A Structure-Programmable Palette of Compact Cationic Dyes Enables Predictable Organelle Addressing and Multicolor Mitochondrial Imaging

Cationic pyrylium/pyridinium (Katritzky-type) frameworks have a long history in dye chemistry and have been repeatedly adapted as compact, modular fluorophores for bioimaging. Building on this foundation, we assembled a 20-member library of diversifiable pyrylium/pyridinium salts accessible in one to two steps from readily available precursors, providing a multicolor palette that spans the visible-to-far-red region while maintaining high absorptivity, large Stokes shifts, and bright emission in organic media. In live A549 cancer cells at nanomolar loading, most derivatives rapidly accumulate in mitochondria and show strong colocalization with commercial mitochondrial markers. Importantly, by systematically relating the side-chain structure to calculated lipophilicity, we uncover a practical and predictive localization map: mitochondrial staining is maximized within a narrow cLogP window (ca. 4-6), whereas increased hydrophobicity promotes aqueous aggregation and progressively shifts uptake toward endo/lysosomal compartments. This lipophilicity-governed "address switch" enables organelle destination to be programmed without changing the fluorophore core, providing a practical design guideline for building next-generation chemical imaging tools and functional reporters on pyrylium/pyridinium scaffolds. In addition, the probes can be used for mitochondrial staining in the pathogenic yeast Candida albicans, extending their applicability beyond mammalian cells.