Copper (II) Based Metal‐Organic Compounds for Selective Detection of Tumor Biomarker Glutathione, Cysteine, and Homocysteine by Perceiving Luminescence Turn‐On

ABSTRACT

Biological thiols such as glutathione (GSH), cysteine (Cys), and homocysteine (Hcy) play important roles in maintaining cellular redox balance. Abnormal changes in their levels are closely linked to cancer and other diseases. We report two Cu(II)‐based metal–organic compounds, RT‐3a and RT‐3b which were prepared using pyrazine‐2‐carboxylate ligands by room‐temperature layer diffusion method. Single‐crystal x‐ray diffraction analysis reveal that the Cu(II) centers adopt distorted octahedral coordination geometries. Both compounds exhibit stable luminescence in aqueous media (pH 4–10). They exhibit a strong, selective luminescence turn‐on response toward thiol‐containing amino acids, including Cys, Hcy, and GSH, under physiological conditions. In contrast, nonthiol amino acids produce negligible changes in emission intensity. Quantitative studies demonstrate high sensitivity, with limits of detection in the submicromolar range. Mechanistic studies, based on photoluminescence analysis and supported by FTIR data and DFT calculations, suggest that the sensing behavior arises from strong Cu─S interactions between the thiol group and the Cu(II) centers. Hydrogen‐bonding interactions involving the ─SH group also contribute. Consequently, the luminescence intensity increases. The combination of strong luminescence response, high selectivity, and good aqueous stability establishes RT‐3a and RT‐3b as promising probes for the detection of biologically relevant thiols, particularly the tumor biomarker glutathione.