Dithiophene chemosensor for ultrasensitive intracellular detection of Al3+: Design, DFT analysis, and ESIPT-PET mechanisms

Abstract

Metal ions play essential roles in living cells, yet their biological functions, which depend on intracellular concentrations, are not fully understood. Therefore, there is a critical need for efficient and sensitive methods to monitor metal ion levels in biological systems. Herein, we report the development of a fluorescent probe, 2-hydroxy-1-naphthaldehyde-(dithiophen-2-yl)ethanediamine (NS), for the precise and sensitive detection of intracellular Al³⁺ at concentrations as low as 3.92 × 10⁻⁸ M. The probe features a bifunctional thienyl ethanol ligand, consisting of two thiophene rings and a hydroxyl group, which forms stable coordination with Al³⁺. This interaction modifies the electron allocation within the ligand, suppressing the excited-state intramolecular proton transfer (ESIPT) mechanism and significantly increasing fluorescence intensity. Notably, in the presence of Al³⁺, compared to other ions, the fluorescence intensity of NS at 452 nm increases by 77-fold, with an exceptional sensitivity and selectivity for Al³⁺. Furthermore, the hydroxyl group enhances the probe’s solubility and stability in aqueous solutions, making it highly effective for intracellular detection of Al³⁺ in prostate cancer RM-1 cells. The response mechanism is further investigated through ¹H NMR and DFT studies, revealing the contributions of ESIPT, photoinduced electron transfer (PET), and CN isomerization to the probe’s fluorescence behavior. This work provides a promising and advanced tool for ionobiology, opening new avenues for research into metal ion-related biological processes.