Hydrogen sulfide detection: Recent advancement and future perspectives towards fluorescence as a versatile Biophysical method

Hydrogen Sulfide (H₂S) is an essential gaseous signaling molecule involved in various physiological processes, including vasodilation, neurotransmission, and anti-inflammatory responses. Accurate detection and quantification of H₂S in biological systems are crucial for elucidating its physiological and pathological roles. Fluorescent probes have emerged as indispensable tools for H₂S detection, offering high sensitivity, specificity, and the ability for real-time and non-invasive monitoring. This review discusses recent advances in the design and development of fluorescent probes for H₂S detection, focusing on their mechanisms, properties, and applications. We explore the different strategies employed in probe design, including reduction-based mechanisms, nucleophilic addition reactions, and cleavage of sulfide bonds. Innovations such as ratiometric probes, two-photon fluorescent probes, and multi-functional probes have significantly enhanced the capabilities of H₂S detection. These advancements have facilitated cellular and subcellular imaging, real-time monitoring in live organisms, and the investigation of H₂S-related pathologies. Despite these progresses, challenges remain, including improving probe selectivity, stability, and biocompatibility, as well as developing methods for accurate quantification in complex biological matrices. Future research directions include designing probes with higher selectivity and sensitivity, integrating advanced computational modeling, and combining fluorescent probes with mass spectrometry for precise quantification. The continued development of sophisticated fluorescent probes will expand our understanding of H₂S biology, offering new insights into its physiological and pathological roles and paving the way for novel therapeutic strategies.