Fine-tuning bromide AIE probes for Hg2+ detection in mitochondria with wash-free staining

Abstract

Mercury ions (Hg²⁺) primarily target mitochondria in the cells. Therefore, the development of novel probes that specifically target mitochondria in the presence of Hg²⁺ is of immense importance. Most previously reported probes that utilize the softness of S, Te, O, and/or N atoms for Hg²⁺ binding often face problems such as fluorescence quenching and off-target signals. In this study, bromide-hydrocarbon pyridinium salts were designed to target the mitochondria and chelate Hg²⁺ via Hg-Br coordination bonds. As a prototype, four aggregation-induced emission (AIE) fluorogens, namely TPP-Br, TPP-Cl, R1, and R2, with a similar D-π-A structure but slight differences in their halogen substituents, were designed. Among them, only TPP-Br achieved the highly selective and sensitive detection of Hg²⁺ by triggering its AIE properties, resulting in remarkable emission enhancement (80-fold), colorimetry, and the Tyndall effect. TPP-Br exhibited high selectivity and sensitivity to Hg²⁺ with a detection limit of 0.35 μM, rapid response time (<10 s), and large Stokes shift of 185 nm. Their interaction modes were studied using a combination of ¹H nuclear magnetic resonance spectroscopy, scanning electron microscopy, fluorescent lifetime decay, and theoretical calculations. TPP-Br exhibited a low emission background in cells, whereas in the presence of Hg²⁺, mitochondria were lit up with wash-free staining. This study provides a powerful tool for accurately diagnosing mercury poisoning-related diseases in mitochondria.

Keywords: Aggregation-induced emission; Hg(2+) detection; Mitochondria-targeting; Wash-free staining.