Synthetic cannabinoids constitute the second largest and most diverse category of new psychoactive substances (NPS) available on the market, while achieving their highly sensitive and interference-resistant on-site detection is of great significance for safeguarding public health and social stability. Xinjiang Key Laboratory of Trace Chemical Substances Sensing, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, has recently conducted systematic research in areas such as the fluorescent probes design for synthetic cannabinoids and the related mechanisms exploration (Angew. Chem. Int. Ed. 2025, 64, e202423576; Anal. Chem. 2025, 97, 9819; Anal. Chem. 2025, 97, 11589; ACS Omega 2025, 10, 14306), as well as strategies for identifying synthetic cannabinoids by integrating SERS technology with machine learning (Sensor. Actuat. B Chem. 2025, 441, 138024; Anal. Chem. 2025, 97, 10812).

The substituent design and photophysical property manipulation are of paramount importance in fluorescent probe design, particularly crucial for chemically inactive molecules that lack reactive functional groups, such as synthetic cannabinoids. To address these challenges, the team from the Xinjiang Key Laboratory of Trace Chemical Substances Sensing at the Xinjiang Technical Institute of Physics and Chemistry has successfully developed an organic fluorescent probe design strategy based on the through-space charge transfer (TSCT). Specifically, leveraging a pyrimido[4,5-d]pyridazine group as the fluorophore, three 5-phenylpyrimido[4,5-d]pyridazin-2-yl)phenol derivative probes were rationally designed with tailored donor-acceptor substituents of R group at the para-position of the benzene ring. By precisely modulating non-covalent interactions and TSCT between the probe and JWH-018, our team significantly enhanced both their binding energy and the optical signal contrast after detection, resulting in a distinct ratiometric fluorescent response (blue-to-green emission shift). The optimized probe, 2-(5-phenyl-8-(4-(trifluoromethyl)phenyl)pyrimido[4,5-d]pyridazin-2-yl)phenol (DPTF), achieved an ultra-low detection limit of 2.16 nmol/mL for JWH-018 with a naked-eye detection limit of 101 nmol/mL, and exhibited excellent selectivity and anti-interference against 18 potential interfering illicit drugs. To facilitate real-world applications, the researchers constructed a sponge-based DPTF-probe-embedded sensing chip and integrated it into a portable self-developed Drugs Analyst, enabling the on-site rapid detection of JWH-018 in complex matrices, such as E-liquid, urine, artificial saliva and local sewage. Overall, this study advances the development of sensing materials based on noncovalent interactions, and deepens our understanding of intermolecular TSCT photophysical mechanisms, while providing available approaches for drug inspection and criminal scene investigation.

This work was published in the journal Analytical Chemistry under the title “Electron-Donating/Accepting Group Modulation Enhanced Fluorescent Sensing of Synthetic Cannabinoid JWH-018 via Through-Space Charge Transfer”, Yali Feng, a joint master’s student from Xinjiang University, and Dr. Luyan Yang from Xinjiang Technical Institute of Physics and Chemistry, are the co-first authors, while Senior Engineer Jinhui Yang from Xinjiang University and Prof. Baiyi Zu from Xinjiang Technical Institute of Physics and Chemistry are the co-corresponding authors. This work was supported by the National Natural Science Foundation of China, the International Science and Technology Cooperation Program of Xinjiang, the Key Research and Development Program of Xinjiang, the Natural Science Foundation of Xinjiang, the Tianshan Innovation Team Plan, the Youth Innovation Promotion Association of CAS, and the Tianchi Talent Program.

Pyrimido[4,5-d]pyridazine derivative probe design and modulation strategy against JWH-018