrole core structure.•Strong fluorescence solvatochromism was observed by the obtained dyes.•One of the dyes had high sensitivity to the low polarity environment.•The dye also showed voltage sensitivity. We synthesized novel environment-sensitive fluorophores using a unique fluorogenic core quinolyl-pyrrole (QP, 2-(1H-pyrrol-2-yl)quinoline). QP was obtained from isatins and 2-acetylpyrrole by Pfitzinger quinoline synthesis. Derivatization at the quinoline and pyrrole rings was carried out using the Sonogashira–Hagiwara cross coupling and Vilsmeier–Haack reactions, respectively. The obtained dyes showed strong fluorescence solvatochromism, but their absorption spectra remained nearly unchanged. The introduction of a dimethylaminophenylethynyl moiety at the quinoline side of the QP resulted in a change in the fluorescence color from blue to red within a narrow relative permittivity range of roughly 2–10, demonstrating that the substitution strengthened the sensitivity of the dye to the low polarity environment. The dye also reflected voltage changes across liposomal membranes, showing a 3.7-fold enhanced fluorescence intensity when tested under the same conditions as di-4-ANEPPS, a popular voltage sensitive dye, which only changed its fluorescence intensity by a factor of 1.2. The voltage sensitivity of the dye was calculated to be 2.3%/mV, much larger than that of di-4-ANEPPS (0.13 – 0.18%/mV). These dyes may be utilized for the studies on the activities of neurons or chloroplasts.