Design and Expeditious Synthesis of Quinoline‐Pyrene‐Based Ratiometric Fluorescent Probes for Targeting Lysosomal pH

Abstract

Intracellular pH plays a significant role in many pathological and physiological processes. A series of quinoline‐pyrene probes were synthesized in one‐step fashion through an oxonium‐ion‐triggered alkyne carboamination sequence involving C−C, C−O and C−N bond formation for intracellular pH sensing. The quinoline‐pyrenes showed significant red shifts at low pH. Fluorescence lifetime decay measurements of the probes showed decreases in lifetime at pH 4. The probes showed excellent selectivity in the presence of various potential interfering agents such as amino acids and cations/anions. Furthermore, the probes were found to show completely reversible emission behaviour in the window between pH 4 and 7. A morpholine‐substituted quinoline‐pyrene probe efficiently stained lysosomes with high Pearson correlation coefficients (0.86) with Lysotracker Deep Red DND‐99 as a reference. A co‐localization study of the probe with Lysotracker DND‐99 showed selective intracellular targeting and a shift in fluorescence emission due to acidic lysosomal pH.

Comparison of two diphenyl polyenes as acid‐sensitive additives during the biodegradation of a thermoset polyester polyurethane coating

“…There are several classes of highly π‐conjugated chromophores suitable for studying pH changes with biological systems. The most common are xanthene (Mohamed et al, 2020), boron dipyrromethene (BODIPY) (Qiu et al, 2018) and pyrene (Hande et al, 2020) dyes. Xanthene dyes and their derivatives are useful for measuring the intracellular pH of living cells due to their varying intensities of fluorescence at different acidities (Martineau et al, 2017; Zhou et al, 2013).…”

Novel Dual-Organelle-Targeting Probe (RCPP) for Simultaneous Measurement of Organellar Acidity and Alkalinity in Living Cells

“…We ,, and others − ,− have previously developed a series of lysosome-targeting fluorescent probes for the study of lysosomal activity. In our present study, two fluorophores (rhodamine and coumarin) were selected to construct a broad pH probe.…”

“…For the determination of the lysosomal pH, two types of lysosomal markers are employed, including weak basic amines (e.g., neutral red, acridine orange) and LysoTracker probes, the latter demonstrating the capacity to selectively accumulate in the lysosome. , Nonetheless, all of the previously reported probes, for both lysosomes − and mitochondria, − have limitations primarily associated with fluorescence intensity alterations in the respective organelle. Recently, we reported a series of novel fluorescent probes (LysoProbes and Superior LysoProbes) with the capacity for monitoring lysosomal pH, which are an improvement over commercially available lysosomal markers (e.g., LysoTracker) as fluorescent signals are both stable and highly selective.…”

TMSOTf-Mediated Formal [4 + 2] Cycloaddition–Retro-aza-Michael Cascade of Vinylogous Carbamates for the Synthesis of Highly Fluorescent Pyridocarbazoles

“…The Sonogashira coupling reaction was also used to synthesize the morpholine-based carbazole 22e with a good yield. Since morpholine is known for the selective labeling of lysosomes, 15 carbazole 22e can be potentially used for selective lysosomal location in cell-imaging studies.…”