Highlighting Nuclear DNA in Live Cells With an Activatable BODIPY–Hoechst Conjugate

The development of fluorescent probes to image the nucleus of live cells with high contrast and negligible photodamage is essential to overcome the limitations of existing nuclear stains and enable the visualization of chromatin dynamics with minimal perturbations on cellular functions. To this end, we synthesized a molecular construct integrating a borondipyrromethene (BODIPY) fluorophore and a Hoechst ligand within its covalent skeleton. In organic solvents, the Hoechst ligand has negligible influence on the photophysical properties of the BODIPY component. However, the characteristic fluorescence of the latter chromophore is completely suppressed in aqueous environments. Binding of the Hoechst ligand to double‐stranded DNA inhibits the quenching pathway to activate fluorescence. As a result, our fluorophore–ligand construct allows the imaging of nuclear DNA in live cells with no background fluorescence from the extranuclear space under excitation wavelengths in the green portion of the electromagnetic spectrum, ensuring minimal autofluorescence and photodamage.