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

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.