Aromatic Sulfonyl Research Articles

Substituent-Dependent, Switchable Synthesis of Nonaromatic and Aromatic Heterocyclic Sulfones Using Visible Light.

In this Letter, we described a visible-light-induced switchable synthesis of nonaromatic and aromatic sulfonyl heterocycles. The product selectivity between 2,5-dihydropyrrole and pyrrole can be tuned by altering the substituent on the N atom of 1,6-diyne. We highlight the intricacy and efficiency of this approach in constructing molecular frameworks under mild conditions with a high functional group tolerance. This study elucidates the mechanism underlying product selectivity, highlighting its potential as a compelling alternative to traditional synthetic techniques.

Efficient and Robust Dynamic Crosslinking for Compatibilizing Immiscible Mixed Plastics through In Situ Generated Singlet Nitrenes.

Creating a sustainable economy for plastics demands the exploration of new strategies for efficient management of mixed plastic waste. The inherent incompatibility of different plastics poses a major challenge in plastic mechanical recycling, resulting in phase-separated materials with inferior mechanical properties. Here, this study presents a robust and efficient dynamic crosslinking chemistry that effectively compatibilizes mixed plastics. Composed of aromatic sulfonyl azides, the dynamic crosslinker shows high thermal stability and generates singlet nitrene species in situ during solvent-free melt-extrusion, effectively promoting C─H insertion across diverse plastics. This new method demonstrates successful compatibilization of binary polymer blends and model mixed plastics, enhancing mechanical performance and improving phase morphology. It holds promise for managing mixed plastic waste, supporting a more sustainable lifecycle for plastics.

Ultra-high throughput-based screening for the discovery of antiplatelet drugs affecting receptor dependent calcium signaling dynamics

Distinct platelet activation patterns are elicited by the tyrosine kinase-linked collagen receptor glycoprotein VI (GPVI) and the G-protein coupled protease-activated receptors (PAR1/4) for thrombin. This is reflected in the different platelet Ca2+ responses induced by the GPVI agonist collagen-related peptide (CRP) and the PAR1/4 agonist thrombin. Using a 96 well-plate assay with human Calcium-6-loaded platelets and a panel of 22 pharmacological inhibitors, we assessed the cytosolic Ca2+ signaling domains of these receptors and developed an automated Ca2+ curve algorithm. The algorithm was used to evaluate an ultra-high throughput (UHT) based screening of 16,635 chemically diverse small molecules with orally active physicochemical properties for effects on platelets stimulated with CRP or thrombin. Stringent agonist-specific selection criteria resulted in the identification of 151 drug-like molecules, of which three hit compounds were further characterized. The dibenzyl formamide derivative ANO61 selectively modulated thrombin-induced Ca2+ responses, whereas the aromatic sulfonyl imidazole AF299 and the phenothiazine ethopropazine affected CRP-induced responses. Platelet functional assays confirmed selectivity of these hits. Ethopropazine retained its inhibitory potential in the presence of plasma, and suppressed collagen-dependent thrombus buildup at arterial shear rate. In conclusion, targeting of platelet Ca2+ signaling dynamics in a screening campaign has the potential of identifying novel platelet-inhibiting molecules.

Enhanced gene transfection ability of sulfonylated low-molecular-weight PEI and its application in anti-tumor treatment.

With the continuous progress of nanotechnology in the field of tumor vaccines, immunotherapy has been regarded as one of the most powerful approaches for cancer treatment. Currently, DNA vaccines are used to efficiently deliver plasmids encoding tumor-associated antigens to antigen-presenting cells (APCs) and enhance the activation of immune cells. In this work, a series of aromatic sulfonyl small-molecule-modified polymers R-P based on low-molecular-weight polyethylenimine (PEI) were prepared, and their structure-activity relationship was studied. Among them, Ns-P with high transfection efficiency and low toxicity was applied to deliver antigen ovalbumin (OVA)-encoded plasmid DNA to APCs for triggering the immune activation of dendritic cells (DCs). It was also found that Ns-P could be used as an immune adjuvant to activate the STING pathway in DCs, integrating innate stimulating activity into the carrier to enhance antitumor immunity. Moreover, the modification of Ns-P/pOVA complexes with oxidized mannan could not only improve the biocompatibility of the complex, but also enhance the uptake of DCs, further inducing OVA antigen presentation and immune stimulation. In vivo antitumor assays indicated that Ns-P/pOVA/Man immunization could inhibit the growth of OVA-expressing E.G7 tumors in C57BL/6 mice. These results demonstrated that Ns-P/pOVA/Man is promising for gene delivery and immunotherapy application.

Transition‐metal‐free Cyclization of Mucohalic Acids with Sulfonyl Hydrazides: An Approach to Pyridazin‐3(2H)‐ones

AbstractAn eco‐friendly and efficient synthesis of pyridazin‐3(2H)‐ones from aromatic sulfonyl hydrazides and mucohalic acids has been developed. This facile strategy is carried out smoothly via the promotion of simple organic acid p‐toluenesulfonic acid, and able to form two C−N bonds and a heterocycle linking a potentially bioactive sulfonyl group at one‐step. The protocol is tolerant to various readily available substrates in good yields, and pyridazin‐3(2H)‐ones as the desired products are key structural fragments of many bioactive compounds. More importantly, the gram‐scale cyclization reaction of aromatic sulfonyl hydrazides and mucohalic acids as a novel approach to pyridazin‐3(2H)‐ones derivatives successfully reveals its practicability.

Photoinduced FeCl3-Catalyzed Chlorination of Aromatic Sulfonyl Chloride via Extrusion of SO2 at Room Temperature.

We report, herein, a photoinduced iron-catalyzed direct chlorination of aromatic sulfonyl chloride at room temperature. In this protocol, FeCl3-catalyzed direct chlorination has been realized at room temperature under the irradiation of light (400-410 nm). During the process, many commercially or readily available substituted aromatic sulfonyl chlorides could produce the corresponding aromatic chlorides in moderate to good yields.

Novel Ir(III) Complexes with NHC-Based Ancillary Ligands for Efficient Nondoped OLEDs

Nondoped organic light-emitting diodes (OLEDs) are of paramount importance for display and lighting applications owing to their advantages of facile fabrication and outstanding stability. However, nondoped OLEDs achieving extraordinary electroluminescence (EL) performance and low turn-on voltage (Von) remain sparse. Here, three Ir(III) complexes featuring N-heterocyclic carbene (NHC) auxiliary ligands functionalized with electron-deficient aromatic sulfonyl or phosphine oxide groups are reported as promising emitters for nondoped OLEDs. All Ir(III) complexes exhibit green emission with relatively high neat film efficiency. Although the photoluminescence spectra of three complexes reveal similarities, there are distinct differences in the nondoped EL performance. The nondoped device N3 based on tBu-Ir-ISO displays the most eminent EL performances and presents a low Von of 2.1 V, a power efficiency of 30.7 lm W-1, and a maximum current efficiency of 27.0 cd A-1, which can be attributed to steric hindrance and balanced carrier-transporting ability induced by electron-deficient substituents. Moreover, doped devices D1-D3 also realize excellent EL performance. It is believed that the strategy reported herein is a simple and efficient way of constructing excellent Ir(III) complexes for nondoped phosphorescent OLEDs.

Chiral sulfonamides with various N-heterocyclic and aromatic units – Synthesis and antiviral activity evaluation

Chiral sulfonamides with aromatic fragments are important chemical building blocks found widely in many natural products, catalysts, and molecules of biological importance. In this report, we describe the efficient synthesis of a series of chiral sulfonamides which, in addition to the aromatic part (phenyl, biphenyl, and dansyl units), possess N-heterocyclic systems. The described compounds were obtained by nucleophilic substitution of chiral N-heterocyclic amines and commercially available aromatic sulfonyl chlorides under mild conditions. All derivatives were examined in antiviral assay against AdV5, HSV-1, HPIV-3, HCMV, and EMCV viruses.

Water Determination in Aromatic Sulfonyl Chlorides Using the Karl Fischer Titration Method: Scope and Limitations

AbstractThe scope and limitations of the Karl Fischer titration was studied for various aromatic sulfonyl chlorides. Standard addition determination of water content was performed using p‐toluenesulfonyl chloride samples; it was confirmed that the method had high accuracy. A set of substituted aromatic sulfonyl chlorides (95 compounds) was subjected to the Karl Fischer titration in order to establish the relevance of the method depending on the compound structure. It was shown that the method gave satisfactory results and was applicable to most aromatic sulfonyl chlorides, except the compounds possessing strong electron‐withdrawing substituents.

Реакционная способность арилсульфонилгалогенидов как функция молекулярного электростатического потенциала реакционного центра

To study the reactivity of arylsulfonyl halides, the molecular electrostatic potential (MEP) was considered for the first time as a descriptor. The reaction of hydrolysis of aromatic sulfonyl halides in the medium of mixed acetone-water solvents (according to the literature data of rate constants) was used as a model. The calculation of the structural parameters of the molecules of substituted arylsulfonyl halides was carried out using the ADF2014 software package at the level of the DFT/M06/6-311+G* (PCM) theory. It was found that the magnitude of the MEP on the sulfonyl sulfur atom is very sensitive to changes in the structure of substrates, which makes it possible to determine the change in the ratio between the rate of nucleophilic attack and anionoid abstraction of the leaving group. In particular, using the example of the hydrolysis reaction of substituted thiophenesulfonyl chlorides, it was shown that the acceleration of the reaction is observed with an increase in the donor properties of the substituents and the associated increase in the negative MEP value on the sulfonyl sulfur atom. The antibate character of the dependence of the hydrolysis constant values on the IEP value indicates that not the nucleophilic attack is the rate determining in the interaction of thiophene sulfonyl chlorides and the hydroxyl anion in this sample, but the abstraction of the chloride anion. This reaction has an unstable mechanism, when the ratio between the degree of S-nucleophile bond formation and S-halogen bond cleavage changes. This makes it possible to use MEP as a descriptor of reactivity in the hydrolysis of aryl sulfonyl halides and to elucidate the details of changes in the structure of transition states during the implementation of mechanisms other than pure SN2 mechanism.

Design, Synthesis, and Antitumor Activity of a Series of Novel 4-(Aromatic Sulfonyl)-1-oxa-4-azaspiro[4.5]deca-6,9-dien-8-ones.

Many sulfonamides show anticancer activity. Based on benzenesulfonylazaspirodienone (HL-X9) identified in our previous work, we optimized the lead compound for better efficacy, thereby synthesizing a series of novel 4-(aromatic sulfonyl)-1-oxa-4-azaspiro[4.5]deca-6,9-dien-8-one derivatives through a key step of metal-catalyzed cascade cyclization. The preliminary antiproliferative tests have shown that the anticancer activities of acetyl-protected mannose-linked sulfonylazaspirodienone derivatives (7i–7l) have been greatly improved. Among them, 7j is the most potent derivative, with IC50 values of 0.17 µM, 0.05 µM, and 0.07 µM for A549, MDA-MB-231, and HeLa cell lines, respectively. Flow cytometry analysis shows that 7j arrests MDA-MB-231 cells in the G2/M phase and has a certain effect on the apoptosis of MDA-MB-231 cells. In addition, the acute toxicity of 7j was lower than that of adriamycin.

Design, Synthesis, and Characterization of Novel Linomide Analogues and their Evaluation for Anticancer Activity.

According to WHO, in 2017, about 90.5 million people suffered from cancer and about 8.8 million deaths occurred due to disease. Although the chemotherapeutic agents have decreased the mortality among the cancer patients but high toxicity and non-specific targets are still major drawbacks. Many researchers have identified linomide, a 4-hydroxy-2-quinolone derivative, as a lead molecule for the development of anticancer agents. With this background, we thought of the following objective. The objective of this research work involves the synthesis of a series of N-(2-(4- hydroxy-2-oxo-1-phenyl-1,2-dihydroquinolin-3-yl)-2-oxoethyl)-N-alkyl substituted benzene sulfonamides IVa-d (1-3) by replacing the anilide moiety at the third position of linomide with sulfamoylacyl and also N-methyl by N-phenyl functionality. To perform in silico anticancer activity by using Molegro Virtual Docker (MVD-2013, 6.0) software and in vitro anticancer activity by MTT assay. The starting material 4-hydroxy-1-phenylquinolin-2(1H)-one was treated with N-bromosuccinamide to yield compound II. Condensation of compound II with primary amines resulted in compounds IIIa-d, which, on coupling with substituted aromatic sulfonyl chlorides yield the title compounds IVa-d (1-3). All the synthesized compounds were satisfactorily characterized by spectral data. The results of docking revealed that the synthesized compounds exhibited well-conserved hydrogen bonds with one or more amino acid residues in the active pocket of EGFRK tyrosine kinase domain (PDB ID: 1m17). The MolDock Score of compound IVd-1 (-115.503) was the highest amongst those tested. The in vitro anticancer activity results showed that compound IVc-1 (R= - (CH2) 2-CH3 ; R'= -H) and IV d-1 (R= -CH2-C6H5; R'= -H) were found to be most potent against K562 cell line with an IC50 of 0.451 μM/ml and 0.455 μM/ml respectively. Compound IVd-1 also showed better potency against A549 cell line with IC50 value of 0.704 μM/ml. The results of in silico and in vitro anticancer activity are in agreement with each other. Compound IV d-1 was found to be most active of the series.

Arylsulfochlorination of β-aminopropioamidoximes giving 2-aminospiropyrazolylammonium arylsulfonates

The reaction of P-(morpholin-1-yl)propioamidoxime with aromatic sulfonyl chlorides (p-XC6H4SO2Cl; X = CH3O, CH3, H, Br, Cl, NO2) in chloroform in the presence of triethyl-amine does not produce expected O-arylsulfonyl-β-(morpholin-1-yl)propioamidoximes; instead, this reaction affords isomers of the latter compounds, 2-amino-8-oxa-l,5-diazaspiro[4.5]dec-1-ene-5-ammonium arylsulfonates. The structures of the reaction products were established by physicochemical methods, spectroscopy, and X-ray diffraction.

Sulfonamide-Based Azaheterocyclic Schiff Base Derivatives as Potential Carbonic Anhydrase Inhibitors: Synthesis, Cytotoxicity, and Enzyme Inhibitory Kinetics.

A series of sulfonamide-bearing azaheterocyclic Schiff base derivatives 3(a-j) were synthesized as carbonic anhydrase inhibitors. The substituted benzene sulfonyl chlorides 1(a-d) were reacted with N2H4 to get aromatic sulfonyl hydrazides 2(a-d). The intermediate hydrazides 2(a-d) were treated with substituted aldehydes to afford azaheterocyclic sulfonamide Schiff bases 3(a-j). The spectral data of synthesized compounds confirmed the formation of the final products. The inhibitory effects of 3(a-j) on carbonic anhydrase activity were determined, and it was found that derivative 3c exhibited the most potent activity with IC500.84 ± 0.12 μM among all other derivatives and is also more active than standard acetazolamide (IC500.91 ± 0.12). The enzyme inhibitory kinetics results determined by Lineweaver-Burk plots revealed that compound 3c inhibits the enzyme by noncompetitive mode of inhibition with Ki value 8.6 μM. The molecular docking investigations of the synthesized analogues 3(a-j) were evaluated which assured that synthesized compounds bind well inside the active binding site of the target enzyme. Cytotoxicity on human keratinocyte (HaCaT) and MCF-7 cell lines was performed, and it was found that most of the synthesized analogues were nontoxic on these cell lines and the toxic effects follow the dose-dependent manner. Based on our investigations, it was suggested that analogue 3c may serve as core structure to project carbonic anhydrase inhibitors with greater potency.

Surface modification of polyetheretherketone by grafting amino groups to improve its hydrophilicity and cytocompatibility

Although special engineering plastics polyether ether ketone (PEEK) have many excellent properties, its hydrophobicity and biological inertia limit its application in the field of implant materials. In this study, amino modification of PEEK was conducted to endow it with good hydrophilicity and bioactivity. PEEK was sulfonated with concentrated sulfuric acid, and reacted with sulfoxide chloride to obtain aromatic sulfonyl chloride. Finally, amino (–NH2) was introduced onto the surface of PEEK by acylation reaction between acyl chloride group and ethylenediamine (EDA) to improve its hydrophilicity and cell compatibility. The PEEKs before and after modification were characterized by FTIR, XPS and WCA. The cell compatibility was evaluated by human umbilical vein endothelial cells (HUVEC). The results showed that –NH had been successfully introduced onto the surface of PEEK, and the hydrophilicity of the aminated PEEK was significantly improved. Compared with the PEEK before amino modification, the aminated PEEK significantly promoted adhesion and spread of cells, indicating good cell compatibility. This study breaks through the limitations of traditional wet chemical methods and provides a new way for further modification of PEEK.

Copper-Catalyzed Aerobic Oxidative Coupling of Aromatic Sulfonyl Hydrazides with Amines:A New Access to Aromatic Sulfonamides

Copper-Catalyzed Aerobic Oxidative Coupling of Aromatic Sulfonyl Hydrazides with Amines:A New Access to Aromatic Sulfonamides

Synthesis, spectral characterization, docking studies and biological activity of urea, thiourea, sulfonamide and carbamate derivatives of imatinib intermediate.

A series of new urea/thiourea derivatives 3a-j were synthesized by simple addition reaction of functionalized phenyl isocyanates/isothiocyanates 2a-j with N-(5-amino-2-methylphenyl)-4-(3-pyridyl)-2-pyrimidinamine (imatinib intermediate) (1) in the presence of 1,4-dimethyl piperazine (DMPZ) as a base, and another series of new sulfonamide/carbamate derivatives 5a-k were synthesized by reacting 1 with various substituted aromatic sulfonyl chlorides 4a-f and aromatic/aliphatic chloroformates 4g-k in the presence of DMPZ as a base. The title compounds 3a-j and 5a-k were characterized by IR, 1H, 13C NMR and mass spectral data. Antimicrobial, antioxidant and in silico molecular docking studies were made against aromatase.

Novel aromatic sulfonyl naphthalene-based boronates as 20S proteasome inhibitors

A novel series of non-peptide proteasome inhibitors (PIs) that act on chymotrypsin-like (ChT-L) of the proteasome were developed. These PIs bearing 4-aromatic sulfonyl naphthalene-based scaffold and Leu-boronic moiety as covalent bonding group displayed far better activity than PI-8182 for inhibiting ChT-L in preliminary biological activity test. The results showed that 2a (IC50 = 6.942 μM, MCF-7) and 2c (IC50 = 6.905 μM, MCF-7) displayed higher anti-proliferative activities than Bortezomib (IC50 = 18.37 μM, MCF-7) under our experimental conditions. Furthermore, in the microsomal stability assay, 2a demonstrated excellent metabolic stability profiles with 56% remaining after 40 min, as compared to Bortezomib of which approximately 30% was remaining. The compounds 2a, 2c emerged as promising lead compounds for the development of novel non-peptide boronate PIs.

Organocatalyzed Photoredox Polymerization from Aromatic Sulfonyl Halides: Facilitating Graft from Aromatic C–H Bonds

Aromatic sulfonyl halides are readily accessible from many sources. With newly synthesized N-arylphenothiazine catalysts, organocatalyzed photoredox polymerization has been developed with arylsulfonyl halides initiators using white or purple LEDs light sources. This method allows the preparation of poly(meth)acrylates and poly(meth)acrylamides possessing a broad scope of (hetero)aryl chain ends without metal-contamination concern. Investigations such as MALDI-TOF analysis, chain extension, and “ON/OFF” control experiments confirmed the fidelity of the polymer structure and reliability of this method. Moreover, this method facilitates the two-step preparation of brush polymers from polystyrene through an electrophilic aromatic substitution/organocatalyzed photopolymerization sequence.

SuFEx Postpolymerization Modification Kinetics and Reactivity in Polymer Brushes

Since its introduction in 2014, the sulfur(VI) fluoride exchange (SuFEx) reaction has emerged as a promising new reaction in the field of polymer chemistry, in both polymerization of diverse polymer backbones and postpolymerization modification (PPM). Previously, we successfully reported the use of SuFEx chemistry as a method for surface derivatization through the PPM of sulfonyl fluoride containing polymer brushes. However, with the diversity of conditions, substrate scope, and catalyst selection afforded by this reaction, it is advantageous to expand the use of SuFEx for PPM on polymer brushes to discern the advantages and limitations of this reaction in surface conjugation. In this work, we used three different polymer brush systems—alkyl sulfonyl fluorides, aromatic sulfonyl fluorides, and aromatic fluorosulfonates—and each was reacted with three different silyl ether derivatives (aryl, alkyl, and benzyl). Each of these reactions was subjected to different catalysts, and herein, we present rates, cond...