Search

International audience; Synthesis, bonding and chemistry of mono- and bimetallic complexes supported by chelating thiolato ligands have been established. Treatment of [Cp*VCl2](3) (1) with [LiBH4 center dot THF] followed by the addition of ethane-1,2-dithiol led to the formation of an EPR active bimetallic vanadium thiolato complex [(Cp*V){mu-(SCH2CH2S)-kappa S-2,S')(2){V(SCH2CH2S-SH)}] (2). In complex 2, two ethane-1,2-dithiolato ligands are symmetrically coordinated to two vanadium atoms through mu-S atoms. Interestingly, when similar reactions were carried out with heavier group 5 metal precursors, such as [Cp*NbCl4] (3 a), it afforded monometallic thiolato complex [Cp*Nb(SCH2CH2S)(SCH2CH2S-CH2S)] (4 a). On the other hand, the Ta-analogue [Cp*TaCl4] (3 b) yielded thiolato species [Cp*Ta(SCH2CH2S)(SCH2CH2S-CH2S)] (4 b) and [Cp*Ta(SCH2CH2S) (SCH2CH2S-S)] (5). In complexes 4 a and 4 b, one ethane-1,2-dithiolato and one trithiolato ligand are coordinated to Nb and Ta centers, respectively. Whereas, in complex 5, one ethane-1,2-dithiolato and one 2-disulfanylethanethiolato is coordinated to the Ta center. Moreover, the photolytic reaction of 5 with [Mo(CO)(5) center dot THF] yielded heterobimetallic thiolato complex [(Cp*Ta){mu-(SCH2CH2S)-kappa S-2,S '}{mu-(SCH2CH2S-CH2(CH3)S)kappa S-2 '' : kappa S-1-'''' : kappa S-1 '''''}{Mo(CO)(3)}] (6). All the complexes have been characterized by multinuclear NMR spectroscopy and single crystal X-ray diffraction studies. Further, computational analyses were performed to provide an insight into the bonding of these complexes.

Interfacial modular assembly has emerged as an adaptable strategy for engineering the surface properties of substrates in biomedicine, photonics, and catalysis. Herein, we report a versatile and robust coating (pBDT-TA), self-assembled from tannic acid (TA) and a self-polymerizing aromatic dithiol (i.e., benzene-1,4-dithiol, BDT), that can be engineered on diverse substrates with a precisely tuned thickness (5-40 nm) by varying the concentration of BDT used. The pBDT-TA coating is stabilized by covalent (disulfide) bonds and supramolecular (π-π) interactions, endowing the coating with high stability in various harsh aqueous environments across ionic strength, pH, temperature (e.g., 100 mM NaCl, HCl (pH 1) or NaOH (pH 13), and water at 100 °C), as well as surfactant solution (e.g., 100 mM Triton X-100) and biological buffer (e.g., Dulbecco's phosphate-buffered saline), as validated by experiments and simulations. Moreover, the reported pBDT-TA coating enables secondary reactions on the coating for engineering hybrid adlayers (e.g., ZIF-8 shells) via phenolic-mediated adhesion, and the facile integration of aromatic fluorescent dyes (e.g., rhodamine B) via π interactions without requiring elaborate synthetic processes.

Diversity-oriented synthesis (DOS) is a rich source for novel lead structures in Medicinal Chemistry. In this study, we present a DOS-compatible method for synthesis of compounds bearing a free thiol moiety. The procedure relies on Rh(II)-catalyzed coupling of dithiols to diazo building blocks. The synthetized library was probed against metallo-β-lactamases (MBLs) NDM-1 and VIM-1. Biochemical and biological evaluation led to identification of novel potent MBL inhibitors with antibiotic adjuvant activity.

An amperometric chemosensor for the detection of hydrogen peroxide is reported. The sensor is based on 1,4-benzoquinone immobilized on the gold electrode using self-assembled monolayer of short chain symmetrical dithiol as an anchor layer. Sensor analysis was performed by cyclic voltammetry at the potential range from −0.6 V till +0.9 V as well as in the anodic or cathodic potential ranges only. The results indicate oxidative electrochemical decomposition of hydrogen peroxide at the potential of ∼+0.4 V leading to the formation of oxygen while at cathodic potentials a reduction of the formed oxygen as well as of the hydrogen peroxide occur. A decrease in the oxidation potential of hydrogen peroxide on the gold electrode coated by self-assembled monolayer with 1,4-benzoquinone in comparison with that measured on the electrodes coated by the same self-assembled monolayer without 1,4-benzoquinone, indicates electrocatalytic effect of this moiety on oxidative decomposition of hydrogen peroxide. Analytical evaluation of the sensor performance was done in the voltammetric as well as in the chronoamperometric mode. The sensor exhibited linear response over the concentration range till 2.5 mM with a limit of detection ∼4 μM.

Thiol-ene cationic and radical reactions were conducted for 1:1 addition between a thiol and vinyl ether, and also for cyclization and step-growth polymerization between a dithiol and divinyl ether. p-Toluenesulfonic acid (PTSA) induced a cationic thiol-ene reaction to generate a thioacetal in high yield, whereas 2,2'-azobisisobutyronitrile resulted in a radical thiol-ene reaction to give a thioether, also in high yield. The cationic and radical addition reactions between a dithiol and divinyl ether with oxyethylene units yielded amorphous poly(thioacetal)s and crystalline poly(thioether)s, respectively. Under high-dilution conditions, the cationic and radical reactions resulted in 16- and 18-membered cyclic thioacetal and thioether products, respectively. Furthermore, concurrent cationic and radical step-growth polymerizations were realized using PTSA under UV irradiation to produce polymers having both thioacetal and thioether linkages in the main chain.

At the redox-active center of thioredoxin reductase (TrxR), a selenenyl sulfide (Se-S) bond is formed between Cys497 and Sec498, which is activated into the thiolselenolate state ([SH,Se- ]) by reacting with a nearby dithiol motif ([SHCys59 ,SHCys64 ]) present in the other subunit. This process is achieved through two reversible steps: an attack of a cysteinyl thiol of Cys59 at the Se atom of the Se-S bond and a subsequent attack of a remaining thiol at the S atom of the generated mixed Se-S intermediate. However, it is not clear how the kinetically unfavorable second step progresses smoothly in the catalytic cycle. A model study that used synthetic selenenyl sulfides, which mimic the active site structure of human TrxR comprising Cys497, Sec498, and His472, suggested that His472 can play a key role by forming a hydrogen bond with the Se atom of the mixed Se-S intermediate to facilitate the second step. In addition, the selenenyl sulfides exhibited a defensive ability against H2 O2 -induced oxidative stress in cultured cells, which suggests the possibility for medicinal applications to control the redox balance in cells.

Bis(1,3-dithiol-2-ylidene)-substituted subtriazachlorin was formed because of an unusual reaction of a 1,3-dithiole-2-one-fused subphthalocyanine in a triethylphosphite-mediated tetrathiafulvalene synthesis. In this novel molecule, the bis(1,3-dithiol-2-ylidene)ethane moiety and subtriazachlorin structure are fused, resulting in an electron-donating ability and broad absorption in the near-infrared region.

Due to the “click” chemistry characteristics of the thiol–ene reaction, these transformations have been gaining an increasing amount of attention in current chemical research. The high efficiency and selectivity of these transformations have been useful for many areas of study, from small molecule organic synthesis, to polymer synthesis and functionalization, to bio‐conjugation reactions. In this work, a study of a novel method of photochemical thiol–ene reactions using alkyl halides and an tris[2‐phenylpyridinato‐C2,N]iridium(III) (Ir(ppy)₃) photocatalyst is investigated. This process is shown to progress rapidly and has the benefit of low catalyst and initiator concentrations relative to reagents as well as mild conditions associated with photochemical processes. To understand the mechanism of this process, catalyst and initiator concentrations and other reaction conditions are varied. To demonstrate the utility of this process, a step‐growth thiol–ene polymer is synthesized using dithiol and diene monomers and a crosslinked polymer network is synthesized as well. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1931–1937

Joint crosslinked gels containing disulfide linkage have been synthesized by oxidation reaction of multi-functional thiol monomers, trimethylolpropane tris(3-mercaptopropionate), tris-[3-mercaptopropionyloxy-ethyl]-isocyanurate, pentaerythritol tetrakis (3-mercaptopropionate), and dipenta-erythritol hexakis (3-mercaptopropionate) in dimethyl sulfoxide (DMSO). Both the oxidation reactions with DMSO at 85 °C and Albright-Goldman oxidation in the presence of acetic anhydride at 50 °C yielded the corresponding gels. The oxidation reaction with DMSO showed higher reaction conversion than that with Albright-Goldman oxidation. Network structure of the gels was quantitatively characterized by means of a scanning microscopic light scattering. The reactions formed homogeneous network structure with about 0.5 nm of mesh in the gels. Mechanical properties of the obtained gels were investigated by compression test. Increasing of the crosslinking density with increasing of the monomer concentration, number of thiol group of the monomer or reaction conversion, raised Young's modulus, and breaking stress of the gels. Cogelation of the tri-, tetra-, of hexa-thiol monomer and dithiol monomers yielded soft and flexible gels. Reduction of the disulfide bonds in the gels by dithiothreitol turned the gel into solution. Heating of the resulting solution induced the regelation by reforming of the disulfide bonds. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 3749–3756

X-ray structure analysis of the [5]radialene with quintuple 1,3-benzodithiol-2-ylidenes (4) and its tetracation salt, 4 a⋅CS2 and (4 a)4+(ReO4–)4(CH3CN), was successfully carried out. The neutral [5]radialene molecule in 4⋅CS2 adopted a non-planar structure with an envelope conformation of the central five-membered ring. In contrast, the central five-membered ring of 4 a4+ in (4 a)4+(ReO4−)4(CH3CN) adopted a planar structure with significant contribution of an aromatic cyclopentadienide structure. An anion-π interaction was observed between the ReO4– anion and the central five-membered ring in (4 a)4+(ReO4–)4(CH3CN). The electronic structures of 4 a and its oxidative species (4 a2+ and 4 a4+) were estimated by density functional theory (DFT) calculations. The optimized structure of 42+ suggested the delocalization of a positive charges over two 1,3-benzodithiol-2-ylidene units through the central five-membered ring.

International audience; The reaction mechanism for the formation of alkyl thiol self-assembled monolayers (SAM) on Au(111) is still not clearly understood. Especially, the role of defects on the chemisorption process is an important goal to be addressed. In this work, different minimum energy reaction paths for R−SH dissociation of thiols (with long and short chains and dithiol species) adsorbed on gold adatom are calculated by using periodic density functional theory (DFT). Our results show a lower energy barrier for the RS−H bond dissociation when two thiols are adsorbed per adatom. In addition, in contrast with the formation of an adatom at the Au(111) which has been shown to depend on the alkyl chain length, the activation energy of the RS−H bond dissociation of thiols adsorbed on an adatom was shown to be independent of the alkyl chain length. The presented results and derived hypothesis support the model that thiols with long alkyl chain thiols mainly adsorb molecularly on Au(111), while for short alkyl chain thiols the S−H bond breaks. This result is explained by the fact that short-chain thiols have lower interchain interaction energies and are thus more mobile compared to the long alkyl chain thiols on the Au(111) surface. This feature enables the short chains to reach adequate geometries, driven by entropy, which could deform the Au(111) more drastically and probably pull Au atoms out from surface to form adatoms. With these results a new mechanism is proposed for the formation of alkyl chain thiols on Au(111).

A new use of the thiol-ene reaction to generate functional, redox-tunable polymers is described. To illustrate the versatility of this approach, tailored divinyl ether monomers were polymerized with triethylene glycol dithiol to yield polymers containing either a carbonate or zwitterionic phosphocholine within the polymer backbone. Similarly, dithioerythritol was polymerized with triethylene glycol divinyl ether to yield a polymer with pendant diols and show how functional groups can be designed into either the divinyl ether or dithiol monomer. Using the thioether functional group inherent to this polymerization, all three polymers were selectively and quantitatively oxidized to either sulfoxides or sulfones by treatment with dilute hydrogen peroxide or mCPBA, respectively. With these illustrative examples, it is shown that the thiol-ene polymerization is a broad-reaching method to access a class of new redox-active polymers which contain varied and dense functional-group compositions.

Remote transport of material is an utmost useful, but challenging, property expanding the design possibilities of many applications such as microfluidics or robotics where species can be carried without interfering with its environment. Nature has solved the problem of transport in e.g., the respiratory system by a concerted motion of cilia. This study addresses a new method to fabricate an array of small parallel fibers acting as cilia placed side by side on a substrate. The fibers consist of a crosslinked liquid crystal main chain polymer functionalized with coreactant azobenzene molecules. The fibers bend toward a light source in a concerted manner. When placed in a liquid, the cooperative bending motion of the fibers creates a flow able to efficiently carry objects. The proposed fabrication process of the fibers is scalable to large area and requires an optimized rheology which is achieved by converting low molecular weight reactive liquid crystal acrylate monomers to oligomers using a multiplication of the monomeric units by the Michael addition reaction with dithiol. The oligomer properties and the elasticity of the fibers are adjusted by changing the thiol spacer leading to optimized manufacturing and maximized optical response.

International audience; High‐performance flexible strain sensors are key components for the next generation of wearable health monitoring devices. Here, the authors have fabricated a novel strain sensor based on gold nanoparticles (AuNPs) interconnected by flexible and responsive molecular linkers. The combination of conductive AuNPs (25 nm in diameter) with tetra(ethylene glycol) dithiol (SH‐TEG‐SH) linkers yields a covalent 3D network which can be directly deposited onto prepatterned flexible supports exposing interdigitated Au electrodes. The electrically insulating nature of the linkers effectively defines the tunneling modulated charge transfer through the AuNPs network. When compressive/tensile strain is applied, the molecular linkers adopt a compressed/stretched conformation thus decreasing/increasing the interparticle distance, ultimately yielding an exponential increase/decrease of the tunneling current when voltage is applied. The strain sensor displays state‐of‐the‐art performances including a highly sensitive response to both tensile and compressive strain, as quantified by a high gauge factor (GF≈126) combined with other superior sensing properties like high flexibility, short response time (16.1 ms), and good robustness (>2000 cycles). Finally, the applicability of the device for health monitoring is demonstrated: high‐resolution artery pulse waves are acquired by placing the strain sensor onto the skin allowing the extraction of important physical parameters for human‐health assessment.

Metal nanoparticle dimers with controllable gap distance have attracted considerable attention because of their promising application in plasmonics. Generally, gaps with nanometer or subnanometer dimensions generate localized surface plasmon resonance (LSPR) coupling effect, thus contributing to a strong electromagnetic field for improving surface enhanced Raman scattering (SERS) effect. Here, we developed a facile approach to fabricate Au@SiO2 dimers through the steric hindrance effect, in which the SiO2 shell functioned as a block and a rigid dithiol molecule was employed as linker. The thickness of the SiO2 shell played a critical role in improving the yield of dimers. The dimerization efficiency increased significantly as the shell thickness decreased to ~1 nm. When 1,4-benzenedithiol was used as linker molecule, the yield of dimers was ~30%. Few dimers were obtained when mecaptobenzonic acid was used as linker. A thicker shell is associated with a low yield of dimer, whereas a thinner shell resulted in the formation of multimers and linear structures. The low number of linker molecules on the exposed area of monodisperse single nanoparticles and the lack of LSPR coupling effect (‘hot spots’) resulted in the disappearance of SERS signals of the linkers. The estimated SERS enhancement factor was about eight fold because of the strong coupling effect in the gap of the dimer with the distance of the dithiol molecular length. From the above results, SERS combined with SEM could be developed into powerful tools for monitoring the formation of dimers and positioning of single dimers. It may aid the control of assembly of Au nanoparticles and in probing key issues about SERS enhancements. Copyright © 2015 John Wiley & Sons, Ltd.

Summary The adsorption of graphene onto solid surface is vital for the numerous device applications. In the present work, we studied interaction of graphene with chemically modified surfaces. We formed the self-assembled monolayers (SAM) of octadecanethiol (ODT), mercapto undecanoic acid (MUA) and biphenyl dithiol (BPD) onto the gold substrates. The nature of the surfaces obtained for ODT and MUA were hydrophobic and hydrophilic, respectively. The SAM of BPD yields the surface with phenyl rings having delocalized π-electrons. Due to hydrophobic nature of the graphene, it adsorbs onto the SAMs of ODT and BPD. The surface morphology of the graphene onto SAMs was studied using atomic force microscope. Due to π−π stacking interaction between the graphene and BPD molecules, graphene prefers planar adsorption onto the SAM of BPD. The hydrophobic interaction between the graphene and ODT leads to random and non-uniform adsorption of graphene onto the SAM of ODT. Surface plasmon resonance (SPR) phenomenon is extremely sensitive technique to detect minute change in dielectrics at the given interface. The adsorbed layers of the organic materials were studied using a SPR instrument.

A new strategy is developed to prepare both α,ω-dithiol and α,ω-divinyl linear telechelic polythiolether oligomers by visible light induced thiol-ene chemistry in the presence of a fac-Ir(ppy)3 photoredox catalyst. Polythiolether oligomers of well-defined end groups and controlled molecular weights have been successfully synthesized at varying monomer molar ratios of 1,4-benzenedimethanethiol (BDMT) to diethylene glycol divinyl ether (DEGVE). 1H NMR and MALDI-TOF MS analyses demonstrate that as-prepared polythiolethers possess high end-group fidelity, which is further supported by the successful polyaddition of polythiolethers bearing α,ω-dithiol and α,ω-divinyl groups. For example, with the α,ω-dithiol- (Mn = 1900 g mol−1, PDI = 1.25) and α,ω-divinyl-terminated (Mn = 2000 g mol−1, PDI = 1.29) polythiolethers as macromonomers, the molecular weight of resulting polythiolether is up to 7700 g mol−1 with PDI as 1.67. The reactivity of the terminal thiol group is further confirmed by the addition reaction with N-(1-pyrenyl)maleimide. UV-vis spectra and fluorescene measurements suggest that fac-Ir(ppy)3 undergo a redox quenching process reacted with BDMT to generate thiyl free radicals. With these results, the mechanism of the thiol-ene reaction catalyzed by photoredox catalyst is proposed. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 740–749

Invited for the cover of this issue is the group of Anna Dolega at the Gdansk University of Technology, Poland. The cover image shows the electronic structure and simplified formula of bis-1,3-[bis(2,6-diisopropylphenoxy)]disiloxane-1,3-dithiol, a suitable ligand for the synthesis of chelating metal complexes, against a background of a more popular compound of silicon, sand.

A ferrocene-based dithiol 1,1′-[fc(C{O}OCH2CH2SH)2] has been prepared and treated with a AgI salt to form the stable dithiolate compound [fc(C{O}OCH2CH2SAg)2]n (fc=[Fe(η5-C5H4)2]). This is used as a reagent for the preparation of the nanocluster [Ag74S19(dppp)6(fc(C{O}OCH2CH2S)2)18] which was obtained in good yield (dppp=1,3-bis(diphenylphosphino)propane).

A fluorescent protein-labeling strategy was developed in which a protein of interest (POI) is genetically tagged with a short peptide sequence presenting two Cys residues that can selectively react with synthetic fluorogenic reagents. These fluorogens comprise a fluorophore and two maleimide groups that quench fluorescence until they both undergo thiol addition during the labeling reaction. Novel fluorogens were prepared and kinetically characterized to demonstrate the importance of a methoxy substituent on the maleimide in suppressing reactivity with glutathione, an intracellular thiol, while maintaining reactivity with the dithiol tag. This system allows the rapid and specific labeling of intracellular POIs.

Thioredoxin superfamily proteins introduce disulfide bonds into substrates, catalyze the removal of disulfides, and operate in electron relays. These functions rely on one or more dithiol/disulfide exchange reactions. The flavoenzyme quiescin sulfhydryl oxidase (QSOX), a catalyst of disulfide bond formation with an interdomain electron transfer step in its catalytic cycle, provides a unique opportunity for exploring the structural environment of enzymatic dithiol/disulfide exchange. Wild-type Rattus norvegicus QSOX1 (RnQSOX1) was crystallized in a conformation that juxtaposes the two redox-active di-cysteine motifs in the enzyme, presenting the entire electron-transfer pathway and proton-transfer participants in their native configurations. As such a state cannot generally be enriched and stabilized for analysis, RnQSOX1 gives unprecedented insight into the functional group environments of the four cysteines involved in dithiol/disulfide exchange and provides the framework for analysis of the energetics of electron transfer in the presence of the bound flavin adenine dinucleotide cofactor. Hybrid quantum mechanics/molecular mechanics (QM/MM) free energy simulations based on the X-ray crystal structure suggest that formation of the interdomain disulfide intermediate is highly favorable and secures the flexible enzyme in a state from which further electron transfer via the flavin can occur.

The combination of efficient and harmonious aza-Michael and thiol-Michael reactions in one pot is first reported for the convenient synthesis of thermo-, oxidation-, pH-, and CO2 -responsive polymers. The simultaneous two-type Michael reactions are proved to proceed smoothly without additional catalyst. The dithiol and diamine are involved in the copolymerization competitively and thus in a random distribution. A wide range of commercially available starting materials are utilized for the simultaneous two-type Michael reactions in one pot to obtain various responsive polymers with different structures. The cloud point of the thermo-responsive polymers is easily tuned by adjusting the copolymerization ratio of monomers or using monomers with different structures. Besides, the oxidation- and pH-/CO2 - responsiveness are also demonstrated.

RATIONALE This study aimed at evaluating the collision-induced dissociation tandem mass spectrometric (CID-MS/MS) fragmentation patterns of novel β-cyclodextrin-substituted- and bis-pyridinium gemini surfactants currently being explored as nanomaterial drug delivery agents. In the β-cyclodextrin-substituted gemini surfactants, a β-cyclodextrin ring is grafted onto an N,N-bis(dimethylalkyl)-α,ω-aminoalkane-diammonium moiety using variable succinyl linkers. In contrast, the bis-pyridinium gemini surfactants are based on a 1,1'-(1,1'-(ethane-1,2-diylbis(sulfanediyl))bis(alkane-2,1-diyl))dipyridinium template, defined by two symmetrical N-alkylpyridinium parts connected through a fixed ethane dithiol spacer. METHODS Detection of the precursor ion [M]2+ species of the synthesized compounds and the determination of mass accuracies were conducted using a QqTOF-MS instrument. A multi-stage tandem MS analysis of the detected [M]2+ species was conducted using the QqQ-LIT-MS instrument. Both instruments were equipped with an electrospray ionization (ESI) source. RESULTS Abundant precursor ion [M]2+ species were detected for all compounds at sub-1 ppm mass accuracies. The β-cyclodextrin-substituted compounds, fragmented via two main pathways: Pathway 1: the loss of one head-tail region produces a [M–(N(Me)2-R)]2+ ion, from which sugar moieties (Glc) are sequentially cleaved; Pathway 2: both head-tail regions are lost to give [M–2(N(Me)2-R)]+, followed by consecutive loss of Glc units. Alternatively, the cleavage of the Glc units could also have occurred simultaneously. Nevertheless, the fragmentation evolved around the quaternary ammonium cations, with characteristic cleavage of Glc moieties. For the bis-pyridinium gemini compounds, they either lost neutral pyridine(s) to give doubly charged ions (Pathway A) or formed complementary pyridinium alongside other singly charged ions (Pathway B). Similar to β-cyclodextrin-substituted compounds, the fragmentation was centered on the pyridinium functional groups. CONCLUSIONS The MSn analyses of these novel gemini surfactants, reported here for the first time, revealed diagnostic ions for each compound, with a universal fragmentation pattern for each compound series. The diagnostic ions will be employed within liquid chromatography (LC)/MS/MS methods for screening, identification, and quantification of these compounds within biological samples. Copyright © 2014 John Wiley & Sons, Ltd.

A considerable quantity of an alkylation by-product is observed when using 3,6-dioxa-1,8-octanedithiol as a scavenger during acidic release of peptides containing the thioether amino acid methionine from the solid support. Adjustment of the cleavage conditions by replacement of 3,6-dioxa-1,8-octanedithiol with ethane dithiol or by using methionine sulfoxide as an alternative to methionine resulted in no such impurity. The by-product was detectable by liquid chromatography and mass spectrometry and characterised by NMR spectroscopy of an isolated model peptide. It could be effectively removed in a separate post cleavage step by treatment with dilute aqueous acid at 37 °C. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.

A powerful variation of traditional radical thiol-yne reaction with diphenylacetylene (DPA)-based starting materials leading to the quantitative and selective formation of the corresponding vinyl sulfides is reported. A variety of different thiols are shown to undergo reaction with DPA and the influence of their structure on reactivity is studied. The results obtained from the model reactions are then used to guide the efficient synthesis of hyperbranched poly(vinyl sulfide) (hb-PVS) systems by employing a dithiol and a trialkyne in an A2 + B3 approach. The polymers obtained show excellent solubility in common organic solvents and exhibit high refractive indices (e.g., 1.70 at 589 nm). The combined ease of processability and potential for cross-linking make these materials very interesting for applications, such as coatings for optical devices. The selective mono-addition thiol-yne reaction on DPA serves not only as a synthetic method for the preparation of PVS but could also be applied to the general modification of acetylene-containing materials.

Biobased monomers derived from castor oil as well as from limonene suitable for thiol–ene copolymerization were synthesized. Di-10-undecenylether 2 was obtained via GaBr3-catalyzed reduction of 10-undecenyl 10-undecenoate 1. Diene ether 2 and (R)-limonene 5 were reacted in two steps using radical thiol–ene addition reactions to dithiol ether 4 and dithiol 7, respectively. Diene ether 2 and dithiols 4 and 7 were copolymerized using thermal initiation with AIBN and photochemically initiated thiol–ene reaction, respectively. DSC characterization revealed that these monomers can be used to synthesize polyether polysulfides with good and adjustable thermal properties. Moreover, the synthesized polymers P1 and P2 have successfully been transformed into polyether polysulfones P3 and P4 by oxidation with H2O2. An increase of the melting transition of 40–50°C was observed after oxidation.

New diene and dithiol monomers, based on aromatic imides such as benzophenone-3,3′,4,4′-tetracarboxylic diimide were synthesized and used in thiol-ene polymerizations which yield poly(imide-co-thioether)s. These linear polymers exhibit limited solubility in various organic solvents. The molecular weights of the polymers were found to decrease with increasing imide content. The glass transition temperature (Tg) of these polymers is dependent on imide content, with Tg values ranging from −55 °C (with no imide) up to 13 °C (with 70% imide). These thermal property improvements are due to the H-bonding and rigidity of the aromatic imide moieties. Thermal degradation, as studied by thermogravimetric analysis, was not significantly different to the nonimide containing thiol-ene polymers made using trimethyloylpropane diallyl ether and 3,5-dioxa-1,8-dithiooctane. It is expected that such monomers may lead to increased glass transition temperatures in other thiol-ene polymer systems as these normally exhibit low glass transition temperatures. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4637–4642

Radical catalyzed thiol-ene reaction has become a useful alternative to the Huisgen-type azide-yne click reaction as it helps expand the variability in reaction conditions as well as the range of clickable entities. In this study, the direct generation of a hyperbranched polyether (HBPE) having decyl units at the periphery and a pendant allyl group on every repeat unit of the polymer backbone is described; the allyl groups serve as a reactive handle for postpolymerization modifications and permits the generation of a variety of internally functionalized HBPEs. In this design, the AB(2) monomer carries two decylbenzyl ether units (B-functionality), an aliphatic OH (A-functionality) and a pendant allyl group within the spacer segment; polymerization of the monomer readily occurs at 150 degrees C via melt transetherification process by continuous removal of 1-decanol under reduced pressure. The resulting HBPE has a hydrophobic periphery due to the presence of numerous decyl chains, while the allyl groups that remain unaffected during the melt polymerization provides an opportunity to install a variety of functional groups within the interior; thiol-ene click reaction with two different thiols, namely 3-mercaptopropionic acid and mercaptosuccinic acid, generated interesting amphiphilic structures. Preliminary field emission scanning electron microscope (FESEM) and Atomic Force Microscopy (AFM) imaging studies reveal the formation of fairly uniform spherical aggregates in water with sizes ranging from 200 to 400 nm; this suggests that these amphiphilic HBPs is able to reconfigure to generate jellyfish-like conformations that subsequently aggregate in an alkaline medium. The internal allyl functional groups were also used to generate intramolecularly core-crosslinked HBPEs, by the use of dithiol crosslinkers; gel permeation chromatography traces provided clear evidence for reduction in the size after crosslinking. In summary, we have developed a simple route to prepare core-clickable HBPEs and have demonstrated the quantitative reaction of the allyl groups present within the interior of the polymers; such HB polymeric systems that carry numerous functional groups within the core could have interesting applications in analyte sequestration and possibly sensing, especially from organic media. (c) 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4125-4135

Endogenous vicinal-dithiol-containing proteins (VDPs) that have two thiol groups close to each other in space play a significant importance in maintaining the cellular redox microenvironment. Approaches to identify VDPs mainly rely on monitoring the different concentration of monothiol and total thiol groups or on indirect labeling of vicinal thiols by using p-aminophenylarsenoxide (PAO). Our previous work has reported the direct labeling of VDPs with a highly selective receptor PAO analogue, which could realize fluorescence detection of VDPs directly in living cells. Herein, we developed a conjugated approach to expand detectable tags to nitrobenzoxadiazole (NBD), fluorescein, naphthalimide, and biotin for the synthesis of a series of probes. Different linkers have also been introduced toward conjugation of VTA2 with these functional tags. These synthesized flexible probes with various features will offer new tools for the potential identification and visualization of vicinal dithiols existing in different regions of VDPs in living cells. These probes are convenient tools for proteomics studies of various disease-related VDPs and for the discovery of new drug targets.

A polybenzoxazine bearing allyl group in the side chain was synthesized by the ring-opening polymerization of N-allyl-benzoxazine and was crosslinked by the two different processes, (1) thermally induced oligomerization of the allyl side chains and (2) radical addition of dithiol (thiol-ene reaction) to the allyl side chains. The former process was promoted by adding 2,5-dimethyl-2,5-di(tert-butylperoxy)hexane as a radical source, leading to the improved yield of the networked polymer isolated as acetone-insoluble fraction. The thiol-ene reaction with using 1,6-hexanedithiol was also an efficient method for crosslinking the polybenzoxazine. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013

The wire-like properties of four S-(4-{2-[4-(2-phenylethynyl)phenyl]ethynyl}phenyl) thioacetate derivatives, PhC≡CC(6)H(4)C≡CC(6)H(4)SAc (1), H(2)NC(6)H(4)C≡CC(6)H(4)C≡CC(6)H(4)SAc (2), PhC≡CC(6)H(2)(OMe)(2)C≡CC(6)H(4)SAc (3) and AcSC(6)H(4)C≡CC(6)H(4)C≡CC(6)H(4)SAc (4) (Figure 1), all of which possess a high degree of conjugation along the oligo(phenyleneethynylene) (OPE) backbone, were investigated as self-assembled monolayers (SAMs) on gold and platinum electrodes by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The redox probe [Fe(CN)(6)](4)(-) was used in both the CV and impedance experiments. The results indicate that the thiolates derived from thioacetate-protected precursor molecules 1 and 2 form well-ordered monolayers on a gold electrode, whereas SAMs derived from 3 and 4 exhibit randomly distributed pinholes. The electron tunnelling resistance and fractional coverage of SAMs of all four compounds were examined using electron tunnelling theory. The analysis of the results reveal that the well-ordered SAMs of 1 and 2 exhibit higher charge-transfer resistance in comparison to the defect-ridden SAMs of 3 and 4. The additional steric bulk offered by the methoxy groups in 3 is likely to prevent efficient packing within the SAM, leading to a microelectrode behaviour, when assembled on a gold electrode surface. The protected dithiol derivative 4 probably binds to the surface through both terminal groups which prevents dense packing and leads to the formation of a monolayer with randomly distributed pinholes. Atomic force microscopy (AFM) was used to examine the morphology of the monolayers, and height images gave root-mean-square (RMS) roughness's which are in agreement with the proposed SAM structures.

In this study, microcapsules containing fragrance oils as active agent were synthesized by interfacial thiol-ene polymerization in oil-in-water emulsion. One water-soluble dithiol and four oil-soluble acrylates were used as “click”able monomers. The polymerization kinetics was studied by HPLC and 1H-NMR. The size and morphology of the microcapsules were characterized by means of light scattering, optical microscope, and scanning electron microscope, and their thermal property was examined by TGA. The encapsulation efficiency and stability of the microcapsules were monitored at room temperature and 45 °C for 1 month. In general, this interfacial thiol-ene polymerization was demonstrated to be a facile and efficient approach for fragrance microencapsulation with new and stable shell materials. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43905.

The first catalytic asymmetric thioacetalization of salicylaldehyde and dithiol is reported.

Selected 5-substituted derivatives 4 of 1,1-diethoxy-5-hydroxypent-3-yn-2-one were treated with propane-1,3-dithiol under various conditions. The unprotected hydroxy ketones underwent cyclization during the dithiol addition and gave the corresponding 3-(diethoxymethyl)-2-oxa-6,10-dithiaspiro[4.5]decan-3-ols 5 in 80–90% yield as the only products (Scheme 3 and Table 1). These products can be regarded as partly modified carbohydrates in the furanose form. When the benzyl-protected analogues 10-Bn of the 1,1-diethoxy-5-hydroxypent-3-yn-2-one derivatives were treated with the same dithiol, however, no cyclization occurred; instead the corresponding 3-{2-[(benzyloxy)methyl]-1,3-dithian-2-yl}-1,1-diethoxypropan-2-one derivatives 11-Bn were formed in good yield (up to 99%; Table 4). These 1,3-dithianes were and are in the process of being converted to a number of new carbohydrate analogues, and here are reported high-yield syntheses of functionalized molecules 17 belonging to the 5,5-diethoxy-1,4-dihydroxypentan-2-one family of compounds (Table 7), via 15-Bn (Table 5) and 16-Bn (Table 6 and Scheme 8).

Biosynthesis of the dithiolopyrrolone antibiotic holomycin in Streptomyces clavuligerus involves the closure of a pair of enethiols to a cyclic disulfide. We have shown that the dithiol oxidase HlmI is responsible for the disulfide formation and this enzyme also plays a role in self-protection. In the present study, we examine how S. clavuligerus deals with the proposed toxic dithiol intermediates when hlmI is deleted. We used differential NMR spectroscopy and mass spectrometry to profile the metabolomes of hlmI deletion mutants along with the wild-type strain and a holomycin-overproducing strain. A number of metabolites unique to ΔhlmI strains were identified. In these metabolites the enethiols have been incapacitated by a combination of mono- and di-S-methylation. We also observed an intriguing dimeric thioether adduct in low quantities in the wild-type strain and at much higher levels in the ΔhlmI strains. The structures of these novel metabolites highlight the reactivity of the dihydrodithiolopyrrolone scaffold. Furthermore, bioassays suggest that modification of the enethiol warhead by S-alkylation provides a host strategy for detoxification, one that is shared amongst multiple species producing such bioactive disulfide natural products.

Summary Mycobacteria produce millimolar concentrations of mycothiol (MSH) as their major low molecular weight thiol redox buffer. MSH-deficient mutants display increased sensitivity towards reactive oxygen, nitrogen and electrophilic species as well as alkylating agents and antibiotics. MSH is maintained in its reduced thiol state by the NADPH-dependent mycothiol disulphide reductase (Mtr). However, the redoxin that uses the MSH/Mtr/NADPH pathway for reduction of MSH-mixed protein disulphides, formed during oxidative stress, has long remained unknown. In this issue, Van Laer et al. report that MSH provides the reducing power for mycoredoxin-1 (Mrx1) in reduction of synthetic MSH-mixed disulphides. The reduced (dithiol) and oxidized (disulphide) solution structures of Mrx1 have been solved by nuclear magnetic resonance (NMR) spectroscopy. NMR time course experiments have also demonstrated the transient S-mycothiolation of the active site Cys14 of oxidized Mrx1 during reduction by the MSH/Mtr/NADPH electron pathway. The paper opens a new era of research to identify S-mycothiolated Mrx1 substrates and the function of MSH in redox regulation and virulence in Mycobacterium tuberculosis.

The chloro alcohols 4–6 derived from TADDOLs (=α,α,α′,α′-tetraaryl-1,3-dioxolan-4,5-dimethanols) are used to prepare corresponding sulfanyl alcohols, ethers, and amines (Scheme 1 and Table 1). The dithiol analog of TADDOL and derivatives thereof, 45–49, were also synthesized. The crystal structures of 16 representatives of this series of compounds are reported (Figs. 1–3 and Scheme 2). The thiols were employed in Cu-catalyzed enantioselective conjugate additions of Grignard reagents to cyclic enones, with cycloheptenone giving the best results (er up to 94 : 6). The enantioselectivity reverses from Si-addition with the sulfanyl alcohol to Re-addition with the alkoxy or dimethylamino thiols (Table 4). CuI-Thiolates, 50–53, could be isolated in up to 84% yield (Scheme 2) and were shown to have tetranuclear structures in the gas phase (by ESI-MS), in solution (CH2Cl2, THF; by vapor-pressure osmometry and by NMR pulsed-gradient diffusion measurements; Table 5), and in the solid state (X-ray crystal structures in Scheme 2). The Cu complex 50 of the sulfanyl alcohol is stable in air and in the presence of weak aqueous acid, and it is a highly active catalyst (0.5 mol-%) for the 1,4-additions, leading to the same enantio- and regioselectivities observed with the in situ generated catalyst (6.5 mol-%; Scheme 3). Since the reaction mixtures contain additional metal salts (MgX2, LiX) it is not possible at this stage, to propose a mechanistic model for the conjugate additions.

New π-extended tetrathiafulvalenes (exTTF) 4a, 4b, 5a, and 5b have been synthesized by direct phosphite-mediated cross-couplings of anthraquinone with 1,3-dithiole-2-thione derivatives. Further coordination reactions of the exTTF ligands including the phenanthroline unit (5a and 5b) with [Re(CO)5Cl] afford interesting tricarbonylrhenium(I) complexes 6a and 6b, respectively. The X-ray crystal structures of compounds 4a and 4b show a saddlelike conformation of the exTTF framework. The electrochemical and spectroscopic properties of compounds 4a–6a and 4b–6b have been studied. The results suggest that the oxidation of the exTTF derivatives shows the typical quasi-reversible two-electron oxidation wave of the exTTF core at potentials that vary depending on the substituents.

The ability of thiyl radicals to add to terminal unsaturations in an efficient way made them considered being one of the click reactions. Recently, thiol-yne addition reactions have been used extensively for the synthesis of crosslinked networks and dendrimers and postpolymerization functionalization protocols. Herein, we report a novel step-growth type reaction for highly functional linear polymers using a monoalkyne and dithiol compound. First, we investigated the model reaction between 1-octyne and 1-octanethiol as well as 1,4-butanedithiol compounds, which were initiated via self-, thermal-, and UV-initiation; the UV-initiation was found to be the most efficient method and completed within 2-h reaction time. The same conditions were applied for the polymerization of four different functional alkynes bearing different functional groups with two dithiol compounds. All polymerizations resulted in highly functional linear polymers with number averaged molecular weights ranging from 5 to 30 kDa, except for propargylic acid and its methyl ester, where only oligomers formed. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Glutaredoxins (Grx) play an important role in reduction of protein glutathione mixed disulphides. An IbGrx cDNA (561 bp, EF362614) encoding a putative dithiol Grx was cloned from sweet potato (Ipomoea batatas [L.] Lam). The deduced amino acid sequence is conserved among the reported dithiol Grx, having a CGYC dithiol motif at the active site. A 3-D structural model was created based on the known crystal structure of a poplar Grx (GrxC1). To characterise the IbGrx protein, the coding region was subcloned into an expression vector and transformed into Escherichia coli. The recombinant His(6) -tagged IbGrx was expressed and purified by metal affinity chromatography. The purified enzyme showed a monomeric band, as demonstrated with 15% SDS-PAGE. The Michaelis constant (K(M) ) for s-hydroxyethyl disulphide (HED) was 0.50 ± 0.08 Mm. The enzyme retained 60% activity at 80 °C for 16 min. The enzyme was active over a broad pH range from 6.0 to 11.0, and in the presence of imidazole up to 0.4 M. The enzyme was susceptible to protease.