Presence Of Thiols Research Articles

Mn2+-ZnSe/ZnS@SiO₂ Nanoparticles for Turn-on Luminescence Thiol Detection.

Biological thiols are antioxidants essential for the prevention of disease. For example, low levels of the tripeptide glutathione are associated with heart disease, cancer, and dementia. Mn2+-doped wide bandgap semiconductor nanocrystals exhibit luminescence and magnetic properties that make them attractive for bimodal imaging. We found that these nanocrystals and silica-encapsulated nanoparticle derivatives exhibit enhanced luminescence in the presence of thiols in both organic solvent and aqueous solution. The key to using these nanocrystals as sensors is control over their surfaces. The addition of a ZnS barrier layer or shell produces more stable nanocrystals that are isolated from their surroundings, and luminescence enhancement is only observed with thinner, intermediate shells. Tunability is demonstrated with dodecanethiol and sensitivities decrease with thin, medium, and thick shells. Turn-on nanoprobe luminescence is also generated by several biological thiols, including glutathione, N-acetylcysteine, cysteine, and dithiothreitol. Nanoparticles prepared with different ZnS shell thicknesses demonstrated varying sensitivity to glutathione, which allows for the tuning of particle sensitivity without optimization. The small photoluminescence response to control amino acids and salts indicates selectivity for thiols. Preliminary magnetic measurements highlight the challenge of optimizing sensors for different imaging modalities. In this work, we assess the prospects of using these nanoparticles as luminescent turn-on thiol sensors and for MRI.

Temporal Labeling of Nascent RNA Using Photoclick Chemistry in Live Cells.

We report the first cellular application of a photoclick SPAAC reagent to label azide-functionalized RNA. 350 nm irradiation of a cyclopropenone caged oxo-dibenzocyclooctyne (photo-ODIBO) biotin yields formation of the SPAAC reactive species, which rapidly forms adducts with RNA containing 2'-azidoadenosine (2'N3-A). Photo-ODIBO was found to be highly stable in the presence of thiols, conferring greater stability relative to ODIBO. Light activated photo-ODIBO enabled tagging of cellular RNA, in addition to fluorescent imaging as well as enrichment of RNA in cell subpopulations via selective irradiation.

Oxygen-mediated Polymerization Initiated by Oltipraz-derived Thiones.

A pyrrolopyrazine-thione derived from oltipraz, a compound that has been investigated as a chemopreventive agent, affords radicals in the presence of thiols and oxygen via a redox cycle, an attribute that suggests its suitability as an initiator for oxygen-mediated polymerization. Here, we explore the utilization of this pyrrolopyrazine-thione, generated in situ from a precursor, as an initiator for the radical-mediated thiol-ene polymerization. While the pyrrolopyrazine-thione was shown to be capable of generating radicals in the presence of atmospheric oxygen and thiol groups, the reaction extents achievable were lower than desired owing to the presence of unwanted side reactions that would quench radical production and, subsequently, suppress polymerization. Moreover, we found that complex interactions between the pyrrolopyrazine-thione, its precursor, oxygen, and thiol groups determine whether or not the quenching reaction dominates over those favorable to polymerization.

Ag59(2,5-DCBT)32]3-: a new cluster and a precursor for three well-known clusters.

We report the synthesis of a new silver cluster, [Ag59(2,5-DCBT)32]3- (I) (2,5-DCBT: 2,5-dichlorobenzenethiol), which acts as a precursor for the synthesis of three well-known silver clusters, [Ag44(2,4-DCBT/4-FTP)30]4- (II) (4-FTP: 4-fluorothiophenol and 2,4-DCBT: 2,4-dichlorobenzenethiol), [Ag25(2,4-DMBT)18]- (III) (2,4-DMBT: 2,4-dimethylbenzenethiol) and [Ag29(1,3-BDT)12(PPh3)4]3- (IV) (1,3-BDT: 1,3-benzenedithiol and PPh3: triphenylphosphine). This newly synthesized silver cluster, I, is characterized using UV-vis absorption studies, high resolution electrospray ionization mass spectrometry (ESI MS) and other analytical tools. The optical absorption spectrum shows distinct features which are completely different from the previously reported silver clusters. We perform the rapid transformations of I to other well-known clusters II, III and IV by reaction with different thiols. The time-dependent UV-vis and ESI MS measurements reveal that I dissociates into distinct thiolate entities in the presence of thiols and the thiolates recombine to produce different clusters. The conversion mechanism is found to be quite different from the previous reports where it occurs through the initial formation of ligand exchanged products. Here, we also show the synthesis of a different cluster core, [Ag44(2,4-DCBT)30]4- (IIa) using 2,4-DCBT, a structural isomer of 2,5-DCBT under the same synthetic conditions used for I. This observation demonstrates the effect of isomeric thiols on controlling the size of silver clusters. The conversion of one cluster to several other clusters under ambient conditions and the effect of ligand structure in silver cluster synthesis give new insights into the cluster chemistry.

Selenium uptake through cystine transporter mediated by glutathione conjugation.

Selenium (Se) is an essential trace element and is regarded as a protective agent against cancer. In particular, antioxidant effects of selenoenzymes contribute to cancer prevention. Se can also produce reactive oxygen species and, thereby, exert cancer-selective cytotoxicity. Selenodiglutathione (SDG) is a primary Se metabolite conjugated to two glutathione (GSH) moieties. SDG increases intracellular Se accumulation and is more toxic than selenous acid (H2SeO3), but the mechanisms for importing Se compounds into cells are not fully understood. Here, we propose a novel mechanism for importing Se, in the form of SDG. Cellular intake of Se compounds was assessed based on Se accumulation, as detected by ICP-MS. SDG incorporation was decreased in the presence of thiols (GSH, cysteine or their oxidized forms, GSSG and cystine), whereas H2SeO3 uptake was increased by addition of GSH or cysteine. Cellular SDG uptake was decreased by pretreatment with specific inhibitors against gamma-glutamyl transpeptidase (GGT) or the cystine/glutamate antiporter (system xc-). Furthermore, siRNA against xCT, which is the light chain component of system xc-, significantly decreased SDG incorporation. These data suggest an involvement of SDG in Se incorporation, with SDG processed at the cell surface by GGT, leading to formation of selenodicysteine which, in turn, is likely to be imported via xCT. Because GGT and xCT are highly expressed in cancer cells, these mechanisms mediated by the cystine transporter might underlie the cancer-selective toxicity of Se. In addition, the system described in our study appears to represent a physiological transport mechanism for the essential element Se.

Antibacterial activity of the nitrovinylfuran G1 (Furvina) and its conversion products.

2-Bromo-5-(2-bromo-2-nitrovinyl)furan (G1 or Furvina) is an antimicrobial with a direct reactivity against thiol groups. It is active against Gram-positive and Gram-negative bacteria, yeasts and filamentous fungi. By reacting with thiol groups it causes direct damage to proteins but, as a result, is very short-living and interconverts into an array of reaction products. Our aim was to characterize thiol reactivity of G1 and its conversion products and establish how much of antimicrobial and cytotoxic effects are due to the primary activity of G1 and how much can be attributed to its reaction products. Stability of G1 in growth media as well as its conversion in the presence of thiols was characterized. The structures of G1 decomposition products were determined using NMR and mass-spectroscopy. Concentration- and time-dependent killing curves showed that G1 is bacteriostatic for Escherichia coli at the concentration of 16 μg/ml and bactericidal at 32 μg/ml. However, G1 is inefficient against non-growing E. coli. Addition of cysteine to medium reduces the antimicrobial potency of G1. Nevertheless, the reaction products of G1 and cysteine enabled prolonged antimicrobial action of the drug. Therefore, the activity of 2-bromo-5-(2-bromo-2-nitrovinyl)furan is a sum of its immediate reactivity and the antibacterial effects of the conversion products.

Spectrophotometric Determination of Phenolic Antioxidants in the Presence of Thiols and Proteins.

Development of easy, practical, and low-cost spectrophotometric methods is required for the selective determination of phenolic antioxidants in the presence of other similar substances. As electron transfer (ET)-based total antioxidant capacity (TAC) assays generally measure the reducing ability of antioxidant compounds, thiols and phenols cannot be differentiated since they are both responsive to the probe reagent. In this study, three of the most common TAC determination methods, namely cupric ion reducing antioxidant capacity (CUPRAC), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt/trolox equivalent antioxidant capacity (ABTS/TEAC), and ferric reducing antioxidant power (FRAP), were tested for the assay of phenolics in the presence of selected thiol and protein compounds. Although the FRAP method is almost non-responsive to thiol compounds individually, surprising overoxidations with large positive deviations from additivity were observed when using this method for (phenols + thiols) mixtures. Among the tested TAC methods, CUPRAC gave the most additive results for all studied (phenol + thiol) and (phenol + protein) mixtures with minimal relative error. As ABTS/TEAC and FRAP methods gave small and large deviations, respectively, from additivity of absorbances arising from these components in mixtures, mercury(II) compounds were added to stabilize the thiol components in the form of Hg(II)-thiol complexes so as to enable selective spectrophotometric determination of phenolic components. This error compensation was most efficient for the FRAP method in testing (thiols + phenols) mixtures.

Tuning the Growth Mode of 3D Silver Nanocrystal Superlattices by Triphenylphosphine

Here, we show that the residual presence of reaction products markedly influences the growth mode of 3D superlattices made of silver nanocrystals. The silver nanocrystals (5 or 6 nm in diameter) are synthesized via the reduction of a silver triphenylphosphine complex in the presence of thiols. The presence of triphenylphosphine, coming from the decomposition of the silver precursor, is shown to change the superlattice growth mode in hexane from heterogeneous to homogeneous. In toluene, it remains homogeneous. This is in agreement with simulations based on a Flory-type model, which shows that the interaction potential between the silver nanocrystals in the presence of triphenylphosphine changes from repulsive to attractive in hexane and becomes even more attractive in toluene. Ex situ investigation of the different superlattices following solvent evaporation by scanning electron microscopy reveals different morphologies depending on the growth mode. A transition from films to individual hexagonal-shaped su...

Reaction Mechanisms of Metals with Hydrogen Sulfide and Thiols in Model Wine. Part 1: Copper-Catalyzed Oxidation.

Sulfidic off-odors as a result of hydrogen sulfide (H2S) and low-molecular-weight thiols are commonly encountered in wine production. These odors are usually removed by the process of Cu(II) fining, a process that remains poorly understood. The present study aims to elucidate the underlying mechanisms by which Cu(II) interacts with H2S and thiol compounds (RSH) under wine-like conditions. Copper complex formation was monitored along with H2S, thiol, oxygen, and acetaldehyde concentrations after the addition of Cu(II) (50 or 100 μM) to air-saturated model wine solutions containing H2S, cysteine, 6-sulfanylhexan-1-ol, or 3-sulfanylhexan-1-ol (300 μM each). The presence of H2S and thiols in excess to Cu(II) led to the rapid formation of ∼1.4:1 H2S/Cu and ∼2:1 thiol/Cu complexes, resulting in the oxidation of H2S and thiols and reduction of Cu(II) to Cu(I), which reacted with oxygen. H2S was observed to initially oxidize rather than form insoluble copper sulfide. The proposed reaction mechanisms provide insight into the extent to which H2S can be selectively removed in the presence of thiols in wine.

Formation of Ag(I) Thiolate‐layered Materials and Thiol‐capped Ag Nanoparticles by the Reduction of Silver Nitrate with Sodium Borohydride in the Presence of Thiol: Control of the Selectivity by the Ag+ to Thiol Mole Ratio

Formation of Ag(I) Thiolate‐layered Materials and Thiol‐capped Ag Nanoparticles by the Reduction of Silver Nitrate with Sodium Borohydride in the Presence of Thiol: Control of the Selectivity by the Ag⁺ to Thiol Mole Ratio

Life Sciences Discovery and Technology Highlights

Life Sciences Discovery and Technology Highlights

Garlic-Derived Organic Polysulfides and Myocardial Protection

For centuries, garlic has been shown to exert substantial medicinal effects and is considered to be one of the best disease-preventative foods. Diet is important in the maintenance of health and prevention of many diseases including cardiovascular disease (CVD). Preclinical and clinical evidence has shown that garlic reduces risks associated with CVD by lowering cholesterol, inhibiting platelet aggregation, and lowering blood pressure. In recent years, emerging evidence has shown that hydrogen sulfide (H2S) has cardioprotective and cytoprotective properties. The active metabolite in garlic, allicin, is readily degraded into organic diallyl polysulfides that are potent H2S donors in the presence of thiols. Preclinical studies have shown that enhancement of endogenous H2S has an impact on vascular reactivity. In CVD models, the administration of H2S prevents myocardial injury and dysfunction. It is hypothesized that these beneficial effects of garlic may be mediated by H2S-dependent mechanisms. This review evaluates the current knowledge concerning the cardioprotective effects of garlic-derived diallyl polysulfides.

An aldehyde group-based P-acid probe for selective fluorescence turn-on sensing of cysteine and homocysteine

A highly sensitive and selective turn on fluorescent probe P-acid-aldehyde (P-CHO) is developed for the determination of cysteine (Cys) and homocysteine (Hcy). The probe is designed and synthesized by incorporating the specific functional group aldehyde group for thiols into a stable π-conjugated material 4,4′-(2,5-dimethoxy-1,4-phenylene) bis(ethyne-2,1-diyl) dibenzoic acid (P-acid). The probe fluorescence is quenched through donor photoinduced electron transfer (d-PET) between the fluorophore (P-acid) and the recognition group (aldehyde group). In the presence of thiols, Cys and Hcy can selectively react with aldehyde group of the probe because the inhibition of d-PET between fluorophore and recognition group. Therefore, a turn-on fluorescent sensor was established for the fluorescence recovery.Under the optimized conditions, the fluorescence response of probe is directly proportional to the concentration of Cys in the range of 4–95nML−1, with a detection limit 3.0nM. In addition, the sensing system exhibits good selectively toward Cys and Hcy in the presence of other amino acids. It has been successfully applied for bioimaging of Cys and Hcy in living cells with low cell toxicity.

Simultaneous evaluation of one-electron reducing systems and radical reactions in cells by nitroxyl biradical as probe.

In the present study, a novel probe for the simultaneous evaluation of one-electron reducing systems (electron transport chain) and one-electron oxidizing systems (free radical reactions) in cells by electron chemical detection was developed. Six-membered cyclic nitroxyl radicals (2,2,6,6-tetramethylpiperidine-1-oxyl; TEMPO series) are sensitive to one-electron redox systems, generating the hydroxylamine form [TEMPO(H)] via one-electron reduction, and the secondary amine form [TEMPO(N)] via one-electron oxidation in the presence of thiols. In contrast, the sensitivities of five-membered cyclic nitroxyl radicals (2,2,5,5-tetramethylpyrrolidine-1-oxyl; PROXYL series) to the one-electron redox systems are comparatively low. The electron chemical detector can detect 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), TEMPO(H) and PROXYL but not TEMPO(N). Therefore, nitroxyl biradical, TEMPO-PROXYL, as a probe for the evaluation of one-electron redox systems was employed. TEMPO-PROXYL was synthesized by the conjunction of 4-amino-TEMPO with 3-carboxyl-PROXYL via the conventional dicyclohexyl carbodiimide reaction. TEMPO-PROXYL, TEMPO(H)-PROXYL and TEMPO(N)-PROXYL were simultaneously quantified by HPLC with Coularray detection. Calibration curves for the quantification of TEMPO-PROXYL, TEMPO(H)-PROXYL and TEMPO(N)-PROXYL were linear in the range from 80 nm to 80 μm, and the lowest quantification limit of each molecule was estimated to be <80 nm. The relative standard deviations at 0.8 and 80 μm were within 10% (n = 5). Copyright © 2015 John Wiley & Sons, Ltd.

The effect of aromatic amines and phenols in the thiyl-induced reactions of polyunsaturated fatty acids

Thiols are well known for their role in cellular redox homeostasis, while aromatic amines and phenols are the best known classes of chain-breaking antioxidants. On the other hand, thiyl radicals are known to catalyse the double bond isomerization in PUFA. We investigated the role and interplay of 2-mercaptoethanol and diphenylamine in the parallel processes of peroxidation and cis–trans isomerization of linoleic acid (LA) during gamma radiolysis, both in solution and micelles. Both compounds, used alone were able to protect LA from oxidation; however pro-oxidant activity and enhanced isomerization was observed when they were used together, depending on the experimental settings. Instead, α-tocopherol protected LA from both oxidation and isomerization in the presence of thiols under any tested settings. The mechanistic scenario is discussed highlighting the role of diphenylaminyl radicals in promoting thiyl-radical-induced cis–trans isomerization in the presence of oxygen.

Structure and activity study of gold(I) catalysts in the presence of thiols and amines

Structure and activity study of gold(I) catalysts in the presence of thiols and amines

A gold nanoparticle-based fluorescence sensor for high sensitive and selective detection of thiols in living cells.

A novel gold nanoparticle (AuNP)-based sensor for detecting thiols in aqueous solution has been developed. Due to the weak N···Au interactions, meso-(4-pyridinyl)-substituted BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) dyes were coordinated to AuNP surfaces, which effectively quenched the fluorescence of organic/inorganic hybrid systems. The fluorescent quenching mechanism was mainly ascribed to the highly efficient fluorescent resonance energy transfer (FRET) and the inner filter effect. In the presence of thiols, meso-(4-pyridinyl)-substituted BODIPY chromophore were displaced and released from the AuNP surfaces and thus restored the fluorescence of BODIPY chromophore. The modulation of the fluorescence quenching efficiency of BODIPY–AuNPs in the presence of thiols can achieve a large turn-on fluorescence enhancement (40-fold) in aqueous solution. The new AuNP-based fluorescence sensor displayed desired properties such as high specificity, relatively low detection limit (30 nM for Cys), appreciable water solubility and rapid response time (within 2 min for Cys/Hcy). Moreover, the sensor has been successfully applied for monitoring and imaging of intracellular thiols within living HeLa cells.

Reductant-responsive poly(N-isopropylacrylamide) microgels and microgel-based optical materials

Poly(N-isopropylacrylamide) based hydrogel particles (microgels) crosslinked with N,N′-bis(acryloyl)cystamine were prepared using free-radical precipitation polymerization. By coating a single layer of microgels on a gold-coated glass substrate followed by the addition of another gold layer, an optical device (etalon) was fabricated. The devices were shown to exhibit optical properties that are typical of microgel-based etalons, i.e., they exhibit visual color and unique multipeak reflectance spectra. Unique to the devices here are their ability to change their optical properties in the presence of thiols. Specifically, in the presence of dithiothreitol, the microgel crosslinks were reduced, leading to microgel swelling, which ultimately changes the optical properties of the etalon. We observed a linear relationship between the shift in the position of the reflectance peaks and the concentration of dithiothreitol, which suggests that they can be used to quantify thiols in solution.

Bioactivation of clopidogrel and prasugrel: factors determining the stereochemistry of the thiol metabolite double bond.

The antithrombotics of the tetrahydrothienopyridine series, clopidogrel and prasugrel, are prodrugs that must be metabolized in two steps to become pharmacologically active. The first step is the formation of a thiolactone metabolite. The second step is a further oxidation with the formation of a thiolactone sulfoxide whose hydrolytic opening leads to a sulfenic acid that is eventually reduced into the corresponding active cis thiol. Very few data were available on the formation of the isomer of the active cis thiol having a trans configuration of the double bond, the most striking result in that regard being that both cis and trans thiols were formed upon the metabolism of clopidogrel by human liver microsomes in the presence of glutathione (GSH), whereas only the cis thiol was detected in the sera of patients treated with this drug. This article shows that trans thiols are also formed upon the microsomal metabolism of prasugrel or its thiolactone metabolite in the presence of GSH and that metabolites having the trans configuration of the double bond are only formed when microsomal incubations are done in the presence of thiols, such as GSH, N-acetyl-cysteine, and mercaptoethanol. Intermediate formation of thioesters resulting from the reaction of GSH with the thiolactone sulfoxide metabolite appears to be responsible for trans thiol formation. Addition of human liver cytosol to the microsomal incubations led to a dramatic decrease of the formation of the trans thiol metabolites. These data suggest that cytosolic esterases would accelerate the hydrolytic opening of thiolactone sulfoxide intermediates and disfavor the formation of thioesters resulting from the reaction of these intermediates with GSH that is responsible for trans isomer formation. This would explain why trans thiols have not been detected in the sera of patients treated with clopidogrel.

Trapping hydrogen sulfide (H₂S) with diselenides: the application in the design of fluorescent probes.

Here we report a unique reaction between phenyl diselenide-ester substrates and H2S to form 1,2-benzothiaselenol-3-one. This reaction proceeded rapidly under mild conditions. Thiols could also react with the diselenide substrates. However, the resulted S–Se intermediate retained high reactivity toward H2S and eventually led to the same cyclized product 1,2-benzothiaselenol-3-one. Based on this reaction two fluorescent probes were developed and showed high selectivity and sensitivity for H2S. The presence of thiols was found not to interfere with the detection process.