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A coumarin-appended calixarene derivative (  CouC4A  ) and a hybrid material generated by covalently linking this onto a silica surface (  CouC4A@SiO2   ) were synthesized and were characterized by various analytical, spectroscopy, and microscopy methods. Both these materials are capable of sensing Fe 3+ with greater sensitivity and selectivity. The sensitivity is enhanced by 30,000 fold on going from a simple solution phase to the silica surface with the limit of Fe 3+ detection being 1.75 ± 0.4 pM when CouC4A@SiO    2   is used, and the sensing is partially reversible with phosphates, while it is completely reversible with adenosine 5'-triphosphate (ATP). While the calix precursor,  CouC4A  , has a limitation to work in water, anchoring this onto SiO 2 endowed it with the benefit of its use in water as well as in buffer and thereby extends its application toward Fe 3+ sensing even in the biorelevant medium such as fetal bovine serum and human serum. The hybrid material is biocompatible and shows ∼90% cell viability in the case of MDA-MB231 and 3T3 cell lines.  CouC4A@SiO2   functions as a reversible sensor for Fe 3+ with the use of ATP in vitro as well as in biological cells. Thus, the inorganic-organic hybrid material, such as,  CouC4A@SiO2   , is an indispensable material for sensitive and selective detection of Fe 3+ in a picomolar range in solution and in nanomolar to micromolar range in biorelevant fluids and biological cells, respectively.

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Coumarin–Calix[4]arene Conjugate-Anchored SiO<sub>2</sub> Nanoparticles as an Ultrasensor Material for Fe<sup>3+</sup> to Work in Water, in Serum, and in Biological Cells

Coumarin–Calix[4]arene Conjugate-Anchored SiO2 Nanoparticles as an Ultrasensor Material for Fe3+ to Work in Water, in Serum, and in Biological Cells

Coumarin–Calix[4]arene Conjugate-Anchored SiO₂ Nanoparticles as an Ultrasensor Material for Fe³⁺ to Work in Water, in Serum, and in Biological Cells