Identification of a new source of interference leached from polypropylene tubes in mass-selective analysis

An interference leached from polypropylene tubes was identified to be a sulfoxide oxidative product of didodecyl 3,3'-thiodipropionate (DDTDP) that is used to prevent oxidative degradation of synthetic polymers. A sulfone oxidative product of DDTDP leached from the polypropylene tubes was also observed. The interfering compounds were isolated by LC and characterized using time-of-flight mass spectrometry and NMR. Authentic sulfoxide and sulfone products of DDTDP were also prepared by reacting DDTDP with hydrogen peroxide reaching an unequivocal structural assignment. In conclusion, when analytes of interest are solubilized in predominantly organic solvents and kept in polypropylene containers, the possibility of contamination from leached chemicals should be taken into account.     

Reaction of trifluoromethanesulfonamide with heterodienes under oxidation conditions

Reactions of trifluoromethanesulfonamide with divinyl sulfone, divinyl sulfoxide, divinyl sulfide, diphenyl sulfide, vinyl allyl and diallyl ethers was investigated in the presence of oxidation system t-BuOCl + NaI. The reaction with divinyl sulfone afforded a product of 1,5-heterocyclization, 2,6-diiodo-4-[(trifluoromethyl) sulfonyl]thiomorpholine 1,1-dioxide. The same product was obtained in the reaction with divinyl sulfoxide apparently due to its preliminary oxidation to sulfone. In reactions with divinyl sulfide and unsaturated ethers only the oxidation of substrates was observed accompanied with strong tarring; the products of a reaction with trifluoromethanesulfonamide were absent. With diphenyl sulfide a product was formed resulting from the oxidation at the sulfur atom [S(II) → S(IV)], N-(diphenyl-λ⁴-sulfanylidene)trifluoromethanesulfonamide.     

Synthesis and properties of poly(dipropargyl sulfoxide)

The preparation and cyclopolymerization of dipropargyl sulfoxide were studied. The polymerization of dipropargyl sulfoxide was carried out by various transition metal catalysts. WCl₆–EtAlCl₂, MoCl₅, and PdCl₂ catalyst systems were very effective. The resulting poly(dipropargyl sulfoxide) structures were characterized by NMR (¹H and ¹³C), IR, and elemental analysis to have conjugated polyene units. Poly(dipropargyl sulfoxide) prepared by PdCl₂ was mostly soluble in organic solvents such as DMF and DMSO. Thermal and oxidative properties of poly(dipropargyl sulfoxide) were also studied. The electrical conductivity of iodine-doped poly(dipropargyl sulfoxide) was 5.2 × 10^?2 Ω^?1 cm^?1. Comparisons of poly(dipropargyl sulfoxide) properties with other similar polymers from dipropargyl sulfur derivatives such as dipropargyl sulfide and dipropargyl sulfone were also carried out. © 1993 John Wiley & Sons, Inc.     

Decarboxylation of α-keto carboxylic acids by persulfoxide

Photosensitized oxygenation of diethyl sulfide in the presence of α-keto carboxylic acids caused oxidative decarboxylation of the acids by persulfoxide and gave carboxylic acids, carbon dioxide, diethyl sulfoxide and diethyl sulfone.     

Alkoxide- and hydroxide-induced nucleophilic trifluoromethylation using trifluoromethyl sulfone or sulfoxide

[reaction: see text] The first alkoxide- and hydroxide-induced nucleophilic trifluoromethylation of carbonyl compounds, disulfides, and other electrophiles, using phenyl trifluoromethyl sulfone 1a (sulfoxide 1b) is reported. The trifluoromethyl sulfone 1a or sulfoxide 1b acts as a "CF(3)(-)" synthon. Both sulfone 1a and sulfoxide 1b are commercially available and can also be conveniently prepared from trifluoromethane. The new methodology provides a convenient route for efficient trifluoromethylation.     

Discrimination of Methionine Sulfoxide and Sulfone by Human Neutrophil Elastase

Human neutrophil elastase (HNE) is a uniquely destructive serine protease with the ability to unleash a wave of proteolytic activity by destroying the inhibitors of other proteases. Although this phenomenon forms an important part of the innate immune response to invading pathogens, it is responsible for the collateral host tissue damage observed in chronic conditions such as chronic obstructive pulmonary disease (COPD), and in more acute disorders such as the lung injuries associated with COVID-19 infection. Previously, a combinatorially selected activity-based probe revealed an unexpected substrate preference for oxidised methionine, which suggests a link to oxidative pathogen clearance by neutrophils. Here we use oxidised model substrates and inhibitors to confirm this observation and to show that neutrophil elastase is specifically selective for the di-oxygenated methionine sulfone rather than the mono-oxygenated methionine sulfoxide. We also posit a critical role for ordered solvent in the mechanism of HNE discrimination between the two oxidised forms methionine residue. Preference for the sulfone form of oxidised methionine is especially significant. While both host and pathogens have the ability to reduce methionine sulfoxide back to methionine, a biological pathway to reduce methionine sulfone is not known. Taken together, these data suggest that the oxidative activity of neutrophils may create rapidly cleaved elastase “super substrates” that directly damage tissue, while initiating a cycle of neutrophil oxidation that increases elastase tissue damage and further neutrophil recruitment.     

Dissipation behavior of phorate and its toxic metabolites in the sandy clay loam soil of a tropical sugarcane ecosystem using a single‐step sample preparation method and GC–MS

The dissipation of phorate in the sandy clay loam soil of tropical sugarcane ecosystem was studied by employing a single‐step sample preparation method and gas chromatography with mass spectrometry. The limit of quantification of the method was 0.01 μg/g. The recoveries of phorate, phorate sulfoxide, phorate sulfone, and phorate oxon were in the range 94.00–98.46% with relative standard deviations of 1.51–3.56% at three levels of fortification between 0.01 and 0.1 μg/g. The Half‐life of phorate and the total residues, which include phorate, phorate sulfoxide and phorate sulfone, was 5.5 and 19.8 days, respectively at the recommended dose of insecticide. Phorate rapidly oxidized into its sulfoxide metabolite in the sandy clay loam soil. Phorate sulfoxide alone accounted for more than 20% of the total residues within 2 h post‐application and it was more than 50% on the fifth day after treatment irrespective of the doses applied. Phorate sulfoxide and phorate sulfone reached below the detectable level on 105 and 135 days after treatment, respectively as against 45 days after treatment for phorate residues at the recommended dose. Thus, the reasonably prolonged efficacy of phorate against soil pests may be attributed to longer persistence of its more toxic sulfoxide and sulfone metabolites.     

Study of Clethodim Degradation and By-Product Formation in Chlorinated Water by HPLC

Two of the most commonly used chlorinating agents for water disinfection, hypochlorite and chloramines, were employed to investigate the degradation of clethodim in conditions simulating tap water treatment. The main clethodim degradation products were identified by using liquid chromatography (LC) coupled with mass spectrometry (MS). The main degradation process was oxidation to sulfoxide and then to sulfone. Degradation half-life was calculated for both parent clethodim and the first degradation product, clethodim sulfoxide. Whereas some other different minor by-products were identified when the degradation occurs with either sodium hypochlorite or chloramines, no other chlorinated by-products were found under the conditions tested.     

Determination of sulfur amino acids in foods as related to bioavailability

During the processing of feedstuffs and foods, methionine can be oxidized to methionine sulfoxide and methionine sulfone, and cysteine can be oxidized to cysteic acid. Methionine sulfone and cysteic acid are nutritionally unavailable, but methionine sulfoxide can be utilized, at least to some degree. The degree of utilization depends on the levels of methionine, cysteine, and methionine sulfoxide in the diet, but there is no consensus in the literature on the quantitative impact of these dietary constituents on methionine sulfoxide utilization. Methionine and cysteine are most often determined after quantitative oxidation to methionine sulfone and cysteic acid, respectively, using performic acid oxidation prior to hydrolysis. However, this method may overestimate the methionine content of processed foods, as it will include any methionine sulfoxide and methionine sulfone present. A selection of analytical methods has been developed to allow the separate determination of the 3 oxidized forms of methionine, the merits of which are discussed in this review. An additional consideration for determining methionine and cysteine bioavailability is that not all dietary methionine and cysteine is digested and absorbed from the small intestine. Selected methods designed to determine the extent of digestion and absorption are discussed. Finally, a concept for a new assay for determining methionine bioavailability, which includes determining the digestibility of methionine and methionine sulfoxide as well as the utilization of methionine sulfoxide, is presented.     

Propellanes—XXXVIII : Reaction of tetraenic thiapropellanes and their derivatives with 4-phenyl-1,2,4-triazoline-3,5-dione

The direction of attack of tetraenic and dienic propellanes containing thio-ether, sulfoxide and sulfone rings, by the title dienophile, has been determined. In the dienic series attack occurs only from above in all the substrates but in the tetraenic series there is exclusive attack from below in the thio-ether, mainly attack from above in the sulfone and a complex array of products is obtained from the sulfoxide.     

Kinetics, products, and mechanism of the reaction of diphenylcarbonyl oxide with sulfoxides

The kinetics of the reactions of diphenylcarbonyl oxide with dimethyl, di-n-hexyl, diphenyl, dibenzyl, andn-hexylbenzyl sulfoxides in acetonitrile was studied by flash photolysis at 295 K. The oxidation of sulfoxide affords the corresponding sulfone as the main reaction product, and diphenyl sulfide also forms in the case of Ph₂SO. Solvent effect on the reaction kinetics and the composition of the reaction products was studied. The reaction mechanism is discussed, which includes two parallel pathways: the nucleophilic attack of carbonyl oxide at the sulfur atom of sulfoxide and the formation of the cyclic sulfurane intermediatevia the electrophilic 1,3-cycloaddition of Ph₂COO at the S=O bond. The sulfurane undergoes fragmentationvia parallel channels to form sulfone or sulfide. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1504–1509, September, 2000.     

A simple LC-MS/MS method to determine plasma and cerebrospinal fluid levels of albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in patients with neurocysticercosis

The development and validation of an LC-MS/MS method for the simultaneous determination of albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in human plasma are described. Samples of 200 μL were extracted with ether-dichloromethane-chloroform (60:30:10, v/v/v). The chromatographic separation was performed using a C(18) column with methanol-formic acid 20 mmol/L (70:30) as the mobile phase. The method was linear in a range of 20-5000 ng/mL for albendazole sulfoxide and 10-1500 ng/mL for albendazole sulfone. For both analytes the method was precise (RSD < 12%) and accurate (RE <7%) with high recovery (>90%). The method was successfully applied to determine the plasma and cerebrospinal fluid levels of albendazole sulfoxide and albendazole sulfone in patients with subarachnoidal neurocysticercosis who received albendazole at 30 mg/kg per day for 7 days. This LC-MS/MS method yielded a quick, simple and reliable protocol for determining albendazole sulfoxide and albendazole sulfone concentrations in plasma and cerebrospinal fluid samples and is applicable to therapeutic monitoring.     

Thiophene 1-oxides. V. Comparison of the crystal structures and thiophene ring aromaticity of 2,5-diphenylthiophene,its sulfoxide and sulfone

The detailed preparation of 2,5-diphenylthiophene 1-oxide (2) is reported as well as the comparative study of the crystal structures of 2,5-diphenylthiophene, 1 , its sulfoxide 2 and sulfone 3 obtained by X-ray diffraction. This work represents the first experimental study of a complete heterocyclic series, including a thiophene derivative, and the corresponding sulfoxide and sulfone. On the basis of the geometrical parameters, the first unequivocal experimental parameters obtained for a thiophene 1-oxide derivative, we have also examined the evolution of the aromatic character of the thiophene ring when oxidizing the sulfur atom to the sulfoxide and the sulfone. Paolini's bond orders and Julg and Francois's aromaticity indices have also been calculated for the three compounds and compared to those previously calculated for related thiophene derivatives by semi-empirical or ab initio methods [6], [7]. All the data examined showed that, in spite of its non planarity, the thiophene ring of 2,5-diphenylthiophene 1-oxide 2 could still exhibit some de localization of its p electrons indicating a certain degree of aromaticity lower than in thiophene 1 but higher than in the sulfone 3 .     

Enantioselective synthesis of natural polyoxygenated cyclohexanes and cyclohexenes from [(p-tolylsulfinyl)methyl]-p-quinols

Exploitation of the beta-hydroxysulfoxide fragment present in a number of enantiomerically pure (SR)- and (SS)-[(p-tolylsulfinyl)methyl]-p-quinols allowed chemo- and stereocontrolled conjugate additions of different organoaluminium reagents to the cyclohexadienone moiety. The same fragment was also shown to act as an efficient chiral masking carbonyl group, after oxidation to sulfone and retroaddition in basic medium, with elimination of methyl p-tolyl sulfone. Through the use of both transformations as key steps, enantiocontrolled syntheses of different natural products-such as the two enantiomers of dihydroepiepoformin, (-)-gabosine O, (+)-epiepoformin, (-)-theobroxide and (+)-4-epigabosine A (an epimer of the natural product gabosine A)-has been achieved. The presence of the beta-hydroxy sulfone moiety makes the cyclic structures rigid, allowing a number of stereoselective transformations such as carbonyl reductions, enone epoxidations or cis-dihydroxylations, en route to the natural structures. The observed selectivities were dependent on the particular substitution in each substrate, providing evidence of a strong influence of remote groups on the preferred approach of the reactants to the reactive conformations. An advanced precursor of natural (+)-harveynone was also synthesized, but the isolation of the natural product was not possible because of the instability of the corresponding enone, containing a triple bond, under the basic conditions necessary to eliminate the beta-hydroxy sulfone. This demonstrated that the limitations of the use of the beta-hydroxy sulfoxide as a chiral protecting carbonyl group were dependent on the relative stabilities of the final targets in the presence of the required base.     

The degradation mechanism of sulfonated poly(arylene ether sulfone)s in an oxidative environment

The degradation of sulfonated aromatic hydrocarbons based polymer electrolyte membranes is an important issue for fuel cell stability. However, its mechanism is relatively unclear. We have conducted accelerated radical tests and degradation product analysis for various sulfonated poly(arylene ether sulfone) (SPES) compounds. We evaluated the chemical durability of SPES, and observed its degradation mechanism under oxidative attack by hydrogen peroxide. Various SPES compounds were synthesized from 4,4′-biphenol, 4,4′-dihydroxy diphenyl sulfone, and 4,4′-dihydroxy benzophenone comonomers, and their physical properties were evaluated. SPES copolymerized with 4,4′-dihydroxy diphenyl sulfone had a higher durability towards oxidative attack compared with the other compounds studied, and SPES copolymerized with 4,4′-dihydroxy benzophenone exhibited the lowest durability.     

Reaction of magnesium alkylidene carbenoids with lithium alpha-sulfonyl carbanions: a novel synthesis of tri- and tetra-substituted allenes from 1-chlorovinyl p-tolyl sulfoxides and sulfones

Treatment of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from ketones and chloromethyl p-tolyl sulfoxide, with ethylmagnesium chloride or isopropylmagnesium chloride at below -78 degrees C gave magnesium alkylidene carbenoids in about 90% yields. The reaction of the generated carbenoids with lithium alpha-sulfonyl carbanions was found to afford tri- and tetra-substituted allenes. Both cyclic ketones and acyclic ketones were useful in this procedure. However, the 1-chlorovinyl p-tolyl sulfoxides derived from aldehydes gave only rearranged products, acetylenes, under the reaction conditions. The magnesium alkylidene carbenoid derived from an optically active 1-chlorovinyl p-tolyl sulfoxide was treated with lithium alpha-carbanion of 1-naphthyl phenyl sulfone; however, the obtained allene was found to be racemic. The mechanism of this reaction is also discussed.     

1H chemical shifts in NMR. Part 27: proton chemical shifts in sulfoxides and sulfones and the magnetic anisotropy, electric field and steric effects of the SO bond

The (1)H chemical shifts of a series of sulfoxide and sulfone compounds in CDCl(3) solvent were obtained from experiment and the literature. These included dialkyl sulfoxides and sulfones (R(2)SO/R(2)SO(2), R = Me, Et, Pr, n-Bu), the cyclic compounds tetramethylene sulfoxide/sulfone, pentamethylene sulfoxide/sulfone and the aromatic compounds p-tolylmethylsulfoxide, dibenzothiopheneoxide/dioxide, E-9-phenanthrylmethylsulfoxide and (E) (Z)-1-methylsulfinyl-2-methylnaphthalene. The spectra of the pentamethylene SO and SO(2) compounds were obtained at -70 degrees C to obtain the spectra from the separate conformers (SO) and from the noninverting ring (SO(2)). This allowed the determination of the substituent chemical shifts (SCS) of the SO and SO(2) functional groups, which were analyzed in terms of the SO bond electric field, magnetic anisotropy and steric effect for long-range protons together with a model (CHARGE8d) for the calculation of the two and three bond effects. After parameterization, the overall root mean square (RMS) error (observed-calculated) for a dataset of 354 (1)H chemical shifts was 0.11 ppm. The anisotropy of the SO bond was found to be very small, supporting the dominant single bond S(+)--O(-) character of this bond.     

Chemistry of the phenoxathiins and isosterically related heterocycles. XXXIII . The influence of intramolecular sulfur-nitro group interactions on the reactivity at sulfur

Nitro-groups positioned ortho to thio-esters have been shown to engage in strong, non-bonded intramolecular interactions between the sulfur atom and one of the nitro-group oxygens. The effect of the sulfur-nitro group oxygen interaction on the chemical reactivity at the sulfur atom of 9-nitro-1-azaphenoxathiin is reported. Conditions which normally produce the sulfone exclusively have been shown to yield the sulfoxide with only a minimal quantity of the sulfone produced. Protracted periods of reflux are required to produce the sulfone from the sulfoxide.     

Selective oxidation of organic sulfides by mononuclear and dinuclear peroxotungsten(VI) complexes

Clean conversion of a variety of sulfides and dibenzothiophene (DBT) to the corresponding sulfoxide or sulfone could be achieved in high yields at room temperature using mononuclear as well as dinuclear diperoxo complexes of tungsten as oxidants, by a variation of reaction conditions. The compounds could also effectively catalyze oxidation of sulfides by H₂O₂ to selectively yield sulfone with reasonably good turnover frequency (TOF).     

Gas chromatographic analysis of methiocarb and its metabolites in soil and rice

Summary A new method to determine the amount of methiocarb and its two metabolites, the sulfoxide and sulfone in soil and rice plant is described. The method consists of extraction of samples with acetone, filtration, separation of methiocarb and its metabolites through a Florisil column, and gas chromatographic determination. Since the degradation of methiocarb to 3,5-dimethyl-4-methylthiophenol (DMMP) is commonly observed during GC analysis, methiocarb was converted to DMMP via chemical hydrolysis after column chromatography. Reasonable recoveries for routine analysis were obtained and the limit of quantitation (LOQ) with GC/FPD were 0.5, 2 and 2 ng for DMMP sulfoxide and sulfone, with a signal to noise ratio of 4. In all rice samples, no detectable residues were found, however DMMP and methiocarb sulfoxide were found in some straw samples. In field soil samples, no sulfone was detected in all samples and methiocarb showed typical degradation curves with a half life of 8 days after treatment. A five-fold longer half life was observed in indoor studies.