[1,3]Oxazine-based NIR molecular switches: Hydrochromic behavior, viscosity sensing, and targeted cell imaging

Molecular switches based on [1,3] oxazine show distinctive properties between their ring-closed and ring-opened forms (RCF and ROF), differing in conjugation length, charge, hydrophilicity, and optical behavior. These features enable low background interference and organelle-selective targeting, which are highly valuable for intracellular fluorescence imaging. However, related studies remain scarce. In this work, two near-infrared (NIR) molecular switches, BOA-1 and BOA-2, were designed using [1,3] oxazine as the core scaffold. They exhibit excellent hydrochromic behavior with a 300 nm absorption red-shift, supporting applications in water-ink painting. BOA-1 shows a pKa of 8.78 and specific endoplasmic reticulum (ER) targeting in living cells. It also presents specific fluorescence activation toward viscosity, with two non-overlapping emission peaks separated by 230 nm, ensuring high anti-interference performance and quantitative ratiometric detection. Notably, BOA-1 shows great potential for Alzheimer's disease (AD) diagnosis and therapeutic monitoring. This work first reports the NIR fluorescent sensing of [1,3] oxazine derivative toward intracellular microenvironments, which provides a promising platform for disease diagnosis and further biological fluorescence sensing applications.