Sulfide Derivatives Research Articles

Tertiary Thiols from Allylic Thiocarbamates by Tandem Enantioselective [3,3]-Sigmatropic Rearrangement and Stereospecific Arylation

The synthesis of tertiary thiols in enantiomerically enriched form is accomplished by lithiation of enantiomerically enriched N-aryl allylic thiocarbamates. Formation of an allyllithium derivative promotes intramolecular N to C aryl migration to the position α to sulfur, generally with good stereospecificity. The substrates may themselves be obtained by Pd-catalyzed enantioselective [3,3]-sigmatropic rearrangement of N-aryl O-allyl thiocarbamates. Solvolysis of the product thiocarbamates yields tertiary thiols, which may be converted to sulfide derivatives.

Toxicity of the Insecticide Fipronil and Its Degradates to Benthic Macroinvertebrates of Urban Streams

Fipronil is a phenylpyrazole insecticide with increasing urban use. Sixteen urban waterways and municipal wastewater were sampled for fipronil, its environmental degradates, and pyrethroid insecticides. Because findings could not be interpreted with existing data on fipronil degradate toxicity, EC50s and LC50s for fipronil and its sulfide and sulfone derivatives were determined for 14 macroinvertebrate species. Four species were more sensitive than any previously studied, indicating fipronil's toxicity to aquatic life has long been underestimated. The most sensitive species tested, Chironomus dilutus, had a mean 96-h EC50 of 32.5 ng/L for fipronil and 7-10 ng/L for its degradates. Hyalella azteca, a common testing species, was among the least sensitive. The typical northern California creek receiving urban stormwater runoff contains fipronil and degradate concentrations twice the EC50 of C. dilutus, and approximately one-third the EC50 for a stonefly, a caddisfly, and two mayfly species. The present study substantially increases data available on toxicity of fipronil degradates, and demonstrates that fipronil and degradates are common in urban waterways at concentrations posing a risk to a wide variety of stream invertebrates.

Sulfur-containing fatty acid-based plasticizers via thiol–ene addition and oxidation: synthesis and evaluation in PVC formulations

A new family of sulfur-containing plasticizers derived from fatty acids has been developed. The synthetic approach is based on the thiol–ene addition of alkyl thiols to the double bond of technical oleic acid, followed by oxidation of the sulfide group to either sulfoxide or sulfone groups. It has been found that both sulfide and sulfoxide derivatives are not suitable as plasticizers due to their unpleasant odor and limited thermal stabilities. However, the sulfone derivatives are odorless, thermally stable, and show plasticizing properties similar to those of established PVC plasticizers such as cyclohexane-1,2-dicarboxylic acid diisononyl ester (ELATUR® CH) and diisononyl phthalate (VESTINOL® 9). A wide range of application tests is reported to support this conclusion. Furthermore, a mixture of fatty acids obtained from commercial rapeseed oil has been used as a cheap and readily available alternative source of oleic acid to obtain such plasticizers.

Domino reactions of alkane dithiolates with 2,3-dichloro-1-propene in hydrazine hydrate – KOH medium

2,3-Dichloro-1-propene reacts with alkane dithiolates in hydrazine hydrate – KOH medium to produce derivatives of dithiin, dithiepin, chloropropenyl, and allenyl sulfides depending on conditions and dithiolate structure. The formation of the heterocyclic products is a result of possible domino reactions, including a substitution of an allylic chlorine atom, dehydrochlorination, and intramolecular heterocyclization.

OP03 Absorption behaviour and blood baseline concentrations of sulfide monitored with gas chromatography/mass spectrometry

The reported sulfide absorption values and baseline blood concentrations are still controversial [1] . We modified an existing gas chromatographic/mass spectrometric method of routine sulfide quantification using a bis-pentafluorobenzyl derivative [2] . This approach allows sensitive determination of sulfide in small sample volumes under mild chemical conditions. In addition, in in vitro experiments, it allows to distinguish between endogenous and exogenous sulfide by administration of the stable isotope 34 S 2− . A standard protocol utilises 100 μl of blood, but can be scaled down to 25 μl for rodent samples. In brief, a mixture, consisting of 400 μl internal standard (5 μg/ml tribromobenzene in isooctane), 200 μl of alkylation reagent (10 μ l/ml pentafluorobenzylbromide in isooctane) and 400 μl of phase transfer catalyst (2 mg/ml tetradecyldimethylbenzylammonium chloride in sodium tetraborate saturated water) was prepared. After addition of 100 μl sample, the mixture was vigorously shaken for 1 min, 400 μl of saturated potassium dihydrogenphosphate solution were added and the cup was shaken for another 10 s. 2 μl of the isooctane phase were injected into an Agilent 5890/5970 gas chromatography/mass spectrometry instrument, housing a 12 m Macherey–Nagel Optima-5MS capillary column. In sim mode ions m/z 313.7 for the internal standard and 394.0 for the sulfide derivative (or 396.0 for 34 S 2− ) were recorded. The method was used to determine basal sulfide blood concentrations in pigs and to measure the sulfide release from the sulfide releasing drug GYY4137 over 24 h in cell culture medium. In addition this method reproducibly was used to determine the absorption of a spike of 100 μM 34 S 2− at pH 7.4 in buffer, blood, plasma, cysteine, glutathione and albumine. Baseline blood sulfide concentrations in pigs were between 0.2 and 2.1 μM. Sulfide concentrations of a 300 μ M solution of GYY4137 in cell culture medium (in cell culture flask, gas exchange enabled) were 1.02 μM (10 min after GYY addition), 1.32 μM (2 h), 1.37 μM (4 h), 1.60 μM (8 h), 1.58 μM (12 h) and 1.81 μM (24 h). The sulfide concentration of the corresponding medium without GYY4137 ranged between 0.25 and 0.50 μM. An initial 100 μM spike of 34 S 2− in blood decreased to 23 μM after 1 min, 12 μM after 10 and 1 μM after 60 min. The corresponding values for plasma were 60, 41 and 3 μM, for phosphate buffer (pH 7.4) 103, 96 and 85 μM. In a 50 mg/ml solution of albumine the 34 S 2− concentration decreased to 22, 15, 3 μM, in 5 mg/ml oxidized glutathione to 32, 18, 3 μM, in 5 mg/ml reduced glutathione to 79, 76, 75 μM, in 120 μg/ml cystine to 91, 64, 12 μM and in 1 mg/ml cysteine to 110, 102, 99 μM. Our findings show, that sulfide baseline concentrations in blood are in the low micromolar range. Added sulfide is rapidly absorbed by blood, plasma and disulfide bridge containing peptides and proteins, but much lower by the reduced species. Adding the sulfide releasing drug GYY4137, increased the sulfide concentration of cell culture media for 24 h.

P53 Absorption behaviour and blood baseline concentrations of sulfide monitored with gas chromatography/mass spectrometry

The reported sulfide absorption values and baseline blood concentrations are still controversial [1]. We modified an existing gas chromatographic/mass spectrometric method of routine sulfide quantification using a bis-pentafluorobenzyl derivative [2]. This approach allows sensitive determination of sulfide in small sample volumes under mild chemical conditions. In addition, in in vitro experiments, it allows to distinguish between endogenous and exogenous sulfide by administration of the stable isotope 34S2−. A standard protocol utilises 100 μl of blood, but can be scaled down to 25 μl for rodent samples . In brief, a mixture, consisting of 400 μl internal standard (5 μg/ml tribromobenzene in isooctane), 200 μl of alkylation reagent (10 μl/ml pentafluorobenzylbromide in isooctane) and 400 μl of phase transfer catalyst (2 mg/ml tetradecyldimethylbenzylammonium chloride in sodium tetraborate saturated water) was prepared. After addition of 100 μl sample, the mixture was vigorously shaken for 1 min, 400 μl of saturated potassium dihydrogenphosphate solution were added and the cup was shaken for another 10 s. 2 μl of the isooctane phase were injected into an Agilent 5890/5970 gas chromatography/mass spectrometry instrument, housing a 12 m Macherey-Nagel Optima-5MS capillary column. In sim mode ions m/z 313.7 for the internal standard and 394.0 for the sulfide derivative (or 396.0 for 34S2−) were recorded. The method was used to determine basal sulfide blood concentrations in pigs and to measure the sulfide release from the sulfide releasing drug GYY4137 over 24 h in cell culture medium. In addition this method reproducibly was used to determine the absorption of a spike of 100 μM 34S2− at pH 7.4 in buffer, blood, plasma, cysteine, glutathione and albumine. Baseline blood sulfide concentrations in pigs were between 0.2 and 2.1 μM. Sulfide concentrations of a 300 μM solution of GYY4137 in cell culture medium (in cell culture flask, gas exchange enabled) were 1.02 μM (10 min after GYY addition), 1.32 μM (2 h), 1.37 μM (4 h), 1.60 μM (8 h), 1.58 μM (12 h) and 1.81 μM (24 h). The sulfide concentration of the corresponding medium without GYY4137 ranged between 0.25 and 0.50 μM. An initial 100 μM spike of 34S2− in blood decreased to 23 μM after 1 min, 12 μM after 10 and 1 μM after 60 min. The corresponding values for plasma were 60, 41 and 3 μM, for phosphate buffer (pH 7.4) 103, 96 and 85 μM. In a 50 mg/ml solution of albumine the 34S2− concentration decreased to 22, 15, 3 μM, in 5 mg/ml oxidized glutathione to 32, 18, 3 μM, in 5 mg/ml reduced glutathione to 79, 76, 75 μM, in 120 μg/ml cystine to 91, 64, 12 μM and in 1 mg/ml cysteine to 110, 102, 99 μM. Our findings show, that sulfide baseline concentrations in blood are in the low micromolar range. Added sulfide is rapidly absorbed by blood, plasma and disulfide bridge containing peptides and proteins, but much lower by the reduced species. Adding the sulfide releasing drug GYY4137, increased the sulfid concentration of cell culture media for 24 h.

Antitermite Activity of β-Caryophyllene Epoxide and Episulfide

Caryophyllene-6,7-epoxide and caryophyllene-6,7-episulfide can be easily synthesized from beta-caryophyllene by autoxidation or episulfidation. The bioactivities of beta-caryophyllene and its derivatives were investigated against the subterranean termite Reticulitermes speratus Kolbe. The antifeedant, feeding, and termiticidal activities of each compound were tested using no-choice, dual-choice, and non-contact methods. Antitermitic activities were not shown by beta-caryophyllene, but were observed for the oxide and sulfide derivatives. Caryophyllene-6,7-episulfide showed especially high antifeedant and termiticidal activities. Thus, naturally abundant, non-bioactive beta-caryophyllene can be easily converted into an antitermite reagent via a non-biological process.

RAFT Polymerization of S-Vinyl Sulfide Derivatives and Synthesis of Block Copolymers Having Two Distinct Optoelectronic Functionalities

Well-defined sulfur-containing polymers and block copolymers were synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization of S-vinyl sulfide derivatives, in which the thioether moiety is directly connected to the vinyl group. We initially investigated RAFT polymerization of four different S-vinyl sulfide derivatives, phenyl vinyl sulfide (PVS), 4-chlorophenyl vinyl sulfide (CPVS), 2,4-dichlorophenyl vinyl sulfide (DCPVS), and 4-bromophenyl vinyl sulfide (BPVS). Three xanthate-type chain transfer agents (CTAs), a dithiocarbamate-type CTA, and a dithioester-type CTA were compared for these RAFT polymerizations. Reasonable control of the polymerization of PVS was confirmed by an observed linear increase in the molecular weight with the conversion, feasibility to control molecular weight based on the ratio of monomer consumed to the amount of CTA used, chain end structure determined by 1H NMR, and chain extension experiment. The RAFT polymerization of the bromo-substituted monome...

Explorations into the Potential of Chiral Sulfonium Reagents to Effect Asymmetric Halonium Additions to Isolated Alkenes

While methods for the racemic dihalogenation and halohydroxylation of alkenes have been known for decades, enantioselective variants of these processes remain elusive. Initial attempts were made to overcome this long-standing challenge by exploring the potential of chiral, crystalline, sulfur-derived halonium reagents to accomplish the asymmetric dichlorination and iodohydroxylation of 1,2-dihydronaphthalene. Asymmetric dichlorination of this substrate was achieved in 57% yield and 14% enantiomeric excess (ee), but asymmetric iodohydroxylation was much more successful, giving 67% yield and 63% ee. Thorough studies were made of these processes, including investigation of various chiral sulfide derivatives, their substrate scopes, and the reaction conditions.

11C and 18F PET radioligands for the serotonin transporter (SERT)

The serotonin transporter (SERT) has been implicated in a variety of neuropsychiatric disorders including depression, anxiety, and suicide, and is the target of the selective serotonin reuptake inhibitor (SSRI) class of antidepressants. The availability of SERT-specific positron emission tomography (PET) radioligands will allow the SERT to be studied noninvasively in living subjects through PET imaging of the SERT and occupancy studies of SSRIs. Numerous diaryl sulfide and tropane derivatives have been developed and radiolabeled with (11) C or (18) F for imaging the SERT with PET.

Synthesis of Some New 5-Arylazothiazole Derivatives as Disperse Dyes for Dyeing Polyester Fibers

A series of 5-arylazo-2-(arylidenehydrazino)-2-th iazo lin -4-one dyes 3 and 4 was prepared by cyclocondensation of hydrazonoyl bro mides 2 with various thiosemicarbazone derivatives 1. While the synthesis of 3-amino-N-(5-arylazo-2-thiazo lyl)-thieno(2,3-b)pyrid ine-2-carbo xamide dyes 8 was achieved by the reaction of 2-(N-chloroacetyl)-5-ary lazo-thiazo le derivatives 5 with 4,6-dimethyl-2-mercaptonicotinonitrile fo llowed by heterocyclizat ion of the obtained sulfide derivatives 7 in a solution of ethanol containing sodium etho xide. These dyes were applied as disperse dyes for dyeing polyester fibers and their characteristics and fastness properties have been measured. The dyed fibers exh ibit very good to excellent washing, perspiration and sublimat ion fastness properties, with little variation in good to excellent rubbing and light fastness.

Synthesis and Antimicrobial Activities of Some New Heterocyclic Compounds Based on 6‐Chloropyridazine‐3(2H)‐thione

Three tricyclic ring system, pyridazino[6,1‐b]quinazolin‐10‐ones, benzimidazolo‐pyridazine thione, and 1,2,4‐benzotriazino‐pyridazinethione along with imidazo‐[1,2‐b]‐pyridazinethione, 1,2,4‐triazolo[4,3‐b]pyridazine‐thione derivatives were synthesized starting from 6‐chloropyridazin3‐(2H)‐thione. Some disulfide and sulfide derivatives were also prepared. The antimicrobial activity of the synthesized compounds was tested. Some of these compounds possess a highly response against gram‐positive and gram‐negative bacteria as well as fungi.

Mercury detection in a microfluidic device by using a molecular sensor soluble in organoaqueous solvent

A series of fluorescent sensor molecules based on a phosphane sulfide derivative that is soluble in an organoaqueous solvent were designed and synthesized. The structure of the fluorophore has been optimized in order to have the best compromise in terms of solubility and photophysical properties. The obtained properties are in full agreement with quantum chemical calculations. A fluorescent molecular sensor containing one polyoxoethylene group has been synthesized and an efficient quenching upon mercury complexation has been observed. Finally, this sensing molecule has been introduced in a microfluidic chip in which fluorescence detection has been integrated. An efficient fluorescence response was observed upon mercury addition.

ChemInform Abstract: Unexpectedly Ligand‐Free Copper‐Catalyzed C—S Cross‐Coupling of Benzothiazole with Aryl Iodides in Aqueous Solution.

AbstractTreatment of benzothiazole with iodobenzenes under conditions A) produces unexpectedly 2‐aminophenyl sulfide derivatives instead of the expected 2‐arylated heterocyclic derivatives (mechanism).

Antibacterial, Antioxidant and Binding Studies of Some Novel Diaryl Sulphide Derivatives

A series of novel acyclic and cyclic diaryl sulphides was synthesized from 2,2′-dithiobenzoic acid. The various diaryl sulphides were characterized by use of spectral (IR, 1H and 13C NMR, ESI/MS) and elemental analyses. The antimicrobial activities of the compounds were evaluated in terms of their minimum inhibition concentration (MIC) against a panel of clinical isolates bacteria and were found to possess only moderate antimicrobial activities. N,N′-Bis(2-hydroxyphenyl)-2,2′-thiodibenzamide (13), exhibiting a hydroxy group at the phenyl ring, was the most active antimicrobial agent within the series, with MIC values of 0.05 mg mL–1 and 10 mg mL–1 against Staphylococcus aureus and Bacillus cereus, respectively. The antioxidant efficiency of the diaryl sulphides was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity with 13 being the most active compound. The interaction of 2,2′-thiodibenzanilide, N,N′-bis(2-methylphenyl)-2,2′-thiodibenzamide, and N,N′-bis(2-hydroxyphenyl)-2,2′-thiobenzamide with guanine, glutamic acid, and urea were studied quantitatively with binding constants ranging from 1 × 103 M−1 to 2.7 × 104 M−1.

The Role of Diallyl Sulfides and Dipropyl Sulfides in the In Vitro Antimicrobial Activity of the Essential Oil of Garlic, Allium sativum L., and Leek, Allium porrum L.

The in vitro antibacterial activity of essential oils (EOs) obtained from fresh bulbs of garlic, Allium sativum L., and leek, Allium porrum L. ( Alliaceae), was studied. A. sativum (garlic) EO showed a good antimicrobial activity against Staphylococcus aureus (inhibition zone 14.8 mm), Pseudomonas aeruginosa (inhibition zone 21.1 mm), and Escherichia coli (inhibition zone 11.0 mm), whereas the EO of A. porrum (leek) had no antimicrobial activity. The main constituents of the garlic EO were diallyl monosulfide, diallyl disulfide (DADS), diallyl trisulfide, and diallyl tetrasulfide. The EO of A. porrum was characterized by the presence of dipropyl disulfide (DPDS), dipropyl trisulfide, and dipropyl tetrasulfide. The antimicrobial activities of the DADS and DPDS were also studied. The results obtained suggest that the presence of the allyl group is fundamental for the antimicrobial activity of these sulfide derivatives when they are present in Allium or in other species (DADS inhibition zone on S. aureus 15.9 mm, P. aeruginosa 21.9 mm, E. coli 11.4 mm).

Unexpectedly ligand-free copper-catalyzed C–S cross-coupling of benzothiazole with aryl iodides in aqueous solution

A novel synthetic protocol for 2-aminophenyl sulfide derivatives via the reactions of benzothiazole with aryl iodides was reported for the first time. The reactions were catalyzed by CuCl with tetrabutylammonium hydroxide as the base and water as the solvent without ligand at 50°C or room temperature. A variety of aryl iodides underwent the C–S cross-coupling reaction with benzothiazole to afford smoothly the corresponding products in excellent yield.

The interdependence of the reactive species of oxygen, nitrogen, and carbon

This mini-review tries to summarize the main interdependences between the free radicals of oxygen, nitrogen, and carbon. Also, the main metabolic pathways for these radical species are described, as well as how these affect their interaction and functional implications. Emphasis is made on the metabolic disturbances induced by stressing aggressions that produce radical species. In this way, cellular oxidative imbalances created by the superiority of reactive oxygen species over the antioxidant systems produce both activation of nitroxide synthases and the oxidation of terminal nitrogen from L-arginine, as well as the metabolization of heme until carbon monoxide by nitric oxide-activated hemoxygenase. Also, multiple cellular protein and nucleoprotein alterations determined by these three kinds of radical species are completed by the involvement of hydrogen sulfide, which results from the degradation of L-cysteine by cistationine-γ-lyase. In this way, sufficient experimental data tend to demonstrate the involvement of hydrogen sulfide and other thiol derivatives in the interrelations between oxygen, nitrogen, and carbon, which results in a true radical cascade. Thus, oxidative stress, together with nitrosative and carbonilic stress, may constitute a central point where other factors of vulnerability meet, and their interactions could have an important impact in many modern diseases. Considering that the actions of reactive species can be most of the time corrected, future studies need to establish the therapeutical importance of various agents which modulate oxidative, nitrosative, or carbonilic stress.

Thermal stability of selenium, sulfur and nitrogen analogous phthalazine derivatives

Differential scanning calorimetry (DSC) and thermogravimetry (TG) are analytical and quantitative methods capable of providing reliable, fast and reproducible results. These data allow establishing the thermal stability, purity degree and the polymorphic behavior of organic compounds. Thermal analysis of fusion and degradation processes was carried out on organonitrogen, organosulfur and organoselenium phthalazine derivatives to establish thermal stability criteria. Decomposition and fusion temperatures of 27 biological active compounds, synthesized by our research group were determined using TG and DSC. Analysis of the thermal data indicated that: (a) in general, nitrogen compounds are more stable than sulfur and selenium compounds; (b) thioderivatives possess degradation temperatures higher than selenium compounds; (c) the presence of selenium atoms in molecular structure has associated a minor thermal stability; (d) sulfide derivatives decomposition process have higher Tonset values than disulfide compounds; (e) there are differences in the stability due to groups selenol, methylseleno, and cyanoseleno; (f) the nature of the substituent located on the benzyl ring has no effects on selenophthalazines thermal stability.

1,2,4-Oxadiazoles: A new class of anti-prostate cancer agents

Sulfide and sulfonyl derivatives of 1,2,4-oxadiazoles were synthesized and screened by MTT assay on the prostate cancer cells, DU-145. Six compounds were identified as potential anti-prostate cancer agents with IC50 values ranging from 0.5 to 5.1μM. These compounds exhibited good activity on the androgen independent cells PC-3, while the results were moderate on androgen dependent LNCaP cells, suggesting the possibility of a mechanism of action different from that of the bioisosteric bicalutamide. Also a very low cytotoxicity was observed on non-cancerous cells MCF-10A.