Sulfoxide Compound Research Articles

Synthesis, spectroscopic characterization, electronic elucidation, chemical reactivity, topological and molecular docking investigations of cefadroxil sulfoxide

The cefadroxil sulfoxide (CDSO) para-hydroxy derivative, derived from cefadroxil, has enormous significance in pharmaceutical applications. The cefadroxil sulfoxide (CDSO) compound was synthesized and characterized by spectroscopic (FT-IR, FT-Raman, and UV–Visible) assessments. Computational investigations have been carried out concurrently with a B3LYP-6-311++G(d,p) basis set and density functional theory (DFT). The molecular vibrational assignments, chemical reactivity, electronic properties, and optical activities are calculated using gas and different solvent phases. The stable ground state configuration of the given molecular compound is investigated using PES analysis. Furthermore, the chemical behavior of the CDSO was thoroughly investigated for different solvent aspects through HOMO-LUMO, MEP, UV–Visible and electron-hole excitation analyses. The molecular occupancy, virtual occupancy, and overlapping bonding energies are investigated by TDOS, PDOS, and COOP spectrum studies. Fukui function and dual descriptor investigations extend to the chemical reactivity of individual atomic sites. The intra-molecular analysis provided a deeper understanding of the molecular interactions performed by natural bond orbitals (NBO) and non-linear optics (NLO), which provided optical activity for the title compound. Additionally, electron localization function (ELF), localized orbital locator (LOL), and reduced density gradient (RDG) analyses were also accomplished to provide insight into the delocalized orbitals in the header composite. The molecular docking was achieved, and the ligand with 4EVM protein is providing the potential antimicrobial biological activity (binding energy −7.12 kcal/mol) of the CDSO compound.

Novel Meta-Diamide Compounds Containing Sulfide Derivatives Were Designed and Synthesized as Potential Pesticides.

The meta-diamide (m-diamide) insecticide, Broflanilide, was characterized by its high efficiency, low toxicity and lack of cross-resistance with traditional GABA receptors. In accordance with the principles of drug molecular design, easily derivable sulfur with diverse bioactivities was introduced while leading with the parent Broflanilide. Twelve novel m-diamide target compounds containing sulfide derivatives were synthesized through exploration guided by the literature. Their structures were confirmed by melting points, 1H NMR, 13C NMR and HRMS. Insecticidal activity assessments revealed that most target compounds A-D exhibited 100% lethality against Plutella xylostella (P. xylostella) and Aphis craccivora Koch (A. craccivora) at 500 mg·L-1. Notably, for P. xylostella, compounds C-2, C-3, C-4 and D-2 demonstrated 60.00-100.00% insecticidal activity even at a concentration as low as 0.625 mg·L-1. As determined by structure-activity relationship (SAR) analysis, compounds with R1 = CH3 and R2 = Br (B-1, C-2 and D-2) and sulfoxide compound C-3 contained 100.00% lethality against A. craccivora at 500 mg·L-1, surpassing the lethality when leading with the parent Broflanilide in terms of efficacy. Consequently, it can be inferred that the sulfoxide compound (C-3) requires further investigation as a potential active molecule for new insecticides. These explorations provide valuable references for future research on the synthesis and insecticidal activities of sulfide-containing m-diamide compounds.

Hypoglycemic and hypolipidemic effect of S-allyl-cysteine sulfoxide (alliin) in DIO mice

Alliin (S-allyl cysteine sulfoxide) is a bioactive sulfoxide compound derived from garlic. To evaluate the preventive effect of alliin against metabolic risk factors in diet induced obese (DIO) mice, we treated the C57BL/6J DIO mice with drinking water with or without alliin (0.1 mg/ml) for 8 weeks. Results showed that alliin had no significant effect on the body weight, adiposity or energy balance. However, alliin treatment enhanced glucose homeostasis, increased insulin sensitivity and improved the lipid profile in the DIO mice. This was, at least partly, attributable to alliin induced modulation of the intestinal microbiota composition, typically decreased Lachnospiraceae and increased Ruminococcaceae. From above, we conclude that alliin has nutraceutical or even medicinal potential in prevention of diabetes and lipid metabolic disorders.

Catalytic oxidative desulfurization technology of supported ceria based catalyst: Physicochemical and mechanistic studies

The catalytic oxidative desulfurization (Cat-ODS) process has emerged as a new technology to achieve ultra-low sulfur levels in diesel fuels. Various cerium based catalysts impregnated with Mn/Al2O3 were developed in this study. The catalytic activity of Mn/Ce/Al2O3 was higher than the monometallic catalysts, Ce/Al2O3. Under these optimum conditions: tert-butyl hydroperoxide (TBHP)/sulfur ratio of 3, 5.26%Mn/11.68%Ce/Al2O3, temperature of 45 °C, 30 min of reaction, complete removal of model organosulfur compounds were obtained. In addition, >90% of sulfur was removed in commercial diesel. High resolution transmission electron microscopy (HRTEM) analysis of 5.26%Mn/11.68%Ce/Al2O3 showed the presence of Al2O3, CeO2 and MnO2. The active sites responsible for the higher oxidative desulfurization activity were CeO2 and MnO2. The mechanistic study showed that the reaction between TBHP and DBT was efficient to produce corresponding sulfone, instead of sulfoxide compound using 5.26%Mn/11.68%Ce/Al2O3 catalyst.

Biotechnological production of chiral organic sulfoxides: current state and perspectives.

Chiral organic sulfoxides (COSs) are important compounds that act as chiral auxiliaries in numerous asymmetric reactions and as intermediates in chiral drug synthesis. In addition to their optical resolution, stereoselective oxidation of sulfides can be used for COS production. This reaction is facilitated by oxygenases and peroxidases from various microbial resources. To meet the current demand for esomeprazole, a proton pump inhibitor used in the treatment of gastric-acid-related disorders, and the (S)-isomer of an organic sulfoxide compound, omeprazole, a successful biotechnological production method using a Baeyer-Villiger monooxygenase (BVMO), was developed. In this review, we summarize the recent advancements in COS production using biocatalysts, including enzyme identification, protein engineering, and process development.

High-contrast, high-resolution photochromic silicone polymer based on photoswitchable [Ru(bpy)_2OSO]PF_6 building blocks

The implementation of photoinduced linkage isomerism in molecular-based optical materials represents a promising approach for the synthesis of high-contrast, high-resolution photosensitive materials that are necessary for high-density (holographic) data storage and/or real-three-dimensional (holographic) displays. The unsolved task of embedding a photofunctional coordination complex into a matrix like polymer polydimethylsiloxane (PDMS) with photoinduced isomerism of a SO-bond in the sulfoxide compound [Ru(bpy)2OSO]PF6 is addressed. This approach allows to preserve the spectral properties within the solid dielectric environment, with an impact of PDMS on population and relaxation dynamics. All data are discussed in the framework of photofunctionality, storage, and display applications.

Luminescence of Lanthanide–Dimethyl Sulfoxide Compound Solutions

Dimethyl sulfoxide (DMSO) has the ability to penetrate living tissues without causing significant damage. Of foremost importance to our understanding of the possible functions of DMSO in biological systems is its ability to replace some of the water molecules associated with the cellular constituents or to affect the structure of the omnipresent water. Luminescence probes have been widely used for biological studies such as labeling, imaging, and detection. Luminescence probes formed in DMSO may find new applications. Here luminescence compounds formed by refluxing lanthanide nitrates of Ce, La, Tb, Yb, Nd, Gd, and Eu in DMSO are reported and their luminescence properties investigated. On the basis of their luminescence spectral properties, the compounds can be classified into four classes. For compounds I with Yb, Ce, and La, the excitation and emission spectra are very broad and their excitation or emission peaks are shifted to longer wavelengths when the monitored emission or excitation wavelength is longer. For compounds II with Gd and Nd, both the excitation and emission spectra are very broad but their emission wavelengths change little at different excitation wavelengths. For Tb-DMSO as compound III, both the typical emissions from the f-f transitions of Tb(3+) and a broad emission at 445 nm are observed. At low reaction temperatures, the f-f emissions are dominant, while at high reaction temperatures such as 180 °C, the broad emission at 445 nm is dominant. For compound IV, Eu-DMSO, the dominant emissions are from the f-f transitions of Eu(3+) and only a weak broad emission is observed, which is likely from the d-f transition of Eu(2+) rather than from metal-to-ligand charge transfer states.

Withanolide sulfoxide from Aswagandha roots inhibits nuclear transcription factor‐kappa‐B, cyclooxygenase and tumor cell proliferation

Investigation of the methanol extract of Aswagandha (Withania somnifera) roots for bioactive constituents yielded a novel withanolide sulfoxide compound (1) along with a known withanolide dimer ashwagandhanolide (2) with an S-linkage. The structure of compound 1 was established by extensive NMR and MS experiments. Compound 1 was highly selective in inhibiting cyclooxygenase-2 (COX-2) enzyme by 60% at 100 microm with no activity against COX-1 enzyme. The IC(50) values of compound 1 against human gastric (AGS), breast (MCF-7), central nervous system (SF-268) and colon (HCT-116) cancer cell lines were in the range 0.74-3.63 microm. Both S-containing dimeric withanolides, 1 and 2, completely suppressed TNF-induced NF-kappaB activation when tested at 100 microm. The isolation of a withanolide sulfoxide from W. somnifera roots and its ability to inhibit COX-2 enzyme and to suppress human tumor cell proliferation are reported here for the first time. In addition, this is the first report on the abrogation of TNF-induced NF-kappaB activation for compounds 1 and 2.

Mechanism of Increase of Electrostatic Charging Tendency in Insulating Oil for Oil-immersed Transformer

Both of the mechanism and the causing compound to increase the electrostatic charging tendency (ECT) of insulating oil was investigated by accelerated deterioration tests with the addition of various compounds. Although the ECT of the insulating oil was almost constant when only sulfoxide compounds were added, remarkable increase was observed when either of hydrochloric acid or moisture, which was considered to be generated by the aging of insulating oil, was further added to the oil containing sulfoxide compounds. It is presumed that sulfonium ion, which is generated by the reaction between sulfoxide compound and hydrogen ion, is the compound to directly contribute the increase in ECT. Hydrogen ion can be supplied from the organic acids, which is generated by the oxidation of hydrocarbon in aging insulating oil. It is considered that the increase in ECT of insulating oil is caused by the generation of sulfoxide by the oxidation of sulfide, which is contained in new oil (origin compound), and the generation of sulfonium ion from the reaction between sulfoxide and hydrogen ion, which is generated due to aging.

Rapid, Nondestructive Near-Infrared Assay for Water in Sealed Dimethyl Sulfoxide Compound Repository Containers

Water contamination in dimethyl sulfoxide (DMSO) compound libraries is a recognized problem in the pharmaceutical industry. We describe a nondestructive, near-infrared (NIR) assay for water contamination inside the sealed containers used for compound libraries. This assay does not require opening the containers. We also report our observation of the permeation of water from laboratory air through the sealed container and into the DMSO solution over a period of months, as well as the rate of water absorption by DMSO directly exposed to laboratory air.

Highly Potent and Orally Active CCR5 Antagonists as Anti-HIV-1 Agents: Synthesis and Biological Activities of 1-Benzazocine Derivatives Containing a Sulfoxide Moiety

Chemical modification has been performed on an orally bioavailable and potent CCR5 antagonist, sulfoxide compound 4, mainly focusing on replacement of the [6,7]-fused 1-benzazepine nucleus. We designed, synthesized, and evaluated the biological activities of ring-expanded [6,8]-, [6,9]-, and [6,10]-fused compounds containing S-sulfoxide moieties, which led to the discovery of 1-benzazocine and 1-benzazonine compounds that exhibited potent inhibitory activities (equivalent to compound 4) in a binding assay. In addition, 1-benzazocine compounds possessing the S-sulfoxide moiety ((S)-(-)-5a,b,d,e) showed greater potency than compound 4 in a fusion assay. From further investigation in a multi-round infection assay, it was found that 1-isobutyl-1-benzazocine compound (S)-(-)-5b, containing the S-{[(1-propyl-1H-imidazol)-5-yl]methyl}sulfinyl group, showed the most potent anti-HIV-1 activity (IC90=0.81 nM, in MOLT4/CCR5 cells). Compound (S)-(-)-5b (TAK-652) also inhibited the replication of six macrophage-tropic (CCR5-using or R5) HIV-1 clinical isolates in peripheral blood mononuclear cells (PBMCs) (mean IC90=0.25 nM). It was also absorbed after oral administration in rats, dogs, and monkeys and was thus selected as a clinical candidate. The synthesis and biological activity of the 1-benzazocine compound (S)-(-)-5b and its related derivatives are described.

Synthesis and Antitumor Activity of Sulfur-Containing 9-Anilinoacridines

A series of sulfur-containing 9-anilinoacridines related to amsacrine were synthesized and evaluated for their anticancer potential. Among the compounds, both diol-containing compounds, 2a and 3, were the most cytotoxic of the sulfide series against V-79 cells in vitro (IC(90) = 2.1 microM and 1.9 microM, respectively). Among the non-alkyl-substituted compounds (7-9), compounds with electron-donating substitution para to the sulfide (7 and 9) were more cytotoxic than the electron-withdrawing nitro-substituted compound 8. The limited SAR suggested the importance of hydroxyl functionality along with its location for the cytotoxicity in the series. A preliminary anticancer screening against P388 leukemia showed that 2a is highly active in vivo as well. Topoisomerase II inhibitory activity appeared to be involved in the cytotoxicity of compound 2a. Sulfoxide compound 2b, which is 6-7-fold less cytotoxic than its sulfide 2a, appears to be a potential bioreductive anticancer prodrug on the basis of its bioreductive metabolism findings.

REAKTIONEN VON HEXACHLORBUTEN MIT DITHIOLEN

Abstract Compounds 4a, 5a, 6a, 4b, 5b, 6b, 4c, 5c, 6c have been obtained from hexachlorobutene (I) or from pentachlorobutadiene 2 and dithiolates in aqueous ethanol solution at room temperature. By the reaction of 4a and 8 moles of 3-chloroperbenzoic acid in chloroform sulfone compounds 7a and 8a are obtained. If 4 moles of 3-chloroperbenzoic acid are used at the same conditions a sulfoxide compound 9a is obtained.

Disposition kinetics of ML‐1035 sulfoxide enantiomers and the prochiral sulfide in rats

ML-1035, 4-amino-5-chloro-2-[2-(methylsulfinyl)ethoxy]-N-[2- (diethyl-amino)ethyl]benzamide, is a sulfoxide compound and a racemic gastroprokinetic agent with a chiral center at the sulfur atom. We have investigated the disposition kinetics of (R)-ML-1035 sulfoxide (R) and (S)-ML-1035 sulfoxide (S) after the single enantiomers and the racemic mixture were administered to rats in separate experiments. There was no noticeable chiral inversion after either enantiomer dose. Both enantiomers were rapidly absorbed. After dosing with enantiomers or with the racemate, the resulting plasma concentration-time curve of R was closely parallel to that of S in both intravenous and oral experiments, suggesting that the two enantiomers have approximately the same disposition kinetics. After intravenous enantiomer doses, only S underwent conversion to sulfide, suggesting that sulfidation in the liver is enantioselective. However, the enantioselective sulfidation after intravenous dosing did not introduce a difference in the global plasma disposition profiles between R and S, since the reduction reaction is a minor metabolic process. Other metabolic reactions such as sulfonation and mono-N-desethylations were not enantioselective. After oral administration, conversion to sulfide was observed for both enationers, implicating the existence of a nonhepatic pathway in sulfidation. Administration of a prochiral sulfide dose was associated with an enantioselective sulfoxidation, in which the R/S concentration ratios increased as a function of time. In addition, enatiomeric interaction causing changes in pharmacokinetic parameters was observed after the oral racemate dose, while the interaction is negligible after an intravenous racemate dose, indicating a route dependency in enantiomeric interaction.

REAKTIONEN VON PERCHLORBUTADIEN MIT DITHIOLEN

Abstract Compounds 3a, 3b, 4a, 5a and have been obtained from hexachlorobutadiene (1) and dithiolates in aqueous ethanol solutions at room temperature. Compound 3a gives a sulfoxide compound 6a and a sulfone compound 7a with 3-chloroperbenzoic acid in chloroform.

Synthetic studies on spiroketal natural products. II. An enantioselective synthesis of (R)- and (S)-1,7-dioxaspiro[5.5]undecane.

Both enantiomers of 1, 7-dioxaspiro[5.5]undecane, a chiral compound with C2 symmetry, were stereoselectively synthesized from an (R)-sulfoxide compound 8. The reaction of menthyl (S)-p-toluenesulfinate with a Grignard reagent gave the chiral sulfoxide (8), which was derived to a dihydropyran (12) by a several-step sequence. The base-catalyzed intramolecular Michael reaction of 12 exclusively afforded a dioxaspiro product (13) as a single stereoisomer. An acidic treatment of 13 resulted in isomerization of the spiro center to give 14. Desulfurization of 13 and 14 over Raney nickel in the presence of sodium hydroxide gave (R) -and (S)-1, 7-dioxaspiro[5.5]undecane (R-1 and S-1), respectively.