Novel Meso-Benzothiazole-Substituted BODIPY-Based AIE Fluorescent Rotor for Imaging Lysosomal Viscosity and Monitoring Autophagy

Abstract

Meso-substituted boron dipyrromethenes (BODIPYs) provide a potential and innovative strategy for the synergistic construction of aggregation-induced emission (AIE) probes and fluorescent rotors for monitoring cellular viscosity changes, which play critical roles in understanding the function of viscosity in its closely associated diseases. Therefore, for the first time, a BODIPY-based fluorescent probe (1) with a rotatable meso-benzothiazole group was rationally designed and synthesized, showing both good viscosity-responsive and AIE properties. Probe 1 through direct linkage with the thiazole group, showed nearly no emission in low viscous solvents; however, a strong emission at 534 nm appeared and increased gradually with the increase in viscosity, attributing to the efficient restriction of the rotatable meso-benzothiazole group. The intensity (log I 534) displayed a good linear relationship with viscosity (log η) in the viscous range of 0.59–945 cP in methanol/glycerol mixtures. Interestingly, 1 showed enhanced emission at 534 nm in 70% water compared to pure acetonitrile due to the aggregation-induced inhibited rotations. Cellular imaging suggested that 1 could successfully sense lysosomal viscosity changes induced by lipopolysaccharide, nystatin, low temperature, and dexamethasone in living cells, which could be further applied in autophagy monitoring by tracing viscosity changes. As a comparison, its analogue 2 directly linking with the phenyl group showed no viscosity-responsive or AIE properties. Therefore, for the first time, we reported a meso-benzothiazole-BODIPY-based fluorescent rotor with AIE and lysosomal viscosity-responsive properties in nervous cells, which was further applied in monitoring autophagy, and this work thus could provide an innovative strategy for the design of potential AIE and viscosity-responsive probes.

Recent Development of Advanced Fluorescent Molecular Probes for Organelle-Targeted Cell Imaging

“…BDHA can be used to image the viscosity and OCl- level of HeLa cells and zebrafish. In 2022, Shi et al designed and synthesized a BODIPY-based fluorescence probe ( 55 , Scheme 6 ) with a rotatable meso-benzothiazole group, showing both good viscosity responsiveness and AIE properties [ 165 ]. This probe can sense lysosomal viscosity changes induced by lipopolysaccharides, nystatin, a low temperature, and dexamethasone in living cells, which can be further applied in autophagy monitoring via tracking viscosity changes.…”

Development of meso-Five-Membered Heterocycle BODIPY-Based AIE Fluorescent Probes for Dual-Organelle Viscosity Imaging

“…29 Recently, a meso-benzothiazole BODIPY has been investigated by us, which showed good viscosity response in lysosomes without the morpholine ring and AIE in 70% aqueous solution. 31 Based on our previous studies, we believe that the five-membered heterocyclic ring at the meso position of the BODIPY core could work as a good rotation group and a potential targeting group. However, exploration of structure− property relationships between their responsive/AIE properties and five-membered heterocyclic ring remains still rare.…”

“…[4][5][6][7]20 Meanwhile, boron dipyrromethenes (BODIPYs), as an excellent emerging fluorophore, could potentially serve as a good candidate for viscosity imaging, attributing to its easily modified structures, tunable spectroscopic properties, and relatively high fluorescence quantum yields. 21−23 Among the reported fluorescent probes for viscosity, except the commonly used C�C 24−26 or C� C 27,28 bonds as the rotation positions, some novel mesosubstituted BODIPY derivatives have aroused more interest recently, such as CF 3 , 29,30 benzothiazole, 31 C�O, 32,33 and phenyl groups. 34−38 It is worth to mention that some other meso-five-membered ring-substituted BODIPYs have also been reported for their spectroscopic properties or as fluorescent sensors for oxidants and metal ions.…”

Triphenylamine-equipped 1,8-naphthaolactam: a versatile scaffold for the custom design of efficient subcellular imaging agents

“…Most commercial and published fluorescence bioprobes, such as anthocyanins, 25 fluoresceins, 26 rhodamines, 27 and boron dipyrromethenes, 28 belong to the aggregation-caused quenching (ACQ) type fluorophore, and the aggregation-induced emission (AIE) ones are flourishing as the next-generation fluorophore. [29][30][31][32][33][34][35] However, it is worth noting that both ACQ-and AIE-active fluorescence bioprobes still suffer from concentration-dependent erroneous signal reading in practical bioimaging, even leaving aside the above four requirements. [36][37][38][39][40][41] As such, new types of ideal fluorescent bioprobes should be driven by efforts rooted in innovative concepts and, therefore, increase their efficacy and practicability in bioimaging.…”