Targeted Conversion\nfrom Mitochondria to the Nucleus\nof Hydroxystyrylpyridinium by Introducing Only an Additional <i>o</i>‑Hydroxyl Group

Aromatic cationic groups serve as crucial building blocks\nfor the\ndesign of fluorescent probes targeting both the nucleus and mitochondria.\nTherefore, it is a significant challenge to develop aromatic cation-based\nprobes that accurately image the nucleus without interference from\nmitochondria. However, this also presents an opportunity for rational\ndesign by modifying probes originally targeting mitochondria to redirect\ntheir targeting toward the nucleus. This study showcases the rapid\ndevelopment of a novel nucleus-targeting probe (DHSP) through a targeted\nconversion strategy based on structure modification of hydroxystyrylpyridinium\n(HSP), a well-established two-photon fluorescent probe that targets\nmitochondria. Importantly, DHSP, which is derived exclusively from\nintroducing only an additional <i>o</i>-hydroxyl group into\nHSP, exhibits robust DNA-binding capability comparable to a commercially\navailable nuclear dye 4′,6-diamidino-2-phenylindole (DAPI).\nAs a result, it rapidly enters the nucleus within 5 min and finds\nsuccessful application in two-photon cellular and intravital imaging\nof the nucleus.