Recent Advances in Small Molecule‐Based Intracellular pH Probes

Abstract

Intracellular pH plays an important role in many biological and pathological processes. Small‐molecule based pH probes are found to be the most effective for pH sensing because of ease of preparation, high sensitivity, and quick response. They have many advantages such as small perturbation to the functions of the target, functional adaptability, cellular component‐specific localization, etc. The present review highlights the flurry of recent activity in the development of such probes. The probes are categorized based on the type of fluorophore used like quinoline, coumarin, BODIPY, rhodamine, indolium, naphthalimide, etc., and their analytical performance is discussed.

Near-infrared rhodol dyes bearing salicylaldehyde moieties for ratiometric pH sensing in live cells during mitophagy and under hypoxia conditions

“…The pH level within a cell exerts a crucial role in the cell's functions and pathological processes including cell metabolism, homeostasis, apoptosis, proliferation, enzyme activity, ion transport, drug resistance, and endocytosis. [1][2][3][4] The cells maintain appropriate pH values inside different organelles for their functions and normal physiology. [1][2][3][4] Abnormal intracellular pH is often associated with pathophysiologic states and can result in cell dysfunction, and diseased states including cancer, neurodegenerative and cardiopulmonary diseases.…”

“…[1][2][3][4] The cells maintain appropriate pH values inside different organelles for their functions and normal physiology. [1][2][3][4] Abnormal intracellular pH is often associated with pathophysiologic states and can result in cell dysfunction, and diseased states including cancer, neurodegenerative and cardiopulmonary diseases. [1][2][3][4] Accurate and precise determination of intracellular pH fluctuations with self-calibration capability will offer an insightful understanding of the physiological and pathological developments closely associated with intracellular pH variations.…”

“…[1][2][3][4] Abnormal intracellular pH is often associated with pathophysiologic states and can result in cell dysfunction, and diseased states including cancer, neurodegenerative and cardiopulmonary diseases. [1][2][3][4] Accurate and precise determination of intracellular pH fluctuations with self-calibration capability will offer an insightful understanding of the physiological and pathological developments closely associated with intracellular pH variations. [4][5][6][7][8][9][10][11][12][13][14] Rhodol dyes have gained a lot of attention in fluorescence sensing and imaging applications due to excellent and distinctive photophysical properties including excellent photostability, high quantum yields, high molar absorption coefficient, solubility in a variety of solvents, and good pH sensitivity.…”

“…[4][5][6][7][8][9][10][11][12][13][14] Rhodol dyes have gained a lot of attention in fluorescence sensing and imaging applications due to excellent and distinctive photophysical properties including excellent photostability, high quantum yields, high molar absorption coefficient, solubility in a variety of solvents, and good pH sensitivity. [1][2][3][15][16][17][18][19] Several rhodol dyes have been synthesized using different strategies such as replacing the central oxygen atom with a C, N, B, Si, S, P, Se, or Te atom, the introduction of electron donating groups to the N atom, and enhancement of p-conjugation by introducing different moieties to the xanthene core for near-infrared emission to prevent photodamage to cells and tissues. 1,3,[15][16][17][18][19] Although a variety of rhodol-based probes have been reported, many of them are based on a single wavelength, and often encounter systematic bias due to excitation wavelength fluctuations and the concentration variations of the intensity-based probes in live cells.…”

Ratiometric i-Motif-Based Sensor for Precise Long-Term Monitoring of pH Micro Alterations in the Nucleoplasm and Interchromatin Granules

“…To uncover molecular mechanisms of acidification-driven pathologies, pH imaging with a high spatiotemporal resolution is needed. Available techniques rely on the use of microelectrodes, NMR spectroscopy, fluorescence microscopy, etc. − Available molecular devices for optical imaging include genetically encoded indicators, small-molecule organic dyes, and DNA nanomachines based on pH-responsive cytosine-reach sequences that form intercalated motifs (iMs). − This sensor toolbox is being constantly expanded to meet the growing interest in pH gradient aberrations at subcellular levels. − …”