Se-containing Compounds Research Articles

Selenium speciation analysis of selenium-enriched Shiitake mushrooms (Lentinula edodes) by HPLC-ESI-MS

Selenium (Se) is an essential component of critical enzymes and is intricately linked to human health. Shiitake mushrooms (Lentinula edodes) are considered as good dietary supplements for producing Se-enriched foods due to their high protein content and ability to absorb minerals from growth substrates. In this study, the distribution of soluble Se in Se-enriched L. edodes was analyzed by microwave digestion and hydride generation-atomic fluorescence spectrometry (HG-AFS). In order to evaluate the absorption and conversion effect of Se by L. edodes, the Se-containing compounds in selenized L. edodes were quantitatively and qualitatively analyzed by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS). It can be shown that L. edodes possessed a good biological transformation ability of organic Se enrichment though the quantitative analysis of three seleno-amino acids, selenocystine (Se-Cys2), methylselenocysteine (Se-MeSeCys) and selenomethionine (Se-Met), in selenized L. edodes. The structures of three unknown Se-containing compounds were identified by qualitative analysis, the results indicated that the possible structures were selenomethylmethionine (C6H14NO2Se), N-Acetyl-selenomethionine (C7H13NO3Se) and Se-methyl-5-selenoadenosinese-oxide (C12H18N5O3Se). The discovery of these Se compounds filled the research gap and provided a theoretical basis for molecular structure identification and mechanism study of organic Se in Se-enriched L. edodes.

Aluminum-catalyzed direct conversion of lactones to selenolactones in the presence of elemental selenium and its application in the indium-catalyzed syntheses of dibenzyl selenides from benzyl acetates

Se-containing compounds exhibit novel chemical properties and unique pharmacological effects. Although various methods of preparing selenoesters have been reported, the synthetic focus on the related cyclic selenoesters remains insufficient. The conventional methods of synthesizing selenolactones generally involve multistep processes. In this study, an AlBr3/PhSiH3 (Ph = Phenyl) reducing system selectively catalyzed the one-pot conversion of γ-aryl-γ-lactones and elemental Se to γ-aryl-γ-selenolactones in good yields. This reducing system strongly activates elemental Se rather than elemental S. Additionally, an In(OAc)3/PhSiH3 (OAc = acetate) reducing system effectively catalyzed the direct conversion of linear benzyl acetates, which constitute substructures of lactones, and elemental Se to dibenzyl selenide derivatives.

Design, synthesis and bioactivity evaluation of selenium-containing PI3Kδ inhibitors

PI3Kδ inhibitors play an important role in the treatment of leukemia, lymphoma and autoimmune diseases. Herein, using our reported compounds as the lead compound, we designed and synthesized a series of selenium-containing PI3Kδ inhibitors based on quinazoline and pyrido[3,2-d]pyrimidine skeletons. Among them, compound Se15 showed sub-nanomolar inhibition against PI3Kδ and strong δ-selectivity. Moreover, Se15 showed potent anti-proliferative effect on SU-DHL-6 cells with an IC50 value of 0.16 μM. Molecular docking study showed that Se15 was able to form multiple hydrogen bonds with PI3Kδ and was close proximity and stacking with PI3Kδ selective region. In conclusion, the Se-containing compound Se15 bearing pyrido[3,2-d]pyrimidine scaffold is a novel potent and selective PI3Kδ inhibitor. The introduction of selenium can enrich the structure of PI3Kδ inhibitors and provide a new idea for design of novel PI3Kδ inhibitors.

Nontoxic Levels of Se-Containing Compounds Increase Survival by Blocking Oxidative and Inflammatory Stresses via Signal Pathways Whereas High Levels of Se Induce Apoptosis.

Selenium is a main group element and an essential trace element in human health. It was discovered in selenocysteine (SeC) by Stadtman in 1974. SeC is an encoded natural amino acid hailed as the 21st naturally occurring amino acid (U) present in several enzymes and which exquisitely participates in redox biology. As it turns out, selenium bears a U-shaped toxicity curve wherein too little of the nutrient present in biology leads to disorders; concentrations that are too great, on the other hand, pose toxicity to biological systems. In light of many excellent previous reviews and the corpus of literature, we wanted to offer this current review, in which we present aspects of the clinical and biological literature and justify why we should further investigate Se-containing species in biological and medicinal contexts, especially small molecule-containing species in biomedical research and clinical medicine. Of central interest is how selenium participates in biological signaling pathways. Several clinical medical cases are recounted; these reports are mainly pertinent to human cancer and changes in pathology and cases in which the patients are often terminal. Selenium was an option chosen in light of earlier chemotherapeutic treatment courses which lost their effectiveness. We describe apoptosis, and also ferroptosis, and senescence clearly in the context of selenium. Other contemporary issues in research also compelled us to form this review: issues with CoV-2 SARS infection which abound in the literature, and we described findings with human patients in this context. Laboratory scientific studies and clinical studies dealing with two main divisions of selenium, organic (e.g., methyl selenol) or inorganic selenium (e.g., sodium selenite), are discussed. The future seems bright with the research and clinical possibilities of selenium as a trace element, whose recent experimental clinical treatments have so far involved dosing simply and inexpensively over a set of days, amounts, and time intervals.

HOCl-Activated Reactive Organic Selenium Delivery Platform for Alleviation of Inflammation.

Selenium plays an important role in the biological system and can be used to treat various types of diseases. However, the current selenium delivery systems face the problems of low activity of released Se-containing compounds or nonspecific toxicity of reactive organic selenium donors in living systems. In response to these problems, we constructed a reactive organic selenium delivery platform by the activation of HOCl. Compared with prodrugs without activation capability, the hypochloroselenoite derivatives released from the present platform after activation displayed higher reactivity and could react with various nucleophiles to participate in specific life processes. Taking the selected compound (DHU-Se1) as an example, we found that it could alleviate the process of inflammation by blocking the polarization of macrophages from M0 to M1. Therefore, the development of this system is of great significance for expanding the application of selenium-containing compounds and treating related diseases.

Clickable Selenylation - a Paradigm for Seleno-Medicinal Chemistry.

Selenium (Se) is an emerging versatile player in medicinal chemistry. The incorporation of Se into small molecules and natural products could have multiple benefits. However, the lack of efficient methods for the synthesis of Se-containing chemical library has greatly hindered the development of seleno-medicinal chemistry. With the aim to address this issue, we proposed the development of "clickable selenylation" reactions, which can be used in the synthesis of Se-containing in situ library and DNA-encoded library (SeDEL), thereby quickly producing ultra-large collections of Se-containing compounds and boosting the development of seleno-medicinal chemistry. This research paradigm can be concluded as "clickable selenylation chemistry development→in situ library construction/SeDEL synthesis→phenotype- or target-based screening→seleno-hit compound".

Tuning the photocatalytic properties of porphyrins for hydrogen evolution reaction: An in-silico design strategy

Porphyrins constitute a class of attractive materials for harvesting sunlight and promote chemical reactions following their natural activity for the photosynthetic process in plants. In this work, we employ an in-silico design strategy to propose novel porphyrin-based materials as photocatalysts for hydrogen evolution reaction (HER). More specifically, a set of meso-substituted porphyrins with donor-acceptor architecture are evaluated within the density functional theory (DFT) framework, according to these screening criteria: i) broad absorption spectrum in the ultraviolet–visible (UV–Vis) and near infrared (NIR) range, ii) suitable redox potentials to drive the uphill reaction that lead to molecular hydrogen formation, iii) low exciton binding free energy ( E b ), and iv) low hydrogen binding free energy (ΔG H ), a quantity that should present low HER overpotentials, ideally ΔG H = 0. The outcomes indicate that the Se-containing compound, where the donor ligands are attached to the porphyrin core by the spacer, outstands as the most promising candidate that is presented in this work. It displays a broad absorption in the visible and NIR regions to up to 1000 nm, suitable catalytic power, low E b (in special in high dielectric constant environment, such as water) and the lowest ΔG H = +0.082 eV. This is comparable, in absolute values, to the value exhibited by platinum (ΔG H = −0.10 eV), one of the most efficient catalysts for HER. • Novel porphyrin-based materials are proposed as photocatalysts for HER. • The screening strategy includes the UV–Vis absorption profile, catalytic power and ΔG H . • All candidates have catalytic power for electron transfer. • The Se-based compound is the most promising candidate in the series. • Nitrogen is the most relevant catalytic site for hydrogen production in these materials.

Selenium Valence-to-Core X-ray Emission Spectroscopy and Kβ HERFD X-ray Absorption Spectroscopy as Complementary Probes of Chemical and Electronic Structure.

Selenium X-ray absorption spectroscopy (XAS) has found widespread use in investigations of Se-containing materials, geochemical processes, and biologically active sites. In contrast to sulfur Kβ X-ray emission spectroscopy (XES), which has been found to contain electronic and structural information complementary to S XAS, Se Kβ XES remains comparatively underexplored. Herein, we present the first Se Valence-to-Core (VtC) XES studies of reduced Se-containing compounds and FeSe dimers. Se VtC XES is found to be sensitive to changes in covalent Se bonding interactions (Se–Se/Se–C/Se–H bonding) while being relatively insensitive to changes in Fe oxidation states as selenide bridges in FeSe dimers ([Fe2Se2]2+ vs [Fe2Se2]+). In contrast, Se Kβ HERFD XAS is demonstrated to be quite sensitive to changes in the Fe oxidation state with Se Kβ HERFD XAS demonstrating experimental resolution equivalent to Kα HERFD XAS. Additionally, computational studies reveal both Se VtC XES and XAS to be sensitive to selenium protonation in FeSe complexes.

Small molecule selenium-containing compounds: Recent development and therapeutic applications.

Selenium (Se) is an essential micronutrient of organism and has important function. It participates in the functions of selenoprotein in several manners. In recent years, Se has attracted much attention because of its therapeutic potential against several diseases. Many natural and synthetic organic Se-containing compounds were studied and explored for the treatment of cancer and other diseases. Studies have showed that incorporation of Se atom into small molecules significantly enhanced their bioactivities. In this paper, according to different applications and structural characteristics, the research progress and therapeutic application of Se-containing compounds are reviewed, and more than 110 Se-containing compounds were selected as representatives which showed potent activities such as anticancer, antioxidant, antifibrolytic, antiparasitic, antibacterial, antiviral, antifungal and central nervous system related effects. This review is expected to provide a basis for further study of new promising Se-containing compounds.

Improving the biological properties of Fomes fomentarius MG835861 exopolysaccharide by bioincorporating selenium into its structure

Selenium (Se) is one of the essential elements for human health, where Se-containing compounds can prevent cancer and reduce mortality by regulating of the cell cycle and apoptosis. Exopolysaccharides from Fomes fomentarius have been used in traditional medicine to treat cancer. It appears that the combination of Se and fungal polysaccharides may be more effective. The effect of adding Na2SeO3 to the culture medium of the Iranian medicinal fungus F. fomentarius is investigated in this study. Adding 20 mg/L Na2SeO3 to the culture medium changed the F. fomentarius morphology and improved the structure of exopolysaccharides. Several methods, including FTIR, EDS, and ICP-OES, confirmed the presence of Se in the exopolysaccharides of F. fomentarius. The results demonstrated that the addition of Na2SeO3 increased the antibacterial activity against S.aureus (60%) and antioxidant activity (17.4%) significantly (p < 0.05). The cytotoxicity of these exopolysaccharides against 5637, A549, and KYSE30 cancer cells was also significantly increased (p < 0.05), and the viability of EPS-Se treated 5637 cells reached less than 10% after 72 h. Finally, F. fomentarius Se-polysaccharides can be used as a dietary supplement.

Selenium Compounds as Novel Potential Anticancer Agents.

The high number of new cancer incidences and the associated mortality continue to be alarming, leading to the search for new therapies that would be more effective and less burdensome for patients. As there is evidence that Se compounds can have chemopreventive activity, studies have begun to establish whether these compounds can also affect already existing cancers. This review aims to discuss the different classes of Se-containing compounds, both organic and inorganic, natural and synthetic, and the mechanisms and molecular targets of their anticancer activity. The chemical classes discussed in this paper include inorganic (selenite, selenate) and organic compounds, such as diselenides, selenides, selenoesters, methylseleninic acid, 1,2-benzisoselenazole-3[2H]-one and selenophene-based derivatives, as well as selenoamino acids and Selol.

Selenium metabolism and toxicity in the yeast Saccharomyces cerevisiae

Selenium (Se) is an essential trace element of considerable interest in humans from both a nutritional and a toxicological perspective because of the narrow margin between intakes that result in efficacy and toxicity. It is used as selenocysteine in a few selenoproteins with important physiological functions. Moreover, at supranutritional doses, Se-containing compounds have attracted interest as potential anticancer agents with high efficacy and selectivity against cancer cells. Thus, Se is becoming a widely used dietary supplement. However, accumulating evidence indicate that adverse health effects are associated with excess dietary supplementation. Therefore, characterizing the toxicity of Se metabolic intermediates are important steps to better understand both the beneficial and toxic mechanisms of Se. This review focuses on the metabolism of Se and the biological mechanisms explaining the toxicity of important Se-metabolites in the yeast Saccharomyces cerevisiae, which can be used as a model system to understand the mode of action and the biological effects of supranutritional Se in higher eukaryotes.

Regulation of Selenium/Sulfur Interactions to Enhance Chemopreventive Effects: Lessons to Learn from Brassicaceae.

Selenium (Se) is an essential trace element, which represents an integral part of glutathione peroxidase and other selenoproteins involved in the protection of cells against oxidative damage. Selenomethionine (SeMet), selenocysteine (SeCys), and methylselenocysteine (MeSeCys) are the forms of Se that occur in living systems. Se-containing compounds have been found to reduce carcinogenesis of animal models, and dietary supplemental Se might decrease cancer risk. Se is mainly taken up by plant roots in the form of selenate via high-affinity sulfate transporters. Consequently, owing to the chemical similarity between Se and sulfur (S), the availability of S plays a key role in Se accumulation owing to competition effects in absorption, translocation, and assimilation. Moreover, naturally occurring S-containing compounds have proven to exhibit anticancer potential, in addition to other bioactivities. Therefore, it is important to understand the interaction between Se and S, which depends on Se/S ratio in the plant or/and in the growth medium. Brassicaceae (also known as cabbage or mustard family) is an important family of flowering plants that are grown worldwide and have a vital role in agriculture and populations’ health. In this review we discuss the distribution and further interactions between S and Se in Brassicaceae and provide several examples of Se or Se/S biofortifications’ experiments in brassica vegetables that induced the chemopreventive effects of these crops by enhancing the production of Se- or/and S-containing natural compounds. Extensive further research is required to understand Se/S uptake, translocation, and assimilation and to investigate their potential role in producing anticancer drugs.

Selenium-containing core-expanded naphthalene diimides for high performance n-type organic semiconductors

The incorporation of heavy atoms into molecular backbone is an extremely straightforward strategy for fine-tuning the optoelectronic properties of organic semiconductors. However, it is rarely studied in n-type small molecules. Herein, by selenium substitution of NDI3HU-DTYM2, two Se-decorated core-expanded naphthalene diimides (NDI) derivatives DTYM-NDI3HU-DSYM ( 1 ) and NDI3HU-DSYM2 ( 2 ) were synthesized. In comparison with the reference S-containing compound NDI3HU-DTYM2, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels of 1 and 2 were fine-tuned with ∆HOMO of about 0.2 eV, ∆LUMO of 0.1 eV and the narrowed HOMO-LUMO gaps. More surprisingly, the as-spun organic thin film transistors (OTFTs) based on 1 and 2 both showed µ e,sat values as high as 1.0 cm2 V−1 s−1, which are 2-fold higher than that of NDI3HU-DTYM2 with the same device structure and measurement conditions. In addition, the single crystal OFET devices based on Se-containing compound NDI2BO-DSYM2 showed a high µ e,sat value of 1.30 cm2 V−1 s−1. The molecular packing of NDI2BO-DSYM2 in single crystals (two-dimensional supramolecular structure formed by intermolecular Se···Se interactions) is quite different from that of a S-containing compound NDI-DTYM2 (one dimensional supramolecular structure formed by intermolecular π-π stacking). Therefore, the Se substitution can cause dramatic change about molecular stacking model, giving rise to high n-type OTFT performance. Our results demonstrated an effective strategy of the heavy atom effect for designing novel organic semiconductors.

Investigation of Different Selenium Sources and Supplying Methods for Selenium Enrichment of Basil Vegetable (A Case Study under Calcareous and Non-calcareous Soil Systems).

Selenium (Se) is a crucial component of selenoaminoacids and selenoproteins. Therefore, Se-enriched agricultural products can reduce health complications induced by Se deficiency. This research was carried out to investigate the effects of Se bio-enrichment on Basil grown in calcareous and non-calcareous soil systems and also to evaluate the changes in Se concentration in the soil after harvesting. The experiment executed in two calcareous and one non-calcareous soil systems, and different Se application methods (control, soil application, seed inoculation, foliar application, and soil + foliar application) were administered. Selenobacteria, a plant growth-promoting rhizobacteria (PGPR), derived from the soil was used as a biofertilizer, compared to the other Se sources. The results showed that both soil types and the methods of Se application had significant effects (P ˂ 0.01) on root and shoot dry weights and concentrations of P, K, Zn, Fe, and Se in both of the root and shoot. Shoot dry weight of plants treated with foliar Se was maximum in the calcareous soil. Compared to the control treatment, foliar application of Se increased shoot Se content in both calcareous and non-calcareous soils by 242% and 204%, respectively. Furthermore, the increase in shoot Se concentration in calcareous soil induced by Se application increased the concentration of other nutrients in the shoot and root. Plant growth parameters and concentrations of nutrients were significantly increased by using selenobacter inoculum. The application of Se-containing compounds can improve vegetable quality. Considering the daily requirement of the human body for minerals and nutrients, enriching basil with Se can play an important role in community health. Moreover, some patents have reported the effectiveness of endophyte bacteria.

Accumulation and speciation of selenium in biofortified vegetables grown under high boron and saline field conditions

Selenium (Se) biofortification, as an agronomic-based strategy, is utilized to produce Se-enriched food products for increasing Se intake in inhabitants in Se-deficient regions. This strategy can be accomplished by soil and foliar application of Se or by growing crops in soils naturally high in Se. In this study, different cruciferous vegetables were field-grown in high boron (B) and saline soils of central California containing naturally high levels of Se. We investigated whether Se biofortification occurs in salt- and B-tolerant vegetables grown in poor-quality soil. The uptake of Se and other elements occurred in all vegetables. In plant tissues, Se speciation analyses showed greatest percentages of Se-containing compounds were contained in organic Se forms (monomethylated) and as selenate in the inorganic Se forms. Selenium-enriched vegetables produced from saline soils high in B and Se can be a natural source of Se-biofortified food that can be consumed as bioactive food products.

Computational Investigation into the Ni(SeNHC2(CN)2)2 and Ni(SNHC2(CN)2)2 Complexes as Potential Catalysts for Hydrogen Production.

To reduce our carbon footprint, we must look at alternative non-carbon-containing fuels to prevent continued global climate change. One environmentally friendly alternative fuel is molecular hydrogen. Herein the Ni(SeNHC2(CN)2)2 complex was studied using DFT to determine the thermodynamics associated with the electrocatalytic formation of H2(g). From the calculated thermodynamics, it appears that the Ni(SeNHC2(CN)2)2 complex is predicted to catalyze the production of H2 gas under mildly reducing conditions relative to the SHE. Notably, the thermodynamics are better than the values calculated for the analogous Ni(SNHC2(CN)2)2 complex which has been shown experimentally to catalyze the formation of H2 gas in aqueous solution. Regarding possible kinetic reactivity, the HOMO-LUMO gap energies were calculated. From the gap energies, it is expected that the Se-containing compounds would be more reactive to electron transfer in the third reduction step, meaning therefore that a smaller overpotential would be needed to drive the reduction of Red2-H2 relative to SRed2-H2 in agreement with past experimental work. Thus, the use of Se in such compounds may offer a means to improve the catalysts for H2 production.

Selenium-doped carbon: An unexpected efficient solid acid catalyst for Beckmann rearrangement of ethyl 2-(2-aminothiazole-4-yl)-2-hydroxyiminoacetate

In this study, Se-doped carbon, which is different from reported Se-containing compounds or materials, did not act as an oxygen carrier catalyst in the reaction of ethyl 2-(2-aminothiazole-4-yl)-2-hydroxyiminoacetate with H2O2 but participated in the reaction as a solid acid catalyst, and thus, the Beckmann rearrangement occurred to produce the useful Cefixime derivative. Unique steric hindrance of carbon support restrained the side reactions through nucleophilic reaction paths. As the first example for using Se-containing materials as solid acid catalyst, this work may inspire new ideas for Se catalyst development. This novel material has advantages of easy fabrication method and high catalyst turnover number (TON = 1.1 × 104).

Sulfur- and Selenium-Containing Compounds Potentially Exhibiting Al Ion Conductivity.

We have created a set of crystalline model structures exhibiting straight lines of Al3+ connected to chalcogenides (O2- , S2- , and Se2- ) connected to metal cations of varying valence (Sr2+ , Y3+ , Zr4+ , Nb5+ , and Mo6+ ). They were relaxed with density functional theory computations and analysed by Bader partitioning. As Al3+ ions are supposed to strongly interact with their atomic environment, we studied the electron density topology induced by higher-valent cations in the extended chemical neighbourhood of Al. In fact, we found a general decrease of ionic charges and an increasing displacement of the chalcogenides towards higher-valent ions for the heavier chalcogens. Therefore, we comprehensively screened S- and Se-containing compounds for candidates theoretically exhibiting low migration barriers for Al3+ ions by using Voronoi-Dirichlet partitioning and bond valence site energy calculations. The basis for this search is the Inorganic Crystal Structure Database. Indeed, we could extract six promising candidates with low Al3+ migration barriers. which are even lower than the barriers for any other element inside of these materials. This will encourage efforts towards preparing suitable Al3+ conductors.

Selenocysteine inhibits human osteosarcoma cells growth through triggering mitochondrial dysfunction and ROS-mediated p53 phosphorylation.

Osteosarcoma represents the most common primary malignant bone tumor in children and adolescents, which shows severe resistance toward standard chemotherapy because of high invasive capacity and growing incidence. Selenocysteine (SeC) is a naturally available Se-containing amino acid that displays splendid anticancer activities against several human tumors. However, little information about SeC-induced growth inhibition against human osteosarcoma is available. Herein, the anticancer efficiency and underlying mechanism of SeC against human osteosarcoma were evaluated in vitro and in vivo. The results revealed that SeC significantly inhibited MG-63 human osteosarcoma cells growth in vitro through induction of S-phase arrest and apoptosis, as reflected by the decrease of cyclin A and CDK-2, PARP cleavage, and caspases activation. SeC treatment also resulted in mitochondrial dysfunction through affecting Bcl-2 family expression. Moreover, SeC triggered p53 phosphorylation by inducing reactive oxygen species (ROS) overproduction. ROS inhibition effectively blocked SeC-induced cytotoxicity and p53 phosphorylation. Importantly, MG-63 human osteosarcoma xenograft growth in nude mice was significantly suppressed in vivo through triggering apoptosis and p53 phosphorylation. These results indicated that SeC had the potential to inhibit human osteosarcoma cells growth in vitro and in vivo through triggering mitochondrial dysfunction and ROS-mediated p53 phosphorylation, which validated the potential application of Se-containing compounds in treatment of human osteosarcoma.