Water-induced supramolecular self-assembly of porphyrin integrated with multivalent metal–organic framework for enhanced electrochemiluminescence and ultrasensitive aptasensing of 4-fluoromethamphetamine

Technical Summary: Water-Induced Supramolecular Self-Assembly of Porphyrin-Integrated MOF for Enhanced ECL and Ultrasensitive Aptasensing

Problem Statement
The application of polycyclic aromatic hydrocarbons (PAHs), such as porphyrins, as electrochemiluminescence (ECL) luminophores is severely restricted by two inherent limitations: poor aqueous solubility and the aggregation-caused quenching (ACQ) effect. Traditional methods to mitigate ACQ, such as immobilizing PAHs within metal–organic frameworks (MOFs) via coordination anchoring, often rely on solvothermal synthesis. These conventional approaches involve long reaction times, complex procedures, expensive organic solvents, and harsh high-temperature/pressure conditions, hindering low-cost, large-scale preparation and field deployment. Furthermore, the detection of 4-fluoromethamphetamine (4-FMA), a potent new psychoactive substance (NPS), currently relies on high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). While sensitive, this mainstream method is cumbersome, expensive, and dependent on large-scale instrumentation, making it unsuitable for rapid, on-site screening in grassroots drug control and forensic toxicology.

Methodology
To address these challenges, the authors propose a green, water-induced supramolecular self-assembly strategy combined with a multifunctional signal amplification carrier.

1. Synthesis of Luminophore (TCPP NPs): A simple reprecipitation route was employed using tetrahydrofuran (THF) and water. Meso-tetrakis(4-carboxyphenyl)porphyrin (TCPP) was dispersed in THF and rapidly poured into water under sonication. This process induced the spontaneous self-assembly of TCPP into ordered supramolecular aggregates (TCPP NPs) driven by noncovalent interactions. This strategy effectively suppressed $\pi$–$\pi$ stacking and the ACQ effect, resulting in nanosheet-like morphologies.
2. Synthesis of Amplifier (MMS): An iron-based MOF supported on molybdenum disulfide (MIL-101@MoS$_2$, referred to as MMS) was synthesized via a hydrothermal method. This composite features a flower-like structure composed of MIL-101(Fe) and MoS$_2$ arrays.
3. Fabrication of Composite (MMST): The MMST nanoparticles were prepared by mixing the MMS aqueous solution with the TCPP solution, followed by freeze-drying. The MMS particles were uniformly anchored onto the TCPP supramolecular sheets.
4. Sensor Construction: A glassy carbon electrode (GCE) was modified with the MMST composite, followed by the immobilization of a DNA-cyanine dye (Cy7) aptamer specific to 4-FMA. The sensing mechanism relies on target-triggered displacement: in the presence of 4-FMA, the target competitively binds to the aptamer, displacing the Cy7 dye and altering the ECL signal.
5. Detection Conditions: The system utilizes K$_2$S$_2$O$_8$ as a coreactant. ECL measurements were conducted at a low triggering potential of −1.0 V in a phosphate-buffered saline (PBS) solution.

Key Contributions and Mechanisms

• Suppression of ACQ: The water-induced self-assembly transformed TCPP from irregular bulk structures into ordered nanosheets. Characterization (Raman, UV-Vis, and fluorescence lifetime measurements) confirmed a reduction in $\pi$–$\pi$ stacking and a prolonged excited-state lifetime (11.60 ns for TCPP NPs vs. 10.60 ns for monomeric TCPP), effectively mitigating the ACQ effect and enhancing luminescence efficiency.
• Multivalent Redox Cycling: The MIL-101(Fe)@MoS$_2$ carrier acts as a multifunctional amplifier. The reversible valence interconversion of Fe$^{2+}$/Fe$^{3+}$ and Mo$^{4+}$/Mo$^{6+}$ sustains continuous redox cycling. This accelerates the decomposition of the coreactant (S$_2$O$_8^{2-}$) and promotes the generation of reactive species (SO$_4^{\bullet-}$), significantly boosting ECL intensity.
• Oxygen Vacancy Activation: The composite possesses abundant oxygen vacancies (confirmed by XPS and EPR), which serve as active centers to adsorb and activate dissolved O$_2$, further enhancing electron transfer and coreactant activation.
• Low-Voltage Operation: The synergistic effects of the supramolecular assembly and the multivalent MOF carrier lowered the ECL triggering potential to −1.0 V, facilitating energy-efficient detection.

Results

• Performance Metrics: The constructed aptasensor achieved an ultralow limit of detection (LOD) of 1.87 × 10$^{-15}$ g/L (S/N = 3) with a broad linear range from 1.0 × 10$^{-14}$ to 1.0 × 10$^{-6}$ g/L.
• Selectivity and Stability: The sensor demonstrated high specificity for 4-FMA, showing negligible interference from other NPS analogs (e.g., furanyl fentanyl, flu alprazolam) even at 10,000-fold higher concentrations. The system exhibited excellent stability (RSD < 5.0% over 10 cycles) and storage stability over 15 days.
• Real Sample Analysis: The method was validated using real e-cigarette samples. Standard addition experiments yielded recoveries between 95.0% and 104.0% with RSDs less than 5.0%, confirming the sensor's robustness in complex, viscous matrices containing propylene glycol, glycerol, nicotine, and flavoring agents.

Significance
This work presents a green and facile route for developing high-performance PAH-based ECL luminophores by overcoming the intrinsic ACQ defect through water-induced supramolecular assembly. By integrating these luminophores with a multivalent MOF carrier, the study establishes a reliable, label-free analytical tool for the rapid screening of emerging psychoactive contaminants. The proposed method offers distinct advantages in efficiency, portability, and cost-effectiveness compared to traditional mass spectrometry, holding significant potential for application in drug control, public security monitoring, forensic toxicology, and food safety detection.