Phenothiazine-based fluorescent probes: Molecular engineering, multifunctional applications, and future horizons in biosensing and environmental monitoring

Phenothiazine (PTZ)-based fluorescent probes have emerged as a transformative platform in chemical sensing and bioimaging, offering unparalleled advantages in selectivity, sensitivity, and versatility. Over the past four years (2022–2025), significant advancements in molecular engineering have expanded their applications across diverse fields, from elucidating redox biology to monitoring environmental pollutants. This review systematically summarizes the design principles, mechanisms, and applications of PTZ-based probes, focusing on four key areas: (1) Reactive oxygen and sulfur species detection, including HOCl, H₂O₂, ·OH, H₂S, and biothiols, where PTZ's electron-rich sulfur atom enables selective oxidation or nucleophilic reactions; (2) Environmental pollutant sensing, such as toxic amines, heavy metals (Hg²⁺, CN⁻), and explosives (picric acid), leveraging PTZ's tunable photophysics and analyte-specific reactivity; (3) Lipid droplet (LD) imaging, exploiting PTZ's polarity-sensitive emission for tracking metabolic disorders; and (4) Emerging applications, including formaldehyde and chlorine dioxide detection. We highlight how PTZ's structural flexibility, large Stokes shifts (>100 nm), and resistance to photobleaching address limitations of conventional fluorophores. Furthermore, innovations such as organelle-targeted probes, dual-modal theranostic systems, and aggregation-induced emission (AIE)-active designs are critically evaluated. This work not only consolidates recent breakthroughs but also provides strategic insights for developing next-generation PTZ-based sensors with enhanced biocompatibility, multi-analyte detection capabilities, and clinical translation potential.