The dicyanoisophorone Scaffold: A versatile platform for near-infrared, large stokes shift fluorescent probes in sensing and bioimaging

Abstract

Dicyanoisophorone (DCI) derivatives are an emerging platform for NIR, large‑Stokes‑shift fluorescent probes. We synthesize recent advances in DCI probe design, photophysics, and applications, with emphasis on structure–property rules and translational use. These characteristics make DCI-based probes highly suitable for demanding applications in complex biological systems and in vivo imaging, overcoming limitations associated with traditional fluorophores such as autofluorescence interference and limited tissue penetration. This review summarizes the significant advancements in the design and application of functional fluorescent probes based on the DCI scaffold reported in recent literature. Compared with BODIPY and rhodamine (often narrow Stokes shifts) and cyanines/hemicyanines (photostability and quantum‑yield limitations), DCI derivatives offer NIR emission with large Stokes shifts driven by robust ICT, supporting deep imaging with reduced crosstalk. We systematically categorize these probes based on their target analytes, encompassing reactive oxygen species (ROS), reactive nitrogen species (RNS), reactive sulfur species (RSS), reactive carbonyl species (RCS) including carbon monoxide (CO), cellular microenvironment parameters (viscosity, pH, polarity), environmental pollutants (metal ions, organic contaminants), enzyme activities (hydrolases, oxidoreductases), and specific subcellular organelles (lipid droplets, lysosomes) or biomolecules (amino acids, proteins, amyloid aggregates). Key design strategies, including analyte-triggered modulation of ICT, PET, FRET, ESIPT, and TICT mechanisms, as well as aggregation-induced emission (AIE) and specific binding interactions, are discussed. The diverse applications highlighted herein, ranging from fundamental cell biology studies, in vivo imaging in various disease models (e.g., cancer, neurodegeneration, diabetes, inflammation, liver injury), environmental monitoring, and food safety analysis to potential diagnostics and theranostics, underscore the remarkable versatility and growing impact of DCI-based probes. This comprehensive overview aims to provide valuable insights and guide future research in the rational design and application of advanced NIR fluorescent probes with large Stokes shifts for biomedical and analytical sciences.