A Water-Soluble Near-Infrared Ratiometric Fluorescent Probe for Selective Detection of Monoamine Oxidase A Activity

Monoamine oxidase A (MAO-A) plays a crucial role in neurotransmitter metabolism and oxidative stress regulation and is implicated in various neurological disorders and cancer progression. However, its detection is hindered by high structural similarity to its isoform MAO-B and limitations of conventional methods, which exhibit poor specificity, low sensitivity, and spectral crosstalk. To overcome these challenges, Cyma, a water-soluble near-infrared ratiometric probe engineered on a cyanine platform, is developed. Cyma integrates a sulfonated cyanine core for improved water solubility, a clorgyline-derived recognition unit to confer MAO-A selectivity, and a propylamine moiety to enable enzymatic activation. Upon interaction with MAO-A, Cyma undergoes a specific 1,6-elimination and Smiles rearrangement, yielding a distinct fluorescence shift from 805 nm to 740 nm. Cyma demonstrates excellent selectivity for MAO-A over MAO-B and exhibits high sensitivity (detection limit: 0.0035 μg mL⁻¹), with a strong linear correlation between ratiometric fluorescence intensity and MAO-A concentration. Furthermore, excellent biocompatibility and MAO-A detection ability of Cyma are demonstrated in SH-SY5Y cells. These findings establish Cyma as a powerful tool for selectively detecting MAO-A activity, offering significant potential for disease diagnosis, therapeutic monitoring, and intraoperative imaging.