Dynamic molecular crystals with inherent conformational flexibility could offer a promising platform for fluorescence sensing by exhibiting analyte-specific conformational and fluorescence responses. Herein, we materialize this notion through a donor–acceptor (D–A) molecule featuring a D-D-A-D-D backbone, with a thiadiazolopyridine acceptor flanked by carbazole donors. The molecule self-assembles into crystalline nanofibers endowed with a dynamic conformational twisting capability, which arises from the synergistic effect of the unique A group’s electrostatic repulsion and the spatial freedom provided by the alkyl chains. This dynamic nature is validated by a rapid and reversible emission toggle between yellow and red upon cycling exposure to and evaporation of solvents like n-hexane. Crucially, the dynamic nanofibers also allow analyte binding to drive specific conformational changes, thereby perturbing intermolecular interactions and yielding distinct fluorescence responses. These responses, including variations in kinetics and intensity, enable the multiplexed discrimination of amines with high selectivity and sensitivity against humidity and background volatile organic compounds. The dynamic nanofibers function robustly in complex environments such as hair spray and car exhaust, and exhibit high sensitivity toward amine-type drugs, with detection limits as low as 1 ng for methamphetamine and fentanyl. This work underscores the potential of dynamic molecular crystals to deliver substantially expanded signal diversity for advanced sensing applications.

