Sensing Mechanism of a Fluorescent Probe for Cysteine: Photoinduced Electron Transfer and Invalidity of Excited-State Intramolecular Proton Transfer

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Vol. 124; no. 34; pp. 6920 - 6927
• Main Authors: Tang, Zhe, Bai, Tianxin, Zhou, Panwang
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27.08.2020
• Subjects: A: Spectroscopy, Molecular Structure, and Quantum Chemistry; Cysteine - chemistry; Electron Transport; Fluorescent Dyes - chemistry; Models, Molecular; Molecular Conformation; Photochemical Processes; Protons
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/acs.jpca.0c06171

The abnormal level of cysteine (Cys) in the human body will cause a series of diseases, and the study of the sensing mechanism is of great significance for the design of efficient fluorescent probes. Here, we used time-dependent density functional theory to study the sensing mechanism of a newly synthesized imidazo [1,5-α] pyridine-based fluorescent probe (MZC-AC) for the detection of Cys, which is proposed to be designed based on excited-state intramolecular proton transfer (ESIPT). We first show that the fluorescence quenching mechanism of MZC-AC is due to a nonclassical photoinduced electron transfer (PET) process in which the curve crossing between local excited and charge-transfer states is observed and the acrylate group acts as an electron acceptor. When the acrylate group is replaced by the hydroxyl group due to the reaction between MZC-AC and Cys, the PET is off and a significant fluorescence enhancement of the formed MZC is observed. Our theoretical results indicate that the fluorescence enhancement mechanism of MZC is not based on the ESIPT. The calculated potential energy curve along the proton transfer pathway shows that the electronic energy of MZC-keto is larger than that of MZC-enol. Moreover, the computed emission energy of MZC-enol is closer to the experimental data than that of MZC-keto. The experimentally observed large Stokes shift was ascribed to the intramolecular charge transfer character of the first excited state of MZC. Our theoretical results can explain well the fluorescence behavior of MZC-AC and MZC and invalidate the experimentally proposed ESIPT mechanism of MZC.