Aryl Sulfone Research Articles

Quantum mechanical parameters-based study of aryl sulphonamides as 5-HT6 serotonin ligand using DFT methods

In the present work, quantum mechanical descriptors have been used for the development of quantitative structure activity relationship (QSAR) models for the thirty-two derivatives of aryl sulphonamide and sulfone based 5-HT6 antagonists. Among several classes of serotonin 5-HT6 receptor ligands, aryl sulphonamides reported better affinity towards the receptor. Drugs acting as serotonin ligands are useful in the treatment of a variety of mental disorders. The descriptors that have been used in our study are total energy, log P, molecular weight, dipole moment, heat of formation, LUMO energy, HOMO energy and electrophilicity index. The geometry optimization and evaluation of descriptors of all the compounds has been done with the help of CAChe Pro software using DFT-B88-LYP method with double-zeta valence polarized (DZVP) basis set. The best QSAR model for this set of derivatives has been obtained by combination of descriptors molecular weight, dipole moment and heat of formation. The descriptor molecular weight gives a mono-parametric QSAR model with remarkable predictive ability with positive contribution. The descriptor molecular weight is present in all best bi-parametric and tri-parametric QSAR models. Statistical parameters such as correlation coefficient, cross validation coefficient, standard error etc. were used to validate the predictability of QSAR models.

Nickel-catalyzed cross-electrophile coupling of unactivated (hetero)aryl sulfone with aryl bromide

A nickel-catalyzed cross-electrophile coupling of unactivated (hetero)aryl sulfones with aryl bromides via CS bond activation at ambient temperature is developed. By relying on the use of nickel as catalyst, 2,2′-bipyridine (bpy) as ligand, magnesium turnings as mediator, and THF as solvent, a myriad of biaryls could be facilely prepared in moderate to good yields with reasonable functionality compatibility. The present method potentially serves as an attractive alternative to conventional methods, for the use of unreadily available, relatively expensive, and sensitive organometallic reagents could be avoided.

Shining light for organophotocatalysed site-selective sulfonylation of anilides.

The site-selective sulfonylation of C(sp2)-H bonds of anilide and quinoline amide derivatives has been developed using organophotocatalysis. This mild and sustainable protocol, which operates at room temperature, precludes the requirement for any metal-based catalyst or photocatalyst and oxidant, which are the challenges associated with existing methodologies. Furthermore, the generation of aryl sulfonyl radicals from commercially available aryl sulfonyl chlorides has been achieved through the use of Rose Bengal as an organophotocatalyst, an approach that was previously unexplored. The detailed mechanistic investigation unveiled the underlying mechanism for site-selective sulfonylation at both the proximal and distal positions, thereby establishing a straightforward approach for building valuable aryl sulfone scaffolds.

Targeting carbonic anhydrases II/IX/XII with novel series of coumarin-based compounds: Synthesis, biological activity and molecular dynamics analysis

In the current study, unique series of coumarin sulfonate and sulfamate derivatives were synthesized. Their selectivity and inhibitory activity against glaucoma and cancer-associated CAs (hCA II, IX, and XII) were evaluated compared to standard acetazolamide. In addition, the cytotoxic effects of the synthesized compounds on colorectal carcinoma (HCT116) were examined. Generally, structure-activity relationship (SAR) analysis revealed that potent inhibitors bearing zinc binding group (ZBG) dimethyl sulfamate (4a-c) were shown to lack selectivity against three isoforms owing to the classical inhibitory mode of action. The incorporation of aryl or fluoro aryl sulfone moiety in non-sulfamate coumarin derivatives shifted selectivity toward cancer-related isoforms XII and IX, respectively. Para-fluorine substituted derivative 3c with IC50 value of 0.62 µM exhibited excellent activity and selectivity against hCA IX, while benzene sulfone possessing derivative 3b demonstrated selectivity toward hCA XII with IC50 value of 0.56 µM. Moreover, coumarin derivatives with ethyl sulfone (3e, 3i, and 6a) reported excellent selectivity toward CAII. In-silico studies were also conducted over selective, potent compounds. Molecular docking studies have shown that potent compounds could interact with the active site by different modes of action. The molecular dynamic analysis confirmed the stability of the protein in the presence of a potent ligand.

A New Avenue to Diversity‐Oriented Synthesis of Diaryl Sulfones

AbstractWe describe a highly efficient route for the sulfonylation (C‐SO2) of various halo arenes, boronic acids, and aromatic diazonium salt through a cross‐coupling reaction. The protocol incorporates the efficient use of Cu(OAc)2/K2CO3 and N‐Hydoxy aryl sulfonamide as an aryl sulfone surrogate. Various substrates and functional groups were well tolerated in this reaction system.

Nickel-Catalyzed Desulfonylative Reductive Cross-Coupling of Aryl Sulfones with Aryl Bromides

Herein, a nickel catalysis system for desulfonylative C(sp2)-C(sp2) reductive cross-coupling reactions of aryl sulfone derivatives with a range of aryl bromides has been established to form diverse biaryl compounds. The complex Ar-Ni(II)-SO2CF3 bearing a phosphine ligand through oxidative addition of aryl sulfone to Ni(0) species was isolated and confirmed by an X-ray, which provides solid evidence for the understanding of the C(Ar)-SO2 bond activation and reaction mechanism.

Poly (aryl sulfone)s containing 5,11-dihydroindolo[3,2-b] carbazole moieties in the main chain: non-conjugated blue-light-emitting materials

The substituents at the C6/C12 positions of DHIC could efficiently affect the electron cloud distribution and light-emitting performance of the DHIC derivative polymers.

Room temperature, simple and efficient synthesis and functionalization of aromatic poly(arylene sulfide)s, poly(arylene sulfoxide)s and poly(arylene sulfone)s

Aromatic polysulfides and polysulfones are a large group of sulfur-containing polymers representing an important class of materials with diverse applications, ranging from high performance engineering plastics, gas separation, ultrafiltration, nanofiltration, ion-exchange membranes, and materials for biomedical applications. All these polymers are produced by high temperature nucleophilic substitution reactions of dichlorobenzene with sodium sulfide (PPS) and dichlorodiphenyl sulfone with bis-phenols in the presence of basic catalysts (PAES). In the present work, novel poly(arylene sulfide)s were obtained in nearly quantitative yields, by one-pot, room temperature, metal-free, highly regioselective, non-stoichiometric step-polymerizations of diphenyl sulfide (DPS) with 1,1,1-trifluoroacetone and isatin, in a mixture of trifluoromethanesulfonic acid (TFSA) with CH2Cl2. The polymers obtained were soluble in common solvents. The oxidation of the poly(arylene sulfide)s with H2O2 at room temperature afforded poly(arylene sulfoxide)s and poly(arylene sulfones) with high oxidation selectivity. On heating, sulfoxide groups of the poly(arylene sulfoxide)s are converted into sulfide groups and oxygen, which acts as an expanding agent, is released in the process to form nanofoams with homogeneous pore distribution. Controlled incorporation of hydroxymethyl-, carboxy-, and “click” able allyl- and propargyl- functionalities is carried out by room temperature, post-modification reactions of the polymers bearing reactive oxindole groups.

Evaluation of the effectiveness of poly (phenyl sulfone) / nanoclay mixed matrix membranes for carbon dioxide/methane separation

Poly (phenyl sulfone) (PPSU) is a recently introduced poly (aryl sulfone) polymer that has attracted much attention for membrane fabrication. PPSU could fabricate both porous and non-porous membranes. Intrinsic gas permeability of pure PPSU is low, but it has good selectivity for CO2/CH4 separation. Therefore, this study aimed to investigate the effect of adding a layered nanoclay material to PPSU on CO2 permeability and CO2/CH4 selectivity. The fabricated membranes were characterized by FTIR, FESEM, XRD, DSC, EDS, Contact angle, gas solubility, and gas permeability. The permeability of each gas was measured by the constant volume-variable pressure method, and ideal selectivity was determined. The effect of nanoclay loading (1-3 wt.%) and feed pressure (2-8 bar) on the gases' permeability and CO2/CH4 selectivity was investigated at a constant temperature of 27 ± 2°C. The results showed that the addition of the nanoclay to PPSU has a considerable effect on CO2 permeability (up to 52% increase) while CO2/CH4 selectivity remains nearly unchanged or slightly decreases (down to 6%). Solubility measurement results revealed that adding the nanoclay to the PPSU polymer increases the solubility selectivity by 22%, while the diffusivity selectivity is decreased by 23%, revealing the formation of an intercalated morphology, confirmed by XRD analysis.

A Fruitful Decade of Organofluorine Chemistry: New Reagents and Reactions

A Fruitful Decade of Organofluorine Chemistry: New Reagents and Reactions

Structure elucidation of the novel synthetic cannabinoid Cumyl-Tosyl-Indazole-3-Carboxamide (Cumyl-TsINACA) found in illicit products in Germany.

New chemical moieties continue to appear in synthetic cannabimimetics (SC), the largest group of new psychoactive substances in the EU. We describe the first comprehensive characterisation of the novel SC Cumyl-Tosyl-Indazole-3-Carboxamide (Cumyl-TsINACA) (N-[2-phenylpropan-2-yl]-1-tosyl-1H-indazole-3-carboxamide) from seized case samples. Structure elucidation was performed within the EU-project ADEBAR plus to facilitate confident identification by other researchers and practitioners worldwide. Characteristic MS fragmentations include the cleavage of the sulfonamide bond (S-N), the aryl sulfone bond (C-S) and the elimination rearrangement of SO2 in the side chain. Cumyl-TsINACA is a full receptor agonist at hCB1 (Emax = 228%) with very weak binding affinity (Ki = 292 nm) and low functional activity (EC50 = 31 μm). Thermal degradation of Cumyl-TsINACA was observed under GC conditions. The degree to which the tosyl side chain is cleaved due to pyrolysis primarily depends on solvent, the use of glass wool in the liner and injector temperature. The determination of the constitution by NMR spectroscopy was ambiguous due to the high number of neighbouring, non-proton-bearing atoms. Therefore, other possible structures compatible with the NMR correlations were generated using the WebCocon software. The unambiguous structural evidence was finally obtained by spectra comparison after the synthesis of Cumyl-TsINACA. The low thermal stability, as well as the low affinity and potency, renders this compound unfavourable for the use as a psychoactive substance. Thus, we do not expect widespread adoption of this SC.

Computational development of aryl sulfone compounds as potential NNRTIs

Human immunodeficiency virus (HIV) attacks the host’s immune system and affects millions of people globally. Due to the high mutation rate of HIV, it is of great importance that novel drugs are found to combat new strains. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are allosteric inhibitors that bind to the HIV reverse transcriptase and prevent replication. Indolyl aryl sulfones (IAS) and IAS derivatives have been found to be highly effective against mutant strains of HIV-1 reverse transcriptase. Here, we analyzed molecules designed using aryl sulfone scaffolds paired to cyclic compounds (that have previously been found to be beneficial groups for NNRTIs) as potential NNRTIs through the computational design and docking of 100 novel NNRTI candidates. Moreover, we explored the specific combinations of functional groups and aryl sulfones that resulted in the NNRTI candidates with the strongest binding affinity while testing all compounds for carcinogenicity. We hypothesized that the combination of an IAS scaffold and pyrimidine would produce the compounds with the best binding affinity. Our hypothesis was correct as the series of molecules with an IAS scaffold and pyrimidine exhibited the best average binding affinity. Additionally, this study found 32 molecules designed in this procedure with higher or equal binding affinities to the previously successful IAS derivative 5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]indole-2-carboxyamide when docked to HIV-1 reverse transcriptase. These findings contribute to the search for novel NNRTIs as well as expanding knowledge regarding the characteristics of the NNRTI pharmacophore.

Hydrophilic modification of poly(aryl sulfone) membrane materials toward highly-efficient environmental remediation

Hydrophilic modification of poly(aryl sulfone) membrane materials toward highly-efficient environmental remediation

Novel 3-substituted coumarins as selective human carbonic anhydrase IX and XII inhibitors: Synthesis, biological and molecular dynamics analysis.

In this study, diverse series of coumarin derivatives were developed as potential carbonic anhydrase inhibitors (CAIs). A "tail" approach was adopted by selecting the coumarin motif as a tail that is connected to the ZBG benzenesulfonamide moiety via a hydrazine (4a,b) or hydrazide (5a,b) linker. Thereafter, an aryl sulfone tail was incorporated to afford the dual tailed coumarin-sulfonamide arylsulfonehydrazones (13a-d) and hydrazides (14a,b). Then, the ZBG were removed from compounds 13 and 14 to furnish coumarin arylsulfonehydrazones (11a-d) and hydrazides (12a,b). Coumarin-sulfonamides 4 and 5 emerged as non-selective CAIs as they displayed good inhibitory activities toward all the examined CA isozymes (I, II, IX and XII) in the nanomolar ranges. Interestingly, the "dual-tail" approach (compounds 13 and 14) succeeded in achieving a good activity and selectivity toward CA IX/XII over the physiologically dominant CA I/II. In particular, compounds 13d and 14a were the most selective coumarin-sulfonamide counterparts. Concerning non-sulfonamide coumarin derivatives, coumarins 8 exhibited excellent activity and selectivity profiles against the target hCA IX/XII, whereas, coumarins 11 and 12 reported excellent selectivity profile, but they barely inhibited hCA IX/XII with KIs spanning in the micromolar ranges. Furthermore, molecular modelling studies were applied to get a deep focus about the feasible affinities and binding interactions for target coumarin-sulfonamides 4, 5, 13 and 14 with the active site for CA II, IX and XII isoforms.

Structural investigation on bulky aliphatic-aromatic poly(aryl sulfone)s for fuel cell performance

This paper is focused on the structure-properties relationship of synthesized sulfonated poly(aryl sulfone)s comprised of a bulky aliphatic-aromatic structure. Nucleophilic aromatic substitution together with a coupling step was used to prepare random copolymers with excellent film-forming ability. High thermal, mechanical, and dimensional stability of membranes ascribed to the presence of rigid aromatic sections. The oxidative stability of the optimized membrane with a 50% degree of sulfonation (Z-50) was studied in ex-situ and in-situ accelerated degradation tests. The results were evaluated by Fenton test, scanning electron microscope, nuclear magnetic resonance spectrometry, and open-circuit voltage test. The voltage decay of 0.62 mV/h was attained during 100 h open-circuit voltage test at 80 °C under 100% relative humidity. Temperature and relative humidity-dependent impedance and high-frequency resistance of membranes revealed the structural benefit of membranes. Polarization and performance curves of the optimized sample were collected at three temperatures of 80, 100, and 120 °C under 100% relative humidity. The examination of the membrane polarization under 30–100% relative humidity at the temperature of 80 °C showed a current density of about 732.7 mA/cm2 even at 30% relative humidity. The design of such bulky aliphatic-aromatic poly(aryl sulfone) was responsible for this result.

Synthesis and properties of dications-containing poly(aryl ether sulfone) anion exchange membranes

Since the 21st century, energy and environmental issues have become the focus of global attention. Traditional fossil energy resources such as oil and natural gas are drying up. Meanwhile, a large number of harmful gases and other pollutants would be produced in the use of traditional energy, which has a serious damage to the environment and climate. With the rapid increase of energy consumption and the need of environmental protection, the demand for clean and efficient energy is growing. Fuel cell (FC) is considered as one of the most promising energy conversion technologies that can replace conventional fossil fuels, and it is also an important choice in the use of hydrogen, methanol, ethanol and other renewable energy. As a new energy with great potential, FC can reduce the energy crisis and environmental pollution effectively by directly converting the chemical energy of the external input fuel into electrical energy and continuously supplying power to the outside. Ion exchange membrane (IEM) is an important component of FC, which is responsible for transferring ions and forming a complete FC circuit. According to the types of conducting ions, IEM can be divided into proton exchange membrane (PEM) and anion exchange membrane (AEM), which are applied to proton exchange membrane fuel cell (PEMFC) and alkaline anion exchange membrane fuel cell (AAEMFC), respectively. Compared with PEMFC, AAEMFC has the advantages of using non noble metal catalyst, high electrode reaction reactivity, and low fuel purity requirements and so on. However, the commercial AEM with organic cations often has low ionic conductivity and poor alkali and dimensional stability, which seriously hinders its development and application in AAEMFC. Therefore, it is urgent to design and develop new high-performance AEM materials. In order to improve the conductivity, alkali stability and dimensional stability of AEMs, a novel reactive bisphenol monomer with pendant dimethylphenoxybenzene group, 1,1-bis (4-hydroxyphenyl)-1-(4-(3,5-dimethylphenoxy) phenyl) phenyl-2,2,2-trifluoroethane ( 2 ), was synthesized based on molecular design using 4-fluoro-2,2,2-trifluoroacetophenone, 3,5-dimethylphenol and phenol as starting materials by a two-step organic reaction. Then, two series of poly(aryl ether sulfone) anion exchange membranes (2-PAES-QA- xx and 2-PAES-Im- xx ) with comb structure were prepared through aromatic nucleophilic copolycondensation, bromination and quaternization reaction based on monomer 2 . The structures of the active bisphenol monomer, the poly(aryl sulfone) containing methyl groups, the brominated poly(aryl ether sulfone)s and the ionized polymers were characterized systematically by nuclear magnetic resonance spectroscopy, respectively. The water uptake, swelling ratio, ionic conductivity, thermal stability, mechanical properties, and alkaline resistance stability of the prepared 2-PAES-QA- xx and 2-PAES-Im- xx membranes were studied in detail. The relationship between the structure and properties of different types of AEMs is further compared. The obtained AEMs showed good overall performance, and the OH– conductivity of these membranes at 60°C is 35.9–51.6 and 32.6–44.9 mS/cm, respectively. The IEC values of the representative 2-PAES-QA-60 and 2-PAES-Im-60 maintained at 79.7% and 88.5% of the initial values after immersion in 4 mol/L NaOH at 80°C for 336 h, respectively. This work provides a new strategy for the design and preparation of comb-type AEM materials.

Protective effects of new aryl sulfone derivatives against radiation-induced hematopoietic injury.

The hematopoietic system is sensitive to radiation. In this research, new aryl sulfone derivatives (XH-201 and XH-202) containing a nitrogen heterocycle were designed and synthesized and their radio-protective efficacies with regard to the hematopoietic system were evaluated. XH-201 administration significantly increased the survival rate of mice after 8.0 Gy total body irradiation (TBI). The results showed that XH-201 treatment not only increased the white blood cells, platelets counts and the percentage of hematopoietic progenitor cells and hematopoietic stem cells in mice exposed to 4.0 Gy TBI but also decreased DNA damage, as determined by flow cytometric analysis of histone H2AX phosphorylation. In addition, our data demonstrated that XH-201 decreased the mitochondrial reactive oxygen species (ROS) levels in hematopoietic cells. Overall, these data suggest that XH-201 is beneficial for the protection of the hemoatopoietic system against radiation-induced injuries.

Synthesis and Properties of Novel Side‐Chain Sulfonated Poly(Arylene Ether Sulfone)s for Proton Exchange Membranes

ABSTRACTA series of novel side‐chain sulfonated poly(arylene ether sulfone) (SPAES) multiblock and random copolymers were synthesized by condensation polymerization from a new disulfonated aryl sulfone monomer, 4,4′‐difluoro‐2,2′‐bis(3‐sulfobenzoyl)diphenyl sulfone disodium salt (DFBSPS). The chemical structures of DFBSPS and the SPAESs were characterized by proton nuclear magnetic resonance (1H NMR) and Fourier transform infrared (FTIR) spectra. The SPAES membranes prepared by solution cast method exhibited high tensile strength (50–71 MPa) and high radical oxidative stability. They could keep their morphology and maintain proton conductivities after hydrolysis test in 95 °C water for 1000 h. They also showed smaller swelling ratio in in‐plane direction than in through‐plane direction and such an anisotropic effect was more significant for the multiblock copolymers than for the random ones. The multiblock copolymer membranes exhibited higher proton conductivity than the random ones with similar ion exchange capacities (IECs). Preliminary hydrogen‐oxygen fuel cell tests were performed at 60 °C and 80% relative humidity (RH). The results showed that the single cell equipped with the multibiock copolymer membrane SB3 exhibited 0.12 W cm−2 higher maximum output power density than the one equipped with the random copolymer membrane SR3 (with the same IEC), indicating much better performance of the former. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2304–2313

Generation of 1,3-Dimethylene-Substituted Isobenzofurans via Pd(II)-Catalyzed Selective Oxo-cyclization/SO2 Insertion Cascade of β-Alkynyl Ketones.

A new palladium(II)-catalyzed cyclization-radical addition cascade enables the direct construction of 1,3-dimethylene-substituted isobenzofuran derivatives containing a vinyl aryl sulfone unit in good yields by treating with β-alkynyl ketones, aryl diazonium salts, and DABCO·(SO2)2. The oxidant-free multicomponent reaction features good substrate scope and functional group tolerance, which proceeds through a sequence of Heck coupling, oxo-cyclization, and SO2 insertion.

Intramolecular Desulfitative Coupling: Nickel-Catalyzed Transformation of Diaryl Sulfones into Biaryls via Extrusion of SO2

As a new transformation of organosulfur compounds, intramolecular desulfitative coupling of diaryl sulfones to the corresponding biaryls has been developed with the aid of nickel-NHC catalysts. This catalytic elimination of SO2 was also applicable to alkenyl aryl sulfone to furnish the corresponding alkenyl arene.