Ethynylbenzaldehydes as novel reaction-based “turn-on” fluorescent probes for primary amine detection in solution, vapor, food, proteins, and live cells

Abstract

Amine detection is of great importance as excess volatile amine exposure and increased concentration of biogenic amines in human body can cause adverse effects to human health. Thus, the development of easy-accessible and efficient fluorescent probes for amine detection is of great importance. In this study, we are the first to establish a cascade reaction sequence featuring imine formation followed by 6-endo-dig cyclization reaction for the development of sensitive and selective “turn-on” fluorescent probes toward primary amines by using the ortho-ethynylbenzaldehydes (EBAs) as the reaction site. The corresponding isoquinolinium products generated give a significant red-shifted absorbance change and highly intense “turn-on” fluorescence. Nine EBAs (EBA-1a-1e, EBA-2–5) were designed and synthesized to study the structure-photophysical property relationship (SPPR) for selective primary amine sensing. Our EBAs possessed a highly sensitive response toward primary amines in aqueous conditions within 30 min (LOD as low as 0.45 µM) with tunable absorption (338–430 nm) and emission (410–535 nm), large Stokes shift (up to 115 nm), and high fluorescence quantum yield (up to 0.86). EBA-loaded paper strips were prepared as a portable low cost tool for amine detection in solution, vapor, and food. Fluorogenic protein labelling and in-gel fluorescent imaging were efficiently achieved by using EBAs in which the fluorescence signal was obviously observed by naked eyes under 365 nm UV lamp. Moreover, the favorable membrane permeabilization, low to moderate cytotoxicity, and “turn-on” fluorescent response of EBA-1a-1e and EBA-4–5 allow wash-free live cell imaging. Interestingly, EBA-1a-1e and EBA-4 showed high selectivity to fluorescent imaging of mitochondria.