Aliphatic Thiols Research Articles

A dicyanoisophorone-based near-infrared fluorescent probe and its application for detecting thiophenols in water and living cells

We report herein a new dicyanoisophorone-based colorimetric and near-infrared (NIR) fluorescent probe for rapid detection of thiophenols. This probe possesses a remarkable large Stokes shift (208 nm) and works in almost pure aqueous solution under mild conditions. More importantly, it displays a rapid, highly selective and sensitive dual colorimetric and NIR fluorescent turn-on signal responses for thiophenols and allows the detection of thiophenols in the presence of analytes including amino acids, biothiols and aliphatic thiols. Moreover, the fluorescence of this probe at 655 nm displays a good linear relationship with the thiophenol concentration ranging from 0 to 20 μM, and the detection limit is as low as 12 nM. Furthermore, the practicability of this new probe has been successfully proved by detection of thiophenol in real water samples and bioimaging of thiophenol in living cells.

Highly efficient synthesis of alkyl and aryl primary thiocarbamates and dithiocarbamates under metal- and solvent-free conditions.

A highly efficient, metal-free and solvent-free process is reported for the preparation of novel series of alkyl and aryl primary thiocarbamates and dithiocarbamates through the reaction of aliphatic alcohols, phenols and thiols with thiocyanate salts in the presence of 4-dodecylbenzenesulfonic acid (DBSA) as an inexpensive, readily available and amphipathic acid reagent. All reactions proceeded smoothly, and the products are obtained in good to excellent yields. Using this method, a wide range of structurally diverse primary thiocarbamates was prepared successfully.

Electronic Structure of a Self-Assembled Monolayer with Two Surface Anchors: 6-Mercaptopurine on Au(111).

The electronic structure of aromatic and aliphatic thiols on Au(111) has been extensively studied in relation to possible applications in molecular electronics. In this work, the effect on the electronic structure of an additional anchor to the S-Au bond using 6-mercaptopurine as a model system has been investigated. Results from X-ray photoelectron spectroscopy, near-edge X-ray absorption fine structure spectroscopy, and density functional theory (DFT) confirm that this molecule adsorbs on Au(111) with S-Au and iminic N-Au bonds. Combined ultraviolet photoelectron spectroscopy and DFT data reveal that formation of the 6MP self-assembled monolayer generates a molecular dipole perpendicular to the surface, with negative charges residing at the metal/monolayer interface and positive charges at the monolayer/vacuum interface, which lowers the substrate work function. Scanning tunneling microscopy shows two surface molecular domains: a well-ordered rectangular lattice where molecules are tilted on average 30° with respect to the substrate and aligned 6MP islands where molecules are standing upright. Finally, we found a new electronic state located at -1.7 eV with respect to the Fermi level that corresponds to a localized π molecular state, while the state corresponding to the N-Au bond is hybridized with Au d electrons and stabilized at much lower energies (-3 eV).

Ultrasensitive dicyanoisophorone-based near-infrared fluorescent probe for rapid and specific detection of thiophenols in river water

Thiophenols are a class of highly toxic pollutant compounds, which can cause severe damage to the central nervous system and other nervous systems after long-term exposure. Therefore, it is of significance to develop an effective method to detect trace thiophenols in the environment. Herein, we synthesized a dicyanoisophorone-based near-infrared fluorescent probe (probe 1) with large stokes shift (λem − λabs = 203 nm) for the selective detection of thiophenols. Probe 1 exhibited very high response speed (less than 200 S), sensitivity, and selectivity towards thiophenols, regardless of the presence of aliphatic thiols and other analytes. The detection limit was as low as 3.4 nM and the signal-to-background ratio of fluorescence intensity reached 30. Moreover, probe 1 displayed ultrasensitivity and high reliability in the quantitative detection of trace thiophenol in three river water samples.

A colorimetric and turn-on NIR fluorescent probe based on xanthene system for sensitive detection of thiophenol and its application in bioimaging

Developing fluorescent probes for specific detection of extremely toxic thiophenols is pretty significant in the field of environment, chemistry and biology. We report herein a turn-on red fluorescent xanthene-based probe (RD-Probe) for detecting thiophenol with high selectivity over other analytes including aliphatic thiols. The probe could play the part of a “naked-eye”colorimetric indicator toward thiophenol. Moreover, the relative fluorescence intensity at 653 nm displayed good linearity with the concentration of thiophenol ranging from 0 to 6 μM, and the limit of detection for thiophenol could be as low as 15 nM. Furthermore, the practicability of RD-Probe has been successfully proved through the quantitative thiophenol detection in real water samples and fluorescence bioimaging of thiophenol in HeLa cells.

S-Acetylation of Thiols Mediated by Triflic Acid: A Novel Route to Thioesters

This paper demonstrates an efficient, mild, and chemoselective synthesis of various thioesters via a HOTf-catalyzed S-acetylation of aromatic and aliphatic thiols using isopropenyl acetate as a cheap and convenient acetylating agent. During our tests, we also investigated the differences between the activities of metal triflates and triflic acid as catalysts in the acetylation of thiols. Finally, the potential of our concept has been increased by the implementation of Nafion as a heterogeneous catalyst for S-acetylation of thiols.

Scientific Opinion on Flavouring Group Evaluation 74, Revision 4 (FGE.74Rev4): Consideration of aliphatic sulphides and thiols evaluated by JECFA (53rd and 61st meeting) structurally related to aliphatic and alicyclic mono-, di-, tri-and polysulphides with or without additional oxygenated functional groups from chemical group 20 evaluated by EFSA in FGE.08Rev5.

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to consider evaluations of flavouring substances assessed since 2000 by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), and to decide whether further evaluation is necessary, as laid down in Commission Regulation (EC) No 1565/2000. The present revision of this FGE is on the assessment of recently submitted toxicity data on methyl propyl trisulfide [FL‐no: 12.020], being the representative for a group of seven additional flavouring substances: diallyl trisulfide [FL‐no: 12.009], dimethyl trisulfide [FL‐no: 12.013], dipropyl trisulfide [FL‐no: 12.023], methyl allyl trisulfide [FL‐no: 12.045], diallyl polysulfides [FL‐no: 12.074], methyl ethyl trisulfide [FL‐no: 12.155] and diisopropyl trisulphide [FL‐no: 12.280]. Specifications have been provided for all substances. The Panel decided that the 90‐day study submitted for [FL‐no: 12.020] can be considered only once it is clearly demonstrated that the material tested is representative of the material of commerce and that potential reaction products of the components are not of safety concern. Therefore, no conclusion on the safety of the eight flavouring substances [FL‐no: 12.009, 12.013, 12.020, 12.023, 12.045, 12.074, 12.155 and 12.280] can be reached. For 2‐methyl‐4‐oxopentane‐2‐thiol [FL‐no: 12.169] and 2‐mercapto‐2‐methylpentan‐1‐ol [FL‐no: 12.241], additional subchronic toxicity data are required. The remaining nine substances [FL‐no: 12.088, 12.179, 12.198, 12.212, 12.238, 12.239, 12.255, 12.257 and 12.291] in this FGE are not considered of safety concern under the intended conditions of use.

A near-infrared fluorescent sensor with large Stokes shift for rapid and highly selective detection of thiophenols in water samples and living cells.

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 658nm could be visualized with the aid of nucleophilic aromatic substitution (SNAr) reaction. The sensor displays large Stokes shift (~ 227nm), fast response time (< 30s), high sensitivity (~ 8.3nM), 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.

Reactions of pentachloro-2-nitrobutadiene with some aliphatic and heterocyclic thiols and a crystallographic study

GRAPHICAL ABSTRACT

Reaction-based fluorescent probe for the selective and sensitive detection of thiophenols with a large Stokes shift and its application in water samples.

Although widely used in organic synthesis, pharmaceuticals and agrochemicals, thiophenol has brought about a series of ecological problems due to its high toxicity. Therefore, the development of efficient methods to discriminate thiophenols from aliphatic thiols is of great importance. In this work, a new reaction-based turn-on red fluorescence probe for the detection of thiophenols has been developed for the first time by employing dicyanomethylene-4H-pyran (DCM) as a fluorescence reporter and 2,4-dinitrobenzene-sulfonate (DNBS) as a recognition unit. The probe displayed a highly selective and sensitive (63 fold-fluorescence enhancement) response to thiophenols over aliphatic thiols. Additionally, the probe also exhibited a large Stokes shift (159 nm) and the detection limit reached as low as 8.3 nM. Moreover, this probe was also proved suitable for the quantification of thiophenol in real environmental water samples.

Probing the effect of different graphitic nitrogen sites on the aerobic oxidation of thiols to disulfides: a DFT study.

Functionalized graphene materials are well known for their application in catalyzing the aerobic oxidation of alcohols, hydrocarbons, etc. in an aqueous medium. Despite the fact that a few catalysts are known to oxidize thiols to disulfides, their selectivity is poor and requires oxidants that are not suitable in terms of the principles of green chemistry. Therefore, in this context, an attempt has been made to investigate the possibility of utilizing nitrogen doped graphene for the aerobic oxidation of thiols to disulfides using density functional theory (DFT). Our previous study (V. S. Jeyaraj, M. Kamaraj and V. Subramanian, J. Phys. Chem. C, 2015, 119, 26438-26450) has shed light on the activation of dioxygen to form activated oxygen species (AOS) at different graphitic nitrogen sites. Hence the same has been used to study the two-electron oxidation of thiophenol and methanethiol. The AOS are of three kinds: (1) peroxide type at the edges, (2) superoxide type at the center and (3) ketonic type at edges. The findings from this study indicate that the peroxide type AOS leads to selective formation of diphenyl disulfide, whereas the superoxide type at the center facilitates the formation of hydrogen peroxide which could lead to over-oxidation of disulfide. The oxidation of aromatic thiols (thiophenol) by the ketonic type of AOS is nearly a barrier-less reaction (0.67 kcal mol-1). Similarly, AOS at the edges with the peroxide form can oxidize aliphatic thiols (methanethiol) with a less barrier of 1.55 kcal mol-1, which can be a spontaneous reaction. The mechanism of oxidation is completely different from the oxidative pathway of alcohols by the same AOS. The formation of S-OH species is strictly avoided by the strong stabilization of thiyl radicals over the π-surface of graphene.

Computational Kinetic Modeling of the Catalytic Cycle of Glutathione Peroxidase Nanomimic: Effect of Nucleophilicity of Thiols on the Catalytic Activity.

The catalytic cycle of a new derivative of ebselen, 1, was elucidated via three steps by the density functional theory and solvent-assisted proton exchange procedure involving indirect proton exchange through a hydrogen-bonded transfer network. Different behaviors of the aromatic and aliphatic thiols were investigated in the reduction of selenoxide (step 2 → 3) and selenurane (step 3 → 1) based on their nucleophilicity. The reduction of selenoxide in the presence of thiophenol (ΔG‡ = 15.9 kcal·mol-1) is faster than that of methanethiol (ΔG‡ = 29.3 kcal·mol-1), and methanethiol makes the reduction of selenoxide unspontaneous and kinetically unfavorable (ΔG = 2.8 kcal·mol-1). The nucleophilic attack may be enhanced by using the thiophenol backbone at the selenium center to lower the energy barrier of the selenoxide reduction (ΔG‡ = 15.9 kcal·mol-1). On the basis of the turnover frequency calculations, during the catalytic cycle, the rate of the reaction was analyzed and discussed. Low values of the electron density and Laplacian at the transition states are the evidence of the covalent O-H and O-O bonds rupture in the presence of methanethiol and thiophenol. The nature of the critical bond points was characterized, using the quantum theory of atoms in molecules, based on the electron location function and localized orbital locator values. Finally, the charge transfer process at the rate-determining step was investigated based on the natural bond orbital analysis.

Dual quenching strategy for sensitive detection of toxic thiolphenols based on a NIR-illuminant platform with a large Stokes shift

In view of thiophenol contaminants and their adverse effects in environment, it is valuable to develop an effective probe for thiophenols. Based on a large Stokes shift (126 nm) NIR-illuminant platform (Compound 2), we developed a colorimetric and “off-on” near-infrared (NIR) fluorescent probe (NIRP) to selectively discriminate thiophenols from various analytes including aliphatic thiols. NIRP is dually quenched (ICT blocked quenching and PET quenching), thus achieving large signal-to-noise ratio and high sensitivity for thiophenol detection. For the first time, the unique NIR-illuminant phenomenon of 2′ and the d-PET quenching process on NIRP are revealed by the density functional theory (DFT) calculations. Moreover, we demonstrate the practical applications of NIRP, including the quantitative thiophenol detection in environmental water samples and NIR fluorescent imaging of thiophenol in HeLa cells.

Asymmetric FeII-Catalyzed Thia-Michael Addition Reaction to α,β-Unsaturated Oxazolidin-2-one Derivatives.

A highly enantioselective FeII-catalyzed thia-Michael addition to α,β-unsaturated carbonyl derivatives was developed. The scope of the reaction was demonstrated with a selection of aromatic, heterocyclic and aliphatic thiols, and various Michael acceptors. The corresponding β-thioethers were obtained in good to excellent yields (up to 98%) and moderate to excellent enantioselectivities (up to 96:4 er). Unusual hepta-coordination of the metal and chelation to α,β-unsaturated oxazolidin-2-one derivatives allowed the construction of a coherent model rationalizing the enantioselective event. DFT calculations support the proposed model for observed stereoselectivities.

Solvent Polarity-Dependent Behavior of Aliphatic Thiols and Amines toward Intriguingly Fluorescent AuAgGSH Assembly

Highly stable fluorescent glutathione (GSH)-protected AuAg assembly has been synthesized in water under UV irradiation. The assembly is composed of small Ag2/Ag3 clusters. These clusters gain stability through synergistic interaction with Au(I) present within the assembly. This makes the overall assembly fluorescent. Here, GSH acts as a reducing as well as stabilizing agent. The assembly is so robust that it can be vacuum-dried to solid particles. The as-obtained solid is dispersible in nonaqueous solvents. The interaction between solvent and the assembly provides stability to the assembly, and the assembly shows fluorescence. It is interesting to see that the behavior of long-chain aliphatic thiols or amines toward the fluorescent assembly is altogether a different phenomenon in aqueous and nonaqueous mediums. The assembly gets ruptured in water due to direct interaction with long-chain thiols or amines, whereas in nonaqueous medium, solvation of added thiols or amines becomes pronounced, which hinders the interaction of solvent with the assembly. However, the fluorescence of the assembly is always quenched with thiols or amines no matter what the solvent medium is. In aqueous medium, the fluorescence quenching by aliphatic thiol or amine becomes pronounced with successive decrease in their chain length, whereas in nonaqueous medium, the trend is just reversed with chain length. The reasons behind such an interesting reversal of fluorescence quenching in aqueous and nonaqueous solvents have been discussed explicitly. Again, in organic solvents, thiol or amine-induced quenched fluorescence is selectively recovered by Pb(II) ion without any alteration of excitation and emission maxima. This phenomenon is not observed in water because of the ruptured fluorescent assembly. The fluorescence recovery by Pb(II) and unaltered emission peak only in nonaqueous solvent unequivocally prove the engagement of Pb(II) with thiols or amines, which in turn revert the original solvent-supported stabilization of the assembly.

Comparative Study of the Adsorption of Thiols and Selenols on Au(111) and Au(100).

The effect of the Au crystalline plane on the adsorption of different thiols and selenols is studied via reductive desorption (RD) and X-ray photoelectron spectroscopy (XPS) measurements. Self-assembled monolayers (SAMs) using aliphatic (ATs) and aromatic thiols (ArTs) on both Au(111) and Au(100) were prepared. The electrochemical stability of these SAMs on both surfaces is evaluated by comparing the position of the RD peaks. The longer the AT chain the more stable the SAM on Au(100) when compared to Au(111). By means of XPS measurements, we determine that the binding energy (BE) of the S 2p signal corresponding to the S atoms at the thiol/Au interface, commonly assigned at 162.0 eV, shifts 0.2 eV from Au(111) to Au(100) for SAMs prepared using thiols with the C* (C atom bonded to S) in sp3 hybridization, such as ATs. However, when the thiol presents the C* with an sp2 hybridization, such as in the case of ArTs, the BE remains at 162.0 eV regardless of the surface plane. Selenol-based SAMs were characterized comparatively on both Au(100) and Au(111). Our results show that selenol SAMs become even more electrochemically stable on Au(100) with respect to Au(111) than the analogue sulfur-based SAM. According to our results, we suggest that the electronic distribution around the Au-S/Se bond could be responsible for the different structural arrangements reported in the literature (gold adatoms, etc.), which should be dependent on the crystalline face (Au(hkl)-S) and the chemical nature of the environment of the adsorbates (sp3-C* vs sp2-C* and Au-SR vs Au-SeR).

Triethylsiloxymethyl‐N,N‐dimethylamine, Et3SiOCH2NMe2: A Dimethylaminomethylation (Mannich) Reagent for O–H, S–H, P–H and Aromatic C–H Systems

Triethylsiloxymethylamine, Et3SiOCH2NMe2, readily synthesized in high yield by the hydrosilylation reaction between Et3SiH and DMF, is an excellent (N,N‐dimethylamino)methyl transfer agent to a representative range of aliphatic alcohols, thiols, and Ph2PH (E–H) materials. The reactions are almost instantaneous at room temperature in inert solvents and require no activating agents to produce E–CH2NMe2 products in high yields and illustrate the title compound as an excellent addition to the family of organic reagents. For aromatic alcohols, electrophilic substitution of the aromatic ring occurs in high yield. Crystal structures of new materials such as the cholestero–CH2NMe2 derivative, 2–4‐[bis(N,N‐dimethylamino)methyl]‐1‐naphthol, and the phosphine oxide derived from Ph2PCH2NMe2 are reported.

Highly Efficient and Chemoselective Tertiary and Secondary Benzylation of Thiols Catalyzed by Indium(III) Triflate

Several examples of nucleophilic substitution reactions of compounds that have good leaving groups have been previously reported, but the direct use of simple alcohols still remains a challenge because of the poor leaving ability of the hydroxy group. Herein, an efficient and highly chemoselective method for the S‐benzylation of a wide range of aromatic and aliphatic thiols has been accomplished in the presence of catalytic amounts (0.1–0.2 mol‐%) of indium(III) triflate. Our approach is atom efficient (water is the only byproduct) and suitable to obtain the corresponding unsymmetrical thioethers in excellent yields (up to 99 %). The low loading of catalyst that are needed to obtain extraordinarily high chemoselectivities and the generality of the reaction make this approach unique.

HNO Is Produced by the Reaction of NO with Thiols

Azanone (nitroxyl, HNO) is a highly reactive compound whose biological role is still a matter of debate. One possible route for its formation is NO reduction by biological reductants. These reactions have been historically discarded due to the negative redox potential for the NO,H+/HNO couple. However, the NO to HNO conversion mediated by vitamins C, E, and aromatic alcohols has been recently shown to be feasible from a chemical standpoint. Based on these precedents, we decided to study the reaction of NO with thiols as potential sources of HNO. Using two complementary approaches, trapping by a Mn porphyrin and an HNO electrochemical sensor, we found that under anaerobic conditions aliphatic and aromatic thiols (as well as selenols) are able to convert NO to HNO, albeit at different rates. Further mechanistic analysis using ab initio methods shows that the reaction between NO and the thiol produces a free radical adduct RSNOH•, which reacts with a second NO molecule to produce HNO and a nitrosothiol. The nitrosothiol intermediate reacts further with RSH to produce a second molecule of HNO and RSSR, as previously reported.

Dialkyl Dicyanofumarates as Oxidizing Reagents for the Conversion of Thiols into Disulfides and Selenols into Diselenides

Aliphatic and aromatic thiols react smoothly with dialkyl dicyanofumarates in CH2Cl2 at room temperature to give the corresponding disulfides in excellent yields. Aliphatic 1,2‐, 1,3‐, and 1,4‐dithiols afford cyclic disulfides. Analogous reaction courses were observed for selenols, and the required diselenides also formed in nearly quantitative yields. In all of the reactions, dialkyl dicyanosuccinates formed as 1:1 mixtures of diastereoisomers as the only other product. Cysteamine (2‐mercaptoethylamine) behaved differently; the Michael addition of the primary amine group led to the complete consumption of the dicyanofumarate, and the formation of the disulfide containing an enamine moiety occurred without the formation of dicyanosuccinate.