Vinyl Sulfones Research Articles

Investigation of polyelectrolyte behavior of poly(allylamine hydrochloride), poly(vinyl sulfonic acid), and copolymers in different conditions

Investigation of polyelectrolyte behavior of poly(allylamine hydrochloride), poly(vinyl sulfonic acid), and copolymers in different conditions

EDA Complex-Promoted Cascade Cyclization of Alkynes Enabling the Rapid Assembly of 3-Sulfonylindoles and Vinyl Sulfone Oxindoles.

Herein, we disclose a photoinduced radical cascade cyclization of alkynes with sulfinates via a novel EDA complex for the synthesis of various 3-sulfonylindoles and vinyl sulfone oxindoles, which are crucial motifs in medicinal and biological chemistry. The reaction proceeds under mild, photocatalyst- and transition-metal-free conditions, featuring operational simplicity, broad substrate scope, and easy scalability. Mechanistic studies reveal that the reaction is initiated with a photoinduced intermolecular charge transfer from sulfinates to N-sulfonamides, generating a sulfonyl radical followed by an N-centered radical, thus enabling the cascade cyclization process.

Insights on the role of blocking agent on the properties of the lipase from Thermomyces lanuginosus immobilized on heterofunctional support for hydroesterification reactions

Here, we report a study of the effect of the blocking agent on the properties of the lipase from Thermomyces lanuginosus (TLL) immobilized on a heterofunctional support (Purolite C18-ethylnediamina (EDA)- vinyl sulfone (VS)-TLL-blocking agent) in different reactions. The performance of the biocatalysts was compared to those immobilized on standard hydrophobic support (Purolite C18-TLL) and the commercial one (TLL-IM). The nature of the blocking agent (Cys, Gly and Asp) altered the enzyme features. TLL-IM always gave a comparatively worse performance, with its specificity for the oil being very different to the Purolite biocatalysts. Under optimized conditions, Purolite C18-TLL yielded 97 % of hydrolysis conversion after 4 h using a water/waste cooking soybean oil (WCSO) mass ratio of 4.3, biocatalyst load of 6.5 wt% and a temperature of 44.2 °C (without buffer or emulsification agent). In esterification reactions of the purified free fatty acids (FFAs) obtained from WCSO, the best TLL biocatalysts depended on the utilized alcohol: linear amyl alcohol was preferred by Purolite C18-TLL and Purolite C18-EDA-VS-TLL-Gly, while higher activity was achieved utilizing isoamyl alcohol as nucleophile by Purolite C18-EDA-VS-TLL-Cys, Purolite C18-EDA-VS-TLL-Asp and IM-TLL as catalysts. All the results indicate the influence of the blocking step on the final biocatalyst features.

Evaluation of a Covalent Library of Diverse Warheads (CovLib) Binding to JNK3, USP7, or p53.

Over the last few years, covalent fragment-based drug discovery has gained significant importance. Thus, striving for more warhead diversity, we conceived a library consisting of 20 covalently reacting compounds. Our covalent fragment library (CovLib) contains four different warhead classes, including five α-cyanoacacrylamides/acrylates (CA), three epoxides (EO), four vinyl sulfones (VS), and eight electron-deficient heteroarenes with a leaving group (SNAr/SN). After predicting the theoretical solubility of the fragments by LogP and LogS during the selection process, we determined their experimental solubility using a turbidimetric solubility assay. The reactivities of the different compounds were measured in a high-throughput 5,5'-dithiobis-(2-nitrobenzoic acid) DTNB assay, followed by a (glutathione) GSH stability assay. We employed the CovLib in a (differential scanning fluorimetry) DSF-based screening against different targets: c-Jun N-terminal kinase 3 (JNK3), ubiquitin-specific protease 7 (USP7), and the tumor suppressor p53. Finally, the covalent binding was confirmed by intact protein mass spectrometry (MS). In general, the purchased fragments turned out to be sufficiently soluble. Additionally, they covered a broad spectrum of reactivity. All investigated α-cyanoacrylamides/acrylates and all structurally confirmed epoxides turned out to be less reactive compounds, possibly due to steric hindrance and reversibility (for α-cyanoacrylamides/acrylates). The SNAr and vinyl sulfone fragments are either highly reactive or stable. DSF measurements with the different targets JNK3, USP7, and p53 identified reactive fragment hits causing a shift in the melting temperatures of the proteins. MS confirmed the covalent binding mode of all these fragments to USP7 and p53, while additionally identifying the SNAr-type electrophile SN002 as a mildly reactive covalent hit for p53. The screening and target evaluation of the CovLib revealed first interesting hits. The highly cysteine-reactive fragments VS004, SN001, SN006, and SN007 covalently modify several target proteins and showed distinct shifts in the melting temperatures up to +5.1°C and -9.1°C.

Visible‐Light‐Induced Synthesis of γ‐Amino Sulfones from Vinyl Sulfones and Amino Acids

AbstractA method for the synthesis of γ‐amino sulfones through visible light‐induced oxidative decarboxylation and radical reductive addition is described. Various readily available N‐protected natural amino acids react with aromatic/aliphatic vinyl sulfones to directly produce γ‐amino sulfone derivatives. This reaction is also applicable to α‐N(O)‐acids and other aliphatic carboxylic acids, resulting in the corresponding sulfone derivatives. The method operates without the need for sacrificial reducing agents or additional hydrogen atom donors. The sole by‐product is CO2 released from decarboxylation, rendering the process both atom‐ and step‐economical.

Functional network copolymeric hydrogels derived from moringa gum: Physiochemical, drug delivery and biomedical properties

The article explores the synthesis of network hydrogels derived from moringa gum (MG) through a grafting reaction with poly (vinylsulfonic acid) and carbopol. These hydrogels are designed for use in drug delivery (DD) and wound hydrogels dressing (HYDR) applications. The copolymers were characterized by FESEM, EDX, AFM, FTIR, 13C NMR, XRD and DSC. Tetracycline release from hydrogel occurred gradually with a non-Fickian diffusion and was best described by the Hixson-Crowell kinetic model in artificial wound fluid. The HYDR demonstrated compatibility with blood, exhibited antioxidant properties and possessed tensile strength, in addition to their mucoadhesive characteristics. The copolymer dressings absorbed approximately 7 g of simulated fluid. The copolymers exhibited significant antioxidant activity, measuring at 84 % free radicals scavenging, during DPPH assay. These dressings demonstrated permeability to H2O and O2,. The hydrogel alone did not reveal antibacterial activities; however, when combined with antibiotic drug tetracycline, the dressings revealed notable antibacterial activities against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. The observed biomedical properties suggested that these hydrogels could serve as promising materials for drug delivery HYDR applications.

Transition‐Metal‐Free Annulation of Sulfonyl‐Derived 1,3‐Enynes: Simple and Efficient Construction of 2,4‐Disubstituted Thiophenes and Vinyl Sulfone‐Tethered 1,2,3‐NH‐Triazoles

AbstractThiophenes and 1,2,3‐NH‐triazoles are important frameworks in pharmaceuticals and advanced functional materials. Vinyl sulfones are also blueprint motifs in medicinal chemistry, but hybrid analogues of 1,2,3‐NH‐triazole‐derived from vinyl sulfones still need to be explored. In this report, we present an efficient and transition‐metal‐free [4+1]‐thioannulation of sulfonyl‐tethered 1,3‐enynes with Na2S in the presence of Cs2CO3 to generate 2,4‐disubstituted thiophenes in good to high yields. We also established a formal [3+2]‐cycloaddition of 1,3‐sulfonylenynes with NaN3 under metal‐ and base‐free conditions to synthesize vinyl sulfone‐containing 1,2,3‐NH‐triazole derivatives in moderate to high yields. The scope of these protocols was successfully showcased with various types of 1,3‐enynes bearing sensitive functional groups and complex structural scaffolds. The desired products were readily obtained with good functional group tolerance and compatibility. Based on the existing results and control experiments, plausible mechanistic pathways are also presented.

Nickel-Catalyzed Direct Sulfonylation of Styrenes and Unactivated Aliphatic Alkenes with Sulfonyl Chlorides.

A nickel-catalyzed direct sulfonylation of alkenes with sulfonyl chlorides has been developed using 1,10-phenanthroline-5,6-dione as the ligand. Unactivated alkenes and styrenes including 1,1-, 1,2-disubstituted alkenes can be subjected to the protocol, and a wide range of vinyl sulfones was obtained in high to excellent yields with good functional group compatibility. Notably, the process did not allow the desulfonylation of sulfonyl chloride or chlorosulfonylation of alkenes. Radical-trapping experiment supported that a sulfonyl free-radical was likely produced and triggered subsequent transformation in the process.

Identification of Dihydropyrazolo[1,5-a]pyrazin-4(5H)-ones as Cyclic Products of β-Amidomethyl Vinyl Sulfone Alphavirus Cysteine Protease Inhibitors.

Optimized syntheses of (E)-5-(2-ethoxyphenyl)-N-(3-(methylsulfonyl)allyl)-1H-pyrazole-3-carboxamide (RA-0002034, 1), a promising antiviral covalent cysteine protease inhibitor lead, were developed. The syntheses avoid the contamination of 1 with the inactive cyclic dihydropyrazolo[1,5-a]pyrazin-4(5H)-one 2, which is formed by the intramolecular aza-Michael reaction of the vinyl sulfone warhead under basic conditions and slowly at pH 7.4 in phosphate buffer. The pure cysteine protease inhibitor 1 could be synthesized using either modified amide coupling conditions or through the introduction of a MOM-protecting group and was stable as a TFA or HCl salt. Although acyclic 1 demonstrated poor pharmacokinetics with high in vivo clearance in mice, inactive cyclic 2 showed improved plasma exposure. The potential use of cyclic dihydropyrazolo[1,5-a]pyrazin-4(5H)-ones as prodrugs for the acyclic β-amidomethyl vinyl sulfone warhead was demonstrated by GSH capture experiments with an analog of 2.

Catalyst-Free α-trans-Selective Hydroboration and (E)-Selective Deuterated Semihydrogenation of Alkynyl Sulfones.

Here, we present a straightforward α-trans-selective hydroboration of alkynyl sulfones with NHC-boranes without the need for a catalyst. This reaction is compatible with a wide range of substrates for efficiently producing structurally diverse α-borylated vinyl sulfones in satisfactory yields. The hydride transfer from NHC-borane 2a to alkynyl triflone 1b is studied by density functional theory (DFT) calculations for trans-hydroboration. Moreover, a regiodivergent deuterated semihydrogenation of alkynyl triflones has also been developed using D2O as the deuterium source. A variety of diversity-oriented D-containing vinyl triflones were prepared in good to excellent yields with excellent deuterium incorporation ratios. Synthetic manipulations of the deuterated products are achieved for the conversion into valuable deuterated molecules, indicating the utility of this protocol.

Structure Activity of β-Amidomethyl Vinyl Sulfones as Covalent Inhibitors of Chikungunya nsP2 Cysteine Protease with Anti-alphavirus Activity.

Despite their widespread impact on human health there are no approved drugs for combating alphavirus infections. The heterocyclic β-aminomethyl vinyl sulfone RA-0002034 (1a) is a potent irreversible covalent inhibitor of the alphavirus nsP2 cysteine protease with broad spectrum antiviral activity. Analogs of 1a that varied each of three regions of the molecule were synthesized to establish structure-activity relationships for inhibition of Chikungunya (CHIKV) nsP2 protease and viral replication. The covalent warhead was highly sensitive to modifications of the sulfone or vinyl substituents. However, numerous alterations to the core 5-membered heterocycle and its aryl substituent were well tolerated and several analogs were identified that enhanced CHIKV nsP2 binding. For example, the 4-cyanopyrazole analog 8d exhibited a kinact /Ki ratio >10,000 M-1s-1. 3-Arylisoxazole was identified an isosteric replacement for the 5-membered heterocycle, which circumvented the intramolecular cyclization that complicated the synthesis of pyrazole-based inhibitors like 1a. The accumulated structure-activity data was used to build a ligand-based model of the enzyme active site, which can be used to guide the design of covalent nsP2 protease inhibitors as potential therapeutics against alphaviruses.

Design of chiral acidic molecularly imprinted polymer for the enantioselective separation of (±)‐DOPA

AbstractBackgroundThe study focuses on developing a stable enantioselective matrix for the efficient chiral identification and enantioresolution of l‐DOPA and (±)‐DOPA. The matrix is derived from a copolymeric material made from poly[(vinylsulfonic acid)‐co‐(4‐vinylpyridine)] crosslinked with divinylbenzene.Resultsl‐DOPA‐vinylsulfonamide was synthesized and characterized. This chiral sulfonamide was copolymerized with 4‐vinylpyridine in the presence of a divinylbenzene crosslinker, using azobisisobutyronitrile as a thermal initiator. Post‐polymerization, the polymeric particles were treated with NaOH and subsequently washed with acid to remove the integrated l‐DOPA species. Scanning electron microscopy and Fourier transform infrared spectroscopy confirmed the imprinted l‐DOPA‐IP particles. The manufactured l‐DOPA‐IP demonstrated a tenfold greater affinity for l‐DOPA compared to d‐DOPA. Langmuir adsorption experiments at pH 6 showed a maximum capacity of 162 mg g−1. Enantiomeric excess values for l‐ and d‐DOPA, determined through optical separation using a column approach, were 94% and 82%, respectively, in the loading and recovery solutions.ConclusionThe developed copolymeric material effectively served as an enantioselective matrix, exhibiting high selectivity and capacity for l‐DOPA. The process demonstrated efficient chiral identification and separation, achieving significant enantiomeric excess values for both l‐ and d‐DOPA. © 2024 Society of Chemical Industry (SCI).

Preparation and drug delivery of hydrogels based on grafting of methacrylamide (MAAm) / vinylsulphonic acid (VSA) co monomers onto psyllium

Recently, a plethora of advancements have been made in the area of polysaccharide research to improve their properties for human health care. The present research is an attempt to develop hydrogels from through grafting of methacrylamide (MAAm) and vinyl sulphonic acid (VSA) co monomers onto psyllium for use in drug delivery (DD) applications. Copolymer hydrogels were characterized by scanning electron micrographs (SEM), Atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), 13C nuclear magnetic resonance (13C NMR), thermogravimetric analysis (TGA) and differential thermal analysis (DTG). SEM, AFM and XRD revealed heterogeneous morphology of the copolymer hydrogels with surface roughness and amorphous state of polymer chains in copolymer hydrogels due to graft-copolymerization reactions. The appearance of the FTIR bands at 1636.87 (amide-I), 1618.11 cm−1 (amide- II), 1469.58 cm−1 (amide- III) indicated presence of amide and bands at 1167.12 cm−1, 1112.06 cm−1 band (symmetric vibrations of SO3H groups and anti-symmetric & symmetric stretching modes of C–S) presence of VSA. The appearance of bands at 181.801 ppm and 62.053 ppm indicated presence of CO carbon of functional groups poly (MAAm) and −CH2–SO3H of poly (VSA) in copolymer hydrogels. Diffusion of the antibiotic drug vancomycin occurred in sustained manner with a non-Fickian diffusion mechanism. The release profile was best described by Korsmeyar-Peppas kinetic model. The copolymers exhibited biocompatible nature and revealed haemolytic index less than 5 % during polymer-blood interactions. The hydrogel demonstrated mucoadhesive character and required 0.135 ± 0.01 N force to detach from mucous membrane. These properties demonstrated the suitability of copolymer hydrogels for drug delivery applications.

Interfacial modulation of bifunctional electrolyte additive engineering for dendrite-free and robust lithium metal anode

Anode materials for rechargeable electric car batteries are obtained from Li-metal owing to their extremely high specific capacity and low redox potential. Unfortunately, safety concerns related to dendrite formation on the anode surface caused by the uneven distribution of Li-ions during the discharge process interfere with the use of Li-metal in industrial batteries. In this study, methyl vinyl sulfone (MVS), a sulfone-based functional electrolyte additive, is used in an additive engineering strategy to control Li-electrolyte interactions and address the aforementioned problems. Li dendrite growth may be restricted, and transition metal degradation on the surface of the cathode can be reduced by the MVS-derived functional electrolyte additive interfacial layer. The electrochemical performance of an ethylene carbonate/dimethyl carbonate (EC/DMC) + 1 wt% MVS Li-metal anode of a Li||Li symmetric cell exhibits remarkable cycle stability, maintaining a low overvoltage for over 750 h at 1 mA cm−2, and capacity of 1 mA h cm−2. Additionally, LiNi0.8Co0.1Mn0.1O2 (NCM811) full cells with the MVS additive exhibit enhanced electrochemical stability for 250 cycles at a current density of 100 mA g−1. This study provides an innovative approach for stabilizing the metal-electrolyte interfacial layer that may be used for practical applications in metal-based rechargeable batteries.

Study of reactive dyes and their hydrolyzed forms in a real trichromatic dyeing process by capillary electrophoresis with UV detection.

Detecting the concentration of reactive dyes and their hydrolyzed products is essential for controlling the dyeing process and is an important guide for upgrading and improving textile dyeing technology. In this study, capillary electrophoresis (CE) with UV detection was for the first time applied in a real trichromatic dyeing process to provide qualitative and quantitative determination of reactive dyes and their hydrolyzed forms. Here, three original reactive dyes (SES-Cl-red-195, SES-Cl-yellow-145, and SES-Cl-blue-194), their vinyl sulfone forms (VS-Cl-red-195, VS-Cl-yellow-145, and VS-Cl-blue-194), and complete hydrolyzed forms (HES-OH-red-195, HES-OH-yellow-145, and HES-OH-blue-194) could be baseline separated in our developed BGE comprised of 10.0 mol/L Na2B4O7, 15% (V/V) ACN at pH 8.50 that adjusted by 0.50 mol/L H3BO3. The LODs (S/N = 3) of nine analytes ranged from 0.3 to 1.3 mg/L, and high sensitivities were achieved with UV detection. The RSDs of peak area and migration time were in the ranges of 1.4-3.8% and 0.39-1.29%, which indicated the CE methods were reliable for studying different dye forms in complex dye baths, and for evaluating dyeing process quality. Thus, the percentage of dye-uptake in single and trichromatic combination dyes was calculated based on the concentration of the original and their vinyl sulfone and hydrolyzed forms, and the result was consistent with the traditional UV-Vis method.

Hydrosulfonylation of Alkynes for Stereodivergent Synthesis of Vinyl Sulfones: Synthetic Strategy and Mechanistic Insights.

Direct synthesis of thermodynamically less favorable (Z)-vinyl sulfones presents a notable challenge in organic synthesis. In addition, the development of a stereodivergent synthesis for (E)- and (Z)-vinyl sulfones is crucial but remains elusive. In this study, we present a hydrosulfonylation of aryl-substituted alkynes, achieving a stereodivergent synthesis of (E)- and (Z)-vinyl sulfones by leveraging both thermodynamic and kinetic controls. Notably, the synthesis of challenging (Z)-vinyl sulfones was achieved through a kinetically controlled process without the need for a catalyst. To synthesize (E)-vinyl sulfones, unconventional visible light-mediated isomerization was employed as a means of facilitating the transition to the thermodynamically favored form. The present study encompasses a comprehensive experimental and computational investigation, which provides valuable insights into the reaction mechanism. This investigation reveals two plausible isomerization pathways: a novel double spin-flip mechanism and a hydrogen atom transfer process in the presence of eosin Y. This study not only advances our understanding of isomerization mechanisms beyond conventional energy-transfer routes but also offers a robust and switchable strategy for synthesizing (E)- and (Z)-vinyl sulfones, thereby providing a versatile avenue for the creation of valuable compounds in the fields of organic synthesis and medicinal chemistry.

Inside Back Cover

The cover displays a selective oxidative sulfonylation of alkenes with selenium sulfonate depended on the reaction conditions. The electrochemical C—H sulfonylation proceeded smoothly to afford (E)‐vinyl sulfones with good selectivity in an undivided cell without external oxidant. While aerobic trifunctionalization of alkenes occurred in the presence of KI in the air, which provides β‐keto selenosulfones via the formation of C—O, C—S, and C—Se bonds in one‐pot. This selective synthesis is like interstellar racing, reaching distant planets from the same starting point through different paths. Following control experiments, a plausible mechanism is proposed to rationalize the experimental results. More details are discussed in the article by Cao et al. on page 1367—1372.image

Synthesis of Functionalized Organosilicon Compounds/Distal Ketones via Ring-Opening Giese Addition of Cycloalkanols under Organophotocatalytic Conditions.

Visible-light-induced organophotocatalyzed ring-opening followed by remote Giese addition of tertiary cycloalkanols with β-silylmethylene malonates has been developed under mild reaction conditions for the synthesis of organosilicon compounds, bearing a ketone group distally substituted with a silyl group with an additional dialkyl malonate functional handle in moderate to good yields (34-72%). The protocol also worked well with diverse Michael acceptors, such as alkylidene/benzylidene malonates, trifluoro methylidene malonate, benzylidene malononitrile, α-cyano-enone, and α-cyano vinyl sulfone, and delivered desired valuable distally functionalized ketones. To showcase the potential of the method, various synthetic transformations of the obtained product were also demonstrated.

Biocompatible Thermally Responsive Vinyl Sulfone Silica Nanocapsules as Stabilizing and Softening Agents for Metal-Free Leather Production

Biocompatible Thermally Responsive Vinyl Sulfone Silica Nanocapsules as Stabilizing and Softening Agents for Metal-Free Leather Production

Mucus-coated, magnetically-propelled fecal surrogate to mimic fecal shear forces on colonic epithelium

The relationship between the mechanical forces associated with bowel movement and colonic mucosal physiology is understudied. This is partly due to the limited availability of physiologically relevant fecal models that can exert these mechanical stimuli in in vitro colon models in a simple-to-implement manner. In this report, we created a mucus-coated fecal surrogate that was magnetically propelled to produce a controllable sweeping mechanical stimulation on primary intestinal epithelial cell monolayers. The mucus layer was derived from purified porcine stomach mucins, which were first modified with reactive vinyl sulfone (VS) groups followed by reaction with a thiol crosslinker (PEG-4SH) via a Michael addition click reaction. Formation of mucus hydrogel network was achieved at the optimal mixing ratio at 2.5 % w/v mucin-VS and 0.5 % w/v PEG-4SH. The artificial mucus layer possessed similar properties as the native mucus in terms of its storage modulus (66 Pa) and barrier function (resistance to penetration by 1-μm microbeads). This soft, but mechanically resilient mucus layer was covalently linked to a stiff fecal hydrogel surrogate (based on agarose and magnetic particles, with a storage modulus of 4600 Pa). The covalent bonding between the mucus and agarose ensured its stability in the subsequent fecal sliding movement when tested at travel distances as long as 203 m. The mucus layer served as a lubricant and protected epithelial cells from the moving fecal surrogate over a 1 h time without cell damage. To demonstrate its utility, this mucus-coated fecal surrogate was used to mechanically stimulate a fully differentiated, in vitro primary colon epithelium, and the physiological stimulated response of mucin-2 (MUC2), interleukin-8 (IL-8) and serotonin (5HT) secretion was quantified. Compared with a static control, mechanical stimulation caused a significant increase in MUC2 secretion into luminal compartment (6.4 × ), a small but significant increase in IL-8 secretion (2.5 × and 3.5 × , at both luminal and basal compartments, respectively), and no detectable alteration in 5HT secretion. This mucus-coated fecal surrogate is expected to be useful in in vitro colon organ-on-chips and microphysiological systems to facilitate the investigation of feces-induced mechanical stimulation on intestinal physiology and pathology.