Selenium Chemistry Research Articles

Organoselenium Compounds in Medicinal Chemistry.

The chemical and biological interest in this element and the molecules bearing selenium has been exponentially growing over the years. Selenium, formerly designated as a toxin, becomes a vital trace element for life that appears as selenocysteine and its dimeric form, selenocystine, in the active sites of selenoproteins, which catalyze a wide variety of reactions, including the detoxification of reactive oxygen species and modulation of redox activities. From the point of view of drug developments, organoselenium drugs are isosteres of sulfur-containing and oxygen-containing drugs with the advantage that the presence of the selenium atom confers antioxidant properties and high lipophilicity, which would increase cell membrane permeation leading to better oral bioavailability. This statement is the paramount relevance considering the big number of clinically employed compounds bearing sulfur or oxygen atoms in their structures including nucleosides and carbohydrates. Thus, in this article we have focused on the relevant features of the application of selenium in medicinal chemistry. With the increasing interest in selenium chemistry, we have attempted to highlight the most significant published data on this subject, mainly concentrating the analysis on the last years. In consequence, the recent advances of relevant pharmacological organoselenium compounds are discussed.

Selenium chemistry for spatio-selective peptide and protein functionalization.

The ability to construct a peptide or protein in a spatio-specific manner is of great interest for therapeutic and biochemical research. However, the various functional groups present in peptide sequences and the need to perform chemistry under mild and aqueous conditions make selective protein functionalization one of the greatest synthetic challenges. The fascinating paradox of selenium (Se) - being found in both toxic compounds and also harnessed by nature for essential biochemical processes - has inspired the recent exploration of selenium chemistry for site-selective functionalization of peptides and proteins. In this Review, we discuss such approaches, including metal-free and metal-catalysed transformations, as well as traceless chemical modifications. We report their advantages, limitations and applications, as well as future research avenues.

Asymmetric Synthesis with Organoselenium Compounds - The Past Twelve Years.

The discovery and synthetic applications of novel organoselenium compounds and their reactions proceeded rapidly during the past fifty years and such processes are now carried out routinely in many laboratories. At the same time, the growing demand for new enantioselective processes provided new challenges. The convergence of selenium chemistry and asymmetric synthesis led to key developments in the 1970s, although the majority of early work was based on stoichiometric processes. More recently, greater emphasis has been placed on greener catalytic variations, along with the discovery of novel reactions and a deeper understanding of their mechanisms. The present review covers the literature in this field from 2010 to early 2023 and encompasses asymmetric reactions mediated by chiral selenium-based reagents, auxiliaries, and especially, catalysts. Protocols based on achiral selenium compounds in conjunction with other species of chiral catalysts, as well as reactions that are controlled by chiral substrates, are also included.

Organoselenium Compounds in Catalysis

AbstractIn this article we have focused on the use of selenium in catalysis along with the proposed reaction mechanisms. With increasing interest in selenium chemistry, we have highlighted the most significant features of this subject, mainly in the last years. Selenium-containing catalysts have a key role in many transformations; for example, oxidation reactions that are performed under very mild and controlled conditions. In addition, utilizing the weak selenium–oxygen bonding interaction has proved to be very useful as a catalytic approach for specific transformations. The catalytic cycles of each appropriate transformation are fully reviewed.1 Introduction2 Use of Selenium in Catalysis: Perspectives2.1 Selenium as Directing Group: Preparation of Organoselenium Compounds via C–H Borylation2.2 Multicomponent Reactions Employing Selenium as a Catalyst2.3 Selenium-π-Acid Catalysts2.4 Electrochemical Selenium-Catalyzed Reactions2.5 Stereoselective Synthesis Employing Organoselenium Catalysts2.6 Transition-Metal Catalysts Containing Selenium-Based Ligands2.6.1 Selenium-Ligated Palladium(II) Complexes as Catalysts for the Heck Reaction2.6.2 Pincer Selenium Catalyst for the Allylation of Aldehydes and Closely Related Functional Groups2.6.3 Selenium Employed in Buchwald-Type C–N Coupling Reactions2.6.4 Organoselenium Catalysts in Suzuki–Miyaura Coupling Reactions2.7 Organoselenium Catalysis in Michael-Type Reactions2.8 Catalytic Cycle for Glutathione Peroxidase2.9 Epoxidation2.10 Dihydroxylation2.11 Oxidation2.12 Bromolactonization2.13 Preparation of Alkenes from Vicinal Diols2.14 Preparation of α-Selanyl Enals from Propargylic Alcohols2.15 Miscellanea3 Concluding Remarks

Organoselenium compounds. Chemistry and applications in organic synthesis.

Selenium, originally described as a toxin, turns out to be a crucial trace element for life that appears as selenocysteine and its dimer, selenocystine. From the point of view of drug developments, selenium-containing drugs are isosteres of sulfur and oxygen with the advantage that the presence of the selenium atom confers antioxidant properties and high lipophilicity, which would increase cell membrane permeation leading to better oral bioavailability. In this article we have focused on the relevant features of the selenium atom, above all, the corresponding synthetic approaches to access a variety of organoselenium molecules along with the proposed reaction mechanisms. The preparation and biological properties of selenosugars, including selenoglycosides, selenonucleosides, selenopeptides, and other selenium-containing compounds will be treated. We have attempted to condense the most important aspects and interesting examples of the chemistry of selenium into a single article.

Amelioration Strategies for Silver Diamine Fluoride: Moving from Black to White.

Topical cariostatic agents have become a reasonable alternative for managing dental caries in young children. Silver diamine fluoride (SDF) is a practical topical approach to arrest caries and avoid extensive and risky dental treatment. However, the literature demonstrates a parental hesitation towards accepting SDF because of black unaesthetic tooth discolouration following application. The rapid oxidation of ionic silver darkens demineralised tooth structure permanently. In this regard, nano-metallic antimicrobials could augment or substitute for silver, and thereby enhance SDF aesthetic performance. Recently, biomedical research has drawn attention to selenium nanoparticles (SeNPs) due to their antimicrobial, antioxidant, and antiviral potencies. Various in vitro studies have examined the effect of SeNPs on the virulence of bacteria. This narrative review explores practical issues when using SDF and suggests future directions to develop it, focusing on antimicrobial metals. Several methods are described that could be followed to reduce the discolouration concern, including the use of nanoparticles of silver, of silver fluoride, or of selenium or other metals with antimicrobial actions. There could also be value in using remineralising agents other than fluoride, such as NPs of hydroxyapatite. There could be variations made to formulations in order to lower the levels of silver and fluoride in the SDF or even to replace one or both of the silver and fluoride components completely. Moreover, since oxidation processes appear central to the chemistry of the staining, adding SeNPs which have antioxidant actions could have an anti-staining benefit; SeNPs could be used for their antimicrobial actions as well. Future research should address the topic of selenium chemistry to optimise how SeNPs would be used with or in place of ionic silver. Incorporating other antimicrobial metals as nanoparticles should also be explored, taking into account the optimal physicochemical parameters for each of these.

Peroxynitrite Electrochemical Signature on Selenium and Selenium-Decorated Graphene Depositions

Reactive oxygen species (ROS) such as peroxynitrite have been linked to oxidative stress-induced diseases such as cardiovascular failure. Determining the cause and progression of such disease, as well as testing the efficacy of potential treatments all hinge on the ability to accurately detect these species in biological systems. Antioxidant uses of selenium have garnered the attention of scientists in recent years. Latest investigations have revealed that selenium is essential for redox regulation as a ROS modulator and as a catalytic cofactor of endogenous antioxidative mechanisms.The advantages of preparing selenium electrochemical depositions as sensitive surfaces for peroxynitrite detection and quantification were revealed in our research. Electrochemical sensors with high sensitivity and selectivity were developed by dissolving selenium dioxide in an acidic medium. Graphene nanostructures loaded with selenium were used to modify one set of glassy carbon electrodes (GCEs), while selenium nanoparticles were used to modify another set of GCEs for comparison purposes. The shape and surface chemistry of selenium and selenium-decorated graphene nanostructures were investigated using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). The electrochemical catalytic activity of these systems was determined using cyclic voltammetry and chronoamperometry. The thickness of the deposited selenium interfaces was measured using Quartz Crystal Microbalance (QCM) analysis.Elemental selenium nanoparticles showed an increase in the sensitivity toward peroxynitrite when embedded into graphene sheets. In addition, it allowed for the use of low positive potential, leading to improved segregation of peroxynitrite from other analytes that are sensitive to higher potentials.

Food Chemistry of Selenium and Controversial Roles of Selenium in Affecting Blood Cholesterol Concentrations.

Hypercholesterolemia, one of the major risk factors of cardiovascular diseases, is a worldwide public health problem. Nutraceuticals and phytochemicals are attracting attention as a result of their cholesterol-lowering ability and minimal side effects. Among them, selenium (Se) is on the list. The amount of Se in foods varies by region. Se-enriched fertilizers and feeds can raise the Se content in plants and animals, while some processing methods decrease food Se content. This review summarizes recent studies on (1) the content distribution of Se in foods and factors influencing Se-enriched foods, (2) the bioavailability and metabolism of Se, and (3) the role of Se in affecting blood cholesterol and cholesterol metabolism. Although the hypocholesterolemic effect of Se is equivocal, its cholesterol-lowering activity may be more remarkable when the Se supplementation is 200 μg/day or the baseline blood total cholesterol is above 200 mg/dL in humans with low Se status.

Synergistic effect of T80/B30 vesicles and T80/PN320 mixed micelles with Se/C on nasal mucosal immunity

Selenium doped carbon (Se/C), an easily fabricated material, was found to be bio-active and it can serve as an adjuvant to enhance the immune effect of Tween 80/Brij 30 (T80/B30) vesicles and Tween 80/polymer cationic surfactant PN320 (T80/PN320) mixed micelles. The synergistic effect of the combination of T80/B30 vesicles and T80/PN320 mixed micelles with Se/C on nasal mucosal immunity was studied in this work, which might provide theoretical basis for developing the related new adjuvant for nasal immunization of recombinant protein, peptide and split protein vaccine. Since both selenium and carbon were bio-compatible elements, Se/C might be safe for practical applications, and this was also reflected by the low hemolytic activity of the materials. This work not only reports an efficient protocol for adjuvant development, but also significantly expands the application scope of selenium chemistry.

Discussions of Fluorescence in Selenium Chemistry: Recently Reported Probes, Particles, and a Clearer Biological Knowledge.

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.

Unraveling the Nature of Excellent Potassium Storage in Small-Molecule Se@Peapod-Like N-Doped Carbon Nanofibers.

The potassium-selenium (K-Se) battery is considered as an alternative solution for stationary energy storage because of abundant resource of K. However, the detailed mechanism of the energy storage process is yet to be unraveled. Herein, the findings in probing the working mechanism of the K-ion storage in Se cathode are reported using both experimental and computational approaches. A flexible K-Se battery is prepared by employing the small-molecule Se embedded in freestanding N -doped porous carbon nanofibers thin film (Se@NPCFs) as cathode. The reaction mechanisms are elucidated by identifying the existence of short-chain molecular Se encapsulated inside the microporous host, which transforms to K2 Se by a two-step conversion reaction via an "all-solid-state" electrochemical process in the carbonate electrolyte system. Through the whole reaction, the generation of polyselenides (K2 Sen , 3≤n≤8) is effectively suppressed by electrochemical reaction dominated by Se2 molecules, thus significantly enhancing the utilization of Se and effecting the voltage platform of the K-Se battery. This work offers a practical pathway to optimize the K-Se battery performance through structure engineering and manipulation of selenium chemistry for the formation of selective species and reveal its internal reaction mechanism in the carbonate electrolyte.

Incredible edible selenium nanoparticles produced by food-grade microorganisms

Background: Microorganisms commonly employed in food industry, such as Lactobacillus plantarum and Saccharomyces cerevisiae, are also excellent natural nanotechnologists. They reduce selenite (SeO3 2- ) to form nanoparticles of red selenium (Se0 ) of exceptional quality and with interesting physical and (bio-)chemical properties. Objectives: The production of these nanoparticles has been studied in several relevant microorganisms to gain a better picture of the overall properties and quality of these particles, possible differences between producers, ease of production and, in particular, biological activity. Methods: Several common microorganisms, namely L. plantarum, S. cerevisiae and Escherichia coli have been cultured under standard conditions and 1mM concentrations of SeO3 2- have been converted to red particles of elemental selenium. These particles have been characterized extensively with respect to uniformity, size, shape, consistency and, in particular, biological activity against infectious microbes. Results: Highly uniform amorphous spherical particles of 100 nm to 200 nm in diameter could be produced by several microorganisms, including Lactobacillus. Although originating in bacteria and yeast, these particles exhibit antimicrobial activity when employed at concentrations of around 100 µM. This activity may in part be due to the inherent chemistry of selenium and /or of the protein coating of the particles. Interestingly, yeast also forms larger rod-like structures. These micro-needles with around 85 nm in diameter and up to 3 µm in length exhibit considerable antibacterial activity, possibly resulting from additional, physical interactions with cellular structures. Conclusion: Common microorganisms traditionally employed in the preparation of food produce nanoparticles of selenium which may be harvested and explored as natural antimicrobial agents or antioxidants. These particles provide a fine example of and lead for natural nanotechnology with biological activity and applications in food and food supplementation, medicine, agriculture and cosmetics.

Reversible-Tuning Krafft Temperature of Selenium-Containing Ionic Surfactants by Redox Chemistry.

An easy, effective, and reversible strategy for tuning the Krafft temperature (KT) of selenium-containing ionic surfactants, with head groups ranging in nature from anionic to amphoteric, has been achieved for the first time via the redox chemistry of selenium. After oxidation with H2O2, the selenide group was converted to a more hydrophilic selenoxide group. This made the oxidized forms of the surfactants more water-soluble, which results in a marked reduction in the KT. In contrast, the hydrophilic selenoxide was restored to its reduced form of selenide via reduction reaction, which allowed the KT value to return to its initial value. By alternating the oxidization and reduction treatments, the KT of the selenium-containing surfactants in this work could be reversibly switched over 5-10 cycles without causing obvious adverse distortions.

Didactic approach recounting advances and limitations in novel glutathione and cysteine detection (reduced GSH probe) with mixed coumarin, aldehyde, and phenyl-selenium chemistry.

We describe the pertinent research steps and analysis, many of which are chemical, to achieve a novel molecular probe for glutathione (GSH) which has been published and patented based on two recent articles: "Exceptional time response, stability and selectivity in doubly-activated phenyl selenium-based glutathione-selective platform" and "Enhanced Doubly Activated Dual Emission Fluorescent Probes for Selective Imaging of Glutathione or Cysteine in Living Systems" (Kim et al., 2015; Mulay et al., 2018). The papers involve coumarin probes. Reaction/detection unfolds with aminothiol attack at an electrophilic ring carbon position. An adjacent -CHO group is heavily involved in resonance aspects of the C-Se position, as well as the binding of the pendant N-group; the coumarin lactone carbonyl also allows for resonance to be achieved (vide infra). The leaving group, -SePh, while precedented in some systems, depends on electronic tuning (Fig. 1). For 1, the response times with GSH was ~100ms; a 100-fold fluorescence increase is observed (Compound 1). The probe also reacts with cysteine (Cys) and homocysteine (Hcy), albeit differently. For glutathione probing, the greater wavelength maxima (1: 550nm, DACP-1: 555nm, DACP-2: 590nm) enabled eventual cell studies (confocal microscopy) and animal studies. The limits of detection (LOD, 1: 270nM DACP-1: 10.1nM DACP-2: 17.0nM), as measured using the 3σ/k method. We provide a didactic presentation from probe conception to probe in vivo testing, etc., with additional considerations presented; a variety of factors/issues (2.1-2.28) help maintain a realistic sequence, a flow from wider to narrower, of the factors that go into developing medical, biological and neurodegenerative disease-related probes, meant to help other researchers follow our intention, gain perspective, and overcome current limitations.

Diselenolane‐Mediated Cellular Uptake: Efficient Cytosolic Delivery of Probes, Peptides, Proteins, Artificial Metalloenzymes and Protein‐Coated Quantum Dots

Cyclic oligochalcogenides are emerging as powerful tools to penetrate cells. With disulfide ring tension maximized, selenium chemistry had to be explored next to enhance speed and selectivity of dynamic covalent exchange on the way into the cytosol. We show that diseleno lipoic acid (DiSeL) delivers a variety of relevant substrates. DiSeL-driven uptake of artificial metalloenzymes enables bioorthogonal fluorophore uncaging within cells. Binding of a bicyclic peptide, phalloidin, to actin fibers evinces targeted delivery to the cytosol. Automated tracking of diffusive compared to directed motility and immobility localizes 79 % of protein-coated quantum dots (QDs) in the cytosol, with little endosomal capture (0.06 %). These results suggest that diselenolanes might act as molecular walkers along disulfide tracks in locally denatured membrane proteins, surrounded by adaptive micellar membrane defects. Miniscule and versatile, DiSeL tags are also readily available, stable, soluble, and non-toxic.

In My Element: Selenium

<i>In My Element</i>: Selenium

Selenium-Containing Polymers: Perspectives toward Diverse Applications in Both Adaptive and Biomedical Materials

Selenium is a semimetallic element lying in group XVI of the periodic table with its chemical properties resembling sulfur. But owing to its relatively low electronegativity and large atomic radius compared with sulfur, selenium also shows unique properties. This feature endows selenium-containing compounds with high reactivity and sensitivity. Although organic selenium chemistry has been developing very fast, the successful introduction of selenium into polymer science is rather scarce. Fortunately, we have seen a drastic rising trend in the area of selenium-containing polymers over the past decade. In this Perspective, the synthetic routes of selenium-containing polymers are summarized, and their unique stimuli-responsive properties are elaborated on, together with their diverse applications in the field of adaptive and biomedical materials.

Investigation into the intracellular fates, speciation and mode of action of selenium-containing neuroprotective agents using XAS and XFM

BackgroundA variety of selenium compounds have been observed to provide protection against oxidative stress, presumably by mimicking the mechanism of action of the glutathione peroxidases. However, the selenium chemistry that underpins the action of these compounds has not been unequivocally established. MethodsThe synchrotron based techniques, X-ray absorption spectroscopy and X-ray fluorescence microscopy were used to examine the cellular speciation and distribution of selenium in SH-SY5Y cells pretreated with one of two diphenyl diselenides, or ebselen, followed by peroxide insult. ResultsBis(2-aminophenyl)diselenide was shown to protect against oxidative stress conditions which mimic ischemic strokes, while its nitro analogue, bis(2-nitrophenyl)diselenide did not. This protective activity was tentatively assigned to the reductive cleavage of bis(2-aminophenyl)diselenide inside human neurocarcinoma cells, SH-SY5Y, while bis(2-nitrophenyl)diselenide remained largely unchanged. The distinct chemistries of the related compounds were traced by the changes in selenium speciation in bulk pellets of treated SH-SY5Y cells detected by X-ray absorption spectroscopy. Further, bis(2-aminophenyl)diselenide, like the known stroke mitigation agent ebselen, was observed by X-ray fluorescence imaging to penetrate into the nucleus of SH-SY5Y cells while bis(2-nitrophenyl)diselenide was observed to be excluded from the nuclear region. ConclusionsThe differences in activity were thus attributed to the varied speciation and cellular localisation of the compounds, or their metabolites, as detected by X-ray absorption spectroscopy and X-ray fluorescence microscopy. SignificanceThe work is significant as it links, for the first time, the protective action of selenium compounds against redox stress with particular chemical speciation using a direct measurement approach.

Evaluating Gold and Selenium Chemistry for Selective Transformations of Lignin Model Compounds

AbstractApplications of gold and selenium chemistry are reported as novel approaches to promote lignin depolymerization into more valuable chemicals via selective oxidation reactions (alcohol oxidations and Baeyer‐Villiger reactions). In this study, we proposed two different oxidative methodologies using Au/SiO2 and phenylseleninic acid resin (PAR) as stable and reusable catalysts to promote selective transformations of the β‐O‐4 linkage of lignin model compounds. After evaluating the catalytic systems under batch conditions, they were both applied in a packed‐bed reactor for continuous flow operations. By using Au/SiO2 as a catalyst under flow conditions, ketones were efficiently obtained (up to 86% conversion) from the oxidation of alcohols with a residence time (tR) of 30 min. In the case of Baeyer‐Villiger oxidations catalyzed by phenylseleninic acid resin, the corresponding esters were obtained in up to 91% conversion (tR=30 min). Both systems efficiently catalyzed the conversion of the lignin model compounds.magnified image

Rechargeable aluminum-selenium batteries with high capacity.

Rechargeable aluminum (Al) batteries are emerging as a promising post lithium-ion battery technology. Herein, we demonstrate a conceptually new design of rechargeable aluminum-selenium (Al-Se) batteries by understanding the selenium chemistry and controlling the electrode reaction. The Al-Se battery consists of a composite cathode including selenium nanowires and mesoporous carbon (CMK-3) nanorods, an Al metal anode and chloroaluminate ionic liquid electrolyte. The working mechanism of the Al-Se battery is the reversible redox reaction of the Se2Cl2/Se pair confined in the mesopores of CMK-3 nanorods. Al-Se batteries deliver a high reversible capacity of 178 mA h g-1 (by Se mass), high discharge voltages (mainly above 1.5 V), and good cycling/rate performances.