Designing of a new transdermal antibiotic delivery polymeric membrane modified by functionalized SBA-15 mesoporous filler.

A new drug delivery system using an asymmetric polyethersulfone (PES) membrane modified by SBA-15 and glutamine-modified SBA-15 (SBA-Q) was prepared in this study by the aim of azithromycin delivery enhancement in both in vitro and ex vivo experiments. The research focused on optimizing membrane performance by adjusting critical parameters including drug concentration, membrane thickness, modifier percentage, polymer percentage, and pore maker percentage. To characterize the fabricated membranes, various techniques were employed, including scanning electron microscopy, water contact angle, and tensile strength assessments. Following optimization, membrane composition of 17% PES, 2% polyvinylpyrrolidone, 1% SBA-15, and 0.5% SBA-Q emerged as the most effective. The optimized membranes demonstrated a substantial increase in drug release (906 mg/L) compared to the unmodified membrane (440 mg/L). The unique membrane structure, with a dense top layer facilitating sustained drug release and a porous sub-layer acting as a drug reservoir, contributed to this improvement. Biocompatibility assessments, antibacterial activity analysis, blood compatibility tests, and post-diffusion tissue integrity evaluations confirmed the promising biocompatibility of the optimized membranes. Moreover, long-term performance evaluations involving ten repeated usages underscored the reusability of the optimized membrane, highlighting its potential for sustained and reliable drug delivery applications.

Development of microfiltration membranes based on polysulfone and polyetherimide blends.

In this study, membranes blended with polysulfone (PSU) and polyetherimide (PEI) polymers in different ratios were fabricated. Their potential to remove pollutants from rivers, which are a potential drinking water source, was investigated. Scanning electron microscopy analysis revealed that the PSU membranes had a dense and homogeneous layer, whereas the addition of PEI formed a spongy substrate. The water content of the fabricated membranes varied between 5.37 and 22.42%, porosities 28.73-89.36%, contact angles 69.18-85.81%, and average pure water fluxes 257.25-375.32 L/m2 h. The blended membranes removed turbidity, chloride, alkalinity, conductivity, sulfate, iron, manganese, and total organic carbon up to 98.32, 92.28, 96.87, 90.67, 99.58, 94.63, 97.48, and 79.11%, respectively. These results show that when PEI was added to the PSU polymer, the filtration efficiency increased owing to an increase in the hydrophilicity of the membranes. Blending these two polymers enabled the optimization of membrane properties such as permeability, selectivity, and mechanical strength. In addition, membrane fabrication processes are simple and incur low costs.

Bisphenol A and its structural analogues exhibit differential potential to induce mitochondrial dysfunction and apoptosis in human granulosa cells.

Bisphenol A (BPA) is an endocrine disruptor strongly associated with ovarian dysfunction. BPA is being substituted by structurally similar chemicals, such as bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF). However, the toxicity of these analogues in female reproduction remains largely unknown. This study evaluated the effects of BPA and its analogues BPS, BPF, and BPAF on the mitochondrial mass and function, oxidative stress, and their potential to induce apoptosis of human granulosa cells (KGN cells). BPA and its analogues, especially BPA and BPAF, significantly decreased mitochondrial activity and cell viability. The potential of bisphenols to reduce mitochondrial mass and function differed in the following order: BPAF > BPA > BPF > BPS. Flow cytometry revealed that exposure to bisphenols significantly increased mitochondrial ROS levels and increased mitochondrial Ca2+ levels. Thus, bisphenols exposure causes mitochondrial stress in KGN cells. At the same time, bisphenols exposure significantly induced apoptosis. These results thus emphasize the toxicity of these bisphenols to cells. Our study suggests the action mechanism of BPA and its analogues in damage caused to ovarian granulosa cells. Additionally, these novel analogues may be regrettable substitutes, and the biological effects and potential risks of BPA alternatives must be evaluated.

Biofouling mitigation of Nb2AlC and Mo3AlC2 MXene-precursors doped polyether sulfone mixed matrix membranes for pathogen microorganisms.

This study explores the incorporation of Nb2AlC and Mo3AlC2 MAX phases, known for their nano-layered structure, into polyether sulfone (PES) membranes to enhance their antifouling and permeability properties for pathogen microorganism filtration against bovine serum albumin (BSA) and Escherichia coli (E. coli). The composite membranes were characterized for their structural and morphological properties, and their performance in mitigating biofouling was evaluated. The structural characterizations have been performed for all the prepared MAX phases and corresponding composite membranes. The antioxidant ability of Nb2AlC and Mo3AlC2 MAX phases was defined by the DPPH radical scavenging assay, and the highest antioxidant ability was found to be 59.35 %, while 53.69 % scavenging potential was recorded at 100 mg/L. The percentage scavenging ability was raised with an increase in concentrations. The antimicrobial properties of MAX phases, evaluated as the minimum inhibitory concentration, were stated against several pathogen microorganisms. The tested compounds of Nb2AlC and Mo3AlC2 composites containing MAX phases exhibited excellent chemical nuclease activity, and it was determined that Nb2AlC caused double strand DNA cleavage activity while Mo3AlC2 induced the complete fragmentation of the DNA molecule. Biofilm inhibition of Nb2AlC and Mo3AlC2 MAX phases was studied against Staphylococcus aureus, and Pseudomonas aeruginosa and the maximum biofilm inhibition of Nb2AlC and Mo3AlC2 MAX phases was found to be 77.15 % and 69.07 % against S. aureus and also 69.74 % and 65.01 % against P. aeruginosa. Furthermore, Nb2AlC and Mo3AlC2 MAX phases demonstrated excellent E. coli growth inhibition of 100 % at 125 and 250 mg/L.

Constructing porous ZnFC-PA/PSF composite spheres for highly efficient Cs+ removal.

Radioisotope leaking from nuclear waste has become an intractable problem due to its gamma radiation and strong water solubility. In this work, a novel porous ZnFC-PA/PSF composite sphere was fabricated by immobilization of ferrocyanides modified zinc phytate into polysulfone (PSF) substrate for the treatment of Cs-contaminated water. The maximum adsorption capacity of ZnFC-PA/PSF was 305.38 mg/g, and the removal efficiency of Cs+ was reached 94.27% within 2 hr. The ZnFC-PA/PSF presented favorable stability with negligible dissolution loss of Zn2+ and Fe2+ (< 2%). The ZnFC-PA/PSF achieved high-selectivity towards Cs+ (Kd = 2.24×104 mL/g) even in actual geothermal water. The adsorption mechanism was inferred to be the ion-exchange between Cs+ and K+. What's more, ZnFC-PA/PSF worked well in the fixed-bed adsorption (E = 91.92%), indicating the application potential for the hazardous Cs+ removal from wastewater.

A formal vinylic substitution reaction for the synthesis of α,ß-unsaturated enol esters and their anticancer potential.

Arylsulfonyl group-bearing α,ß-unsaturated enol esters were readily assembled via the Cs2CO3-mediated union of 2-bromoallyl sulfones and cinnamic acids. The overall transformation is equivalent to an sp2 carbon-oxygen coupling reaction, and therefore constitutes a formal vinylic substitution. Several of the products display promising levels of antiproliferative activities higher than that of the anticancer drug carboplatin. Thiophenol reacted with 2-bromoallyl sulfones under identical conditions to afford α-thiophenyl-α'-tosyl acetone via an apparent aerial oxidation.

Polyethersulfone Polymer for Biomedical Applications and Biotechnology.

Polymers stand out as promising materials extensively employed in biomedicine and biotechnology. Their versatile applications owe much to the field of tissue engineering, which seamlessly integrates materials engineering with medical science. In medicine, biomaterials serve as prototypes for organ development and as implants or scaffolds to facilitate body regeneration. With the growing demand for innovative solutions, synthetic and hybrid polymer materials, such as polyethersulfone, are gaining traction. This article offers a concise characterization of polyethersulfone followed by an exploration of its diverse applications in medical and biotechnological realms. It concludes by summarizing the significant roles of polyethersulfone in advancing both medicine and biotechnology, as outlined in the accompanying table.

A novel class of insecticidal alkylsulfones are potent inhibitors of vesicular acetylcholine transport.

Pyridine alkylsulfone derivatives typified by oxazosulfyl (Sumitomo Chemical Company Ltd.) and compound A2 (Syngenta) represent a new class of insecticides, with potent activity against several insect orders. Whilst the MOA of this class has been attributed to interaction with the voltage-gated sodium channel (VGSC), here we present strong evidence that their toxicity to insects is mediated primarily through inhibition of the vesicular acetylcholine transporter (VAChT). Alkylsulfone intoxication in insects is characterised by (i) a reduction in cholinergic synaptic transmission efficiency demonstrated by a depression of cercal afferent activity in giant-interneurone preparations of American cockroach (Periplaneta americana), (ii) selective block of cholinergic-transmission dependent post-synaptic potentials in the Drosophila giant-fibre pathway and (iii) abolition of miniature excitatory post-synaptic currents (mEPSCs) in an identified synapse in Drosophila larvae. Ligand-binding studies using a tritiated example compound ([3H]-A1) revealed a single saturable binding-site, with low nanomolar Kd value, in membrane fractions of green bottle fly (Lucilia sericata). Binding is inhibited by vesamicol and by several examples of a previously identified class of insecticidal compounds known to target VAChT, the spiroindolines. Displacement of this binding by analogues of the radioligand reveals a strong correlation with insecticidal potency. No specific binding was detected in untransformed PC12 cells but a PC12 line stably expressing Drosophila VAChT showed similar affinity for [3H]-A1 as that seen in fly head membrane preparations. Previously identified VAChT point mutations confer resistance to the spiroindoline class of insecticides in Drosophila by Gal-4/UAS directed expression in cholinergic neurones and by CRISPR gene-editing of VAChT, but none of these flies show detectable cross-resistance to this new chemical class. Oxazosulfyl was previously shown to stabilise voltage-gated sodium channels in their slow-inactivated conformation with an IC50 value of 12.3µM but inhibits binding of [3H]-A1 with approximately 5000 times greater potency. We believe this chemistry class represents a novel mode-of-action with high potential for invertebrate selectivity.

Optimization of benzenesulfonyl derivatives as anti-Trypanosomatidae agents: Structural design, synthesis, and pharmacological assessment against Trypanosoma cruzi and Leishmania infantum.

Leishmaniasis and Chagas disease are neglected tropical diseases caused by Trypanosomatidae parasites. Given the numerous limitations associated with current treatments, such as extended treatment duration, variable efficacy, and severe side effects, there is an urgent imperative to explore novel therapeutic options. This study details the early stages of hit-to-lead optimization for a benzenesulfonyl derivative, denoted as initial hit, against Trypanossoma cruzi (T. cruzi), Leishmania infantum (L. infantum) and Leishmania braziliensis (L. braziliensis). We investigated structure - activity relationships using a series of 26 newly designed derivatives, ultimately yielding potential lead candidates with potent low-micromolar and sub-micromolar activities against T. cruzi and Leishmania spp, respectively, and low in vitro cytotoxicity against mammalian cells. These discoveries emphasize the significant promise of this chemical class in the fight against Chagas disease and leishmaniasis.

The vinyl sulfone motif as a structural unit for novel drug design and discovery.

INTRODUCTION: Vinyl sulfones are a special sulfur-containing structural unit that have attracted considerable attention, owing to their important role in serving as key structural motifs of various biologically active compounds as well as serving as versatile building blocks for organic transformations. The synthetic strategy of vinyl sulfone derivatives has been substantially upgraded over the past 30 years, and the wide application of this functional group in drug design and discovery has been promoted. AREA COVERED: In this review, the authors review the application of vinyl sulfones in drug discovery and select optimized compounds which might have significant impact or potential inspiration for drug design. EXPERT OPINION: Vinyl sulfones have been reported to target various macromolecular targets via non-covalent or covalent interactions, including multiple kinases, tubulin, cysteine protease, transcription factor, and so on. Thus, it has been significantly applied as a privileged scaffold in the design of anticancer, anti-infective, anti-inflammatory, and neuroprotective agents. However, much work remains to be done to improve the drug-like properties, such as chemical and metabolic stability, ADME, and toxicity. Besides, the chemical space of vinyl sulfones needs to be expanded, including but not limited to the design of constrained endocyclic and exocyclic vinyl sulfones.

Synthesis and biological evaluation of sulfonylpyridine derivatives as potential anti-chlamydia agents.

Chlamydia trachomatis is the most prevalent sexually transmitted bacterial infection in the United States and the world. This pathogen can cause health problems ranging from trachoma (blindness) to damage of the fallopian tubes or ectopic pregnancy, which can be life-threatening if not treated properly. To this day, there is no chlamydia-specific drug on the market. Previously, we reported the activity and basic structure-activity relationships (SAR) of sulfonylpyridine molecules that possess antichlamydial action. Based on those results, we prepared a new series of derivatives. Our data indicate the new analogs can halt the growth of C. trachomatis. The lead compound, 22, was more active than our previous molecules and did not affect the growth of S. aureus and E. coli, suggesting bacterial selectivity. We performed docking studies on the presumed target, the cylindrical protease of Chlamydia. The in-silico studies partially explained the in vitro biological result as well as predicted a possible binding pose in the binding pocket. The top compound displayed a good cytotoxicity profile towards mammalian cell lines and was stable in both serum and stimulated gastric fluid. The presented data suggests the sulfonylpyridines are promising and selective anti-chlamydial compounds that merit further structural optimization.

Biological treatment of perfluorooctanesulfonic acid (PFOS) using microbial capsules of a polysulfone membrane.

Perfluorooctanesulfonic acid (PFOS) is a persistent organic substance that has been extensively applied in many industries and causes severe, widespread adverse health impacts on humans and the environment. The development of an effective PFOS treatment method with affordable operational costs has been expected. This study proposes the biological treatment of PFOS using microbial capsules enclosing a PFOS-reducing microbial consortium. The objective of this study was to evaluate the performance of the polymeric membrane encapsulation technique for the biological removal of PFOS. First, a PFOS-reducing bacterial consortium, composed of Paracoccus (72%), Hyphomicrobium (24%), and Micromonosporaceae (4%), was enriched from activated sludge by acclimation and subsequent subculturing with PFOS containing media. The bacterial consortium was first immobilized in alginate gel beads, then enclosed in membrane capsules by coating the gel beads with a 5% or 10% polysulfone (PSf) membrane. The introduction of microbial membrane capsules could increase PFOS reduction to between 52% and 74% compared with free cell suspension, which reduced by 14% over three weeks. Microbial capsules coated with 10% PSf membrane demonstrated the highest PFOS reduction at 80% and physical stability for six weeks. Candidate metabolites including perfluorobutanoic acid (PFBA) and 3,3,3- trifluoropropionic acid were detected by FTMS, suggesting the possible biological degradation of PFOS. In microbial membrane capsules, the initial adsorption of PFOS on the shell membrane layer enhanced subsequent biosorption and biological degradation by PFOS-reducing bacteria immobilized in the core alginate gel beads. The 10%-PSf microbial capsules exhibited a thicker membrane layer with the fabric structure of a polymer network, which maintained longer physical stability than 5%-PSf microbial capsules. This outcome suggests the potential application of microbial membrane capsules to PFOS-contaminated water treatment.

Iron-catalyzed regioselective synthesis of (E)-vinyl sulfones mediated by unprotected hydroxylamines.

An Fe-catalyzed unprotected hydroxylamine mediated Heck-type coupling between sulfinic acids and alkenes for the regioselective synthesis of (E)-vinyl sulfones has been developed. Mechanism studies indicated for the first time that a radical process may be involved and that hydroxylamines play multiple roles, including those of a mild oxidant and an in situ base. It was found for the first time that this transformation not only realizes C-S bond construction promoted by unprotected hydroxylamines, but also provides a practical and complementary method for the preparation of structurally important (E)-vinyl sulfones.

Thioterpenoids as Potential Antithrombotic Drugs: Molecular Docking, Antiaggregant, Anticoagulant and Antioxidant Activities.

Natural monoterpenes and their derivatives are widely considered as effective ingredients for the design and production of new biologically active compounds with high antioxidant, antimicrobial and anti-protozoa properties. In this study, we synthesized two series of thiotherpenoids "sulfide-sulfoxide-sulfone", with different bicyclic monoterpene skeleton (bornane and pinane) structures. The effect of the obtained compounds on platelet aggregation was investigated by using the molecular docking technique. The obtained data revealed that all the synthesized compounds may act as potential inhibitors of platelet aggregation. Moreover, the studied sulfides have shown high antioxidant activity as revealed by lipid peroxidation (LPO) process inhibition in a non-cellular substrate containing animal lipids. The sulfides were able to inhibit erythrocyte oxidative hemolysis, to reduce the accumulation of secondary LPO products in cells and to prevent the oxidation of native oxyhemoglobin. Additionally, the corresponding sulfones and sulfoxides exhibited insignificant antioxidant activity. However, the sulfides were found to exhibit significant antiaggregant and anticoagulant effects. These findings suggest as well that the sulfides could serve as a leader compound for future research and possible practical applications.

Synthesis of Quinoline Silyloxymethylsulfones as Intermediates to Sulfonyl Derivatives.

Heterocyclic sulfones, sulfonamides, and sulfonyl fluorides constitute an important structural motif in medicinal chemistry. Methods to make six-membered heteroaromatic sulfonyl compounds, however, remain challenging, and most efforts rely on commercial sulfonyl chlorides. We report herein the reaction of sodium tert-butyldimethyl silyloxymethylsulfinate with quinoline N-oxides to selectively furnish C2-substituted sulfones. The silyloxymethylsulfinate can be deprotected to then form sulfonyl fluorides, sulfonamides, and sulfones. This transformation is scalable and has broad applicability to a wide array of quinoline and isoquinoline functionality.

Decarboxylative Sulfinylation Enables a Direct, Metal-Free Access to Sulfoxides from Carboxylic Acids.

The intermediate oxidation state of sulfoxides is central to the plethora of their applications in chemistry and medicine, yet it presents challenges for an efficient synthetic access, limiting the structural diversity of currently available sulfoxides. Here, we report a data-guided development of direct decarboxylative sulfinylation that enables the previously inaccessible functional group interconversion of carboxylic acids to sulfoxides in a reaction with sulfinates. Given the broad availability of carboxylic acids and the growing synthetic potential of sulfinates, the direct decarboxylative sulfinylation is poised to improve the structural diversity of synthetically accessible sulfoxides. The reaction is facilitated by a kinetically favored sulfoxide formation from the intermediate sulfinyl sulfones, despite the strong thermodynamic preference for the sulfone formation, unveiling the previously unknown and chemoselective radicalophilic sulfinyl sulfone reactivity.

Efficient Synthesis of Orphaned Cyclopropanes Using Sulfones as Carbene Equivalents.

Small molecules containing 1,1-dimethylcyclopropanes are prevalent throughout nature but are difficult to synthesize using state-of-the-art metal-catalyzed carbene transfer methods without competing 1,2-hydride shifts. Herein, we introduce a mechanistically distinct platform to transfer 1,1-dialkylcarbene units to olefins using carbometalation reactions of dialkyl sulfonyl anions. In the presence of NaNH2 or n-BuLi in ethereal solvents, dialkyl sulfones react with styrenes and arylbutadienes between 23 and 70 °C to produce the corresponding 1,1-dialkylcyclopropanes. We report 40 examples of this reactivity including 16 different styrenes (up to 89% isolated yield), 9 arylbutadienes (51-88% yield), and 13 different sulfones (46-80% yield). In addition, we report an example of a sequential cyclopropanation reaction using this method. Preliminary mechanistic studies suggest a stepwise anionic process that is initiated by the direct addition of sulfonyl anions to a carbon-carbon double bond.

Sulfondiimines: synthesis, derivatisation and application.

Sulfondiimines are aza-analogues of sulfones and sulfoximines. In contrast to the latter two compound classes, sulfondiimines are rare in the chemical literature. Although a full understanding of the stability and reactivity of sulfondiimines is wanting, sulfondiimines have recently been recognized as novel bioisosteres for carbonyl moieties enabling expansion of the well-known portfolio of pharmaceutically relevant compounds. In this review, we briefly summarize the structure and stability of sulfondiimines and then focus on syntheses and derivatisations of these interesting compounds with sulfur-nitrogen core units. Furthermore, their use in heterocyclic chemistry and recent applications as bioactive compounds are presented.

Phenyl Sulfones: A Route to a Diverse Family of Trisubstituted Cyclohexenes from Three Independent Nucleophilic Additions.

A novel process is described for the synthesis of di- and trisubstituted cyclohexenes from an arene. These compounds are prepared from three independent nucleophilic addition reactions to a phenyl sulfone (PhSO2R; R = Me, Ph, and NC4H8) dihapto-coordinated to the tungsten complex {WTp(NO)(PMe3)}(Tp = trispyrazolylborate). Such a coordination renders the dearomatized aryl ring susceptible to protonation at a carbon ortho to the sulfone group. The resulting arenium species readily reacts with the first nucleophile to form a dihapto-coordinated sulfonylated diene complex. This complex can again be protonated, and the subsequent nucleophilic addition forms a trisubstituted cyclohexene species bearing a sulfonyl group at an allylic position. Loss of the sulfinate anion forms a π-allyl species, to which a third nucleophile can be added. The trisubstituted cyclohexene can then be oxidatively decomplexed, either before or after substitution of the sulfonyl group. Nucleophiles employed include masked enolates, cyanide, amines, amides, and hydride, with all three additions occurring to the same face of the ring, anti to the metal. Of the 12 novel functionalized cyclohexenes prepared as examples of this methodology, nine compounds meet five independent criteria for evaluating drug likeliness. Structural assignments are supported with nine crystal structures, density functional theory studies, and full 2D NMR analysis.

Hydrosulfonylation of Alkenes with Sulfonyl Imines via Ir/Cu Dual Photoredox Catalysis.

Sulfonamides exhibit the advantages of wide prevalence, excellent prefunctionalization capability, and broad functional group compatibility. We report here utilizing sulfonyl imines as sulfonyl radical precursors for hydrosulfonylation of activated alkenes via visible-light irradiation. By preinstallation of functional groups into the sulfonamides and subsequent hydrosulfonylation, a variety of complex sulfones were synthesized with good efficiency under Ir/Cu dual photoredox catalysis. Additionally, this protocol expands the research in late-stage N-S bond modification in sulfonamides.