Red‐to‐Near‐Infrared Emitting PyrrolylBODIPY Dyes: Synthesis, Photophysical Properties and Bioimaging Application

Near‐infrared (NIR) fluorophores with characteristics such as deep tissue penetration, minimal damage to the biological samples, and low background interference, are highly sought‐after materials for in vivo and deep‐tissue fluorescence imaging. Herein, series of 3‐pyrrolylBODIPY derivatives and 3,5‐dipyrrolylBODIPY derivatives have been prepared by a facile regioselective nucleophilic aromatic substitution reaction (SNAr) on 3,5‐halogenated BODIPY derivatives (3,5‐dibromo or 2,3,5,6‐tetrachloroBODIPYs) with pyrroles. The installation of a pyrrolic unit onto the 3‐position of the BODIPY chromophore leads to a dramatic red shift of both the absorption (up to 160 nm) and the emission (up to 260 nm) in these resultant 3‐pyrrolylBODIPYs with respect to that of the BODIPY chromophore. Their further 5‐positional functionalization provides a facile way to fine tune their photophysical properties, and these resulting dipyrrolylBODIPYs and functionalized pyrrolylBODIPYs show strong absorption in the deep red‐to‐NIR regions (595–684 nm) and intense NIR fluorescence emission (650–715 nm) in dichloromethane. To demonstrate the applicability of these functionalized pyrrolylBODIPYs as NIR fluorescent probes for cell imaging, pyrrolylBODIPY 6 a containing mitochondrion‐targeting butyltriphenylphosphonium cationic species was also prepared. It selectively localized in mitochondria of HeLa cells, with low cytotoxicity and intense deep red fluorescence emission. Series of pyrrolylBODIPYs were regioselectively synthesized through SNAr reactions between pyrroles and 2,3,5,6‐tetrachloroBODIPYs or 3,5‐dibromoBODIPY. The resulting pyrrolylBODIPYs with 5‐Cl substituent can be further functionalized to give a series of red‐to‐near‐infrared emitting dyes and a mitochondrial localization fluorescent probe was further developed.