Unparalleled Ease of Access to a Library of Biheteroaryl Fluorophores via Oxidative Cross-Coupling Reactions: Discovery of Photostable NIR Probe for Mitochondria

• Published in: Journal of the American Chemical Society Vol. 138; no. 14; pp. 4730 - 4738
• Main Authors: Cheng, Yangyang, Li, Gaocan, Liu, Yang, Shi, Yang, Gao, Ge, Wu, Di, Lan, Jingbo, You, Jingsong
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 13.04.2016; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Fluorescent Dyes - chemical synthesis; Fluorescent Dyes - chemistry; Hep G2 Cells; Humans; Indazoles - chemical synthesis; Indazoles - chemistry; Luminescent Measurements - methods; Microscopy, Confocal; Mitochondria, Liver - chemistry; Oxidation-Reduction; Physical Sciences; Science & Technology; Thiophenes - chemical synthesis; Thiophenes - chemistry; MOLECULAR DESIGN; IN-VIVO; RECENT PROGRESS; PHOTOPHYSICAL PROPERTIES; TARGETING MITOCHONDRIA; ACTIVATED DELAYED FLUORESCENCE; FIREFLY BIOLUMINESCENCE; INTRAMOLECULAR CHARGE-TRANSFER; SOLID-STATE; AROMATIC-AMINES
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.5b09241

The development of straightforward accesses to organic functional materials through C–H activation is a revolutionary trend in organic synthesis. In this article, we propose a concise strategy to construct a large library of donor–acceptor-type biheteroaryl fluorophores via the palladium-catalyzed oxidative C–H/C–H cross-coupling of electron-deficient 2H-indazoles with electron-rich heteroarenes. The directly coupled biheteroaryl fluorophores, named Indazo-Fluors, exhibit continuously tunable full-color emissions with quantum yields up to 93% and large Stokes shifts up to 8705 cm–1 in CH2Cl2. By further fine-tuning of the substituent on the core skeleton, Indazo-Fluor 3l (FW = 274; λem = 725 nm) is obtained as the lowest molecular weight near-infrared (NIR) fluorophore with emission wavelength over 720 nm in the solid state. The NIR dye 5h specifically lights up mitochondria in living cells with bright red luminescence. Typically, commercially available mitochondria trackers suffer from poor photostability. Indazo-Fluor 5h exhibits superior photostability and very low cytotoxicity, which would be a prominent reagent for in vivo mitochondria imaging.