The protein disulfide isomerase (PDI) family, found in the endoplasmic reticulum (ER) of the eukaryotic cell, catalyzes the formation and cleavage of disulfide bonds and thereby helps in protein folding. A decrease in PDI activity under ER stress conditions leads to protein misfolding, which is responsible for the progression of various human diseases, such as Alzheimer's, Parkinson's, diabetes mellitus, and atherosclerosis. Here we report that water-soluble cyclic diselenides mimic the multifunctional activity of the PDI family by facilitating oxidative folding, disulfide formation/reduction, and repair of the scrambled disulfide bonds in misfolded proteins.

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Selenoglutathione (GSeH) is a selenium analogue of naturally abundant glutathione (GSH). In this study, this water-soluble small tripeptide was synthesized in a high yield (up to 98%) as an oxidized diselenide form, i.e., GSeSeG (1), by liquid-phase peptide synthesis (LPPS). Obtained 1 was applied to the investigation of the glutathione peroxidase (GPx)-like catalytic cycle. The important intermediates, i.e., GSe and GSeSG, besides GSeOH were characterized by Se NMR spectroscopy. Thiol exchange of GSeSG with various thiols, such as cysteine and dithiothreitol, was found to promote the conversion to GSe significantly. In addition, disproportionation of GSeSR to 1 and RSSR, which would be initiated by heterolytic cleavage of the Se-S bond and catalyzed by the generated selenolate, was observed. On the basis of these redox behaviors, it was proposed that the heterolytic cleavage of the Se-S bond can be facilitated by the interaction between the Se atom and an amino or aromatic group, which is present at the GPx active site. On the other hand, when a catalytic amount of 1 was reacted with scrambled 4S species of RNase A in the presence of NADPH and glutathione reductase, native protein was efficiently regenerated, suggesting a potential use of 1 to repair misfolded proteins through reduction of the non-native SS bonds.

In this review from literature appearing over about the past 5 years, we focus on selected selenide reports and related chemistry; we aimed for a digestible, relevant, review intended to be usefully interconnected within the realm of fluorescence and selenium chemistry. Tellurium is mentioned where relevant. Topics include selenium in physics and surfaces, nanoscience, sensing and fluorescence, quantum dots and nanoparticles, Au and oxide nanoparticles quantum dot based, coatings and catalyst poisons, thin film, and aspects of solar energy conversion. Chemosensing is covered, whether small molecule or nanoparticle based, relating to metal ion analytes, H2S, as well as analyte sulfane (biothiols—including glutathione). We cover recent reports of probing and fluorescence when they deal with redox biology aspects. Selenium in therapeutics, medicinal chemistry and skeleton cores is covered. Selenium serves as a constituent for some small molecule sensors and probes. Typically, the selenium is part of the reactive, or active site of the probe; in other cases, it is featured as the analyte, either as a reduced or oxidized form of selenium. Free radicals and ROS are also mentioned; aggregation strategies are treated in some places. Also, the relationship between reduced selenium and oxidized selenium is developed.