Stabilization of a ring-opened rhodamine probe via multi-noncovalent interactions for the dual-mode detection of nitazenes

Abstract

Nitazene opioids, representing a potent class of emerging synthetic substances, have emerged as a significant threat to public health and biosafety worldwide. However, due to their chemical inertness and structural diversity, conventional sensing mechanisms cannot achieve sensitive and on-site detection. Herein, we report rhodamine B hydrazide (RhB-I), a probe which could be engineered to stabilize in its ring-opened form through multi-noncovalent interactions with nitazenes, enabling their sensitive colorimetric-fluorescent dual-mode detection. The RhB-I probe exhibited superior detection performance, including a desirable limit of detection (LOD, 1.9 ng mL⁻¹), rapid response (4 s), robust anti-interference capability against 22 potential interfering substances, and successful extension to detect eight additional nitazene derivatives. Notably, the RhB-I-based sensing platform enabled accurate nitazene detection in biological matrices including saliva, hair, blood and urine, with saliva and urine requiring no pretreatment, as well as in e-cigarette oil and an authentic specimen (tobacco). This work overturns the traditional paradigm that rhodamine probes rely on the analyte's chemical reactivity, providing a novel strategy for detecting chemically inert small molecules and expanding the application scope of rhodamine-based sensing.