Countless people have been affected by the COVID‐19 pandemic on a global scale. Favipiravir, has shown potential as an effective drug for SARS‐CoV‐2, attracting scientists’ attention. However, overuse of Favipiravir easily leads to serious side effects, requiring real‐time monitoring in body fluids. Given this, a new lanthanide metal‐organic framework (MOF) was prepared under solvothermal conditions from either Eu (Eu‐MOF or (1)) or Tb (Tb‐MOF or (2)) using the highly delocalized imidazoledicarboxylic acid linker H2L (H2L=5‐(4‐(imidazol‐1‐yl) phenyl) isophthalic acid) and could be successfully applied to selective optical detection of Favipiravir. In this MOF framework, the organic linker H2L provides a high excitation energy transfer efficiency that can sensitize luminescence in lanthanides. In addition, through deliberate tuning of Eu/Tb molar ratio and reaction concentration in the lanthanide framework, ratiometric recyclable luminescent EuxTb1‐x‐MOF nanoparticles with open metal sites have been constructed, which present a high detection sensitivity (Ksv=1×107 [M−1], detection limit is 4.63 nM) for Favipiravir. The detection mechanism is discussed with the help of Density Functional Theory (DFT) calculations that sheds light over the selective sensing of Favipiravir over other related COVID‐19 drug candidates. Finally, to explore the practical application of Favipiravir sensing, MOF based thin films have been used for visual detection of Favipiravir and recycled 5 times.
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