Sulfur Analogues Research Articles

Synthesis of Thiaphenanthridinones from Sulfinate Esters and 2-Borylanilines.

A facile palladium-catalyzed synthesis of thiaphenanthridinones from sulfinate esters and 2-borylanilines is disclosed. Various sulfur analogs of phenanthridinones were synthesized by bromide-selective cross-coupling and cyclization in one step. Further transformations of the obtained thiaphenanthridinones allowed preparing a broad range of thiaphenanthridinone derivatives involving analogs of bioactive compounds.

Role of Cyclic Ketene Dithioacetals in Free Radical Polymerization of Vinyl Chloride

AbstractThe role of the sulfur analog of cyclic ketene acetals in the synthesis of polyvinyl chloride is examined in this study. In this context, whether 2‐methylene‐1,3‐dithiolane (S‐CKA5), 2‐methylene‐1,3‐dithione (S‐CKA6), and 2‐methylene‐1,3‐dithiepane (S‐CKA7) monomers are involved in the radical polymerization of vinyl chloride through the ring opening reaction is examined by quantum chemical methods. In light of calculations at the M06‐2X/6‐31+G(d) level, it is concluded that, in general, S‐CKAs undergo little or no ring‐opening and form block copolymers, mainly with the homopolymerization of S‐CKAs and their ring‐retaining step. It is determined that S‐CKA7 is the most prone to ring‐opening reaction and inserting dithioate links to the polymer backbone. However, the radical ring‐opening of S‐CKA7 is strongly reversible, as in other S‐CKAs.

The Chemistry of Selenosilanes: A Topic Overview.

Selenium-containing molecules represent a valuable class of compounds with a variety of applications in chemical and biological fields. Selenated reagents are used as intermediates to introduce functional groups (e.g., double bonds) onto different substrates or in the synthesis of various selenated derivatives. Among the variety of selenium-containing reagents, silyl selenides are frequently used to transfer a selenated moiety due to the smooth functionalization of the Se-Si bond, which allows for the generation of selenium nucleophilic species under mild conditions. While the use of the analogous sulfur nucleophiles, namely silyl sulfides, has been widely explored, a relatively limited number of reports on selenosilanes have been provided. This contribution will focus on the application of selenosilanes as nucleophiles in a variety of organic transformations, as well as under radical and redox conditions. The use of silyl selenides to prepare metal complexes and as selenium precursors of materials for atomic layer deposition will also be discussed.

A Novel Family of Selenazolo[3,2-a]pyridinium Derivatives Based on Annulation Reactions and Comparative Analysis of Antimicrobial Activity of the Selenium and Sulfur Analogs of Chalcogenazolo[3,2-a]pyridiniums

The synthesis of a novel family selenazolo[3,2-a]pyridin-4-ium derivatives in high yields was developed based on the annulation reactions of 2-pyridineselenenyl chloride with unsaturated heteroatom and heterocyclic compounds. The analogous new thiazolo[3,2-a]pyridin-4-ium derivatives were obtained by the annulation reactions of 2-pyridinesulfenyl chloride. The reactions with vinylic ethers and N-vinylimidazole gave 3- substituted selenazolo[3,2-a]- and -[1,3]thiazolopyridin-4-ium derivatives, whereas reactions with allyl alcohol, allyl chloride, allyl bromide, 3-butenoic, 4-pentenoic and 5-hexenoic acids occurred with the opposite regiochemistry, affording 2-substituted [1,3]chalcogenazolo[3,2-a]pyridiniums. The antibacterial activity of the obtained products against gram-positive and gram-negative bacteria was evaluated, and compounds with high activity were discovered. A comparison of the antibacterial properties of [1,3]selenazolo[3,2-a]pyridin-4-ium derivatives with their sulfur analogs shows a higher activity of the selenium compounds.

Monothiolactide, a New Monomer for the Synthesis of Recyclable, Alternating Ester-Thioester Polymers.

Aliphatic polyesters and polythioesters are very interesting alternatives for current fossil-based and degradation-resistant plastics, due to their high (bio)degradability and (chemical) recyclability potential. Two important examples include polylactide (PLD), currently leading the synthetic bioplastics market, and its sulfur analog polythiolactide (PTLD). Both polymers can be made by ring-opening polymerization (ROP) of their corresponding (thio)dilactones, lactide (LD) and thiolactide (TLD) respectively. In this work, the benefits of esters and thioesters were combined in one material by the successful catalytic synthesis and ROP of monothiolactide (MTL), an unprecedented monomer containing half a LD and half a TLD structural unit. MTL can be obtained by a simple direct condensation of biobased lactic acid and thiolactic acid aided by Brønsted acid catalysis. The novel, but simple monomer showed to be easily polymerized with triethylamine to materials containing alternating lactic and thiolactic ester units with a very high molar mass. The lower stability of MTL (vs. TLD) resulted in improved ROP thermodynamics, while also fast and controllable polymerization kinetics were observed. The new polymers feature a good chemical recycling and hydrolytic degradation potential with important improvements compared to PTLD and PLD. Finally, a successful co-polymerization with commercial LD was shown, paving the way towards industrialization.

Scaffold-Hopping Strategies in Aurone Optimization: A Comprehensive Review of Synthetic Procedures and Biological Activities of Nitrogen and Sulfur Analogues.

Aurones, particular polyphenolic compounds belonging to the class of minor flavonoids and overlooked for a long time, have gained significative attention in medicinal chemistry in recent years. Indeed, considering their unique and outstanding biological properties, they stand out as an intriguing reservoir of new potential lead compounds in the drug discovery context. Nevertheless, several physicochemical, pharmacokinetic, and pharmacodynamic (P3) issues hinder their progression in more advanced phases of the drug discovery pipeline, making lead optimization campaigns necessary. In this context, scaffold hopping has proven to be a valuable approach in the optimization of natural products. This review provides a comprehensive and updated picture of the scaffold-hopping approaches directed at the optimization of natural and synthetic aurones. In the literature analysis, a particular focus is given to nitrogen and sulfur analogues. For each class presented, general synthetic procedures are summarized, highlighting the key advantages and potential issues. Furthermore, the biological activities of the most representative scaffold-hopped compounds are presented, emphasizing the improvements achieved and the potential for further optimization compared to the aurone class.

Synthesis and Conformational Dynamics of Selenanthrene (Oxides): Establishing an Energetic Flexibility Index for Scaffolds.

The use of new dynamic scaffolds for constructing inorganic and organometallic complexes with enhanced reactivities is an important new research direction. Toward this fundamental aim, an improved synthesis of the dynamic scaffold selenanthrene, along with its monoxide, trans-dioxide and the previously unknown trioxide, is reported. A discussion of the potential reaction mechanism for selenanthrene is provided, and all products were characterized using 1H, 13C, and 77Se nuclear magnetic resonance (NMR) spectroscopy and single-crystal X-ray crystallography. The dynamic ring inversion processes (i.e., "butterfly motion") for selenanthrene and its oxides were investigated using variable-temperature 1H NMR and density functional theory calculations. The findings suggest that selenanthrene possesses a roughly equal barrier to inversion as its sulfur analogue, thianthrene. However, selenanthrene oxides evidently possess larger inversion barriers as compared to their sulfur analogues due to the enhanced electrostatic intramolecular interactions inherent between the highly polar selenium-oxygen bond and adjacent C-H moieties. Finally, we propose a quantitative "flexibility index" in deg/(kcal/mol) for various tricyclic scaffolds to provide researchers with a comparative scale of dynamic motion across many different systems.

Hypervalent Sulfur Derivatives as Sulfenylating Reagents: Visible-Light-Mediated Direct Thiolation of Activated C(sp2)-H Bonds with Dihalosulfuranes.

In contrast to hypervalent iodine compounds, the chemistry of their sulfur analogues has been considerably less explored. Herein, we report the direct C-H bond thiolation of electron-rich heterocycles, arenes, and 1,3-dicarbonyls by dichlorosulfuranes under mild conditions. Mechanistic studies and density functional theory calculations suggest the radical chain mechanism of the disclosed transformation. The key to success is attributed to a strikingly low S-Cl bond dissociation energy, which enables the generation of radical species upon exposure to daylight.

Recent Advances in the Palladium‐Catalyzed Synthesis of Unnatural Tryptophans

AbstractUnnatural tryptophans are introduced to explore and engineer the dynamics, function and properties of modified proteins because of intrinsic fluorescence decay, participation in various π‐system interactions, and high occurrences of tryptophan nucleolus in proteins. Due to its role in protein stability and utility as a fluorophore, it becomes a useful unit for protein studies. Several unnatural tryptophans including the oxygen and sulfur analogues have been constructed as endogenous tryptophan analogues to modify the fluorescent character with minimal perturbation to the native structure, while others have been synthesized to probe the cellular mechanisms of protein synthesis. A number of efficient methods for the construction of this important building block, including Larock indolisation, Heck coupling, Negishi coupling and Sonagashira coupling followed by cyclisation have been widely studied and patented as well, by different research groups. Surprisingly, there is a scarcity of any comprehensive reviews on palladium catalyzed synthesis of unnatural tryptophans. Therefore, we summarized the development of different palladium catalysts, ligands and synthetic approaches for the unnatural tryptophans from 2005 to the most recent results. To the best of our knowledge, this is the first review on the synthesis of unnatural tryptophans.

Bis(1-methylimidazol-2-yl) diselenide and its evaluation as a chemical radio-protector: role of kinetic rate constants for ROS scavenging and glutathione peroxidase like activity

Bis(1-methylimidazol-2-yl) diselenide (MeImSe), a derivative of selenoneine, has been examined for bimolecular rate constants for scavenging of various radiolytically and non-radiolytically generated reactive oxygen species (ROS). Further, its potential to show glutathione peroxidase (GPx)-like activity and to protect in vitro models of DNA and lipid against radiation induced strand breakage and lipid peroxidation, respectively were studied. The results confirmed that MeImSe scavenged all major short-lived (hydroxyl radical) and long-lived (peroxyl radical, carbonate radical, nitrogen dioxide radical, hypochlorite and hydrogen peroxide) oxidants involved in the radiation toxicity either directly or through GPx-like catalytic mechanism. The rate constants of MeImSe for these oxidants were found to be comparable to analogous sulfur and selenium-based compounds. The enzyme kinetics study established that MeImSe took part in the GPx cycle through the reductive pathway. Further, MeImSe inhibited the radiation induced DNA strand cleavage and lipid peroxidation with half maximal inhibitory concentration (IC50) of ∼ 60 μM and ∼100 μM, respectively. Interestingly, MeImSe treatment in the above concentration range (>100 μM) did not show any significant toxicity in normal human lung fibroblast (WI26) cells. The balance between efficacy and toxicity of MeImSe as a chemical radioprotector was attributed to the formation of less reactive intermediates during its oxidation/reduction reactions as evidenced from NMR studies. Highlights MeImSe, a derivative of selenoneine protects DNA and lipid from radiation damage MeImSe scavenges all major short- and long-lived oxidants involved in radiation toxicity Rate constants of MeImSe for ROS scavenging determined by pulse radiolysis technique First organoselenium compound reported to scavenge nitrogen dioxide radical MeImSe exhibits GPx-like activity through reductive pathway

Reactions of hypobromous acid with dimethyl selenide, dimethyl diselenide and other organic selenium compounds: kinetics and product formation.

Selenium (Se) is an essential micronutrient for many living organisms particularly due to its unique redox properties. We recently found that the sulfur (S) analog for dimethyl selenide (DMSe), i.e. dimethyl sulfide (DMS), reacts fast with the marine oxidant hypobromous acid (HOBr) which likely serves as a sink of marine DMS. Here we investigated the reactivity of HOBr with dimethyl selenide and dimethyl diselenide (DMDSe), which are the main volatile Se compounds biogenically produced in marine waters. In addition, the reactivity of HOBr with further organic Se compounds was tested, i.e., SeMet (as N-acetylated-SeMet), and selenocystine (SeCys2 as N-acetylated-SeCys2), as well as the phenyl-analogs of DMSe and DMDSe, respectively, diphenyl selenide (DPSe) and diphenyl diselenide (DPDSe). Apparent second-order rate constants at pH 8 for the reactions of HOBr with the studied Se compounds were (7.1 ± 0.7) × 107 M-1 s-1 for DMSe, (4.3 ± 0.4) × 107 M-1 s-1 for DMDSe, (2.8 ± 0.3) × 108 M-1 s-1 for SeMet, (3.8 ± 0.2) × 107 M-1 s-1 for SeCys2, (3.5 ± 0.1) × 107 M-1 s-1 for DPSe, and (8.0 ± 0.4) × 106 M-1 s-1 for DPDSe, indicating a very high reactivity of all selected Se compounds with HOBr. The reactivity between HOBr and DMSe is lower than for DMS and therefore this reaction is likely not relevant for marine DMSe abatement. However, the high reactivity of SeMet with HOBr suggests that SeMet may act as a relevant quencher of HOBr.

Sulphur ion implantation into O2, CO, and CO2 ices: Implications for the formation of sulphur-bearing molecules in the Kuiper Belt

Previous experimental work has systematically investigated the radiolytic sulphur chemistry arising as a result of the implantation of reactive sulphur ions into various oxygen-bearing molecular ices (e.g., H2O, CO2) so as to better understand the surface chemistry of the Galilean moons of Jupiter, where sulphur ions are sourced from the giant Jovian magnetosphere. However, significantly less attention has been paid to analogous sulphur chemistry occurring under conditions relevant to the Kuiper Belt, where sulphur ions supplied by the solar wind may implant into the surfaces of icy bodies that are rich in volatile oxygen-bearing molecular ices such as O2, CO, or CO2. This paper presents the results of a study on the implantation of 290–400 keV S+ ions into pure O2, CO, and CO2 ices under temperature, pressure, radiation dose, and ice deposition conditions relevant to the Kuiper Belt, with a particular focus on the potential synthesis of simple inorganic sulphur-bearing molecules (e.g., SO2, OCS, CS2). Experiments involving CO2 ices were also performed at higher temperatures more typically associated with the Galilean moon system so as to determine whether there exist any differences in the chemistry resulting from the implantation of reactive sulphur ions in these two regions of the Solar System. Our results constitute the first systematic investigation of solid-phase sulphur chemistry in the Kuiper Belt mediated by the sulphur ion component of the solar wind, and thus represent an important step forward in our understanding of the astrochemical processes occurring in the outermost depths of the Solar System.

The advantages of methanol-amine solvent mixtures in solution processing of Ge-Sb-S chalcogenide glass thin films

We report on the substantial influence of methanol presence on the dissolution mechanism of Ge20Sb5S75 bulk glass with subsequent superior properties of thin films deposited from such solutions. Raman spectroscopy confirmed significant differences in structural features present in glass solutions prepared from pure amines (n-propylamine and n-butylamine) and their mixtures with methanol. The experiments with dissolved elemental sulfur and Ge25S75 glass analog proved that both antimony and methanol presence induce further splitting of the Ge4S104− cluster structure, which fundamentally affects the properties of deposited thin films. Significant structural and compositional differences were found not only in solutions and as-prepared samples, but also after thin films’ thermal treatment (hard baking up to 210 °C). The as-prepared thin films deposited from amine-methanol mixtures possessed the exact composition of source bulk glass while thin films of other solvent formulations exhibited sulfur deficiency. The annealing up to 210 °C only highlighted this difference. As a result of the different structure of the thin films prepared in this way, the other benefits of methanol addition were found, namely an increase in the refractive index by approx. 0.1 independent of the annealing temperature, or a lower thermally induced thickness contraction (up to 7.5 %).

Chemistry, Metabolism and Neurotoxicity of Organophosphorus Insecticides: A Review

Organophosphorus compounds (OPs) are phosphoric acid derivatives represented by the formula (R2XP=O/S), R as organic groups; however, they need not contain a direct carbon-phosphorus bond. The organophosphorus compounds can be categorized into three classes, viz., organophosphates, carbamates nerve agents. The OPs having application as insecticides are generally phosphorothioates (i.e., containing P=S bond). These sulfur analogs are first bioactivated (in vivo) and converted to oxygen analogs responsible for exerting toxic action. These organophosphorus compounds are esters, fluorides, anhydrides, and amides of phosphoric, phosphorothioate, and phosphorodithioic acids. The toxicity of OPs is related to their molecular structure, metabolism in the targeted organisms, concentration, mode of decomposition, application, ingestion in organisms, etc. Exposure to OPs leads to the appearance of neurological symptoms followed by acute poisoning by targeting the target primarily, acetylcholine (AChE). However, secondary targets and other harmful effects besides nerve system problems are also reported. Organophosphates poison insects and other animals, including birds, amphibians, and mammals. These chemicals can have neural effects (Neurotoxicity), non-neuronal effects, or acute toxicity, which may also result in fatality. Their uncontrollable widespread became a significant threat to the environment; thus, corrective measures have been essential to save living beings and the environment from further damage.

Selenocyanate (SeCN−) acts as an efficient competitive substrate for myeloperoxidase and decreases biological damage induced by hypochlorous acid

The leukocyte-derived enzyme myeloperoxidase (MPO) is a key component of the innate immune response and mediates the killing of pathogens via the generation of the powerful oxidant hypochlorous acid (HOCl). Unintended or excessive formation of this species can however result in damage to host tissues, and this is linked with multiple pathologies associated with acute or chronic inflammation. The active (Compound I) form of MPO is promiscuous and can oxidize multiple alternative anions, in addition to the Cl− used to generate HOCl. These alternative substrates may therefore modulate MPO-mediated HOCl damage. In the current study we examined the hypothesis that selenocyanate (SeCN−), the selenium analogue of thiocyanate (SCN−, a well-established competitive MPO substrate) would inhibit HOCl-mediated damage to human plasma fibronectin (hpFN) or the extracellular matrix laid down by human coronary artery smooth muscle cells. SeCN− modulated HOCl and MPO-mediated damage, in a dose-dependent manner. These data are consistent with SeCN− acting as both a competitive substrate for Compound I of MPO (with IC50 ∼23 μM), and as a direct scavenger of HOCl. Inhibition of protein damage by SeCN− was also detected in the presence of the physiological anions Br−, I− and SCN− at the concentrations typically present in human plasma, consistent with a high affinity of SeCN− for MPO Compound I. In addition, the protective effects of SeCN− and SCN−, as competitive MPO substrates, were additive. Together these data indicate that modest concentrations of SeCN− can, like its sulfur analogue SCN−, act as an effective modulator of inflammation-induced damage.

N-Alkane Biosignatures in a High Arctic Mars Analogue Gossan Deposit

If past life ever existed on Mars, what are the multiple ways it could have been preserved in the Martian geological record? This crucial question is becoming especially relevant the more we uncover about the planet’s ancient wet history. Different acidic and sulfur rich analog environments have been proposed that are comparable to the alteration environments of iron oxides and sulfate minerals on Mars. However, some authors have hypothesized that these past Martian environments might have been cold and semi-dry, similar to polar regions on Earth. As part of the T-MARS team, we studied reactive gossans in the Canadian High Arctic, on Axel Heiberg Island, as an analog environment to similar deposits on Mars. We hypothesized that n-alkane lipids could potentially be an important form of molecular fossils entombed in varying mineral assemblages of sulphates, iron oxides, and phyllosilicates in Arctic gossans, because of their excellent preservation potential relative to most other forms of organic molecules. To determine the preservation potential of lipids in mineralogically varying acidic sulfur rich gossan deposits, this study extracted and quantified n-alkane biomarkers from three different Arctic gossans with gas chromatography–mass spectrometry (GC-MS). Total organic carbon, pH, and mineralogy were also determined. Organic matter was found to be very low in all samples (<1% wt.%). N-alkane analysis also revealed preserved even-over-odd distribution patterns in short chain n-alkanes, most likely from a microbial source, along with evidence for long-chain n-alkanes with odd-over-even distribution from higher plant sources. The presence of these unique chemical biosignatures in low organic, highly acidic, and sulfur rich Mars analog gossans of varying maturity provides evidence that sulfur deposits linked to paleo hydrothermal systems on Mars can be promising targets for preserved organic biosignatures, specifically lipid n-alkanes. The significant diversity in biosignature patterns across samples of varying mineralogy, pH, and oxidation levels within each gossan suggests that n-alkane preservation varies on a small scale in these environments. These factors alone do not definitively account for the variability of n-alkane concentrations and distributions in this study, and additional investigations of these and other influencing factors are needed to determine which specific targets to choose for biosignature search on Mars in future space missions. This exploratory study provides novel insights into the lipid biosignature content in high Arctic Mars analogue gossan deposits.

Determination of Polycyclic Aromatic Hydrocarbons (PAHs) and Sulfur, Nitrogen, and Oxygen Analogs in Fumes from Heated Asphalt by High-Performance Liquid Chromatography – Diode Array Detection (HPLC-DAD)

Polycyclic aromatic hydrocarbons (PAHs), as well as their sulfur (S-PAHs), oxygen (O-PAHs), and nitrogen (N-PAHs) analogs were evaluated in the fumes of asphalt samples produced in Brazilian refineries. The fumes were generated using a laboratory-constructed device for extraction and collection (DEC). Two previously published methodologies for PAHs and S-PAHs evaluation by high-performance liquid chromatography with diode array detection (HPLC-DAD) were employed, together with a new methodology for O and N-PAHs. A total of 54 compounds were assessed. The samples included 31 compounds within the scope of this study, and the emissions were highly dependent upon the heating temperature and asphalt source.

Glutathione is involved in selenium detoxification and suppresses the selenate-induced SULTR1;1 gene expression in plants

Selenium (Se) as a sulfur (S) analog is beneficial to plants. However, excessive Se is toxic. Glutathione (GSH) can protect plant cells from metal toxicity. In this study, we investigated the role of GSH in resistance to Se toxicity and in regulating sulfate/selenate transporter gene expression. We also examined the effects of Se and S treatments on GSH production and growth of Arabidopsis thaliana (a non-Se-accumulator) and broccoli (Brassica oleracea var. italica, a secondary-Se-accumulator). By treating the Arabidopsis wild-type and the glutathione-deficient mutant pad2–1 plants with and without selenate, reduced glutathione, or GSH synthesis inhibitor L-buthionine sulfoximine, we demonstrated that GSH is involved in Se detoxification. The pad2–1 mutant exhibited lower selenate tolerance, and GSH supply alleviated the toxicity. However, selenate treatment reduced GSH levels in a dose-dependent manner, which was further augmented in low sulfur (S) conditions as shown in broccoli plants. Interestingly, the selenate-induced SULTR1;1 gene expression was negatively associated with GSH levels in plants. The pad2–1 mutant showed a much higher AtSULTR1;1 expression than WT under excess Se supply, and GSH supply partially inhibited its expression. Moreover, selenate conferred higher toxicity than selenite under a low S supply in broccoli plants. In contrast, S alleviated selenate toxicity, which was associated with GSH levels. These findings demonstrate the critical role of GSH in resistance to Se toxicity and provide insights into processes related to Se toxicity resistance in plants, which enhances our understanding of metal tolerance for Se biofortification in crops.

Synthesis of Benzoxazinones Sulphur Analogs and Their Application as Bioherbicides: 1.4-Benzothiazinones and 1.4-Benzoxathianones for Weed Control

Eight different compounds inspired by benzoxazinones were synthesized in one simple step with easy purification. These compounds have a sulfur atom instead of the oxygen atom present in benzoxazinones. Furthermore, a new derivative obtained by a Rutkauskas–Beresnevicius reaction was synthesized. These compounds were evaluated in vitro to assess their phytotoxicity in plant cells by the elongation of wheat coleoptiles. The novel compounds showed higher inhibition than benzoxazinones and the positive control, especially at higher concentrations (1000 and 300 μM). Benzoxazinones have been described as histidine deacetylase inhibitors and we therefore evaluated the effect of 1.4-benzothiazinones and 1.4-benzoxathianones against HDA6, one of the most important enzymes of the family, in silico by molecular docking and molecular dynamics. In vitro studies against Echinochloa crus-galli, Lolium rigidum and Portulaca oleracea weeds gave interesting results against the growth of the roots for both monocots and dicots. Specifically, the inhibition was more pronounced against dicots, as in the case of common purslane, whose inhibition at a concentration of 1000 μM was similar to that of the classical herbicide employed as a positive control. Higher inhibition was obtained when an aliphatic group was present in the C2 position of 1.4-benzothiazinones.

Methodologies for the synthesis of 3,4-ethylenedithiothiophene (EDTT) and its derivatives for use as semiconductor materials

In contrast to the wide ranging study of EDOT, its derivatives, and polymer PEDOT that followed its commercialisation by the Bayer research laboratory, far fewer investigations have been devoted to the sulfur analog 3,4-ethylenedithiathiophene (EDTT) 13. To the best of our knowledge, there is no reported review highlighting the methodologies available for the synthesis of EDTT and its derived compounds. Hence, this review sumarises the main methods that have been reported for the synthesis EDTT and its chemistry.