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Ferroptosis is a recently identified form of regulated cell death characterized by iron accumulation and lipid peroxidation. Numerous functions for ferroptosis have been identified in physiological as well as pathological processes, most notably in the treatment of cancer. The intricate balance of redox homeostasis is profoundly altered during ferroptosis, leading to alteration in cellular microenvironment. One such microenvironment is viscosity among others such as pH, polarity, and temperature. Therefore, understanding the dynamics of ferroptosis associated viscosity levels within organelles is crucial. To date, there are a very few reviews that detects ferroptosis assessing reactive species. In this review, we have summarized organelle's specific fluorescent probes that detects dynamics of microviscosity during ferroptosis. Also, we offer the readers an insight of their design strategy, photophysics and associated bioimaging concluding with the future perspective and challenges in the related field. [ABSTRACT FROM AUTHOR]

Functional fluorophores represent an emerging research field, distinguished by their diverse applications, especially in sensing and cellular imaging. After the discovery of quinine sulfate and subsequent elucidation of the fluorescence mechanism by Sir George Stokes, research in the field of fluorescence gained momentum. Over the past few decades, advancements in sophisticated instruments, including super-resolution microscopy, have further promoted cellular imaging using traditional fluorophores. These advancements include deciphering sensing mechanisms via photochemical reactions and scrutinizing the applications of fluorescent probes that specifically target organelles. This approach elucidates molecular interactions with biomolecules. Despite the abundance of literature illustrating different classes of probe development, a concise summary of newly developed fluorophores remains inadequate. In this review, we systematically summarize the chronological discovery of traditional fluorophores along with new fluorophores. We briefly discuss traditional fluorophores ranging from visible to near-infrared (NIR) in the context of cellular imaging and in vivo imaging. Furthermore, we explore ten new core fluorophores developed between 2007 and 2022, which exhibit advanced optical properties, providing new insights into bioimaging. We illustrate the utilization of new fluorophores in cellular imaging of biomolecules, such as reactive oxygen species (ROS), reactive nitrogen species (RNS), and proteins and microenvironments, especially pH and viscosity. Few of the fluorescent probes provided new insights into disease progression. Furthermore, we speculate on the potential prospects and significant challenges of existing fluorophores and their potential biomedical research applications. By addressing these aspects, we intend to illuminate the compelling advancements in fluorescent probe development and their potential influence across various fields. [ABSTRACT FROM AUTHOR]

The intracellular pH (pHi) in organelles, including mitochondria, endoplasmic reticulum, lysosomes, and nuclei, differs from the cytoplasmic pH, and thus maintaining the pH of these organelles is crucial for cellular homeostasis. Alterations in the intracellular pH (ΔpHi) in organelles lead to the disruption of cell proliferation, ion transportation, cellular homeostasis, and even cell death. Hence, accurately mapping the pH of organelles is crucial. Accordingly, the development of fluorescence imaging probes for targeting specific organelles and monitoring their dynamics at the molecular level has become the forefront of research in the last three decades. Among them, ratiometric fluorescent probes minimize the interference from the excitation wavelength of light, auto-fluorescence from probe concentration, environmental fluctuations, and instrument sensitivity through self-correction compared to monochromatic fluorescent probes, which are known as turn-on/off fluorescent probes. Small-molecular ratiometric fluorescent probes for detecting ΔpHi are challenging yet demanding. To date, sixty-two ratiometric pH probes have been reported for monitoring internal pH alterations in cellular organelles. However, a critical review on organelle-specific ratiometric probes for pH mapping is still lacking. Thus, in the present review, we report the most recent advances in ratiometric pH probes and the previous data on the role of mapping the ΔpHi of cellular organelles. The development strategy, including ratiometric fluorescence with one reference signal (RFRS) and ratiometric fluorescence with two reversible signals (RFRvS), is systematically illustrated. Finally, we emphasize the major challenges in developing ratiometric probes that merit further research in the future. [ABSTRACT FROM AUTHOR]

Mitochondria are the powerhouse of the cell and function at pH ∼8.0. Dysfunctions of mitochondria, includes mitochondrial damage, leading to pH alteration. Hence, researchers aim to develop efficient pH probes for tracking mitochondrial pH dynamics. Herein, we developed a PET‐based fluorescent probe for pH monitoring during mitochondrial dysfunctions. Three derivatives were synthesized with a variable spacer's length in pentacyclic pyridinium fluorophores (PM‐C2, PM‐C3, and PM‐C6). An efficient electron transfers from the receptor (tertiary amine) was observed in the case of PM‐C2 compared to the other two derivatives. This PET process was inhibited when tertiary amine was protonated in acidic pH. However, PM‐C3 showed minimal fluorescence intensity at similar conditions and almost negligible change in case of PM‐C6, suggesting poor PET process for both the derivatives. Furthermore, DFT/TD‐DFT quantum chemical calculation well supported this optical phenomena and PET process. Biocompatible, photostable, and mitochondria‐specific PM‐C2 could monitor pH dynamics during mitochondrial damage which were engulfed by lysosome, also known as mitophagy. This mitophagy process were induced by rapamycin and starvation, which can be monitored by turn‐on fluorescence enhancement. This process was further validated by tracking Parkin‐protein translocation from cytoplasm to damaged mitochondria using our developed probe. [ABSTRACT FROM AUTHOR]

This review explains various strategies for developing fluorescent probes to detect reactive carbonyl species (RCS). There are several mono and diacarbonyls among 30 varieties of reactive carbonyl species (RCSs) so far discovered, which play pivotal roles in pathological processes such as cancer, neurodegenerative diseases, cardiovascular disease, renal failure, and diabetes mellitus. These RCSs play essential roles in maintaining ion channel regulation, cellular signaling pathways, and metabolisms. Among RCSs, carbon monoxide (CO) is also utilized for its cardioprotective, anti‐inflammatory, and anti‐apoptotic effects. Fluorescence‐based non‐invasive optical tools have come out as one of the promising methods for analyzing the concentrations and co‐localizations of these small metabolites. There has been a tremendous eruption in developing fluorescent probes for selective detection of specific RCSs within cellular and aqueous environments due to their high sensitivity, high spatial and temporal resolution of fluorescence imaging. Fluorescence‐based sensing mechanisms such as intramolecular charge transfer (ICT), photoinduced electron transfer (PeT), excited‐state intramolecular proton transfer (ESIPT), and fluorescence resonance energy transfer (FRET) are described. In particular, probes for dicarbonyls such as methylglyoxal (MGO), malondialdehyde (MDA), along with monocarbonyls that include formaldehyde (FA), carbon monoxide (CO) and phosgene are discussed. One of the most exciting advances in this review is the summary of fluorescent probes of dicarbonyl compounds. [ABSTRACT FROM AUTHOR]