Dan Wang, Zechen Wang, Yahui Li, Yang Song, Youtao Song, and Haibo Yu

College of Environmental Sciences, Liaoning University

Mingyan Zhang

Liaoning Center of Disease Prevention and Control

Abstract

Mitochondria and lysosomes at some pH values can be potential areas for cellular component recycling, virus dissemination and inflammatory response. These actions are closely related to mitochondrial elimination and autophagy in the processes of cell growth and apoptosis; though there are enormous differences in the pH values and functions between them, lysosomes present near mitochondria and mitolysosomes are difficult to distinguish from mitochondria by a single fluorescent probe. To distinguish these organelles, pH fluorescent probes have been designed to indicate pH changes and localization of mitochondrion or lysosome in living cells. While these probes address tracer ability, they do not enable the targeting of mitochondrion and lysosome for pH monitoring simultaneously. Towards this end, we report the development of Rh-BMDZ, a single rhodamine spirolactam fluorescent probe, for the differentiation and pH monitoring of mitochondria and lysosomes. The probe employs benzimidazole, the presence of which decreases the alkalinity and nucleophilicity of the spiro-N atom, thus allowing for the monitoring of mitochondrial pH by exhibiting varying fluorescence intensities based on pH. Additionally, the alkalescent benzimidazole can also attract Rh-BMDZ into lysosomes and emit strong fluorescence in the lysosomal pH range of 4.0–5.5. Owing to the unique 1H-benzo[d]-imidazole structure and properties, Rh-BMDZ with neutral pK_a (6.9) shows distinct fluorescence changes in the pH range from 5.0 to 8.0. Consequently, Rh-BMDZ can simultaneously localize and accumulate in mitochondria and lysosomes, thus facilitating discrimination between mitochondria and lysosomes according to its fluorescence intensity. These excellent properties make Rh-BMDZ a promising probefor simultaneous tracking and pH monitoring of mitochondria and lysosomes in the biomedical and biological fields.

Read the full article here:   80-A single rhodamine spirolactam probe.pdf