Molecular Design of Single-Molecule Schiff Base Fluorescent Probes for Detection of Al 3+ and Bio Imaging Applications: A Comprehensive Review of In Vitro and In Vivo Studies

Schiff base derivatives are among the most extensively studied classes of compounds due to their straightforward synthesis, strong coordination affinity toward metal ions, and highly tunable photophysical characteristics. The π-conjugated systems often incorporate donor-acceptor frameworks that enable pronounced fluorescence modulation upon interaction with specific analytes, making them particularly suitable for selective chemical sensing and bioimaging applications. Among various metal ions, Al3+ has attracted significant attention because of its biological relevance and potential toxicity in environmental and biological systems. However, selective detection of Al3+ remains challenging due to its strong hydration and interference from competing metal ions. To address this, fluorescent probes have been developed that exhibit high selectivity and sensitivity toward Al3+ through mechanisms. Initially, these probes were widely explored for environmental monitoring, particularly for detecting Al3+ contamination in water and soil samples. Recently, the same sensing phenomena have been extended into biological systems, where these probes have demonstrated significant potential for cancer cell imaging. In vitro studies show efficient cellular uptake and selective fluorescence response in cancer cells, while in vivo models confirm their capability for real-time imaging in living organisms. The aim of this review is to summarize recent advances in single-molecule Schiff base fluorescent probes for selective Al3+ detection and to highlight their advanced applications in bioimaging, both in vitro and in vivo, emphasizing future biomedical prospects. We hope this review will provide valuable insights and assist researchers in further advancing this field.