Fluorescent probe molecule P and its Zn 2+ complex: sensing mechanism elucidation via theoretical approaches

Abstract Zinc ions (Zn 2+ ) are essential for numerous physiological and pathological processes, making their accurate detection critical for biological research and medical diagnostics. In this work, we conducted a systematic theoretical investigation of fluorescent probe molecule P and its Zn 2+ complex to elucidate the underlying Zn 2+ sensing mechanism. Using density functional theory (DFT), we characterized the conformational transition, molecular interaction, and electronic structure changes of probe P upon Zn 2+ coordination. Key findings revealed that Zn 2+ binding induced a 180°→0° change in the N(67)-C(2)-C(9)-N(68) dihedral angle of probe P, with strong electrostatic attraction and weak van der Waals forces dominating the P–Zn 2+ interaction. The S 0 –S 1 electronic transition of probe P was a typical π - π * process, while the complex exhibited an obvious charge-transfer (CT) transition from the probe to Zn 2+ , leading to a red-shifted fluorescence emission (theoretical: 435 nm→541 nm; experimental: 460 nm→560 nm). Average Local Ionization Energy (ALIE) and Dual Descriptor Potential (DDP) analyses identified the two N atoms of probe P as the key electrophilic reaction sites for Zn 2+ coordination. Electron Localization Function (ELF) analysis further clarified the nature of the P–Zn 2+ bonding interaction. Our theoretical results are in excellent agreement with experimental data, providing a fundamental molecular-level understanding of the Zn 2+ sensing behavior of probe P. This work lays a theoretical foundation for the rational design of high-performance ratiometric fluorescent probes for Zn 2+ detection with enhanced selectivity and sensitivity.