An EuL13 with multi-recognition site used as luminescent biosensors for efficiently monitoring exercise therapy for depression.

Depression is a mental disorder characterized by high mortality and recurrence rates, with diagnosis primarily relying on various scales and lacking a gold standard. Neurotransmitters such as dopamine (DA), 5-hydroxytryptamine (5-HT), epinephrine (E), and norepinephrine (NE) are established biomarkers for depression. Therefore, there is a significant need to develop real-time, sensitive sensors for these compounds. Due to the complexity of biological environments, improving the sensitivity of biosensors remains a critical challenge in this field. To enhance sensor sensitivity, we introduced pyridyl groups-capable of forming π-π stacking, cation-π and hydrogen bonding interactions with these biomarkers-onto β-diketone ligands, which can undergo nucleophilic interaction with amino groups. The resulting ligands were then coordinated with lanthanide ions through directed self-assembly, forming single-nuclear lanthanide sensors with multiple reactive sites. The mononuclear structure improves the sensor's solubility, compared with the benzene-ring-based sensor EuL23, the pyridine-incorporated sensor EuL13, featuring additional interaction sites, reduces the detection limit for DA from 12.71 nM to 4.49 nM and shortens the response time from 0.41 s to 0.25 s. The enhanced intermolecular interaction between EuL13 and the biomarker is verified by 1H NMR and NOESY spectroscopy. Furthermore, we applied this sensor to evaluate the intervention effects of moderate intensity continuous training (MICT) in alleviating depression-like behaviors in chronic unpredictable mild stress (CUMS)-induced mice. When hippocampal and medial prefrontal cortex (mPFC) homogenates were added to the EuL1₃ solution, the luminescence intensity of EuL1₃ significantly decreased, yielding results consistent with enzyme-linked immunosorbent assay (ELISA). These results demonstrates the potential of EuL1₃ for application in depression diagnosis and therapeutic efficacy assessment.