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

Abstract

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 2<i>H</i>-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 <b>3l</b> (FW = 274; λ_em = 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 <b>5h</b> specifically lights up mitochondria in living cells with bright red luminescence. Typically, commercially available mitochondria trackers suffer from poor photostability. Indazo-Fluor <b>5h</b> exhibits superior photostability and very low cytotoxicity, which would be a prominent reagent for <i>in vivo</i> mitochondria imaging