Mitochondria-Targeting Multifunctional Fluorescent Probe toward Polarity, Viscosity, and ONOO^– and Cell Imaging

Abstract

Abnormal changes occurring in the mitochondrial microenvironment are important markers indicating mitochondrial and cell dysfunction. Herein, we designed and synthesized a multifunctional fluorescent probe DPB that responds to polarity, viscosity, and peroxynitrite (ONOO − ). DPB is composed of an electron donor (diethylamine group) and electron acceptor (coumarin, pyridine cations, and phenylboronic acid esters), in which the pyridine group with a positive charge is responsible for targeting to mitochondria. D-π−A structure with strong intramolecular charge transfer (ICT) and twisted intramolecular charge transfer (TICT) properties give rise to respond to polarity and viscosity. The introduction of cyanogroup and phenylboronic acid esters increases the electrophilicity of the probe, which is prone to oxidation triggered by ONOO − . The integrated architecture satisfies the multiple response requirements. As the polarity increases, the fluorescence intensity of probe DPB at 470 nm is quenched by 97%. At 658 nm, the fluorescence intensity of DPB increases with viscosity and decreases with the concentration of ONOO − . Furthermore, the probe is not only successfully used to monitor mitochondrial polarity, viscosity, and endogenous/exogenous ONOO − level fluctuations but also to distinguish cancer cells from normal cells by multiple parameters. Therefore, as-prepared probe provides a reliable tool for better understanding of the mitochondrial microenvironment and also a potential approach for the diagnosis of disease.

Improved emission performance of benzo[a]phenoxazine in aqueous solution through host–guest interaction

“…3, sixth column). Generally, a positively charged probe would undergo electrostatic interactions with the mitochondrial membrane, 25 thus favoring its localization in the mitochondria. Moreover, the pH of mitochondria was greater than that of lysosomes, so probe 1a with larger p K a targeted mitochondria.…”

Exploration of Novel Meso-C═N-BODIPY-Based AIE Fluorescent Rotors with Large Stokes Shifts for Organelle-Viscosity Imaging

“…Fluorescent rotors for viscosity have attracted increasing attention in recent years and have served as important tools to monitor microenvironmental viscosity changes in biological systems. − An organic small-molecular rotor mainly consists of a fluorophore and a rotation moiety, and its emission is efficiently quenched by the rotation, which can be enhanced in viscous or steric environments through inhibited rotation. − Among intracellular viscosities, the balance of subcellular lysosomal and mitochondrial viscosities was crucial to maintain the normal subcellular physiological activities in their closed systems. Abnormal fluctuations of lysosomal viscosity could cause many diseases, for example, lysosomal storage diseases, inflammation and neurodegenerative diseases, and cardiovascular diseases. − Meanwhile, the variations of mitochondrial viscosity were closely related to atherosclerosis, cellular malignancy, and dysfunctions. − Recently, various fluorescent probes for sensing subcellular viscosity have been constructed by decorating a targeting group to the rotatable fluorophore, − in which morpholines and ammonium/phosphonium salts , were commonly used as targeting groups for lysosomes and mitochondria, respectively. Therefore, the research on small-molecule fluorescent probes for sensing the subcellular viscosity is still an important and hot topic to gain a full understanding of the relationships between subcellular viscosity and related diseases.…”

Design and Screening of Fluorescent Probes Based upon Hemicyanine Dyes for Monitoring Mitochondrial Viscosity in Living Cells

“…7−9 Recently, a water-soluble mitochondria-targeting molecular rotor, ethyl-4-[3,6-bis(1-methyl-4-vinylpyridium iodine)-9H-carbazol-9-yl)]butanoate (BMVC), has been utilized as a means to monitor changes in viscosity during imaging mitochondrial autophagy. 10 Huang et al 11 designed and synthesized a multifunctional fluorescent probe DPB. The D-π-A structure has strong ICT and twisted intramolecular charge transfer (TICT) properties that allow it to respond to polarity and viscosity.…”