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Concept: Thiols


Autism spectrum disorder (ASD) is a neurological disorder in which a significant number of the children experience a developmental regression characterized by a loss of previously acquired skills and abilities. Typically reported are losses of verbal, nonverbal, and social abilities. Several recent studies suggest that children diagnosed with an ASD have abnormal sulfation chemistry, limited thiol availability, and decreased glutathione (GSH) reserve capacity, resulting in a compromised oxidation/reduction (redox) and detoxification capacity. Research indicates that the availability of thiols, particularly GSH, can influence the effects of thimerosal ™ and other mercury (Hg) compounds. TM is an organomercurial compound (49.55% Hg by weight) that has been, and continues to be, used as a preservative in many childhood vaccines, particularly in developing countries. Thiol-modulating mechanisms affecting the cytotoxicity of TM have been identified. Importantly, the emergence of ASD symptoms post-6 months of age temporally follows the administration of many childhood vaccines. The purpose of the present critical review is provide mechanistic insight regarding how limited thiol availability, abnormal sulfation chemistry, and decreased GSH reserve capacity in children with an ASD could make them more susceptible to the toxic effects of TM routinely administered as part of mandated childhood immunization schedules.

Concepts: Autism, Disulfide bond, Glutathione, Asperger syndrome, Autism spectrum, Cysteine, Thiol, Thiols


A method based on the differential reactivity of thiol and thiolate with monobromobimane (mBBr) has been developed to measure nucleophilicity and acidity of protein and low-molecular weight thiols. Nucleophilicity of the thiolate is measured as the pH-independent second-order rate constant of its reaction with mBBr. The ionization constants of the thiols are obtained through the pH dependence of either second-order rate constant or initial rate of reaction. For readily available thiols, the apparent second-order rate constant is measured at different pHs and then plotted and fitted to an appropriate pH-function describing the observed number of ionization equilibria. For less available thiols, such as protein thiols, the initial rate of reaction is determined in a wide range of pHs and fitted to the appropriate pH-function. The method presented herein shows excellent sensitivity allowing the use of nanomolar concentrations of reagents. The method is suitable for scaling and high-throughput screening. Example determinations of nucleophilicity and pK(a) are presented for captopril and cysteine as low-molecular weight thiols and human peroxiredoxin 5 and Trypanosoma brucei monothiol glutaredoxin 1 as protein thiols.

Concepts: Disulfide bond, Glutathione, Trypanosoma brucei, Cysteine, Rate equation, Reaction rate, Thiol, Thiols


Platinum (Pt) based micromotors have shown many exciting applications when functionalized using gold-thiol chemistry. However, thiols are known to bind to the Pt surface, which can lead to serious deactivation of the catalyst. In this paper, we demonstrate that manganese oxide (MnO2) can be used to protect Pt based micromotors prior to the thiol treatment, thus fully avoiding the catalyst poisoning. This approach will greatly facilitate the use of the functionalized Pt micromotors for which the thiol toxicity has been a limiting factor.

Concepts: Catalysis, Catalytic converter, Protection, Chlorine, Thiol, Manganese, Thiols, Manganese dioxide


Two ‘turn on’ TCF-based fluorescence probes were developed for the detection of biological thiols (TCF-GSH and TCFCl-GSH). TCF-GSH was shown to have a high sensitivity towards glutathione (GSH) with a 0.28 μM limit of detection. Unfortunately, at higher GSH concentrations the fluorescence intensity of TCF-GSH decreased and toxicity was observed for TCF-GSH in live cells. However, TCFCl-GSH was shown to be able to detect GSH at biologically relevant concentrations with a 0.45 μM limit of detection. No toxicity was found for TCFCl-GSH and a clear ‘turn on’ with good photostability was observed for the exogenous addition of GSH, Cys and HCys. Furthermore, TCFCl-GSH was used to evaluate the effects of drug treatment on the levels of GSH in live cells.

Concepts: DNA, Molecular biology, Cell biology, Disulfide bond, Glutathione, Cysteine, Thiol, Thiols


Biological thiols play a key role in biological processes and are involved in a variety of diseases. The discriminative detection of biological thiols is still challenging. In this contribution, a platform, an energy transfer-based quenching system composed of nitrogen and sulphur co-doped carbon dots (N, S-CDs) and gold nanoparticles (AuNPs), was established to discriminate glutathione (GSH) from other competitive biothiols including cysteine (Cys) and homocysteine (Hcy) based on a photoluminescence (PL) “switch-on” signal readout. The presence of GSH can encapsulate AuNPs in priority because of the strong affinity towards AuNPs and the steric hindrance effect of GSH, leaving little chance for the N, S-CDs binding on the surface of AuNPs and thus resulting in the PL recovery of N, S-CDs. Compared with the nitrogen-doped carbon dots (N-CDs), the N, S-CDs can enhance 10 times sensitivity for the designed PL “switch-on” sensing strategy. The proposed method has a detection limit of 3.6 nM and can be successfully applied for the detection of GSH in human serum.

Concepts: Amino acid, Antioxidant, Disulfide bond, Glutathione, Cysteine, Thiol, Methionine, Thiols


Detoxification reaction of chloropicrin in the human body with biological thiols was selected for detection of chloropicrin in the air. The consumption of free sulfhydryl group in biological thiols by chloropicrin is colorimetrically detectable with the addition of the Ellman’s reagent. In this study, glutathione, N-acetyl- l-cysteine, l-homocysteine, cysteamine, and thioglycolic acid were tested as sensing agents for chloropicrin vapor detection in ppb concentration range. The reactivity of the selected biological thiols was investigated based on both their redox properties and the nucleophilic strength of the sulfhydryl groups. Nylon-6 nanofibrous membrane and an organic solvent were used as a sensor matrix and a vapor sorbent, respectively, to provide solid supports with ultrahigh surface area and enhanced adsorption to chloropicrin vapor. The tunable sensitivity and detection range by using different biological thiols were achieved on the sensors due to the different reactivity of thiols towards chloropicrin.

Concepts: Disulfide bond, Human body, Glutathione, Cysteine, Coenzyme A, Thiol, Thiols, Methanethiol


Papain has a relatively small active site consisting of three residues: Cys-25, His-159, and Asn-175. The sulfhydryl group on Cys-25 often forms covalent bonds with substrates. His-159 supports Cys-25, and while Asn-175 does not directly participate in the catalytic mechanism, it keeps histidine-159 in its stabilized imidazole form. It is noticeable that sulfur atom of the catalytic Cys-25 is activated by cysteine through a SN2-type reaction, but the mechanisms by which cysteine enhances papain activity remains unclear. In this study, we found that cysteine increases papain activity by a factor of about 4, increasing Vmaxand decreasing Kmparameters. Moreover, the reaction is a SN2-type that does not require initial binding of thiol group of cysteine to the enzyme.

Concepts: Enzyme, Disulfide bond, Sulfur, Cysteine, Thiol, Cysteine protease, Thiols, Methanethiol


The development of simple methods with high sensitivity and selectivity to differentiate toxic aromatic thiols (thiophenols) from aliphatic thiols (cysteine, homocysteine, and glutathione) and hydrogen sulfide (H2S) is of great significance. Herein, we report on the fabrication of a novel near-infrared (NIR) fluorescent sensor for rapid and highly selective detection of thiophenols through the photoinduced electron transfer (PET) mechanism. In the presence of the thiophenols, an obvious enhancement of NIR fluorescence at 658 nm could be visualized with the aid of nucleophilic aromatic substitution (SNAr) reaction. The sensor displays large Stokes shift (~ 227 nm), fast response time (< 30 s), high sensitivity (~ 8.3 nM), and good biocompatibility. Moreover, the as-prepared sensor possesses an excellent anti-interference feature even when other possible interferents exist (aliphatic thiols and H2S) and has been successfully utilized for thiophenol detection in both water samples and living cells. Graphical abstract Illustration of the sensor for thiophenol imaging in living cells.

Concepts: Fluorescence, Nucleophilic substitution, Substitution reaction, Nucleophilic aromatic substitution, Cysteine, Stokes shift, Nucleophilic acyl substitution, Thiols


Small molecule biothiols, including cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), play many crucial roles in physiological processes. In this work, we have prepared a nitroolefin-based BODIPY fluorescent probe with excellent water solubility for detection thiols, which displayed ratiometric fluorescent signal for thiols. Incorporation of a nitroolefin unit to the BODIPY dye would transform it into a strong Michael acceptor, which would be highly susceptible to sulfhydryl nucleophiles. This probe shows an obvious ratio change upon response with thiols, an increase of the emission at 517 nm along with a concomitant decrease of fluorescence peak at 573 nm. Moreover, these successes of intracellular imaging experiments in A549 cells indicated that this probe is suitable for imaging of ex-/endogenous thiols in living cells.

Concepts: Amino acid, Antioxidant, Solubility, Disulfide bond, Glutathione, Cysteine, Thiol, Thiols


In the presence of CoA, cell-free extracts prepared from porcine liver was found to convert 7,8-dihydroxyflavone (DHF) to a pantetheine conjugate, which was a novel flavonoid. We purified a 7,8-DHF-converting enzyme from the extracts, and identified it as hemoglobin (Hb). The purified Hb showed the following two activities: (i) degradation of CoA into pantetheine through hydrolytic cleavage to yield pantetheine and 3'-phospho-adenosine-5'-diphosphate (ADP) independently of heme, and (ii) addition of a thiol (e.g., pantetheine, glutathione and cysteine) to 7,8-DHF through C-S bond formation. Human Hb also exhibited the above flavonoid-converting activity. In addition, heme-containing enzymes such as peroxidase and catalase added each of pantetheine, glutathione and cysteine to the flavonoid, although no pantetheine conjugates were synthesized when CoA was used as a substrate. These findings indicated that the thiol-conjugating activity is widely observed in heme-containing proteins. On the other hand, only Hb catalyzed the hydrolysis of CoA, followed by the thiol conjugation to synthesize the pantetheine conjugate. To the best of our knowledge, this is the first report showing that Hb has the catalytic ability to convert naturally occurring bioactive compounds, such as dietary flavonoids, to the corresponding conjugates in the presence of thiol donors or CoA.

Concepts: Protein, Metabolism, Enzyme, Catalysis, Ribozyme, Hydrolysis, Thiol, Thiols