A Baldwin-favored Cyclization Inspires the Development of Fluorogenic Polymethine Dyes for Bioimaging

Fluorescence imaging is an invaluable tool to study biological processes, and fluorogenic dyes are crucial to enhance cell permeability and target intracellular structures with high specificity. Polymethine dyes are vitally important fluorophores in single-molecule localization microscopy and in vivo imaging, but their use in live cells has been limited by high background fluorescence and low membrane permeability. Here, we present a general strategy to transform polymethine compounds into fluorogenic dyes by implementing a 5-exo-trig ring-closure. This method provides access to bright, fluorogenic polymethine dyes with emissions across the visible and near-infrared spectrum.