Lighting Up Biology: GFP-Inspired Fluorescent Probes for Sensing and Imaging

Green fluorescent protein (GFP) chromophore analogues are derived from the core structure of the GFP chromophore, p-hydroxybenzylideneimidazolidinone (HBDI). Appealing and readily tunable, HBDI analogues have been adapted for a range of sensing and imaging applications, as is the focus of this perspective. First, common methods for their synthesis will be presented, followed by a discussion of the unique structural and photophysical properties of HBDI derivatives. Structural modifications resulting in tunable photophysical properties will then be highlighted. Finally, this perspective will present representative examples of the use of HBDI analogues for sensing and imaging in biological sciences. This perspective highlights key design strategies, modes of activation, and the associated advantages, limitations, and opportunities of HBDI analogues, illustrated by representative applications in studying biomolecules, cellular processes, and disease biomarkers.