Excited-state intramolecular-proton-transfer-based fluorescent probe for the rapid detection of peroxynitrite in Alzheimer's disease models.

Abstract

Alzheimer's disease (AD) is a prevalent neurodegenerative disease that involves continuous pathophysiological processes and causes irreversible brain damage. Increasing evidence indicates that peroxynitrite (ONOO) plays a vital role in the pathogenesis of AD by mediating neurotoxicity and neuroinflammation. Therefore, developing practical tools for the precise, rapid, and sensitive detection of ONOOlevels is essential for elucidating the multiple pathological processes associated with AD. HBT-PON, a novel fluorescent probe that incorporates a benzothiazole (HBT) derivative as the fluorescent signaling moiety and a 1,1-diphenylhydrazine moiety as the recognition unit, was prepared in this study and employed for the excited-state intramolecular-proton-transfer-based detection of ONOOin AD. HBT-PON is readily synthesized and exhibits excellent selectivity and sensitivity for ONOO(limit of detection: 4.7&#xa0;nM) and responds rapidly (<5&#xa0;s). Moreover, it is an ideal tool for visualizing ONOOin cells, zebrafish, and AD-related biological models owing to its low cytotoxicity and excellent biocompatibility. Furthermore, this probe can effectively monitor dynamic changes in ONOOlevels in an AD cell model and mouse brain tissue, thereby providing a robust method for comprehensively examining the relationship between ONOOand the pathology of AD.