Solid-phase thiolsulfinates for the reversible immobilization of thiols

A new method for the reversible immobilization of thiol-containing substances on agarose beads is presented. It is based on the use of thiolsulfinate (disulfide monoxide) as a solid-phase reactive group. The thiolsulfinate groups are introduced by controlled oxidation of thiol agarose. The method comprises two steps: First, mild oxidation of the agarose thiol groups to disulfide structures with potassium ferricyanide. Second, the oxidation of the so-formed agarose disulfide groups to thiolsulfinate groups by use of a stoichiometric amount of the oxidizing agent magnesium monoperoxyphtalate. The solid-phase thiolsulfinate groups react very easily with thiols, which, as a result of the reaction, will be bound to the agarose beads by disulfide bonds. The adsorbent derivative is very suitable for the reversible immobilization of low as well as high-mol-wt thiols as demonstrated with reduced glutathione, penicillamine, mercaptoethanesulfonic acid, thiolated bovine serum albumin,β-galactosidase, and ±₁-antitrypsine. Since treatment of the agarose derivatives with an excess of low-mol-wt thiols (e.g., dithiothreitol) leads to release of the bound molecules and regeneration of the original thiol groups, the reactive thiolsulfinate groups can easily be regenerated by the mentioned two-step procedure. The cycle of oxidation, binding, reduction, and reoxidation can be performed several times while retaining thiol binding capacity.     

Fluoroalkene chemistry: Part 3. Reactions of arylthiols with perfluoroisobutene, perfluoropropene and chlorotrifluoroethene

Reactions of perfluoroisobutene (PFIB), perfluoropropene (PFP) and chlorotrifluoroethene (CTFE) with benzenethiol and 2-methoxybenzenethiol in acetonitrile, with potassium carbonate as base, were compared. PFIB reacted with benzenethiol to give ketene thioacetal (CF₃)₂CC(SAr)₂ and with 2-methoxybenzenethiol to give mono- and bis-vinyl species (CF₃)₂CCFSAr and (CF₃)₂CC(SAr)₂. PFP reacted with both thiols to give the addition product CF₃CFHCF₂SAr and vinyl isomers CF₃CFCFSAr (6:1 E/Z ratio). CTFE reacted with several methoxy-substituted arylthiols to give addition products of structure CFClHCF₂SAr. The arylthiols used throughout the study imitate biological thiols. Inhalation toxicities of the fluoroalkenes decrease in the order PFIB > PFP > CTFE and correlate with their reactivities towards the model thiols, supporting the current view that their toxicity relates to their ability to react with biological thiols.     

A colorimetric chemosensor for fast detection of thiols based on intramolecular charge transfer

A TCNQ-based triphenylamine derivative (1) with strong intramolecular charge transfer (ICT) character was designed as a colorimetric sensor for thiols. Upon addition of thiols, the absorption spectrum of sensor 1 in aqueous solution was remarkably changed because the adduct of 1 with thiol decreased its ICT character. Sensor 1 showed highly selective and sensitive sensing ability toward thiols over other analytes. This selectivity could be easily observed by naked eyes, indicating that sensor 1 is a potential colorimetric sensor for thiols.     

Synthesis of fluorescent long-chain thiols/disulfides as building-blocks for self-assembled monolayers preparation

New symmetrical disulfides together with the corresponding thiols bearing fluorescent end-groups have been synthesized as building-blocks for self-assembled monolayers (SAMs). The synthesis has been accomplished starting from aromatic nitrogen heterocycles in three steps. The conversion of the tosylated intermediate into the final disulfide is accomplished by use of sodium hydrogen sulfide (NaSH). Both products (thiols and disulfides) were isolated and characterized.      

Eigenschaften und Verwendbarkeit des 10, 11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-yl-Rests (= 5-Dibenzosuberyl-Rests) als neue Schutzgruppe für Amine,Aminosäuren,Alkohole, Thiole und Carbonsäuren

Properties and suitability of the 10,11-dihydro-5 H-dibenzo[a, d]cyclohepten-5-yl group (= 5-dibenzosuberyl group) as a new protecting group for amines, amino-acids, alcohols, thiols and carboxylic acids. The 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl group (5-dibenzosuberyl group): has been found useful for protecting amines, alcohols, thiols, and carboxylic acids. Furthermore, the investigated 5-amino compounds are extremely stable in strongly acidic media (e. g. in hydrogen bromide) and still the amino group is easily cleaved under mild conditions, such as those used for N-trityl compounds (e.g. boiling in dilute acetic acid or catalytic hydrogenation). Hence this ring system could be a valuable and adaptable protecting group, especially in peptide chemistry.     

Determination of the thiol redox state of organisms: new oxidative stress indicators

This study describes a new methodology by which the concentrations of non-protein (NP) thiols glutathione (GSH), cysteine (CSH), N-acetylcysteine (AcCSH), and protein (P) thiols (PSH), as well as the contribution of these components to symmetric and mixed disulfides (NPSSR, NPSSC, NPSSCAc, PSSR, PSSC, PSSCAc, PSSP) can reliably be measured. The methodology consists of a strict sequence of methods which are applied to every sample. Free thiols at any given state of the procedure are measured by Ellmans assay, the CSH fraction is measured by its unique response in the ninhydrin assay, AcCSH is selectively measured with ninhydrin after enzymatic deacylation, proteins are separated from non-protein thiols/disulfides by precipitation with trichloroacetic or perchloric acid, disulfides are reduced into free thiols with borohydride, mixed disulfides between a protein and a non-protein component are measured by extracting the non-protein thiol from the protein pellet after borohydride treatment, and protein thiols/disulfides are measured after resolubilization of the protein pellet.When this method was applied to animal and fungal tissue, new molecular indicators of the thiol redox state of living cells were identified. The findings of the present study clearly show that the new parameters are very sensitive indicators of redox state, while at the same time the traditional parameters GSH and GSSG often remain constant even upon dramatic changes in the overall redox state of biological tissue. Therefore, unbiased assessment of the redox state also requires explicit measurement of its most sensitive thiol indicators.Electronic Supplementary Material Supplementary material is available in the online version of this article at . A link in the frame on the left on that page takes you directly to the supplementary material.     

Asymmetric michael addition of aromatic thiols to 2-cyclohexenone and maleic acid esters via formation of crystalline cyclodextrin complexes

The asymmetric Michael addition of aromatic thiols to 2-cyclohexenone and maleic acid esters has been carried out by utilizing their crystalline cyclodextrin complexes suspended in water. The best chiral induction, 30% enantiomeric excess (ee), was achieved in combinations of 2-cyclohexenone and octyl maleate with the crystalline -cyclodextrin complex of benzenethiol (method A) to afford (S)-3-phenylthiocyclohexanone and (S)-octyl-2-phenylthiosuccinate, respectively, whereas the reaction of benzenethiol with 2-cyclohexenone included in -cyclodextrin (method B) inversely induced the chiral recognition to give the (R)-adduct with 4–9% ee.     

A general thiol assay based on the suppression of fluorescence resonance energy transfer in magnetic-resin core-shell nanospheres coated with gold nanoparticles

A simple, rapid and sensitive fluorescence resonance energy transfer (FRET) method is presented for the determination of thiols. It is based on the thiol-induced enhancement effect of the surfactant sodium dodecyl sulfate (SDS) on the efficiency of fluorescence resonance energy transfer (FRET) in nanospheres consisting of a magnetic (Fe₃O₄) core and a phenol-formaldehyde resin (PFR) shell containing gold nanoparticles (AuNPs). The luminescence of the core-shell nanospheres at excitation/emission wavelengths of 390/445 nm, respectively, is quenched by the AuNPs which act as energy acceptors. The interaction of AuNPs with thiol compounds in the presence of SDS suppresses FRET and gives rise to a fluorescent signal whose intensity is proportional to the thiol concentration. The analytical features of seven thiols (homocysteine, thioglycolic acid, glutathione, dodecanethiol, cysteamine, cysteine and N-acetylcysteine) were studied. Detection limits are in the range from 0.14 to 0.49 μmol L⁻¹. The precision of the method, expressed as the relative standard deviation, ranges from 0.4 to 4.9 %. The method was applied to the determination of total thiols in water samples with recovery values between 88.7 and 104.6 %.

The fluorescence resonance energy transfer in magnetic-resin core-shell nanospheres coated with gold nanoparticles is inhibited by thiol compounds in the presence of sodium dodecyl sulfate. This gives rise to a fluorescent signal whose intensity is proportional to the thiol concentration.

     

Fully automated synthesis of N-labeled nitrosothiols

In the present Letter, a fast, automated, and reproducible method for the synthesis of S-[¹³N]nitrosothiols is reported. The labeling strategy is based on trapping in an anion exchange resin. The reaction with thiols in acidic media led to the formation of the desired nitrosothiols in short reaction times (60 s) with excellent radiochemical conversions (from 48.7% to 74.5%). Final radiotracers were purified by HPLC. Good radiochemical yields (from 33.8% to 60.6%, decay corrected) and radiochemical purities (>99%) were obtained in all cases. Stability of the labeled compounds was checked.     

Reactions ofβ, β-dichlorovinyl organyl sulfides with thiols and the synthesis of bis(organylthio)acetylenes

Conclusions ,-Dichlorovinyl organyl sulfides can react with thiols and KOH by several pathways, depending on the conditions, leading to different unsaturated sulfides. We have found a simple preparative route to bis(alkylthio)acetylenes with identical or different radicals.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 2, pp. 426–431, February, 1978.We thank V. V. Keiko for the preparative separation of isomers (I) and (III).     

A highly efficient,operationally simple and selective thia-Michael addition under solvent-free condition

Abstract

The rapid and very simple conjugate addition of thiols to α,β-unsaturated carbonyl compounds under solvent-free conditions in the presence of catalytic amount of lithium hydroxide at room temperature is reported. The reaction of aryl, alkyl, aliphatic, and hindered thiols with chalcone, enone, and nitrostyrene gave the corresponding Michael adducts with significant advantages, such as high conversions, short reaction time, mild reaction conditions, low cost, simple catalyst, and high to quantitative yields with excellent chemoselectivity.

     

N-Trifluoroacetyl arenesulfenamides, effective precursors for synthesis of unsymmetrical disulfides and sulfenamides

N-Trifluoroacetyl arenesulfenamides (3) were effective precursors for the synthesis of unsymmetrical disulfides (4) and sulfenamides (5). Reactions of 3 with a variety of aromatic thiols at room temperature were generally complete within 5 min and gave unsymmetrical diaryl disulfides in high yields. Aralkyl disulfides were isolated in high yields from the reaction of 3 with aliphatic thiols. The nucleophilic substitution reactions of 3 with amines proceeded smoothly and provided N-substituted sulfenamides in good to excellent yields.     

Measurement of xanthine oxidase inhibition activity of phenolics and flavonoids with a modified cupric reducing antioxidant capacity (CUPRAC) method

Various dietary polyphenolics have been found to show an inhibitory effect on xanthine oxidase (XO) which mediates oxidative stress-originated diseases because of its ability to generate reactive oxygen species (ROS), including superoxide anion radical (O₂⁻) and hydrogen peroxide. XO activity has usually been determined by following the rate of uric acid formation from xanthine-xanthine oxidase (X-XO) system using the classical XO activity assay (UV-method) at 295 nm. Since some polyphenolics have strong absorption from the UV to visible region, XO-inhibitory activity of polyphenolics was alternatively determined without interference by directly measuring the formation of uric acid and hydrogen peroxide using the modified CUPRAC (cupric reducing antioxidant capacity) spectrophotometric method at 450 nm. The CUPRAC absorbance of the incubation solution due to the reduction of Cu(II)-neocuproine reagent by the products of the X-XO system decreased in the presence of polyphenolics, the difference being proportional to the XO inhibition ability of the tested compound. The structure-activity relationship revealed that the flavones and flavonols with a 7-hydroxyl group such as apigenin, luteolin, kaempferol, quercetin, and myricetin inhibited XO-inhibitory activity at low concentrations (IC₅₀ values from 1.46 to 1.90 μM), while the flavan-3-ols and naringin were less inhibitory. The findings of the developed method for quercetin and catechin in the presence of catalase were statistically alike with those of HPLC. In addition to polyphenolics, five kinds of herbs were evaluated for their XO-inhibitory activity using the developed method. The proposed spectrophotometric method was practical, low-cost, rapid, and could reliably assay uric acid and hydrogen peroxide in the presence of polyphenols (flavonoids, simple phenolic acids and hydroxycinnamic acids), and less open to interferences by UV-absorbing substances.     

Determination of total cysteamine in human plasma in the form of its 2-S-quinolinium derivative by high performance liquid chromatography

Cysteamine (mercaptamine) can be determined in plasma by liquid chromatography with ultraviolet detection after precolumn derivatization. The plasma is reduced with sodium borohydride in order to convert disulfides to thiols, and derivatized with 2-chloro-1-methylquinolinium tetrafluoroborate. The 2-S-quinolinium derivative of cysteamine is then separated from other thiols derivatives present in the plasma, and quantitated using high-performance liquid chromatography and then detection at 355 nm. Peaks from the main plasma thiols cysteine, cysteinylglycine, glutathione and homocysteine are also observed and can be measured as needed. The cystamine standards added to the plasma before the reduction step show that the response of the detector is linear within the range studied, from 0.1 to 40 mol/L plasma. The imprecisions at the bottom and the top of the calibration range were 11.17 and 0.8% and the inaccuracies 8.64 and 1.50%, respectively, and the lower limit of quantitation was 0.1 nmol cysteamine in 1 ml of plasma.     

α-Organylthiocrotonaldehydes

Conclusions A method was developed for the preparation of -organylthiocrotonaldehydes based on the reaction of -chlorocrotonaldehyde with aliphatic or aromatic thiols.Translated from Izvestiya Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1676–1678, July, 1986.     

Synthesis of β-Aryl-β-sulfanyl Ketones by a Sequential One-Pot Reaction Using KF/Al2O3 in Glycerol

The title compounds were synthesized by a sequential one-pot reaction of aryl aldehydes, aryl-methyl ketones, and thiols promoted by KF/Al₂O₃. This methodology affords a large number of β-aryl-β-sulfanyl ketone derivatives from aliphatic and aromatic thiols in good yields and is also applicable for solid substrates.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Synthesis of Thiol Esters by the Reaction of Ricinoleic Acid with Thiols Under Solvent-Free Conditions

The synthesis of several ricinoleic acid thiol esters starting from cis-(R)-12-hydroxyoctadec-9-enoic acid and thiols in the presence of N,N′-dicyclohexylcarbodiimide (DCC) is described. The method is efficient for aromatic and aliphatic thiols, selectively affording the respective fat acid thiol esters in good yields under mild, neutral, and solvent-free conditions. The protocol is general and was extended to other carboxylic acids, furnishing the desired products in satisfactory yields. The (R,Z)-12-hydroxy-octadec-9-enylic acid benzylthiol ester 3a was successfully reduced to (R,Z)-12-hydroxyoctadec-9-enal 4.