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Reactions of bipyridyl‐functionalized imidazole‐thiones and selones with MeX (X=I, OTf) afforded sulfenyl and selenenyl cations [(NNC)EMe]X (2/3, E=S, Se). Further reactions of these main‐group cations with [Cu(CH3CN)4]BF4, Cu(OTf) furnished dicationic [{Cu(μ‐I)(NNC)EMe}2][Y]2 (5/6, Y=BF4, OTf) and tricationic copper(I) complexes [Cu{(NNC)EMe}2](OTf)2BF4 (7 a/7 b) when employed [(NNC)EMe]I and [(NNC)EMe]OTf respectively. All these cationic complexes were characterized by various spectroscopic techniques, including X‐ray diffraction analysis. The solid‐state structures revealed novel bonding modes of the cations. The cationic nature of new complexes was analyzed by the 77Se NMR spectroscopy, which indicated different electronic environments around the selenium centers. The cations [(NNC)EMe]X (X= I, OTf), and (NNC)SMe bearing copper complex [{Cu(μ‐I)(NNC)EMe}2][Y]2 proved as potential candidates for alkylation of various Lewis bases and as molecular catalyst in aldehyde‐alkyne‐amine coupling reactions, respectively. The latter catalytic reactions yielded a range of three‐component products in good to excellent yields with low catalyst loading under solvent‐free conditions, which demonstrate the potential utility of group‐16 cations as ancillary ligands in homogeneous catalysis. [ABSTRACT FROM AUTHOR]

Previously unknown betulin and allobetulin derivatives, which are of interest as potential biologically active substances, were synthesized by replacing chlorine in 3,28-bis(chloroacetoxy)betulin and 3-chloroacetoxyallobetulin with pharmacophoric cycloheteryl sulfide groups. [ABSTRACT FROM AUTHOR]

Mesoionic compounds, with positive and negative charges, are expected to have dual‐site highest occupied molecular orbital (HOMO, donor) and lowest unoccupied molecular orbital (LUMO, acceptor) reactivity. Herein, we report a novel class of air‐stable mesoionic N‐heterocyclic thiones (mNHTs) synthesized from abnormal N‐heterocyclic carbenes (aNHCs). DFT studies revealed a highly polarized exocyclic thione moiety and computed Fukui function analysis suggests the dual‐site HOMO/LUMO reactivity of mNHTs predicting donor property at the negatively charged ‘S’ center while acceptor property at the cationic imidazole ring. The independent LUMO reactivity of the mNHT was realized by its chemical reduction to an elusive radical anion, which was characterized by a single crystal X‐raydiffraction study. Further, we explore the reactivity of radical anion for the activation of SO2 gas, C−Br bonds of aryl bromide and photocatalytic functionalization of C−X (X = F, Br) bonds. This work unlocks the independent LUMO reactivity of a mesoionic compound. [ABSTRACT FROM AUTHOR]

A series of new RS−, RS−CH2− and R2N−CH2-functionalized сatechols with heterocyclic fragments such as 1,3,4-oxadiazole, 1,2,4-triazole, thiazole, or pyridine were synthesized by the reaction of 3,5-di-tert-butyl-o-benzoquinone or 3,5-di-tert-butyl-6-methoxymethylcatechol with different heterocyclic thiols. The S-functionalized catechols were prepared by the Michael reaction from 3,5-di-tert-butyl-o-benzoquinone and the corresponding thiols. The starting reagents such as substituted 1,3,4-oxadiazole-2-thiols and 4H-triazole-3-thiols are characterized by thiol–thione tautomerism, therefore their reactions with 3,5-di-tert-butyl-6-methoxymethylcatechol can proceed at the sulfur or nitrogen atom. In the case of mercapto-derivatives of thiazole or pyridine, this process leads to the formation of the corresponding thioethers with a methylene linker. At the same time, thiolated 1,3,4-oxadiazole or 1,2,4-triazole undergo alkylation at the nitrogen atom in the reaction with 3,5-di-tert-butyl-6-methoxymethylcatechol to form the corresponding thiones. The yield of reaction products ranges from 42 to 80%. The crystal structures of catechols with 3-nitropyridine or 1,3,4-oxadiazole-2(3H)-thione moieties were established by single-crystal X-ray analysis. The possibility of forming intra- and intermolecular hydrogen bonds has been established for these compounds. The electrochemical behavior of the studied compounds is influenced by several factors: the nature of the heterocycle and its substituents, the presence of a sulfur atom in the catechol ring, or a thione group in the heterocyclic core. The radical scavenging activity and antioxidant properties were determined using the reaction with synthetic radicals, the cupric reducing antioxidant capacity assay, the inhibition process of superoxide radical anion formation by xanthine oxidase, and the process of lipid peroxidation of rat liver (Wistar) homogenates in vitro.

An efficient method for the oxidative transformation of thioamides and thioketones to their oxygen analogues with singlet oxygen is reported. Singlet oxygen was produced in situ from the fragmentation of the trans-5-hydroperoxy-3,5-dimethyl-1,2-dioxolane-3-yl ethaneperoxate in the presence of KOH, and it has been explored as an effective oxidant for oxidative desulfurization of thioamides and thioketones. This protocol provides amides and ketones in excellent yields (80–90%) at room temperature under mild conditions. The thioamides reacted very well with this reagent system. The conjugation of neighboring NH and C=S groups appears to enhance yields for thioamides. Further investigation showed that this reagent system is also an efficient system for deprotection of thionoesters to esters. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of novel azo-linked 1,2,4-triazolidine-3-ones (thiones) using a recyclable Fe3O4@SP@vanillin@thioglycolic acid magnetic nanocomposite. The researchers aim to utilize greener methods in their synthetic processes, and nanocatalysts play a crucial role in achieving this goal. The study demonstrates that Fe3O4@SP@vanillin@thioglycolic acid MNC is an effective catalyst for the synthesis of the title compounds, with high yields and short reaction times. The article also investigates the recyclability of the catalyst, finding that it can be re-used multiple times with only a slight decrease in product yield. Overall, the Fe3O4@SP@vanillin@thioglycolic acid MNC catalyst is a new, greener, and re-usable catalyst for synthesizing these novel compounds. The document also provides information on the synthesis and characterization of various compounds, including their melting points, infrared spectra, and nuclear magnetic resonance spectra. The authors acknowledge the Research Council of Rasht Branch, Islamic Azad University, for their support. [Extracted from the article]

The conditions were developed and the optimal temperature regime was selected for a selective thionation of 5-aryl-3-[(dimethylamino)-methylidene]furan-2(3H)-ones with Lawesson's reagent. The stereochemistry of the synthesized 3-[(dimethylamino)methylidene]furan-2(3H)-thiones was established. Based on this, a number of 3-arylaminomethylidenefuran-2(3H)-thiones were synthesized via transamination reaction. [ABSTRACT FROM AUTHOR]

In this report, we investigate the toxicity of the ionophore thiomaltol (Htma) and Cu salts to melanoma. Divalent metal complexes of thiomaltol display toxicity against A375 melanoma cell culture resulting in a distinct apoptotic response at submicromolar concentrations, with toxicity of Cu(tma)2 > Zn(tma)2 >> Ni(tma)2. In metal-chelated media, Htma treatment shows little toxicity, but the combination with supplemental CuCl2, termed Cu/Htma treatment, results in toxicity that increases with suprastoichiometric concentrations of CuCl2 and correlates with the accumulation of intracellular copper. Electron microscopy and confocal laser scanning microscopy of Cu/Htma treated cells shows a rapid accumulation of copper within lysosomes over the course of hours, concurrent with the onset of apoptosis. A buildup of ubiquitinated proteins due to proteasome inhibition is seen on the same timescale and correlates with increases of copper without additional Htma.

(Per)thionitrite (SNO−/SSNO−) intermediates play vital roles in modulating nitric oxide (NO) and hydrogen sulfide (H2S) dependent bio‐signalling processes. Whilst the previous preparations of such intermediates involved reactive H2S/HS− or sulfane sulfur (S0) species, the present report reveals that relatively stable thiocarbonyl compounds (such as carbon disulfide (CS2), thiocarbamate, thioacetic acid, and thioacetate) react with nitrite anion to yield SNO−/SSNO−. For instance, the reaction of CS2 and nitrite anion (NO2−) under ambient condition affords CO2 and SNO−/SSNO−. A detailed investigation involving UV/Vis, FTIR, HRMS, and multinuclear NMR studies confirm the formation of SNO−/SSNO−, which are proposed to form through an initial nucleophilic attack by nitrite anion followed by a transnitrosation step. Notably, reactions of CS2 and nitrite in the presence of thiol RSH show the formation of organic polysulfides R‐Sn‐R, thereby illustrating that the thiocarbonyls are capable of influencing the pool of bioavailable sulfane sulfurs. Furthermore, the availability of both NO2− and thiocarbonyl motifs in the biological context hints at their synergistic metal‐free activations leading to the generation of NO gas and various reactive sulfur species via SNO−/SSNO−. [ABSTRACT FROM AUTHOR]

(Per)thionitrite (SNO−/SSNO−) intermediates play vital roles in modulating nitric oxide (NO) and hydrogen sulfide (H2S) dependent bio‐signalling processes. Whilst the previous preparations of such intermediates involved reactive H2S/HS− or sulfane sulfur (S0) species, the present report reveals that relatively stable thiocarbonyl compounds (such as carbon disulfide (CS2), thiocarbamate, thioacetic acid, and thioacetate) react with nitrite anion to yield SNO−/SSNO−. For instance, the reaction of CS2 and nitrite anion (NO2−) under ambient condition affords CO2 and SNO−/SSNO−. A detailed investigation involving UV/Vis, FTIR, HRMS, and multinuclear NMR studies confirm the formation of SNO−/SSNO−, which are proposed to form through an initial nucleophilic attack by nitrite anion followed by a transnitrosation step. Notably, reactions of CS2 and nitrite in the presence of thiol RSH show the formation of organic polysulfides R‐Sn‐R, thereby illustrating that the thiocarbonyls are capable of influencing the pool of bioavailable sulfane sulfurs. Furthermore, the availability of both NO2− and thiocarbonyl motifs in the biological context hints at their synergistic metal‐free activations leading to the generation of NO gas and various reactive sulfur species via SNO−/SSNO−. [ABSTRACT FROM AUTHOR]

(Per)thionitrite (SNO−/SSNO−) intermediates play vital roles in modulating nitric oxide (NO) and hydrogen sulfide (H2S) dependent bio‐signalling processes. Whilst the previous preparations of such intermediates involved reactive H2S/HS− or sulfane sulfur (S0) species, the present report reveals that relatively stable thiocarbonyl compounds (such as carbon disulfide (CS2), thiocarbamate, thioacetic acid, and thioacetate) react with nitrite anion to yield SNO−/SSNO−. For instance, the reaction of CS2 and nitrite anion (NO2−) under ambient condition affords CO2 and SNO−/SSNO−. A detailed investigation involving UV/Vis, FTIR, HRMS, and multinuclear NMR studies confirm the formation of SNO−/SSNO−, which are proposed to form through an initial nucleophilic attack by nitrite anion followed by a transnitrosation step. Notably, reactions of CS2 and nitrite in the presence of thiol RSH show the formation of organic polysulfides R‐Sn‐R, thereby illustrating that the thiocarbonyls are capable of influencing the pool of bioavailable sulfane sulfurs. Furthermore, the availability of both NO2− and thiocarbonyl motifs in the biological context hints at their synergistic metal‐free activations leading to the generation of NO gas and various reactive sulfur species via SNO−/SSNO−. [ABSTRACT FROM AUTHOR]

(Per)thionitrite (SNO−/SSNO−) intermediates play vital roles in modulating nitric oxide (NO) and hydrogen sulfide (H2S) dependent bio‐signalling processes. Whilst the previous preparations of such intermediates involved reactive H2S/HS− or sulfane sulfur (S0) species, the present report reveals that relatively stable thiocarbonyl compounds (such as carbon disulfide (CS2), thiocarbamate, thioacetic acid, and thioacetate) react with nitrite anion to yield SNO−/SSNO−. For instance, the reaction of CS2 and nitrite anion (NO2−) under ambient condition affords CO2 and SNO−/SSNO−. A detailed investigation involving UV/Vis, FTIR, HRMS, and multinuclear NMR studies confirm the formation of SNO−/SSNO−, which are proposed to form through an initial nucleophilic attack by nitrite anion followed by a transnitrosation step. Notably, reactions of CS2 and nitrite in the presence of thiol RSH show the formation of organic polysulfides R‐Sn‐R, thereby illustrating that the thiocarbonyls are capable of influencing the pool of bioavailable sulfane sulfurs. Furthermore, the availability of both NO2− and thiocarbonyl motifs in the biological context hints at their synergistic metal‐free activations leading to the generation of NO gas and various reactive sulfur species via SNO−/SSNO−. [ABSTRACT FROM AUTHOR]

Herein,a protocol for the chemoselective formation of C−N bond using Cu(OTf)2 as catalyst has been described using heterocyclic thiones. The reaction occurs preferentially at the nitrogen centre over the sulphur atom leading to C−N bond formation. Water being the only by‐product, the reaction is environmentally friendly. The reaction proceeds without any additive, ligand or inert atmosphere and shows good tolerance towards variety of alcohols and thiotetrazole derivatives. Our developed protocol could be scaled up to gram scale efficiently, which highlights the efficacy of this method and might offer potential application in synthetic industry. [ABSTRACT FROM AUTHOR]

Insulin-degrading enzyme (IDE) is a human mononuclear Zn2+ -dependent metalloenzyme that is widely regarded as the primary peptidase responsible for insulin degradation. Despite its name, IDE is also critically involved in the hydrolysis of several other disparate peptide hormones, including glucagon, amylin, and the amyloid β-protein. As such, the study of IDE inhibition is highly relevant to deciphering the role of IDE in conditions such as type-2 diabetes mellitus and Alzheimer disease. There have been few reported IDE inhibitors, and of these, inhibitors that directly target the active-site Zn2+ ion have yet to be fully explored. In an effort to discover new, zinc-targeting inhibitors of IDE, a library of ∼350 metal-binding pharmacophores was screened against IDE, resulting in the identification of 1-hydroxypyridine-2-thione (1,2-HOPTO) as an effective Zn2+ -binding scaffold. Screening a focused library of HOPTO compounds identified 3-sulfonamide derivatives of 1,2-HOPTO as inhibitors of IDE (Ki values of ∼50 μM). Further structure-activity relationship studies yielded several thiophene-sulfonamide HOPTO derivatives with good, broad-spectrum activity against IDE that have the potential to be useful pharmacological tools for future studies of IDE.

The review presents approaches to the synthesis of trifluoromethyl-containing N,O,S-heterocyclic compounds such as imidazolidin-2-ones(thiones), 1,2,4-triazine-3-thiones(ones), 1,2,4-triazine-3-amines, bis(trifluoromethyl)-2,3-dihydropyrazine-1,4-dioxides based on reactions of perfluorobiacetyl with bi- and trifunctional nucleophilic agents: urea, N- and N,N′-substituted ureas, thiourea, thiosemicarbazide, semicarbazide hydrochloride, aminoguanidine bicarbonate, and N,N′-dihydroxy-2,3-dimethylbutane-2,3-diamine. The reaction of 4,5-dihydroxy-4,5-bis(trifluoromethyl)imidazilidin-2-one with urea in N,N-dimethylacetamide at elevated temperature afforded bis(trifluoromethyl)-glycoluril. Monosubstituted N-alkyl(aryl)-4,5-dihydroxy-4,5-bis(trifluoromethyl)imidazolidin-2-ones reacted with urea under similar conditions to give 1-alkyl(aryl)bis(trifluoromethyl)imidazooxazoles. The condensation reaction of trifluoromethyl-containing imidazolidin-2-ones(thiones) with thiourea and NH4SCN in a dipolar aprotic solvent at elevated temperature resulted in thioglycolurils, thioxoimidazothiazolones, and oxoimidazothiazolones. The first nitrogen-containing heterocycles containing a CF3 group at the vicinal position to the N-O fragment were synthesized by the reaction of perfluorobiacetyl with N,N′-dihydroxy-2,3-dimethylbutane-2,3-diamine. [ABSTRACT FROM AUTHOR]

The new high selective mAChRs M3 inhibitors with IC50 in nanomolecular ranges, which can be the prototypes for effective COPD and asthma treatment drugs, were discovered with computational approaches among trifluoromethyl containing hexahydropyrimidinones/thiones. Compounds [6‐(4‐ethoxy‐3‐methoxy‐phenyl)‐4‐hydroxy‐2‐thioxo‐4‐(trifluoromethyl)hexahydropyrimidin‐5‐yl]‐phenyl‐methanone (THPT‐1) and 5‐benzoyl‐6‐(3,4‐dimethoxyphenyl)‐4‐hydroxy‐4‐(trifluoromethyl)hexahydropyrimidin‐2‐one (THPO‐4) have been proved to be a highly effective (with IC50 values of 1.62 ⋅ 10−7 M and 3.09 ⋅ 10−9 M, respectively) at the same concentrations significantly competitive inhibit the signal conduction through mAChR3 in comparison with ipratropium bromide, without significant effect on mAChR2, nicotinic cholinergic and adrenergic receptors. [ABSTRACT FROM AUTHOR]

Base-mediated cascade reactions of 3-hydroxymethyl-3-propenylindole-2-thiones afforded diolefins and involved deformylation, thioenolate alkylation and the thio-Claisen rearrangement. Subsequent ring-closing metathesis reactions of the diolefins furnished 3-spiro[cyclopentene-indole]-2-thiones or thiepino[2,3-b]indoles. [ABSTRACT FROM AUTHOR]

By exploiting the unique reactivity of ethynyl‐phosphonites we obtain novel P(V)‐containing five‐membered heterocycles via (3+2)‐cyclization reactions with aldehydes or cycloaliphatic thioketones in satisfactory to excellent yields. Whereas reactions with thioketones to yield 1,3‐thiaphospholes‐3‐oxides occur smoothly at room temperature with equimolar amounts of the starting materials in absence of any catalyst, the analogous conversions with aldehydes to generate 3‐oxides of 1,3‐oxaphospholes require addition of triethylamine as a base. We postulate a step‐wise (3+2)‐cyclization mechanism for the formation of the 1,3‐thiaphosphole ring based on DFT quantum chemical calculations. With this study, we introduce new cyclization reactions originating from unsaturated phosphonites as central synthetic building blocks to yield previously inaccessible stable phosphorus‐containing heterocycles with unexplored potential for the molecular sciences. [ABSTRACT FROM AUTHOR]

Herein, we studied the formation of thiones via C=O group conversion into the C=S functional group-based tricyclic pyrimidinone systems using Lawesson's reagent and phosphorus pentasulfide as thionation agents. Naturally occurring alkaloids deoxyvasicinone and mackinazolinone were selected as templates for the modification of furo[2,3-d]pyrimidinone and pyrrolo[2,3-d]pyrimidinone scaffold. Research work was performed under the combinatorial and parallel synthesis of pyrimidine-based small molecules, along with a one-pot reaction strategy. All synthesized 54 novel pyrimidine-thiones were elucidated by 1H-NMR, 13C-NMR, and HRMS analysis. In addition, both series of thiones were evaluated for their antitumor activity against three types of the human cancer cell: cervical HeLa, breast MCF-7, and colon HT-29 lines. Compound with azepine fragment 13aa (1-methyl-2-(4-(trifluoromethyl)phenyl)-1,6,7,8,9,10-hexahydro-4H-pyrrolo[2',3':4,5]pyrimido[1,2-a]azepine-4-thione) was most active derivative (IC50 = 2.09 ± 0.22 µM) against the HT-29 cell line. [ABSTRACT FROM AUTHOR]

Herein, we report a novel protocol for the direct synthesis of 1,3‐oxathiolan‐5‐ones based on the (3+2)‐cycloaddition between thioketones and acetylenedicarboxylic acid. The products were obtained in a one‐pot reaction within short reaction times and in typically very good yields. The product structure was confirmed by X‐ray diffraction analysis. [ABSTRACT FROM AUTHOR]

We present a high yield synthesis of 1‐ethyl‐3‐methyl‐imidazole‐2‐chalcogenones from readily available imidazolium‐2‐carboxylate zwitterions NHC−CO2 and elemental chalcogens. In sharp contrast to previous syntheses for corresponding thiones and selones from imidazolium salts and bases our reactions proceed fast with full instead of low conversion and selectivity, decarboxylation is the driving force. Furthermore, this strategy is applicable to all heavier chalcogens including tellurium. Vacuum sublimation of imidazole‐2‐chalcogenones is implemented as convenient method of purification leading to solid instead of liquid products reported in literature. Newly prepared 1‐ethyl‐3‐methyl‐imidazole‐2‐tellone was characterized by XRD analysis and a correlation study of 125Te NMR and 13C NMR shifts with respect to known representatives. The reaction of NHC−CO2 with TMS2S leads to NHC−COS, characterized by XRD analysis, whereas heavier chalcogen derivatives TMS2E (E=Se, Te) did not react with NHC activated CO2. [ABSTRACT FROM AUTHOR]

Herein, we discuss the synthesis, in silico studies, antibacterial and antioxidantal activities of titled compounds, which are with biologically active groups. The reaction of chalcones with thiourea produces novel thiopyrimidones with good yields by a simple procedure. In silico studies performed by (a) PASS software, (b) OSIRIS software results are showing that all compounds are having various biological activities; compounds (IV, V, VII and VIII) are having more drug likeness and drug score. In vitro study reveals that, Antibacterial, Antioxidantal activity among the twelve compounds, compounds (I), (X) having good activity, compound (V), (VI) shows excellent activity. The results are supported by the molecular docking study. [ABSTRACT FROM AUTHOR]

This study is designed to synthesize novel degradable polymers by radical addition–fragmentation ring‐opening copolymerization of bio‐based thiocarbonyl compounds with various vinyl monomers. Thiocarbonyl l‐lactide is capable of radical copolymerization with acrylates and styrene via radical addition to the carbon–sulfur double bonds followed by ring‐opening as well as controlled copolymerization in conjunction with the reversible addition–fragmentation chain transfer (RAFT) process. The obtained polymers possess ring‐opened thioester and ring‐retained thioacetal functionalities in the backbone, both of which could be cleaved under appropriate conditions with different chemical stimuli. [ABSTRACT FROM AUTHOR]

A novel class of highly activated donor‐acceptor cyclopropanes bearing only a single, vinylogous acceptor is presented. These strained moieties readily undergo cycloadditions with aldehydes, ketones, thioketones, nitriles, naphth‐2‐ols and various other substrates to yield the corresponding carbo‐ and heterocycles. Diastereocontrol can be achieved through the choice of catalyst (Brønsted or Lewis acid). The formation of tetrahydrofurans was shown to be highly enantiospecific when chiral cyclopropanes are employed. A series of mechanistic and kinetic experiments was conducted to elucidate a plausible catalytic cycle and to rationalize the stereochemical outcome. [ABSTRACT FROM AUTHOR]

Hydroxypyridinethiones (HOPTOs) are strong ligands for metal ions and potentially useful pharmacophores for inhibiting metalloenzymes relevant to human disease. However, HOPTOs have been sparingly used in drug discovery efforts due, in part, to concerns that this scaffold will act as a promiscuous, non-selective metalloenzyme inhibitor, as well as possess poor pharmacokinetics (PK), which may undermine drug candidates containing this functional group. To advance HOPTOs as a useful pharmacophore for metalloenzyme inhibitors, a library of 22 HOPTO isostere compounds has been synthesized and investigated. This library demonstrates that it is possible to maintain the core metal-binding pharmacophore (MBP) while generating diversity in structure, electronics, and PK properties. This HOPTO library has been screened against a set of four different metalloenzymes, demonstrating that while the same metal-binding donor atoms are maintained, there is a wide range of activity between metalloenzyme targets. Overall, this work shows that HOPTO isosteres are useful MBPs and valuable scaffolds for metalloenzyme inhibitors.

Cyclopropenethiones are reported as new bioorthogonal reagents. These motifs react readily with substituted phosphines to provide thiocarbonyl adducts. In some cases, the ligations are >300-fold faster than analogous reactions with bioorthogonal cyclopropenones. Dialkyl cyclopropenethiones are also stable in aqueous buffers and can be used for biomolecule labeling in vitro and in cell lysate. The rapid reactivity and biocompatibility of cyclopropenethiones suggest that they will be useful probes for cellular studies.

The role of distinct actin filament architectures in epithelial plasticity remains incompletely understood. We therefore determined roles for formins and the Arp2/3 complex, which are actin nucleators generating unbranched and branched actin filaments, respectively, in the process of epithelial to mesenchymal transition (EMT). In clonal lung, mammary, and renal epithelial cells, the formin activity inhibitor SMIFH2 but not the Arp2/3 complex activity inhibitor CK666 blocked EMT induced by TGF-β. SMIFH2 prevented the proximal signal of increased Smad2 phosphorylation and hence also blocked downstream EMT markers, including actin filament remodeling, decreased expression of the adherens junction protein E-cadherin, and increased expression of the matrix protein fibronectin and the transcription factor Snail. The short hairpin RNA silencing of formins DIAPH1 and DIAPH3 but not other formins phenocopied SMIFH2 effects and inhibited Smad2 phosphorylation and changes in Snail and cadherin expression. Formin activity was not necessary for the cell surface expression or dimerization of TGF-β receptors, or for nuclear translocation of TAZ, a transcription cofactor in Hippo signaling also regulated by TGF-β. Our findings reveal a previously unrecognized role for formin-dependent actin architectures in proximal TGF-β signaling that is necessary for Smad2 phosphorylation but not for cross-talk to TAZ.

An efficient method has been developed for the synthesis of bis(6,7,13,14,18,19-hexaoxa-16-aza-dispiro[4.2.48.75]nonadecan-16-yl)methanones(thiones) and N-substituted hexaoxaazadispiroalkane-carbox-amides by the reaction of heptaoxadispiroalkanes with thiourea, urea, N,N-dimethylurea, N-phenylurea, and N-allylurea in the presence of Sm(NO3)3·6H2O as catalyst. [ABSTRACT FROM AUTHOR]

Through the combination of heterocyclic thiones with variation in the identity of the heterocyclic elements, namely, imidazolidine‐2‐thione, 2‐mercaptobenzimidazole, 2‐mercapto‐5‐methylbenzimidazole, 2‐mercaptobenzoxazole, and 2‐mercaptobenzothiazole with the common halogen‐bond donors 1,2‐, 1,3‐, and 1,4‐diiodotetrafluorobenzene, 1,3,5‐trifluorotriiodobenzene, and tetraiodoethylene, a series of 18 new crystalline structures were characterized. In most cases, N—H...S hydrogen bonding was observed, with these interactions in imidazole‐containing structures typically resulting in two‐dimensional motifs (i.e. ribbons). Lacking the second N—H group, the thiazole and oxazole hydrogen bonding resulted in only dimeric pairs. C—I...S and C—I...I halogen bonding, as well as C=S...I chalcogen bonding, served to consolidate the packing by linking the hydrogen‐bonding ribbons or dimeric pairs. [ABSTRACT FROM AUTHOR]

This manuscript describes the synthesis of N-heterocyclic thiones and selones of a variety of imidazolium salts involving an eco-friendly and solventless ball-milling technique. The products have been isolated in almost quantitative yield, involving a minimum quantity of solvents only for the isolation of products by column chromatography, and in some cases for purification purposes. Both mono- and bisimidazolium salts afforded N-heterocyclic thiones and selones. The methodology is found to be superior in terms of reaction time, yield and energy efficiency as compared to conventional solution-state reactions. [ABSTRACT FROM AUTHOR]

A highly efficient and environmentally-friendly base-mediated transition metal-free direct thiophilic catalytic approach is reported for the synthesis of S-benzhydryl-phosphorothioates by reacting phosphite nucleophiles with diarylmethanethione. A wide variety of thioketones were coupled with different phosphite derivatives to provide the corresponding phosphorothioates in good to excellent yields. The control experiments and density functional theory (DFT) calculations rely on the regio-selective thiophilic addition of a phosphite nucleophile via umpolung protocols. [ABSTRACT FROM AUTHOR]

Synthesis of novel 5-methyl-1-(4-(6-methylimidazo[1,2-b]isoxazol-3-yl)phenyl)-3-aryl-1,3,5-triazinane-2-thiones 6 has been achieved by the reaction of 3-amino-5-methylisoxazole 1 with p-nitrophenacyl bromide, followed by reduction of 3 with stannous chloride. Compounds 4 on treatment with different aryl isothiocyanates in refluxing benzene, followed by trimolecular condensation with 30% HCHO and methyl amine in ethanol affords the title compounds 6. The newly synthesized compounds 6 have been evaluated for their in vitro antimicrobial activity. Compounds 6 exhibit potent antimicrobial activity compared to that of standard drugs. [ABSTRACT FROM AUTHOR]

Utilizing the N‐heterocyclic chalcogenones hexahydro‐1,3‐bis(2,4,6‐trimethylphenyl)‐2H‐1,3‐diazepine‐2‐thione (SDiazMesS) and hexahydro‐1,3‐bis(2,4,6‐trimethylphenyl)‐2H‐1,3‐diazepine‐2‐selone (SDiazMesSe) as halogen‐bond acceptors, a total of 24 new cocrystals were prepared. The solid‐state structures of the parent molecules were also determined, along with those of their acetonitrile solvates. Through the reaction of the chalcogen atom with molecular diiodine, a variety of S—I—I and Se—I—I fragments were formed, spanning a wide range of I—I bond orders. With acetone as a reaction solvent, molecular diiodine causes the oxidative addition of acetone to the chalcogen atom, resulting in new C—S, C—Se and C—C covalent bonds under mild conditions. The common halogen‐bond donors, iodopentafluorobenzene, 1,2‐, 1,3‐ and 1,4‐diiodotetrafluorobenzene, 1,3,5‐trifluorotriiodobenzene and tetraiodoethylene resulted in halogen‐bond‐driven cocrystal formation. In most cases, the analogous SDiazMesS and SDiazMesSe cocrystals are isomorphic. [ABSTRACT FROM AUTHOR]

The solid state thione-thiol equilibrium in 4,6-diphenyl-3,4-dihydropyrimidine- 2(1H)-thione (C16H14N2S) is analyzed through three different techniques, viz: Single Cristal X-Ray Diffraction (SCXRD), Nuclear Magnetic Resonance (NMR) and Fourier Transformed Infra-Red spectroscopy (FTIR), each one providing complementary information to the solution of the problem. The existence of thione-thiol equilibrium is firmly established, both in solution (by HNMR techniques) as in the solid state (by FTIR methods), and even if no traces of the thiol form could be found via SCXRD, some hints about the way in which the coexistence of both forms could be structurally achieved are provided by the structural analysis. In order to confirm the existence of this equilibrium, theoretical calculations were carried out at the B3LYP/6-311G(d,p) level theory, and a double proton transfer reaction is proposed. [ABSTRACT FROM AUTHOR]

Background: Under normal circumstances, high-density lipoprotein (HDL) is considered to have cardiovascular protective effects, but the impact of oxidized HDL (ox-HDL) on vascular endothelial function remains poorly understood. Mitochondrial function is closely related to endothelial function, and hydrogen sulfide (H₂S) is a gas with endothelial protective properties. The novel hydrogen sulfide donor AP39 can target mitochondria to release H₂S, but the combined effects of ox-HDL and AP39 on vascular endothelium are not well studied., Methods: We established a cell model of ox-HDL-induced endothelial cell damage and mitochondrial dysfunction using human umbilical vein endothelial cells (HUVECs) and conducted AP39 pretreatment. The experiments confirmed the functional damage and mitochondrial dysfunction in HUVECs caused by ox-HDL. Additionally, to further explore the role of SIRT1 in AS, we analyzed SIRT1 expression in AS carotid artery tissue. This included the analysis of differentially expressed genes from AS-related datasets, presented through volcano plots and heatmaps, with enrichment analysis of downregulated genes in KEGG pathways and GO functions. Furthermore, we evaluated the differences in SIRT1 expression in coronary arteries with varying degrees of stenosis and in early and late-stage AS carotid artery tissues, and analyzed data from SIRT1 knockout mouse models., Results: The experimental results indicate that AP39 effectively alleviated ox-HDL-induced endothelial cell damage and mitochondrial dysfunction by upregulating SIRT1 expression. MTT and CCK-8 assays showed that ox-HDL treatment led to decreased cell viability and proliferation in HUVECs, reduced eNOS expression, and significantly increased levels of ICAM-1, IL-6, and TNF-α, along with enhanced monocyte adhesion. These findings reveal the damaging effects of ox-HDL on HUVECs. Transcriptomic data indicated that while SIRT1 expression did not significantly differ in coronary arteries with varying degrees of stenosis, it was notably downregulated in AS carotid artery tissues, especially in late-stage AS tissues. KEGG pathway enrichment analysis revealed that SIRT1 downregulated genes were associated with processes such as vascular smooth muscle contraction, while GO analysis showed that these downregulated genes were involved in muscle system processes and muscle contraction functions, further confirming SIRT1's critical role in AS pathology. In transcriptomic data from the SIRT1 knockout mouse model, elevated levels of inflammation-related proteins IL-6 and TNF-α were observed after SIRT1 knockout, along with decreased expression of the chaperone protein PGC-1α. The expression of mitochondrial-related functional proteins Nrf2 and PGC-1α was positively correlated with SIRT1 expression, while inflammation-related proteins ICAM-1, IL-6, IL-20, and TNF-α were negatively correlated with SIRT1 expression. We further discovered that ox-HDL triggered mitochondrial dysfunction, as evidenced by reduced expression of Mfn2, Nrf2, PGC1-α, UCP-1, and SIRT1, corroborating the results from the previous database analysis. Additionally, mitochondrial dysfunction was characterized by decreased mitochondrial membrane potential (MMP), increased mitochondrial ROS levels, and reduced ATP content, further impacting cellular energy metabolism and respiratory function. Subsequent experimental results showed that the addition of AP39 mitigated these adverse effects, as evidenced by decreased levels of ICAM-1, IL-6, and TNF-α, increased eNOS expression, reduced monocyte adhesion, increased mitochondrial H₂S content, and upregulated expression of SIRT1 protein associated with mitochondrial function, reduced ROS levels, and increased ATP content. Furthermore, validation experiments using the SIRT1 inhibitor EX527 confirmed that AP39 alleviated ox-HDL-induced endothelial cell damage and mitochondrial dysfunction by upregulating SIRT1 expression., Conclusion: Ox-HDL can induce damage and mitochondrial dysfunction in HUVECs, while AP39 inhibits ox-HDL-induced endothelial cell damage and mitochondrial dysfunction by upregulating SIRT1., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Acquired drug resistance is a major challenge in the management of cancer, which underscores the need for discovery and development of novel therapeutic strategies. We report here the mechanism of the anti-cancer activity of a small coordinate complex composed of the rare earth metal praseodymium (Pr) and mercaptopyridine oxide (MPO; pyrithione). Exposure of cancer cells to relatively low concentrations of the conjugate Pr-MPO (5 µM) significantly impairs cell survival in a p53-independent manner and irrespective of the drug resistant phenotype. Mechanistically, Pr-MPO-induced cell death is caspase-independent, not inhibitable by necrostatin, but associated with the appearance of autophagy markers. However, further analysis revealed incomplete autophagic flux, thus suggesting altered integrity of lysosomal machinery. Supporting the lysosomal targeting activity are data demonstrating increased lysosomal Ca 2+ accumulation and alkalinization, which coincides with cytosolic acidification (drop in pH c from 7.75 to 7.00). In parallel, an increase in lysosomal activity of glycosidase alpha acid (GAA), involved in passive glycogen breakdown, correlates with rapid depletion of glucose stores upon Pr-MPO treatment. This is associated with swift cataplerosis of TCA cycle intermediates, loss of NAD + /NADH and increase in pyruvate dehydrogenase (PDH) activity to compensate for pyruvate loss. Addition of exogenous pyruvate rescued cell survival. Notably, lysosomal impairment and metabolic catastrophe triggered by Pr-MPO are suggestive of Zn 2+ -mediated cytotoxicity, which is confirmed by the ability of Zn 2+ chelator TPEN to block Pr-MPO-mediated anti-tumor activity. Together, these results highlight the ability of the small molecule lanthanide conjugate to target the cells' waste clearing machinery as well as mitochondrial metabolism for Zn 2+ -mediated execution of cancer cells, which could have therapeutic potential against cancers with high metabolic activity., (© 2024. The Author(s).)

This study introduces bis(1-cyanocyclohex-1-yl)trithiocarbonate (TTC-bCCH) as a novel trithiocarbonate chain transfer agent and compares its reactivity with the previously described bis(2-cyanopropan-2-yl)trithiocarbonate (TTC-bCP) for the reversible addition-fragmentation chain transfer (RAFT) polymerization of styrene (St), n-butyl acrylate (nBA), and methyl methacrylate (MMA). Significant findings include the effective control of M n and low dispersities from the onset of polymerization of St and nBA showing swift addition-fragmentation kinetics, leading to similar behaviors between the two RAFT agents. In contrast, a fourfold decrease of the chain transfer constant to MMA is established for TTC-bCCH over TTC-bCP. This trend is confirmed through density functional theory (DFT) calculations. Finally, the study compares thermoplastic elastomer properties of all-(meth)acrylic ABA block copolymers produced with both RAFT agents. The impact of dispersity of PMMA blocks on thermomechanical properties evaluated via rheological analysis reveals a more pronounced temperature dependence of the storage modulus (G') for the triblock copolymer synthesized with TTC-bCCH, indicating potential alteration of the phase separation., (© 2024 The Author(s). Macromolecular Rapid Communications published by Wiley‐VCH GmbH.)

Organic-inorganic hybrid nanomaterials have been prepared through cooperative assembly of cetyltrimethylammonium bromide (CTAB), Iron(ΙΙΙ)nitrate, and (Nitrilotris(methylene)) triphosphonic acid (NMPA). Surfactant is used as a structure directing agent, while the other two chemicals are used as precursors for the formation of pore walls. The structure of the synthesized iron phosphonate nanomaterials was fully characterized by using different spectra such as FT-IR, VSM, thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), EDX and XRD. The SEM analyze confirmed a hollow spherical micromorphology with well-defined porosity. Obtained hybrid organic and inorganic Nano catalyst has high performance in the synthesis of heterocyclic compounds. Therefore, the reaction of aldehyde aromatic, urea and ethyl acetoacetate was performed in the presence of the catalytic amount of Fe- NMPA under solvent-free conditions. The 3, 4-dihydropyrimidin (1H)-ones/thiones derivatives were obtained in high yield and short reaction time. The products of the reaction were characterized by physical data and FT-IR spectrum. This method has several advantages such as a recyclable catalyst, easy workup, and not using a volatile organic solvent. [ABSTRACT FROM AUTHOR]

This Review covers wide-ranging electron ionization (EI) dissociation reactions for various acyclic compounds and their derivatives, such as alcohols, aldehydes, ketones, carboxylic acids, amines, halides, thiols, thiones, esters, thioesters, amides, and more. Common derivatives of monofunctional compounds, such as trialkylsilyl, acyl, perfluoroacyl, oxazoline, and nicotinyl derivatives, are also discussed. The behavior of these under mass spectrometry (MS) conditions is determined, structures and stabilities of product ions are considered, and the ions of diagnostic power in their EI spectra are highlighted. Characteristic dissociation pathways for specific structural elements and their application for spectra/structure correlations are presented. Fundamental approaches for identifying unknowns are given. The advantages and limitations of EI-MS are emphasized. This knowledge is the key for successful applications of the exceptional capabilities of EI-MS for initial structure elucidation and then reliable structure determination of unknowns. [ABSTRACT FROM AUTHOR]

In this study, cross-linked poly(4-vinylpyridine)-supported boron trifluoride, [P4-VP]-BF3, has been easily prepared and characterized by Fourier transform infrared (FT-IR), X-ray diffraction pattern, energy-dispersive X-ray spectroscopy analysis, scanning electron microscopy images and mapping. Afterward, catalytic activity of the obtained solid polymer-supported Lewis acid catalyst has been examined in Biginelli reaction for the synthesis of 3, 4-dihydropyrimidin-2(1H)-ones and 3, 4 dihydropyrimidin-2(1H)-thiones via one-pot three-component reaction between aryl aldehydes, β-dicarbonyl compounds and urea or thiourea under solvent-free conditions. The products were confirmed by their melting points (m.p.), FT-IR 1H and 13C nuclear magnetic resonance spectroscopy. The present procedure offers advantages, such as high to excellent yield (68–97% isolated yields), short reaction time (30–45 min), reusability of the catalyst, clean and fast work-up and easy separation of the catalyst by a simple filtration. [ABSTRACT FROM AUTHOR]

Tautomerism in the nitro substituted thione-containing traazatricyclics has been investigated. Evidence from 1H NMR indicating the existence of the tautomers has been augmented with computational studies providing evidence of the stability or otherwise of these tautomers. The role of water and DMSO in the formation of the tautomers has been explained. The role of the nitro group in assisting in the formation of the tautomers has been discussed. [ABSTRACT FROM AUTHOR]

Herein we report secondary pyrrolidin‐2‐ols as a source of cyclic (alkyl)(amino)carbenes (CAAC) for the synthesis of CAAC‐CuI‐complexes and cyclic thiones when reacted with CuI‐salts and elemental sulfur, respectively, under reductive elimination of water from the carbon(IV)‐center. This result demonstrates a convenient and facile access to CAAC‐based CuI‐salts, which are well known catalysts for different organic transformations. It further establishes secondary alcohols to be a viable source of carbenes—realizing after 185 years Dumas' dream who tried to prepare the parent carbene (CH2) by 1,1‐dehydration of methanol. Addressed is also the reactivity of water towards CAACs, which proceeds through an oxidative addition of the O−H bond to the carbon(II)‐center. This emphasizes the ability of carbon‐compounds to mimic the reactivity of transition‐metal complexes: reversible oxidative addition and reductive elimination of the O−H bond to/from the C(II)/C(IV)‐centre. [ABSTRACT FROM AUTHOR]

• 13 new 1,2,4-Triazole-3-thione Schiff bases compounds containing tetrahydrocarbazole moiety were synthesized. • The structures and physical properties of the new hybrid compounds were elucidated. • 1H NMR and 13C NMR data were used to support the presence of intramolecular non-covalent interaction. In the present study, easy and efficient synthesis of triazole-3-thione compounds having tetrahydrocarbazole moiety. A complete explanation of the structural properties would make them candidates to be used in many areas of application. In this study, NMR and IR spectroscopic methods were used to elucidate the structural properties of this compound. [Display omitted] [ABSTRACT FROM AUTHOR]

The inhibition and binding of three metal-binding pharmacophores (MBPs), 2-hydroxycyclohepta-2,4,6-trien-1-one (tropolone), 2-mercaptopyridine-N-oxide (1,2-HOPTO), and 2-hydroxycyclohepta-2,4,6-triene-1-thione (thiotropolone) to human carbonic anhydrase II (hCAII) and a mutant protein hCAII L198G were investigated. These MBPs displayed bidentate coordination to the active site Zn(II) metal ion, but the MBPs respond to the mutation of L198G differently, as characterized by inhibition activity assays and X-ray crystallography. The L198G mutation increases the active site volume thereby decreasing the steric pressure exerted on MBPs upon binding, allowing changes in MBP coordination to be observed. When comparing the binding mode of tropolone to thiotropolone or 1,2-HOPTO (O,O versus O,S donor sets), structural modifications of the hCAII active site were shown to have a stronger effect on MBPs with an O,O versus O,S donor set. These findings were corroborated with density functional theory (DFT) calculations of model coordination complexes. These results suggest that the MBP binding geometry is a malleable interaction, particularly for certain ligands, and that the identity of the donor atoms influences the response of the ligand to changes in the protein active site environment. Understanding underlying interactions between a MBP and a metalloenzyme active site may aid in the design and development of potent metalloenzyme inhibitors.

[Display omitted] • These [3 + 2] cycloaddition reactions energetically prefer the generation of 1,3,4-thiadiazole. • Parr function analysis predicts the regiochemistry in line with the experimental outcome. • Thiobenzophenone shows relatively higher reactivity in agreement with the experiments. • The cycloaliphatic thioketone series shows remarkable substituent effects, changing from a non-polar 32CA reaction to a highly polar one. • For polar reaction, the electron density flows from diazomethane to the thioketon. The reactivity, regiochemistry and substituent effects observed in the [3 + 2] cycloaddition (32CA) reactions of diphenyldiazomethane (PDM) with thiobenzophenone and a series of cycloaliphatic thioketones (TKs) have been studied within the molecular electron density theory at the ωB97XD/6-311G(d,p) computational level. The cycloaliphatic TK series shows remarkable substituent effects, changing from a non-polar 32CA reaction to a highly polar one, with the electron density flowing from PDM to the corresponding TK in a reaction classified as a forward electron density flux (FEDF). These 32CA reactions follow a one-step mechanism through earlier asynchronous transition state structures in which the formation of the two new single bonds has not yet begun, and the energetically predicted regiochemistry towards the generation of 1,3,4-thiadiazole is in complete agreement with the experimental outcome. [ABSTRACT FROM AUTHOR]

Herein, we report the first example of enantioselective (2+1) cycloaddition of thioketones with α‐diazo pyrazoleamides for the direct synthesis of tetrasubstituted thiiranes. In the presence of chiral N,N′‐dioxide/cobalt(ΙΙ) complexes (2–5 mol%), excellent efficiency (up to 99 % yield within 15 mins) and high stereoselectivity (up to >19 : 1 dr and 97 % ee) are available. Elaborations of thiiranes via desulfuration have also been conducted to deliver tetrasubstituted olefins. Density functional theory calculations reveal that the reaction initiates from a doublet state cobalt(ΙΙ) carbenoid, which is followed by a quartet cobalt(ΙΙ)‐bound thiocarbonyl ylide pathway. This work provides a route for the selective construction of tetrasubstituted thiiranes and olefins that are otherwise difficult to access. [ABSTRACT FROM AUTHOR]

The halogen bond has been widely used as an important supramolecular tool in various research areas. However, there are relatively few studies on halogen bonding related to molecular chirality. 3-(2-Halophenyl)quinazoline-4-thione derivatives have stable atropisomeric structures due to the rotational restriction around an N-C single bond. In X-ray single crystal structures of the racemic and optically pure N-C axially chiral quinazoline-4-thiones, we found that different types of intermolecular halogen bonds (C=S⋯X) are formed. That is, in the racemic crystals, the intermolecular halogen bond between the ortho-halogen atom and sulfur atom was found to be oriented in a periplanar conformation toward the thiocarbonyl plane, leading to a syndiotactic zig-zag array. On the other hand, the halogen bond in the enantiomerically pure crystals was oriented orthogonally toward the thiocarbonyl plane, resulting in the formation of a homochiral dimer. These results indicate that the corresponding racemic and optically pure forms in chiral molecules are expected to display different halogen bonding properties, respectively, and should be separately studied as different chemical entities. [ABSTRACT FROM AUTHOR]

Recently, conjugated nanomaterials made of a nano‐metal oxides core and polymers have emerged as a promising candidate in new generation catalysis. Herein, we report a novel heterogeneous catalyst by immobilizing poly triazine‐thiourea‐sulfonamide (PTTSA) on the surface of the Zn−Al−Cu core. In this sense, the sulfonated catalyst was obtained via simple sulfonation using chlorosulfonic acid (Zn−Al−Cu@PTTSA‐SO3H). The post‐synthetically modified nanomaterial was characterized using FT‐IR, FE‐SEM, TGA, EDX, XRD, and WDX. Regarding the catalytic exploration, we aimed at synthesizing furano and pyrano pyrimidinone derivatives via a one‐pot three‐component reaction of urea/thiourea, 2,3‐dihydrofuran/3,4‐dihydro‐2H‐pyran, and aldehydes with a variety of substrates. The catalyst is highly reusable and efficient, especially in terms of time and yield of the desired product. [ABSTRACT FROM AUTHOR]

Herein, we report a Brønsted acid catalyzed approach to access the yet unknown heterocyclic motif of thiazolo[3,4‐a]indoles in a one‐pot reaction under very mild conditions. A broad range of thiazolo[3,4‐a]indoles was generated from indole‐2‐methanols and thioketones with 45–99% yield and good functional group tolerance. The practicality of the process and the synthetic potential of the products were demonstrated with an upscaling experiment and further transformations. Additional control experiments provided mechanistic insights into this cycloaddition. [ABSTRACT FROM AUTHOR]