Copper-Driven Deselenization: A Strategy for Selective Conversion of Copper Ion to Nanozyme and Its Implication for Copper-Related Disorders

Abstract

Synthetic organic molecules, which can selectively convert excess intracellular copper (Cu) ions to nanozymes with an ability to protect cells from oxidative stress, are highly significant in developing therapeutic agents against Cu-related disorder like Wilson’s disease. Here, we report 1,3-bis­(2-hydroxyethyl)-1H-benzoimidazole-2-selenone (1), which shows a remarkable ability to remove Cu ion from glutathione, a major cytosolic Cu-binding ligand, and thereafter converts it into copper selenide (CuSe) nanozyme that exhibits remarkable glutathione peroxidase-like activity, at cellular level of H2O2 concentration, with excellent cytoprotective effect against oxidative stress in hepatocyte. Cu-driven deselenization of 1, under physiologically relevant conditions, occurred in two steps. The activation of CSe bond by metal ion is the crucial first step, followed by cleavage of the metal-activated CSe bond, initiated by the OH group of N–(CH2)2OH substituent through neighboring group participation (deselenization step), resulted in the controlled synthesis of various types of Cu2‑xSe nanocrystals (NCs) (nanodisks, nanocubes, and nanosheets) and tetragonal Cu3Se2 NCs, depending upon the oxidation state of the Cu ion used to activate the CSe bond. Deselenization of 1 is highly metal-selective. Except Cu, other essential metal ions, including Mn2+, Fe2+, Co2+, Ni2+, or Zn2+, failed to produce metal selenide under identical reaction conditions. Moreover, no significant change in the expression level of Cu-metabolism-related genes, including metallothioneines MT1A, is observed in liver cells co-treated with Cu and 1, as opposed to the large increase in the concentrations of these genes observed in cells treated with Cu alone, suggesting the participation of 1 in Cu homeostasis in hepatocyte.

Nearly Monodisperse Copper Selenide Nanoparticles for Recognition, Enrichment, and Sensing of Mercury Ions

“…The satellite peak at 943.5 eV corresponds to the main peak at 934.6 eV, which belongs to Cu­(II) 2p 3/2 . Meanwhile, the satellite peak at 962.6 eV matches the main peak at 954.6 eV, which is ascribed to Cu­(II) 2p 1/2 . The peak area ratio of Cu­(I) to Cu­(II) was calculated to be 3.56, and thus the as-prepared copper selenide nanoparticles could be expressed as Cu­(I) 1.28 Cu­(II) 0.36 Se.…”

“…Meanwhile, the satellite peak at 962.6 eV matches the main peak at 954.6 eV, which is ascribed to Cu(II) 2p 1/2 . 32 The peak area ratio of Cu(I) to Cu(II) was calculated to be 3.56, and thus the asprepared copper selenide nanoparticles could be expressed as Cu(I) 1.28 Cu(II) 0.36 Se. Figure 1f illustrates the high-resolution Se 3d XPS spectrum of Cu(I) 1.28 Cu(II) 0.36 Se nanoparticles.…”

Enhanced Copper–Temozolomide Interactions by Protein for Chemotherapy against Glioblastoma Multiforme

“…The impact of intracellular GSH, particularly in tumor cells in which the cytosolic GSH reaches a high level (1–10 mM), , has the top priority to be investigated because the GSH–copper interaction (Figure a) would potentially lead to dissociation of copper–MTIC coordination and liberation of MTIC into the cytosol (Figure b). GSH interacts with Cu 2+ in the way of both redox reactions and coordination, and multiple forms of GSH-derived products were reported such as Cu­(I)–GSH, Cu­(I)–(GSH) 2 , and Cu­(II)–GSSG complexes under different solvent conditions. − The reduction of Cu­(II) to Cu­(I) by a millimole concentration of GSH is likely, − which could dissociate MTIC from copper binding and induce a release of MTIC. Chelation between Cu 2+ and GSH to form a GSH–Cu­(II) complex is another factor (Figure a) …”

Highly Selective and Rapid Naked-Eye Colorimetric Sensing and Fluorescent Studies of Cu2+ Ions Derived from Spherical Nanocellulose

“…Cu is an indispensable micronutrient required by different living forms . However, Cu 2+ ions have been reported to cause serious health disorders if present in concentration beyond the permissible limits. − Hence, it has become imperative to develop sensing materials for easy detection of Cu 2+ ions from the contaminated water. Exploration of NC for developing new sensors with improved selectivity and sensitivity to Cu 2+ ions has been reported for efficient analytical applications. − Weishaupt et al reported a protein-NC paper sensor for Cu 2+ sensing at the nano- to micromolar level .…”