Synthetic cannabinoids (SCs) are a rapidly evolving class of new psychoactive substances that pose serious threats to public health and forensic control. Due to their structural diversity, high potency, and frequent concealment in complex matrices such as e-liquids and plant materials, rapid on-site identification remains challenging. Traditional laboratory methods, including liquid chromatography–tandem mass spectrometry, provide accurate identification but require bulky instruments, professional operators, and time-consuming procedures. Therefore, developing rapid, portable, and highly specific optical screening methods for synthetic cannabinoids is of great significance for public security and forensic analysis.

To address this challenge, a research team led by Prof. Xincun Dou, Prof. Chengzhi Gu, and Prof. Baiyi Zu proposed a “steric-engineered thermodynamic gating” strategy for the chemical-class discrimination of synthetic cannabinoids. Their findings, published in Angewandte Chemie International Edition, demonstrate that rational regulation of molecular packing can create metastable supramolecular aggregates that selectively respond to target SCs while resisting interference from non-target substances.

In this study, researchers designed a naphthalimide-based fluorescent probe, NAP-Boc, by introducing a bulky tert-butoxycarbonyl group at the 4-phenylamine-N position. This steric group frustrates overly compact molecular packing and drives the probe to form a quenched, metastable H-aggregate. In the absence of target analytes, the aggregate remains in a stable “off” state with low background fluorescence. Upon exposure to suitable synthetic cannabinoids, multivalent non-covalent interactions, including π–π stacking, hydrogen bonding, and hydrophobic effects, trigger aggregate disassembly and switch on fluorescence.

Using EDMB-PINACA as a representative synthetic cannabinoid, the sensing system achieved rapid response within less than one second and a detection limit of 4.7 μM. More importantly, the metastable aggregate acted as a thermodynamic filter: structurally mismatched interferents were unable to overcome the disassembly barrier, whereas target SCs with appropriate headgroup and tail features could selectively unlock the aggregate. This mechanism effectively resolves the long-standing trade-off between aggregate stability and sensing sensitivity in supramolecular fluorescence detection.

Furthermore, the researchers integrated the probe into a 3D-printed portable detection platform equipped with a 365 nm ultraviolet excitation source and a silicon-wafer sensing substrate. The device enabled visual detection of EDMB-PINACA in practical matrices, including e-liquids, flower petals, and green tea. In these complex samples, the target analyte generated a bright fluorescence signal, while blank matrices and non-target interferents produced negligible responses, demonstrating strong anti-interference capability and practical potential for field screening.

In a related study published in Talanta, the team further developed an analyte-templated aggregate remodeling strategy based on an aggregation-induced emission-active coumarin–naphthalimide dyad. This system converted the shared hydrophobic and aromatic-rich features of diverse SCs into a visible yellowish-green-to-cyan fluorescence change, achieving rapid broad-spectrum screening of 22 SC variants.

These studies were supported by the National Natural Science Foundation of China, the Key Research and Development Program of Xinjiang, the S&T Guidance Program, the Tianshan Innovation Team Plan, the International Science and Technology Cooperation Program of Xinjiang, and the Tianchi Talent Plan.

Figure:Schematic illustration of the steric engineered thermodynamic gating strategy and the detection mechanism for synthetic cannabinoid. (Image by the research team)