Diphenyl Diselenide Research Articles

Monosubstituted Doublet Sn(I) Radical Featuring Substantial Unquenched Orbital Angular Momentum

Due to their intrinsic high reactivity, isolation of heavier analogues of carbynes remains a great challenge. Here, we report the synthesis and characterization of a neutral monosubstituted Sn(I) radical (2) supported by a sterically hindered hydrindacene ligand, which represents the first tin analogue of a free carbyne. Different from all Sn(I/III) species reported thus far, the presence of a sole Sn-C σ bond in 2 renders the remaining two Sn 5p orbitals energetically almost degenerate, of which one is singly occupied and the other is empty. Consequently, its S = 1/2 ground state possesses two-fold orbital pseudo-degeneracy and substantial unquenched orbital angular momentum, as evidenced by one component of its g matrix (1.957, 1.896, and 1.578) being considerably less than 2. Consistent with this unique electronic structure, 2 can bind to an N-heterocyclic carbene to afford a neutral two-coordinate Sn(I) radical and initiate a one-electron transfer to benzophenone to furnish a Sn(II)-ketyl radical anion adduct. As a manifestation of its Sn-centered radical nature, 2 reacts with diphenyl diselenide and p-benzoquinone to form Sn-S and Sn-O bonds, respectively.

Synthesis, Reactions, and Antioxidant Properties of Bis(3-amino-1-hydroxybenzyl)diselenide.

Bis(3-amino-1-hydroxybenzyl)diselenide containing two ortho groups was synthesized from 7-nitro-3H-2,1-benzoxaselenole and in situ generated sodium benzene tellurolate (PhTeNa). One-pot synthesis of 1,3-benzoselenazoles was achieved from bis(3-amino-1-hydroxybenzyl)diselenide and aryl aldehydes using acetic acid as a catalyst. The X-ray crystal structure of chloro-substituted benzoselenazole revealed a planar structure with T-shaped geometry around the Se atom. Both natural bond orbital and atoms in molecules calculations confirmed the presence of secondary Se···H interactions in bis(3-amino-1-hydroxybenzyl)diselenide and Se···O interactions in benzoselenazoles, respectively. The glutathione peroxidase (GPx)-like antioxidant activities of all compounds were evaluated using a thiophenol assay. Bis(3-amino-1-hydroxybenzyl)diselenide and benzoselenazoles showed better GPx-like activity compared to that of the diphenyl diselenide and ebselen, used as references, respectively. Based on 77Se{1H} NMR spectroscopy, a catalytic cycle for bis(3-amino-1-hydroxybenzyl)diselenide using thiophenol and hydrogen peroxide was proposed involving selenol, selenosulfide, and selenenic acid as intermediates. The potency of all GPx mimics was confirmed by their in vitro antibacterial properties against the biofilm formation of Bacillus subtilis and Pseudomonas aeruginosa. Additionally, molecular docking studies were used to evaluate the in silico interactions between the active sites of the TsaA and LasR-based proteins found in Bacillus subtilis and Pseudomonas aeruginosa.

Thiol modifier effects of diphenyl diselenides: insight from experiment and DFT calculations

A combination of spectroscopic, chromatographic and computational approaches was employed to investigate the reaction of several diselenides with a thiolate nucleophile, leading to the breaking of the selenium–selenium (Se–Se) bond.

Photoinduced Construction of Thieno[3,4-c]quinolin-4(5H)-ones/Selenopheno[3,4-c]quinolin-4(5H)-ones Using Diphenyl Disulfide or Diphenyl Diselenide as Sulfur or Selenium Sources

A photocatalytic synthesis of thieno[3,4-c]quinolin-4(5H)-ones/selenopheno[3,4-c]quinolin-4(5H)-ones using diphenyl disulfide or diphenyl diselenide as sulfur or selenium sources was developed. Two C-S/Se bonds and one C-C bond were constructed simultaneously without transition metals and other additives.

Controlled CO labilization of tungsten carbonyl precursors for the low-temperature synthesis of tungsten diselenide nanocrystals

We report a low-temperature colloidal synthesis of WSe2 nanocrystals from tungsten hexacarbonyl and diphenyl diselenide in trioctylphosphine oxide (TOPO). We identify TOPO-substituted intermediates, W(CO)5TOPO and cis-W(CO)4(TOPO)2 by infrared spectroscopy. To confirm these assignments, we synthesize aryl analogues of phosphine-oxide-substituted intermediates, W(CO)5TPPO (synthesized previously, TPPO = triphenylphosphine oxide) and cis-W(CO)4(TPPO)2 and fac-W(CO)3(TPPO)3 (new structures reported herein). Ligation of the tungsten carbonyl by either the alkyl or aryl phosphine oxides results in facile labilization of the remaining CO, enabling low-temperature decomposition to nucleate WSe2 nanocrystals. The reactivity in phosphine oxides is contrasted with syntheses containing phosphine ligands, where substitution results in decreased CO labilization and higher temperatures are required to induce nanocrystal nucleation.

Organoselenium functionalized SBA-15 as a new catalyst for the cyanide-free conversion of oximes to nitriles

BackgroundHere we report a new selenium-based heterogeneous catalyst, which was prepared from the immobilization of diphenyl diselenide on amine-functionalized Santa Barbara Amorphous-15 (SBA-15). The catalyst characterization study has been confirmed by different analysis methods including Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction patterns (XRD), field-emission scanning electron microscopy (FE-SEM), and Brunauer–Emmett–Teller (BET) surface area analysis.ResultsThe newly designed catalyst was successfully applied in the green dehydration reaction of oximes to corresponding nitriles in the presence of hydrogen peroxide/air.To demonstrate the role of the catalyst in this study, the model reaction was also carried out in the absence of the catalyst and a trace yield of the relevant product was achieved.ConclusionIn this way, a series of nitrile derivatives were obtained with 72–96% yields, also, the catalyst could be separated easily and recycled for four consecutive runs with no obvious drop in catalytic activity.

Copper(I)-Catalyzed Three-Component Selenosulfonation of Maleimides with Sulfonyl Hydrazides and Diselenides via Radical Relay.

By employing Cu(CH3CN)4PF6 as the catalyst and tert-butyl hydroperoxide as the oxidant, we realized a three-component radical selenosulfonation of substituted maleimides, sulfonyl hydrazides, and diphenyl diselenides, providing a series of 3,4-selenosulfonylated succinimides in moderate to good yields. This reaction features broad substrate scopes, high functional-group tolerability, and feasibility of gram-scale synthesis, enabling one-step construction of C-SO2 and C-Se bonds under mild reaction conditions. Preliminary mechanistic studies support the free-radical-induced pathway.

Locust Bean Gum Nano-Based Hydrogel for Vaginal Delivery of Diphenyl Diselenide in the Treatment of Trichomoniasis: Formulation Characterization and In Vitro Biological Evaluation.

Trichomoniasis is the most common nonviral sexually transmitted infection in the world, but its available therapies present low efficacy and high toxicity. Diphenyl diselenide (PhSe2) is a pharmacologically active organic selenium compound; however, its clinical use is hindered by its lipophilicity and toxicity. Nanocarriers are an interesting approach to overcome the limitations associated with this compound. This study designed and evaluated a vaginal hydrogel containing PhSe2-loaded Eudragit® RS100 and coconut oil nanocapsules for the treatment of trichomoniasis. Nanocapsules presented particle sizes in the nanometric range, positive zeta potential, a compound content close to the theoretical value, and high encapsulation efficiency. The nanoencapsulation maintained the anti-Trichomonas vaginalis action of the compound while improving the scavenger action in a DPPH assay. The hydrogels were prepared by thickening nanocapsule suspensions with locust bean gum (3%). The semisolids maintained the nanometric size of the particles and the PhSe2 content at around the initial concentration (1.0 mg/g). They also displayed non-Newtonian pseudo-plastic behavior and a highly mucoadhesive property. The chorioallantoic membrane method indicated the absence of hemorrhage, coagulation, or lysis. The compound, from both non-encapsulated and nano-based hydrogel delivery systems, remained on the surface of the bovine vaginal mucosa. Therefore, the formulations displayed the intended properties and could be a promising alternative for the treatment of trichomoniasis.

Diphenyl diselenide modulates antioxidant status, inflammatory and redox-sensitive genes in diesel exhaust particle-induced neurotoxicity

This study seeks to determine the influence of diphenyl diselenide (DPDSe) on redox status, inflammatory and redox-sensitive genes in diesel exhaust particle (DEP)-induced neurotoxicity in male albino rats. Male Wistar albino rats were administered nasally with DEP (30 and 60 μg/kg) and treated with intraperitoneal administration of 10 mg/kg DPDSe. Non-enzymatic (lipid peroxidation and conjugated diene concentrations) and enzymatic (catalase, superoxide dismutase, glutathione peroxidase) antioxidant indices and activity of acetylcholinesterase enzyme were evaluated in brain tissues of the rats. Furthermore, the expression of genes linked to oxidative stress (HO-1, Nrf2), pro-inflammatory (NF-KB, IL-8, TNF-α) anti-inflammatory (IL-10) and brain-specific (GFAP, ENO-2) genes were also determined. The results indicated that DPDSe caused a notable reduction in the high levels of thiobarbituric acid reactive substances and conjugated diene observed in the brain of DEP-administered rats. DPDSe also reversed the observed reduction in catalase, superoxide dismutase and glutathione peroxidase enzyme activities in the brain of DEP-administered rats. Lastly, the downregulation of genes associated with redox homeostasis, anti-inflammatory and brain-specific genes and upregulation of pro-inflammatory genes observed in the DEP-treated groups were ameliorated by DPDSe. The immediate restoration of altered biochemical conditions and molecular expression in the brain of DEP-treated rats by DPDSe further validates its use as a promising therapeutic candidate for restoring neurotoxicity linked with DEP-induced oxidative stress.

Diphenyl Diselenide Alleviates Tert-Butyl Hydrogen Peroxide-Induced Oxidative Stress and Lipopolysaccharide-Induced Inflammation in Rat Glomerular Mesangial Cells.

Hyperglycemia, oxidative stress, and inflammation play key roles in the onset and development of diabetic complications such as diabetic nephropathy (DN). Diphenyl diselenide (DPDS) is a stable and simple organic selenium compound with anti-hyperglycemic, anti-inflammatory, and anti-oxidative activities. Nevertheless, in vitro, the role and molecular mechanism of DPDS on DN remains unknown. Therefore, we investigated the effects of DPDS on tert-butyl hydrogen peroxide (t-BHP)-induced oxidative stress and lipopolysaccharide (LPS)-induced inflammation in rat glomerular mesangial (HBZY-1) cells and explored the underlying mechanisms. DPDS attenuated t-BHP-induced cytotoxicity, concurrent with decreased intracellular ROS and MDA contents and increased SOD activity and GSH content. Moreover, DPDS augmented the protein and mRNA expression of Nrf2, HO-1, NQO1, and GCLC in t-BHP-stimulated HBZY-1 cells. In addition, DPDS suppressed LPS-induced elevations of intracellular content and mRNA expression of interleukin (IL)-6, IL-1β and TNF-α. Furthermore, LPS-induced NFκB activation and high phosphorylation of JNK and ERK1/2 were markedly suppressed by DPDS in HBZY-1 cells. In summary, these data demonstrated that DPDS improves t-BHP-induced oxidative stress by activating the Nrf2/Keap1 pathway, and also improves LPS-induced inflammation via inhibition of the NFκB/MAPK pathways in HBZY-1 cells, suggesting that DPDS has the potential to be developed as a candidate for the prevention and treatment of DN.

P075 Initial results of an international effort in screening new agents against Candida auris

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM Candida auris is an emergent fungal pathogen. A global concern regarding this yeast is its resistance to many currently available antifungal drugs, virulence factors, capacity to spread in hospital environments, and its misidentification, resulting in high rates of morbidity, and mortality.ObjectiveIn response to this challenge, new effective options of antifungals against C. auris are urgent. Therefore, our consortium evaluated the in vitro activity of two agents with novel mechanisms of action, and negligible toxicity in studies to date: diphenyl diselenide (PhSe)2 and nikkomycin Z (NikZ), alone and in association with conventional antifungals (azoles, echinocandins, polyenes) against C. auris.MethodsA total of 11 isolates of C. auris were included in this in vitro study, 10 from South Asian clade I and 1 from South Africa clade III. In vitro tests (dilution and interaction assays) were performed according to the CLSI M27-Ed4 protocol. Interactions between (PhSe)2 or nikkomycin Z, and amphotericin B (AmB), fluconazole (FCZ), micafungin (MYC), or caspofungin (CSP) were evaluated by checkerboard assays, resulting in Fractional Inhibitory Concentration Indexes (FICi). Tests were read after incubation for 48 h at 35°C. The minimal inhibitory concentration (MIC) was defined as the lowest concentration able to inhibit 100% (PhSe)2, AmB and NikZ, or 50% (FCZ, MYC, and CSP) of the fungal growth. Interaction between the drugs was classified as strong synergism when FICi <0.5, weak synergism when 0.5 <FICi <1, additive when 1 <FICi <2, indifferent when FICi = 2, or antagonistic when FICi >2.Results(PhSe)2 and NikZ alone were unable to inhibit C. auris even by the higher concentrations tested (32 μg/ml and 64–128 μg/ml, respectively). An additive effect of (PhSe)2 was detected with MYC against 30% of the isolates, however, its combination with AmB was antagonistic against all of the isolates, as well as against one isolate with FCZ. All of the other interactions with (PhSe)2 were indifferent. In contrast, NikZ showed strong or weak synergism in association with CSP, AmB, FLU and MYC against 100%, 90%, 30% and 14% of the C. auris isolates tested, respectively. An additive interaction of NikZ was also detected with MYC against 86% of the isolates. No antagonistic effect was detected in the combination of NikZ with the antifungals tested.ConclusionAlthough (PhSe)2 seems to not have potential as a future anti-C. auris drug, NikZ showed a productive avenue for further studies, mainly in combined therapy against this pathogen.

Molecular Decomposition Routes of Diaryl Diselenide Precursors in Relation to the Phase Determination of Copper Selenides.

1H nuclear magnetic resonance (NMR), 77Se NMR, and powder X-ray diffraction (XRD) were used to monitor the thermal decomposition of diphenyl and dibenzyl diselenide precursors toward the synthesis of copper selenides. Copper was found to promote the decomposition of both precursors. The inorganic nanocrystals and organic byproducts were sensitive to the specific diaryl diselenides and the presence of oleylamine and copper. Molecular mechanistic routes are proposed. Berzelianite (Cu1.8Se), klockmannite (CuSe), umangite (Cu3Se2), and both petřı́čekite (m-CuSe2) and krutaite (p-CuSe2) were identified as products. Multistep transformations between phases were discovered through reactions with the organoselenium precursors, and organic decomposition products are proposed.

Visible‐Light‐Mediated Photocatalytic Synthesis of 2‐Substituted Oxazole‐5‐carbaldehydes Promoted by Benzeneseleninic Acid

AbstractBenzeneseleninic acid was used under visible light irradiation (white LEDs) to promote the oxidative cyclization of N‐propargyl amides to the respective 2‐substituted oxazole‐5‐carbaldehydes. A total of twelve 2‐aryl oxazole‐5‐carbaldehydes, six of them so far unprecedented, were prepared in 30–90 % yield in just 1 hour of reaction at room temperature. No metal catalysts, nor strong oxidants or heating were necessary, making this a mild method to access a valuable class of compounds. The only co‐products are water and diphenyl diselenide, that can be recovered and converted to new benzeneseleninic acid for a new reaction.

Initial Results of the International Efforts in Screening New Agents against Candida auris.

Background: Candida auris is an emergent fungal pathogen and a global concern, mostly due to its resistance to many currently available antifungal drugs. Objective: Thus, in response to this challenge, we evaluated the in vitro activity of potential new drugs, diphenyl diselenide (PhSe)2 and nikkomycin Z (nikZ), alone and in association with currently available antifungals (azoles, echinocandins, and polyenes) against Candida auris. Methods: Clinical isolates of C. auris were tested in vitro. (PhSe)2 and nikZ activities were tested alone and in combination with amphotericin B, fluconazole, or the echinocandins, micafungin and caspofungin. Results: (PhSe)2 alone was unable to inhibit C. auris, and antagonism or indifferent effects were observed in the combination of this compound with the antifungals tested. NikZ appeared not active alone either, but frequently acted cooperatively with conventional antifungals. Conclusion: Our data show that (PhSe)2 appears to not have a good potential to be a candidate in the development of new drugs to treat C. auris, but that nikZ is worthy of further study.

Beneficial Effect of Selenium Doped Carbon Quantum Dots Supplementation on the in vitro Development Competence of Ovine Oocytes.

BackgroundAfter the synthesis of selenium doped carbon quantum dots (Se/CDs) via a step-by-step hydrothermal synthesis method with diphenyl diselenide (DPDSe) as precursor, the beneficial effects of Se/CDs’ supplementation on the in vitro development competence of ovine oocytes were firstly investigated in this study by the assay of maturation rate, cortical granules’ (CGs) dynamics, mitochondrial activity, reactive oxygen species (ROS) production, epigenetic modification, transcript profile, and embryonic development competence.ResultsThe results showed that the Se/CDs’ supplementation during the in vitro maturation (IVM) process not only enhanced the maturation rate, CGs’ dynamics, mitochondrial activity and embryonic developmental competence of ovine oocytes, but remarkably decreased the ROS production level of ovine oocytes. In addition, the expression levels of H3K9me3 and H3K27me3 in the ovine oocytes were significantly up-regulated after the Se/CDs’ supplementation, in consistent with the expression levels of 5mC and 5hmC. Moreover, 2994 up-regulated differentially expressed genes (DEGs) and 846 repressed DEGs were found in the oocytes after the Se/CDs’ supplementation. According to the analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), these DEGs induced by the Se/CDs’ supplementation were positively related to the progesterone mediated oocyte maturation and mitochondrial functions. And these remarkably up-regulated expression levels of DEGs related to oocyte maturation, mitochondrial function, and epigenetic modification induced by the Se/CDs’ supplementation further confirmed the beneficial effect of Se/CDs’ supplementation on the in vitro development competence of ovine oocytes.ConclusionThe Se/CDs prepared in our study significantly promoted the in vitro development competence of ovine oocytes, benefiting the extended research about the potential applications of Se/CDs in mammalian breeding technologies.

In Vitro Activity of Ebselen and Diphenyl Diselenide Alone and in Combination with Drugs against Trichophyton mentagrophytes Strains

Background: Dermatophytoses are one of the most prevalent infectious diseases in the world for which the pace of developing new drugs has not kept pace with the observed therapeutic problems. Thus, searching for new antifungals with an alternative and novel mechanism of action is necessary. Objective: This study aimed to evaluate the antifungal activity of ebselen and diphenyl diselenide against Trichophyton mentagrophytes clinical isolates. Methods: In vitro antifungal susceptibility was assessed for organoselenium compounds used alone or in combination with allylamines and azoles according to the 3rd edition of the CLSI M38 protocol. Results: Ebselen demonstrated high antifungal activity with MICGM equal to 0.442 μg/mL and 0.518 μg/mL in the case of human and animal origin strains, respectively. The values of MICGM of diphenyl diselenide were higher: 17.36 μg/mL and 13.45 μg/mL for the human and animal isolates, respectively. Synergistic or additive effects between terbinafine and ebselen or diphenyl diselenide were observed in the case of 12% and 20% strains, respectively. In turn, the combination of itraconazole with diphenyl diselenide showed a synergistic effect only in the case of 6% of the tested strains, whereas no synergism was shown in the combination with ebselen. Conclusions: The results highlight the promising activity of organoselenium compounds against Trichophyton mentagrophytes. However, their use in combinational therapy with antifungal drugs seems to be unjustified due to the weak synergistic effect observed.

Diphenyl diselenide suppresses key virulence factors of Candida krusei, a neglected fungal pathogen

Candida krusei is a candidiasis etiological agent of relevance in the clinical setting because of its intrinsic resistance to fluconazole. Also, it has opened up new paths in the area of alternative therapeutic techniques. This project demonstrated the effects of diphenyl diselenide (PhSe)2 and p-cloro diphenyl diselenide (pCl-PhSe)2, two organochalcogen compounds, on relevant virulence factors for the early stage of the C. krusei host interaction and infection process. Both compounds inhibited adherence of C. krusei to both polystyrene surfaces and cervical epithelial cells and biofilm formation; the structure of the biofilm was also changed in a dose-dependent manner. In addition, both compounds inhibited C. krusei growth, but (PhSe)2 significantly increased the time duration of the lag phase and delayed the start of the exponential phase in growth kinetics. (PhSe)2 has more potential antifungal activity than (pCl-PhSe)2 in inhibiting the adherence to epithelial cells, biofilm formation, and growth of C. krusei.

TBHP‐Mediated Selenocyclization of N‐Allylbenzamides/Benzthioamides via In‐Situ Generation of “PhSeOH” Species**

AbstractA simple tert‐butyl hydroperoxide (TBHP)‐mediated method has been developed to construct selenated oxazolines/thiazolines under microwave irradiation. The selenocyclization of N‐allylbenzamides/benzthioamides could be achieved owing to the addition of an active electrophilic selenium species, generated in situ from diphenyl diselenide on reacting with TBHP, at their olefinic site. The reaction mechanism was confirmed by intercepting and characterizing all the proposed intermediates by ESI‐QTOF‐MS and NMR study. This method offers several advantages including simpler reaction conditions, shorter reaction time, catalyst‐free, thus rendering a competent alternative to the synthesis of selenated oxazolines/thiazolines in yields of upto 95 %.

Contribution of Opioid and Nitrergic Systems to m-Trifluoromethyl diphenyl Diselenide Attenuates Morphine-Induced Tolerance in Mice

m-Trifluoromethyl diphenyl diselenide (TFDD) has antinociceptive and antidepressant-like properties and attenuates morphine withdrawal signs in mice. This study investigated if TFDD affects the development of morphine tolerance to its antinociceptive and antidepressant-like effects in mice. We also investigated whether TFDD modulates signaling pathways related to morphine tolerance, including the opioid receptors and some parameters of the nitrergic system. Male adult Swiss mice received morphine alone (5 mg/kg, subcutaneous) and in combination with TFDD (10 mg/kg, intragastric) for 7 days. Mice were subjected to hot plate and forced swim tests on days 1, 3, 5, and 7 of the experimental protocol. Repeated TFDD administrations avoided tolerance development mediated by morphine, including its antinociceptive and antidepressant-like effects. A single morphine dose increased MOR and NOx but decreased iNOS contents in the mouse cerebral cortex. In turn, single morphine and TFDD co-administration restored the MOR and iNOS protein levels. On the other hand, morphine repeated doses enhanced DOR and reduced MOR and NOx contents, whereas the morphine and TFDD association reestablished DOR and NOx levels in the mouse cerebral cortex. In conclusion, some opioid and nitrergic system parameters might contribute to TFDD attenuation of antinociceptive and antidepressant-like tolerance induced by morphine in mice.

Diphenyl diselenide as a bifunctional electrolyte additive in a high-voltage LiNi0.8Mn0.1Co0.1O2/graphite battery

To increase the practical energy density and capacity of high-nickel cathode materials, it is crucial to develop a novel electrolyte additive that can enhance the unstable electrolyte/electrode interface over a wide operating voltage range. In this study, diphenyl diselenide (DPDS) is selected as a bifunctional electrolyte additive for high-voltage LiNi0.8Mn0.1Co0.1O2 (NMC811)/graphite batteries, considering the energy levels of its highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). DPDS is oxidized and reduced prior to the decomposition of ethylene carbonate (EC) and diethyl carbonate (DEC), forming protective layers on both electrode surfaces. The DPDS-driven layers prevent parasitic reactions, maintain the structural stability of electrodes, and reduce active lithium loss. As a result, in the high voltage window of 2.8–4.5 V, DPDS enhances the capacity retention of NMC811/graphite batteries from 68.0% to 82.0% after 200 cycles at 1C. This paper provides an understanding of the DPDS operating principle in high voltage NMC811/graphite full cells to achieve high energy density.