ABSTRACT
COVID-19 has afflicted people's lives worldwide. Interleukin-6 (IL-6) is an important COVID-19 biomarker in human body fluids that can be used as a reference to monitor COVID-19 in real-time and therefore to reduce the risk of virus transmission. On the other hand, oseltamivir is a potential COVID-19 curing drug, but its overuse easily leads to hazardous side effects, calling for its real time monitoring in body fluids. For these purposes, a new yttrium metal-organic framework (Y-MOF) has been synthesized, in which the 5-(4-(imidazole-1-yl)phenyl)isophthalic linker contains a large aromatic backbone capable of strongly interacting with DNA sequences through π-π stacking interactions, which makes it appealing to build a unique sensor based on DNA functionalized MOFs. The MOF/DNA sequence hybrid luminescent sensing platform presents excellent optical properties associated with a high Förster resonance energy transfer (FRET) efficiency. Furthermore, to construct a dual emission sensing platform, a 5'-carboxylfluorescein (FAM) labeled DNA sequence (S2) with a stem-loop structure that can specifically interact with IL-6 has been associated with the Y-MOF. The resulting Y-MOF@S2 exhibits an efficient ratiometric detection of IL-6 in human body fluids with an extremely high Ksv value 4.3 × 108 M-1 and a low detection limit (LOD) of 70 pM. Finally, the Y-MOF@S2@IL-6 hybrid platform allows the detection of oseltamivir with high sensitivity (Ksv value is as high as 5.6 × 105 M-1 and LOD is 54 nM), due to the fact that oseltamivir can disconnect the loop stem structure constructed by S2, leading to a strong quenching effect towards Y-MOF@S2@IL-6. The nature of the interactions between oseltamivir and Y-MOF has been elucidated using density functional theory calculations while the sensing mechanism for the dual detection of IL-6 and oseltamivir has been deciphered based on luminescence lifetime tests and confocal laser scanning microscopy.
ABSTRACT
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.