Fluorescent Sensors for Hg 2+ Detection Using Biomolecular Recognition: Amino Acids, Peptides, Proteins, DNA, RNA, and Aptamers

ABSTRACT Fluorescence‐based sensing has emerged as a leading method for detecting Hg 2+ because it is sensitive, selective, and allows real‐time monitoring. Building on our previous investigations into the design strategies and photophysical mechanisms of molecular probes for Hg 2+ detection, this review covers different fluorescence sensing strategies that use amino acids, peptides, proteins, DNA, RNA, and aptamers. Sensors based on amino acids such as histidine and cysteine use specific metal‐ligand interactions to modulate fluorescence. Protein‐based sensors detect Hg 2+ by changes in shape and natural fluorescence, while DNA, RNA, and aptamer probes use Thymine‐Hg 2+ ‐Thymine coordination and flexible structures. The review covers photophysical processes involved in probe design, such as Förster resonance energy transfer (FRET), aggregation‐induced emission (AIE), and chelation‐enhanced fluorescence (CHEF). Despite significant progress, challenges like selectivity in complex samples, photobleaching, and long‐term stability persist. Going forward, combining these sensors with nanomaterials, AI‐based analysis, and portable devices could bridge the gap between laboratory analysis and real‐world applications. This integration is expected to drive the development of the next generation of Hg 2+ biosensors for use in food quality monitoring, environmental analysis, medical diagnostics, intracellular sensing, and diverse industries, where mercury monitoring is critical for safety and compliance.