Trace-Level Detection of a Niacin Metabolite in Human Blood under Phosphonate Pillar[6]arene-Induced Columnar-Like Aggregation Conditions.

A rapid method for quantifying the niacin metabolite 1-methylnicotinamide (1-MNA) in human blood is required to address the limitations of existing low-throughput techniques such as mass spectrometry. In previous studies, we demonstrated that supramolecular pillar[6]arenes (P6As) bearing either carboxylate groups (P6AC) or sulfonate groups (P6AS) functioned as "turn-off" fluorescent sensors for 1-MNA detection in urine by photoinduced electron transfer (PET). However, because the concentration of 1-MNA in blood is very low, PET-based detection in aqueous solutions was insufficient for reliable quantification on its own. Here, we report that phosphonate-functionalized P6A (P6AP) in 90% acetonitrile formed aggregates with columnar morphology, which was associated with markedly enhanced detection sensitivity for 1-MNA. Under these conditions, aggregation-induced emission (AIE) resulted in increases in the fluorescence intensity, photoluminescence quantum yield, and photoluminescence lifetime. The addition of 1-MNA suppressed the formation of columnar aggregates of P6AP, and this was accompanied by decreases in the fluorescence intensity, photoluminescence quantum yield, and photoluminescence lifetime. This solvation-dependent fluorescence response substantially improved the detection sensitivity for 1-MNA, enabling its detection in human blood. By contrast, in 80% acetonitrile, P6AP showed AIE but did not exhibit similar columnar aggregates or increase the sensitivity. Overall, the aggregation-state-associated enhancement of the fluorescence response provides a functional framework that enhances fluorescence-based detection and represents a promising platform for extension to a broad range of biologically relevant analytes.