Selenium (Se) is an essential micronutrient that participates in redox regulation and cellular homeostasis. Selenium-containing ionic liquids (ILsSe) have emerged as hybrid compounds combining the properties of organoselenium molecules with the tunable features of ionic liquids. In this study, we evaluated the cytotoxicity, interaction with mercury (Hg2+), pharmacokinetic profile, and antiproliferative activity of three ILsSe (C1, C2, and C3). Human peripheral blood mononuclear cells (PBMCs) were used to assess cytotoxicity, showing that ILsSe were generally well tolerated at low micromolar concentrations, although their effects were dependent on exposure time and dose. The interaction of ILsSe with Hg2+ was investigated using a thiol oxidase assay, with diphenyl diselenide (DPDS) as a reference compound. The results indicate that ILsSe can interact with Hg2+, likely through the formation of Se-Hg species. In parallel, in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis suggested that these compounds have physicochemical properties compatible with central nervous system exposure, including predicted blood-brain barrier permeability. In U87-MG glioblastoma cells, compound C3 exhibited concentration and time-dependent antiproliferative effects at low micromolar concentrations. These effects were associated with alterations in redox homeostasis, modulation of cell cycle progression, and induction of late-stage cell death. In general, ILsSe are biologically active compounds whose effects depend on dose and exposure time, warranting further investigation to clarify their toxicological profile and mechanisms of action. This study highlights the importance and biological potential of selenium-containing compounds.

This review outlines an overview of selenium-containing gold compounds, framed within the context of gold chemistry. It emphasizes key synthetic strategies and structural features of Au-Se complexes, encompassing both gold-(I) and gold-(III) species. Various classes of selenium ligands are discussed, including selenols, selenoureas, selenones, and selenium-NHCs, among other organoselenium ligands. Despite the relatively limited number of studies, these complexes exhibit diverse biological activities, including anticancer, antimicrobial, and anti-inflammatory effects. Mechanistic evidence suggests that these activities primarily arise from inhibition of thiol- and selenol-containing enzymes (e.g., thioredoxin reductase), disruption of redox homeostasis, or the induction of reactive oxygen species (ROS) formation. The synergistic interplay between gold and selenium centers is crucial for modulating these effects. This review highlights emerging trends in ligand optimization, providing a foundation for the rational design of next-generation selenium-based gold therapeutics.

Cryptococcus neoformans cause cryptococcal meningitis, particularly in individuals with compromised immune systems. In this context, urease plays a crucial role in fungal survival by facilitating infection spread and penetration of the blood-brain barrier, making this enzyme a potential target for antifungal therapy. Eleven benzoylselenoureas (BSU) were synthesized in 15-75% yields via a one-pot approach using benzoyl chloride, KSeCN, and anilines containing electron-donating or electron-withdrawing groups. The antifungal and urease inhibitory activities of these compounds were evaluated against C. neoformans. For comparison, the corresponding benzoylthioureas (BTU) analogs were also synthesized to assess the influence of the chalcogen atom on biological activity. Antifungal activity was determined using the broth microdilution assay, while urease inhibition was evaluated through ammonia quantification. Additionally, inhibitor-enzyme interactions were investigated using homology modeling, molecular docking, molecular dynamics simulations, and density functional theory (DFT) calculations. The BSU compounds demonstrated higher antifungal activity than their BTU analogs, with minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values ranging from 1 to 16 mg/L (except for BSU3, BSU8, and BSU11). The most active compounds against yeast were BSU1 and BSU5, which feature an OMe group at the meta position of the aniline moiety. Furthermore, BSU compounds exhibited strong urease inhibition, with ureIC50 values ranging from 0.95 to 13.95 nM. Computational studies revealed that BSU compounds predominantly coordinate with the Ni-(II) center in a bidentate mode, likely involving the amide oxygen and selenium atoms. These findings indicate that BSU compounds effectively inhibit urease activity and C. neoformans growth at low concentrations, reinforcing urease as a promising target for antifungal therapy. Molecular modeling confirmed the strong affinity of BSU compounds for urease, supporting their potential as novel antifungal agents.

Oxidation of organic substrates is a pivotal transformation, with profound chemical and biological implications. This review covers the synthetic application of organotellurium compounds as promoters or activators of oxidizing agents in such reactions. This research field has evolved from utilizing stoichiometric amounts of organotellurium as oxidizing agents, producing copious amounts of side products, to using this class of compounds as catalysts. Another unique feature associated with using organotellurium compounds as catalysts for oxidation is the possibility of employing less hazardous oxidizing agents, such as peroxides or combinations of oxygen, photosensitizers, and light. These characteristics render the application of organotellurium compounds attractive from both an economic and environmental perspective.

A novel strategy to catalyze alkylation reactions through chalcogen bond interaction using a supramolecular structure is presented herein. Utilizing just 1.0 mol % of selenoxide-pillar[5]arene (P[5]SeO) as the catalyst we achieved efficient catalysis in the cyanation of benzyl bromide in water. Our approach demonstrated high efficiency and effectiveness, with the results supported by designed control experiments and theoretical models, highlighting the catalytic effect of the pillar[5]arene through noncovalent interactions. Quantum-chemical calculations (ωB97X-D/def2-TZVP@SMD) pointed out that the catalyzed cyanation reaction followed an SN2-like mechanism, with energy barriers (ΔH≠) ranging from 16.7 to 18.2 kcal mol-1, exhibiting dissociative character depending on the para-substituent. 1H NMR analysis revealed that P[5]SeO acted as a catalyst through inclusion complex formation, facilitating the transfer of the electrophilic substrate to the aqueous solution for nucleophilic displacement. Our reaction protocol proved applicable to various substrates, including aromatic and alpha-carbonyl derivatives. The use of sodium azide as the nucleophile was also feasible. Importantly, our method allowed scalability, and the catalyst P[5]SeO could be recovered and reused effectively for multiple reaction cycles, showcasing sustainability.

Alkylation reactions and their products are considered crucial in various contexts. Synthetically, the alkylation of a nucleophile is usually promoted using hazardous alkyl halides. Here, we aim to highlight the potential of pnictogen (ammonium or phosphonium) and chalcogen salts (sulfonium, selenonium, and telluronium) to function as alkylating agents. These compounds can be considered as non-volatile electrophilic alkyl reservoirs. We will center our discussion on the strategies developed in recent years to expand the synthetic utility of these salts in terms of transferable alkyl groups, substrate scope, and product selectivity.

The syntheses of previously unknown sulfide- and telluride-pillar[n]arenes are reported here. These macrocycles, among others, were tested as catalysts for alkylation reactions in aqueous solutions. Telluride-pillar[5]arene (P[5]-TePh) showed the best performance, emulating the behavior of the methyltransferase enzyme cofactor S-adenosyl-l-methionine. Using 1.0 mol % of P[5]-TePh, benzyl bromides reacted with NaCN/NaN3 in water, yielding organic nitriles/azides. The catalyst was recycled and efficiently reused for up to six cycles. 1H NMR experiments indicate a possible interaction between the substrate and P[5]-TePh's cavity.

Sodium hypochlorite pentahydrate (NaClO·5H2O, 1) has recently been employed in organic synthesis as an oxidant for alcohols, sulfides, glycols, etc. In most of these reactions, however, reagent 1 functions just as a simple oxidant, and the variations of the reactions have not been well explored. In this study, we report another useful and fascinating reaction, in which reagent 1 functions as a green chlorinating reagent toward β,γ-unsaturated carboxylic acid (2). When substrate 2 was stirred at room temperature with 1 (2 eq) in acetonitrile for 1 h, α,β-unsaturated lactone (3) was obtained in moderate yields (up to 62%). The same reaction proceeded in various organic and aqueous solvents as well. When excess reagent 1 was employed, lactone 3 was further oxidized to the corresponding epoxide (4) for some cases. The conversion is initiated by electrophilic attack of HOCl to the C=C bond of 2 to generate a chloronium ion intermediate, which is cyclized to β-chlorolactone (5) and then 3 through the elimination of HCl. The usefulness of 1 as a chlorinating reagent was further demonstrated in the electrophilic substitution of activated aromatic compounds.

Urease is a metalloenzyme that contains two Ni(II) ions in its active site and catalyzes the hydrolysis of urea into ammonia and carbon dioxide. The development of effective urease inhibitors is crucial not only for mitigating nitrogen losses in agriculture but also for offering an alternative treatment against infections caused by resistant pathogens that utilize urease as a virulence factor. This study focuses on synthesizing and investigating the urease inhibition potential of Biginelli Adducts bearing a boric acid group. An unsubstituted or hydroxy-substituted boronic group in the Biginelli adducts structure enhances the urease inhibitory activity. Biophysical and kinetics studies revealed that the best Biginelli adduct (4e; IC50 = 132 +/- 12 mu mol/L) is a mixed inhibitor with higher affinity to the urease active site over an allosteric one. Docking studies confirm the interactions of 4e with residues essential for urease activity and demonstrate its potential to coordinate with the nickel atoms through the oxygen atoms of carbonyl or boronic acid groups. Overall, the Biginelli adduct 4e shows great potential as an additive for developing enhanced efficiency fertilizers and/or for medical applications.

The application of chalcogenonium salts in organic synthesis has grown enormously in the past decades since the discovery of the methyltransferase enzyme cofactor S-adenosyl-L-methionine (SAM), featuring a sulfonium center as the reactive functional group. Chalcogenonium salts can be employed as alkylating agents, sources of ylides and carbon-centered radicals, partners for metal-catalyzed cross-coupling reactions and organocatalysts. Herein, we will focus the discussion on heavier chalcogenonium salts (selenonium and telluronium), presenting their utility in synthetic organic transformations and, whenever possible, drawing comparisons in terms of reactivity and selectivity with the respective sulfonium analogues.

Organothiocyanates and selenocyanates are valuable compounds, both in terms of functional group interconversion and due to their biological activities. In this contribution, we report the synthesis of a series of these important substances in a mixture of water and dimethyl carbonate (20/1 proportion) using potassium thio- or selenocyanates salts and organic bromides. The key to the effectiveness of the reaction is a chalcogen bond interaction between a selenonium salt catalyst and the organic substrate.

Heterocycles containing chalcogens as heteroatoms or embedded in several different functional groups founded interesting applications in medicinal chemistry, coordination chemistry, and materials. Recent development on their preparation is reported here.

The ability of chalcogenium salts to transfer an electrophilic moiety to a given nucleophile is well known. However, up to date, these reagents have been used in stoichiometric quantities, producing a substantial amount of waste as byproducts of the reaction. In this report, we disclose further investigation of selenonium salts as S-adenosyl-L-methionine (SAM) surrogates for the alkylation of nucleophiles in aqueous solutions. Most importantly, we were able to convert the stoichiometric process to a catalytic system employing as little as 10 mol % of selenides to accelerate the reaction between benzyl bromide and other alkylating agents with sodium cyanide in water. Probe experiments including Se-77 NMR and HRMS of the reaction mixture have unequivocally shown the presence of the selenonium salt in the reaction mixture.

The reaction between Oxone (R) and various di(hetero)aryl or alkyl diselenides enables the formation of an electrophilic selenium species in situ capable to induce the oxyselenocyclization of 2-allylphenols. This versatile and safe protocol was explored to combine two privileged scaffolds into the structure of products: the 2,3-dihydrobenzofuran core and an organoselenium moiety. Fifteen 2-[(organoselanyl)methyl]-2,3-dihydrobenzofurans were produced, broadening considerably the number of known examples of this hybrid compound. Moreover, preparation of sulfur and tellurium 2,3-dihydrobenzofurans derivatives was also successfully demonstrated.

Activation of NBS in acetic acid and a catalytic amount of DBU promotes an intramolecular oxybromination of 2-allylphenols to produce highly aggregated value and densely functionalized 2-bromomethyl-2,3-dihydrobenzofurans.

Electron-deficient and electron-rich alkenes can be efficiently converted to vicinal dichlorides employing a mixture of 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) and zinc chloride. This straightforward protocol offers an easier to handle and safer alternative to the use of chlorine gas or other common chlorinating agents. Experimental evidences suggest that the solubility of the chloride salt is essential for the formation of a chlorine/trichloride anion as the effective chlorinating agent.

Excessive production of reactive species in living cells usually has pathological effects. Consequently, the synthesis of compounds which can mimic the activity of antioxidant enzymes has inspired great interest. In this study, a variety of diselenoamino acid derivatives from phenylalanine and valine were tested to determine whether they could be functional mimics of glutathione peroxidase (GPx) and substrates for liver thioredoxin reductase (TrxR). Diselenides C and D showed the best GPx mimicking properties when compared with A and B. We suppose that the catalytic activity of diselenide GPx mimics depends on the steric effects, which can be influenced by the number of carbon atoms between the selenium atom and the amino acid residue and/or by the amino acid lateral residue. Compounds C and D stimulated NADPH oxidation in the presence of partially purified hepatic mammalian TrxR, indicating that they are substrates for TrxR. Our study indicates a possible dissociation between the two pathways for peroxide degradation (i.e., via a substrate for TrxR or via mimicry of GPx) for compounds tested in this study, except for PhSeSePh, and the antioxidant activity of diselenoamino acids can also be attributed to their capacity to mimic GPx and to be a substrate for mammalian TrxR.

Activation of H2O2by LiBr and AcOH is efficiently achieved for dibromination of alkenes in high yields and selectivity.

1,4-Diazabicyclo[2.2.2] octane (DABCO) is a suitable Lewis base that acts as an organocatalyst in the activation of N-chlorosuccinimide (NCS) towards the chlorination of alkenes. The chloriranium ion formed from NCS and the alkene, can be intermolecularly opened by a nucleophile, such as acetic acid, to produce highly functionalized trans-chloro esters in high yields. The protocol is also applied to the synthesis of chlorohydrins and chloro ethers using water or methanol as nucleophiles instead of acetic acid. Brominated analogs can also be synthesized from alkenes and N-bromosuccinimide (NBS) in the presence of various basic catalysts. However, the reaction patterns seem to be remarkably different. The catalytic performance of bases in the bromoesterification of alkenes was found to be strongly affected by their Bronsted basicity, suggesting that acetyl hypobromite, formed in situ from NBS and acetic acid, acts as a real brominating agent in these systems.

beta-Caryophyllene is one of the most widespread sesquiterpenes, found as a main hydrocarbon component in various essential oils, e.g., copaiba oil, which is used for years in folk medicine and occupies an important position in Brazilian pharmaceutical export. The novel selective oxidation of p-caryophyllene by molecular oxygen using the chloride-free Pd(OAc)(2)/p-benzoquinone (BQ) catalytic system has been developed. The reaction gives two main products, both arising from the allylic oxidation of the sterically encumbered endocyclic double bond, whereas the terminal double bond of the substrate remains intact. The catalytic process efficiently operates under 10 atm of oxygen in the absence of auxiliary metal co-catalysts, which are commonly used in related systems. The reaction can also occur under atmospheric pressure ill the presence of Cu(OAc)(2) to accelerate the re-oxidation of p-hydroquinone by molecular oxygen. Both allylic acetates, obtained from beta-car-yophyllene in 75-85% combined yields in both systems, are natural compounds found in essential oils of some plants and have well pronounced perfume properties. To the best of our knowledge, the present work reports the first synthesis of these functionalized sesquiterpenic compounds potentially useful as ingredients of synthetic perfumes and pharmacological compositions.