A Hydrogen Bonded Non‐Porous Organic‐Inorganic Framework for Measuring Cysteine in Blood Plasma and Endogenous Cancer Cell

An imbalance in cysteine (Cys) levels in the cells and plasma has been identified as the risk indicator for various human diseases. The structural similarity of cysteine with its congener homocysteine and glutathione offers challenges in its measurement. Herein, we report a hydrogen-bonded organic-inorganic framework of Cu(II) (HOIF) for the selective detection of cysteine over other biothiols. The non-fluorescent HOIF showed 12-fold green emission in the presence of cysteine. The monomeric unit of HOIF is stabilized via intermolecular hydrogen bonds, resulting in a non-porous network structure. Non-interference from homocysteine, glutathione, and other competitive bio-analytes revealed explicit affinity of HOIF for cysteine. Fluorimetric titration showed a wide working concentration window (650 nM-800 μM) for measuring cysteine in an aqueous medium. The mechanistic investigation involving HRMS, EPR, and UV-vis spectroscopic studies revealed the decomplexation of HOIF with Cys, resulting in a fluorescence turn-on response from the luminescent ligand. Validation using a commercial dye, "Cysteine Green", confirmed the prospect of HOIF for early diagnostic purposes. Utilizing the fluorescence turn-on property of HOIF in the presence of cysteine, we measured cysteine quantitatively in the blood plasma samples. Bio-imaging of endogenous cysteine in cancer cells indicated the ability of HOIF to monitor the intracellular cysteine.