A novel lysosome‐localized fluorescent probe with aggregation‐induced emission without alkalinizing effect

Abstract

Herein, a novel small molecule probe, tetraphenylethylene-cystein (TPE-Cys), was rationally designed and developed for the intracellular lysosome localization. The combination of tetraphenylethylene and cysteine serve as a novel strategy for lysosome-targeting, with significant aggregation-induced emission increases with the proportion of water by as high as 25-folds. Biofluorescence imaging experiments show that the probe TPE-Cys has a good colocalization effect with the commercially available lysotracker red, with a Pearson correlation coefficient of 0.91. In addition, we also demonstrate that TPE-Cys has good light stability. TPE-Cys, as a neutral compound, is free of alkalinizing effect when applied in lysosome localization. Moreover, molecular dynamics simulations and density function theories are employed to explore the detailed aggregation process and the mechanism of TPE-Cys aggregation in water solution. The mechanism of lysosome localization of probe TPE-Cys was explained by cellular endocytosis process and the formation of larger particle in the more acidic environment of lysosomes. This work not only demonstrates an efficient strategy for the construction of fluorescent probes for lysosome localization, but also indicates that they are promising as live cell imaging tools.

Theoretical Insights into the Luminescence and Sensing Mechanisms of N,N′-Bis(salicylidene)-[2-(3′,4′-diaminophenyl)benzthiazole] for Copper(II)

“…Geometry optimizations of BTS and its complex with Cu­(II) in the S 0 state and S 1 state were implemented using the density functional theory (DFT) method and time-dependent DFT (TDDFT) method, , respectively. Previous studies have proven that the TDDFT method is a useful tool to describe the hydrogen bonding of possible hydrogen bond systems in the excited states; the Becke’s three-parameter hybrid exchange functional with the Lee–Yang–Parr gradient-corrected correlation (B 3 LYP functional) and CAM-B 3 LYP functional is the appropriated functional and basis set for the organic molecular structure optimization and energy calculations. − As the accuracy of a TDDFT calculation is strongly dependent on the functionals, it is essential that TDDFT results are validated by comparing the experimental data prior to a detailed interpretation for the electronic spectra. Here, a test with a series of functionals, such as B3LYP, LC-B3LYP, cam-B3LYP, HSE06, PBE0, and M06-2X, was performed to confirm the proper functional for spectral simulations, and cam-B3LYP was chosen as the functional throughout due to its satisfied consistence with experimental values.…”

Tetraphenylethylene-Incorporated Macrocycles and Nanocages: Construction and Applications

“…Raju and Lin 50 synthesized (Scheme 2) a [2]catenane, 37, wherein one of two macrocycles contains a TPE unit. This [2]catenane demonstrated a reversible selfassembly-induced AIE phenomenon in both aqueous solution and the solid state. Later in 2020, Zeng, Zhao, and coworkers 51 synthesized (Scheme 2) two series of fluorescencetunable macrocycles, namely, two-TPE-unit-incorporated, 38− 43, and three-TPE-unit-incorporated, 44−49, macrocycles.…”

“…Tetraphenylethylene (TPE), as a propeller-like aggregation-induced emission (AIE) chromophore, has attracted considerable attention because of its potential applications as fluorescent probes, , bioimaging agents, − and chemosensors and in imaging and circularly polarized luminescence (CPL) . In addition, the low cost and facile preparation of TPE derivatives have facilitated the considerable increase in research activity into TPE-based molecules and nanomaterials.…”

Molecular to Supramolecular Self-Assembled Luminogens for Tracking the Intracellular Organelle Dynamics

“…The issues related to hydrophobicity, quenched emission in the aggregated state, and the lack of long-term photostability of the molecular probes are circumvented by employing either charged, highly emissive water-soluble probes or by using water-dispersible molecular self-assembled structures (Figure ). − , The bulky terminal substituents and twisted molecular geometry reduce the nonradiative π–π stacking interactions in the molecular aggregates. , Further, the covalent functionalization with hydrophilic/amphiphilic units has been proved to be an effective strategy to enhance the water dispersibility of the π-conjugated fluorophores in the aggregated state. − The highlighting features of the water-dispersible supramolecular self-assembled probes used for imaging of different organelles are summarized in Table .…”

“…Thus, a thoughtful design strategy such as the twisted molecular structures and incorporation of the bulky terminal substituents is desired to circumvent the challenges of nonradiative deactivations in the self-assembled structures (Figure ). ,,− …”