Reduction Of Bonds Research Articles

Synthesis and Characterization of Redox-Responsive Disulfide Cross-Linked Polymer Particles for Energy Storage Applications.

Cross-linking poly(glycidyl methacrylate) microparticles with redox-responsive bis(5-amino-l,3,4-thiadiazol-2-yl) disulfide moieties yield redox-active particles (RAPs) capable of electrochemical energy storage via a reversible 2-electron reduction of the disulfide bond. The resulting RAPs show improved electrochemical reversibility compared to a small-molecule disulfide analogue in solution, attributed to spatial confinement of the polymer-grafted disulfides in the particle. Galvanostatic cycling was used to investigate the impact of electrolyte selection on stability and specific capacity. A dimethyl sulfoxide/magnesium triflate electrolyte was ultimately selected for its favorable electrochemical reversibility and specific capacity. Additionally, the specific capacity showed a strong dependence on particle size where smaller particles yielded higher specific capacity. Overall, these experiments offer a promising direction in designing synthetically facile and electrochemically stable materials for organosulfur-based multielectron energy storage coupled with beyond Li ion systems such as Mg.

Synthesis of Heterospirocycles through Gold‐(I) Catalysis: Useful Building Blocks for Medicinal Chemistry

AbstractGold‐(I) catalysis was used for the intramolecular cyclization of tertiary alcohols with terminal alkynes to form diverse aza‐spirocycles. The reaction was carried out with low catalyst loading under microwave irradiation to give both sulfonylated and acylated spirocyclic nitrogen derivatives. Gram scale spirocyclization was carried out to demonstrate the robustness of the reaction. An intramolecular Mizoroki‐Heck reaction was performed to give several tetracyclic spirocycles. Double bond reduction and selective protecting group manipulation gave spiropiperazine and spiromorpholine derivatives. These compounds were incorporated into biologically relevant scaffolds to give the first selective spirocyclic inhibitors of LIMK1.magnified image

Interfacial engineered PdRu/C with robust poison tolerance for oxygen reduction reaction and zinc-air battery

Developing a highly efficient and robust poison tolerance catalyst for oxygen reduction reaction (ORR) is significantly critical for sustainable energy convert systems. Herein, an interfacial engineered PdRu/C is prepared by reduction of silicon-hydrogen bonds. The interface between Pd and Ru is beneficial for exposing the active site, enhancing charge transfer and adjusting the adsorption energy barrier, resulting in the excellent ORR performances. Compared with commercial Pt/C (0.84 V) and commercial Pd/C (0.84 V), the optimal Pd9Ru1/C demonstrates high electrocatalytic activity with half-wave potential up of 0.86 V in 0.1 M KOH solution. Meanwhile, the experimental results indicate that bimetallic interface engineering can greatly enhance toxicity resistance to various poisons, including CO, methanol, NOx, SOx and POx. When they are applied to zinc-air battery as an air cathode, the battery exhibits an open circuit voltage of 1.48 V. Interestingly, the power density reaches up to 240 mW cm−2, which is superior to those of commercial Pt/C (219 mW cm−2) and commercial Pd/C (128 mW cm−2). This work opens up an effective strategy to conceive interfacial hybrid for electrocatalysis.

Reduction of Aromatic Dimethyl Ene-Dicarboxylates to Dimethyl Succinates with Titanium Ylides

Background: Generally, it was assumed that Tebbe- and Takai-reagents are useful for methenylation reactions. Objective: Applying these reagents to aromatic ene dicarboxylates, unexpectedly the reduction of double bonds was achieved. There is, however, a different behaviour of both reagents. Takai-reagent yields reduction while Tebbe-reagent prefers isomerisation. Methods: A selective and unique method has been shown to reduce a double bond of ene-dicarboxylates while both carboxylic groups are not affected at all. In addition, this method is easy and very cheap using Takai-reagent. Results: If isomerisation is to be carried out, without any reduction of a double bond, Tebbe-reagent can be applied. To our knowledge, such reactions have not been published yet. Conclusion: We have shown a selective methodology to reduce aromatic ene-dicarboxylates with titanium ylides.

Trichinella spiralis: Knockdown of gamma interferon inducible lysosomal thiol reductase (GILT) results in the reduction of worm burden.

Trichinella spiralis is mammalian skeletal muscles parasite which may cause trichinellosis in animals and humans. Gamma interferon inducible lysosomal thiol reductase (GILT) is a widespread superfamily which plays key role in processing and presentation of MHC class II restricted antigen by catalyzing disulfide bond reduction. There are no reports about GILT in T. spiralis. In present study, GILT from T. spiralis (Tsp-GILT) was cloned, analyzed by multiple-sequence alignment, and predicted by 3D structure model. Recombinant Tsp-GILT (about 46 kDa) was efficiently expressed in Escherichia coli and thiol reductase activity suggested that in acidic environment the addition of a reducing agent is needed. Soaking method was used to knockdown expression of Tsp-GILT using small interference RNA (siRNA). Immunofluorescence assay confirmed the transformation of siRNA into muscle larva (ML) and new born larva (NBL). Quantitative real time-PCR (QRT-PCR) analysis revealed that transcription level of Tsp-GILT mRNA can be up-regulated by stimulation of mouse IFN-γ and down-regulated by siRNA2 in vitro. NBLs soaked with siRNA2 showed 32.3% reduction in the generation of MLs. MLs soaked with siRNA2 showed 26.2% reduction in the next generation of MLs, but no significant effect was observed on adult worms or NBLs. These findings concluded that GILT may play important roles in the development of T. spiralis parasite.

Hydrogen/Deuterium Exchange Mass Spectrometry with Integrated Electrochemical Reduction and Microchip-Enabled Deglycosylation for Epitope Mapping of Heavily Glycosylated and Disulfide-Bonded Proteins.

Hydrogen/deuterium exchange mass spectrometry (HDX-MS) is a recognized method to study protein conformational dynamics and interactions. Proteins encompassing post-translational modifications (PTMs), such as disulfide bonds and glycosylations, present challenges to HDX-MS, as disulfide bond reduction and deglycosylation is often required to extract HDX information from regions containing these PTMs. In-solution deglycosylation with peptide-N4-(N-acetyl-β-d-glucosaminyl)-asparagine amidase A (PNGase A) or PNGase H+ combined with chemical reduction using tris-(2-carboxyethyl)phosphine (TCEP) has previously been used for HDX-MS analysis of disulfide-linked glycoproteins. However, this workflow requires extensive manual sample preparation and consumes large amounts of enzyme. Furthermore, large amounts of TCEP and glycosidases often result in suboptimal liquid chromatography-mass spectrometry (LC-MS) performance. Here, we compare the in-solution activity of PNGase A, PNGase H+, and the newly discovered PNGase Dj under quench conditions and immobilize them onto thiol-ene microfluidic chips to create HDX-MS-compatible immobilized microfluidic enzyme reactors (IMERs). The IMERS retain deglycosylation activity, also following repeated use and long-term storage. Furthermore, we combine a PNGase Dj IMER, a pepsin IMER, and an electrochemical cell to develop an HDX-MS setup capable of efficient online disulfide-bond reduction, deglycosylation, and proteolysis. We demonstrate the applicability of this setup by mapping the epitope of a monoclonal antibody (mAb) on the heavily disulfide-bonded and glycosylated sema-domain of the tyrosine-protein kinase Met (SD c-Met). We achieve near-complete sequence coverage and extract HDX data to identify regions of SD c-Met involved in mAb binding. The described methodology thus presents an integrated and online workflow for improved HDX-MS analysis of challenging PTM-rich proteins.

The aggregation characteristics of wheat globulin induced by heating and edible salts and its effects on noodle processing quality

The aggregation characteristics of wheat globulin induced by heating and edible salts were systematically investigated using SDS-PAGE, SE-HPLC, disulfide bonds analysis, and fluorescence and Fourier-transform infrared spectroscopy. The results showed that heating induced the formation of macro-molecular globulin aggregates through disulfide bonds, similar changes occurring when heating with neutral salt. Meanwhile, the surface hydrophobicity increased and protein conformation changed from β-turns to β-sheets. Whereas heating with alkali salt induced the reduction of disulfide bonds, and non-reducible aggregation could be produced when at higher temperatures. Additionally, both the β-turns and β-sheets increased at the expense of α-helixes and random coins, and the surface hydrophobicity was overall lower than that of heat treatment alone, which further confirmed the massive aggregation of globulin. Furthermore, it was found that globulin addition could change the pasting properties as well as the quality of noodles. In particular, after heating with alkali salt, the viscosity and setback value decreased significantly, and the pasting temperature increased; moreover, the hardness and springiness of cooked noodles increased remarkably. These changes observed could attributed to the globulin aggregation analyzed above, which contributed to further strengthen the protein network structure and improve its functional characteristics during flour processing.

Evaluation of Efficient Non-reducing Enzymatic and Chemical Ligation Strategies for Complex Disulfide-Rich Peptides.

Double-knotted peptides identified in venoms and synthetic bivalent peptide constructs targeting ion channels are emerging tools for the study of ion channel pharmacology and physiology. These highly complex and disulfide-rich peptides contain two individual cystine knots, each comprising six cysteines and three disulfide bonds. Until now, native double-knotted peptides, such as Hi1a and DkTx, have only been isolated from venom or produced recombinantly, whereas engineered double-knotted peptides have successfully been produced through enzymatic ligation using sortase A to form a seamless amide bond at the ligation site between two knotted toxins, and by alkyne/azide click chemistry, joining two peptide knots via a triazole linkage. To further pursue these double-knotted peptides as pharmacological tools or probes for therapeutically relevant ion channels, we sought to identify a robust methodology resulting in a high yield product that lends itself to rapid production and facile mutational studies. In this study, we evaluated the ligation efficiency of enzymatic (sortase A5°, butelase 1, wild-type OaAEP 1, C247A-OaAEP 1, and peptiligase) and mild chemical approaches (α-ketoacid-hydroxylamine, KAHA) for forming a native amide bond linking the toxins while maintaining the native disulfide connectivity of each pre-folded peptide. We used two NaV1.7 inhibitors: PaurTx3, a spider-derived gating modifier peptide, and KIIIA, a small cone snail-derived pore blocker peptide, which have previously been shown to increase affinity and inhibitory potency on hNaV1.7 when ligated together. Correctly folded peptides were successfully ligated in varying yields, without disulfide bond shuffling or reduction, with sortase A5° being the most efficient, resulting in 60% ligation conversion within 15 min. In addition, electrophysiology studies demonstrated that for these two peptides, the amino acid composition of the linker did not affect the activity of the double-knotted peptides. This study demonstrates the powerful application of enzymes in efficiently ligating complex disulfide-rich peptides, paving the way for facile production of double-knotted peptides.

Novel Small Molecule Inhibitors That Prevent the Neuroparalysis of Tetanus Neurotoxin.

Tetanus neurotoxin (TeNT) is a protein exotoxin produced by Clostridium tetani that causes the deadly spastic neuroparalysis of tetanus. It consists of a metalloprotease light chain and of a heavy chain linked via a disulphide bond. TeNT binds to the neuromuscular junction (NMJ) and it is retro-axonally transported into vesicular compartments to the spinal cord, where it is released and taken up by inhibitory interneuron. Therein, the catalytic subunit is translocated into the cytoplasm where it cleaves its target protein VAMP-1/2 with consequent blockage of the release of inhibitory neurotransmitters. Vaccination with formaldehyde inactivated TeNT prevents the disease, but tetanus is still present in countries where vaccination coverage is partial. Here, we show that small molecule inhibitors interfering with TeNT trafficking or with the reduction of the interchain disulphide bond block the activity of the toxin in neuronal cultures and attenuate tetanus symptoms in vivo. These findings are relevant for the development of therapeutics against tetanus based on the inhibition of toxin molecules that are being retro-transported to or are already within the spinal cord and are, thus, not accessible to anti-TeNT immunoglobulins.

Reduction of the Double Bond of 6-Arylvinyl-1,2,4-trioxanes Leads to a Remarkable Increase in Their Antimalarial Activity against Multidrug-Resistant Plasmodium yoelii nigeriensis in a Swiss Mice Model.

Novel 6-arylethyl-1,2,4-trioxanes6a–i and 7a–i are easily accessible in one step from the diimide reduction of 6-arylvinyl-1,2,4-trioxanes 5a–i. All of these new trioxanes were assessed for their oral antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in a Swiss mice model. Most of the saturated trioxanes 6c, 6f, 6g, 6h, and 6i, the active compounds of the series, provided 100% protection to the malaria-infected mice at a dose of 24 mg/kg × 4 days. Further, trioxane 6i, the most active compound of the series, also showed 100% protection even at a dose of 12 mg/kg × 4 days and 20% protection at a dose of 6 mg/kg × 4 days. In this model, β-arteether provided 100% protection at a dose of 48 mg/kg × 4 days and only 20% protection at a dose of 24 mg/kg × 4 days via the oral route, which was found to exhibit 4-fold antimalarial activity compared with the currently used drug β-arteether.

Increasing Ionic Conductivity of Poly(ethylene oxide) by Reaction with Metallic Li

Poly(ethylene oxide) (PEO) was the first lithium‐ion conducting polymer developed 50 years ago and is still the most popular electrolyte matrix for solid‐state lithium metal batteries. While many studies focus on increasing PEO ionic conductivity through doping with Li salts, little work has addressed using PEO and Li directly to generate Li+‐conducting species in situ. Reaction between PEO and Li leads to ionic conductivity largely from Li+, in contrast to the case of added salts where the anion contribution dominates. Herein, electrochemical impedance spectroscopy shows the ionic conductivity of PEO thin films increases up to three orders of magnitude (from 10−7 to 10−4 S cm−1) when contacted with Li at elevated temperature. This is due to the reduction of ether bonds, which produces lithium alkoxides that are responsible for Li+ transport. Density functional theory analysis confirms this mechanism as thermodynamically favorable. X‐ray photoelectron spectroscopy also shows the presence of organolithium species and Li2O, which are responsible for propagating reactions with PEO and forming an electronically insulating layer at the PEO–Li interface that halts further reaction, respectively. The underlying mechanisms of Li–polymer electrolyte reactions is clarified and new pathways for in situ Li+ doping of polymer electrolytes is presented.

Finite element investigation of the shear performance of corroded RC deep beams without shear reinforcement

The shear behavior of reinforced concrete (RC) beams has been the principal subject of research studies. However, the structural behavior of RC deep beam without shear reinforcement is still complex and not well-understood. A total of sixteen corroded deep beam specimens without shear reinforcement were investigated in this numerical study. The finite element results confirm the validity of the developed constitutive models by comparing load - displacement curves and failure modes obtained in two experimental studies. It showed that the corrosion of longitudinal reinforcement decreased the load-carrying capacity and has shifted the load-transferring mechanism of corroded deep beams vastly, from combining arch and beam action to a more dominant arch action. Finally, a parametric study of corroded RC deep beam having no shear reinforcement is performed based on various parameters, i.e., degree of corrosion, bond reduction, anchorage condition, shear span-to-depth ratio. The obtained results show a considerable contribution of the corroded deep beam having sufficient anchorage provisions on the load-carrying capacity of beam specimens. Moreover, the shear span-to-depth ratio and corrosion degree do not always bring adverse effects on the failure mode, and shear resistance mechanism of corroded deep beams.

Effect of Cu doping on the secondary electron yield of carbon films on Ag-plated aluminum alloy

Reducing the secondary electron yield (SEY) of Ag-plated aluminum alloy is important for high-power microwave components. In this work, Cu doped carbon films are prepared and the secondary electron emission characteristics are studied systematically. The secondary electron coefficient δ max of carbon films increases with the Cu contents increasing at first, and then decreases to 1.53 at a high doping ratio of 0.645. From the viewpoint of surface structure, the higher the content of Cu is, the rougher the surface is, since more cluster particles appear on the surface due to the small solid solubility of Cu in the amorphous carbon network. However, from viewpoint of the electronic structure, the reduction of the sp2 hybrid bonds will increase the SEY effect as the content of Cu increases, due to the decreasing probability of collision with free electrons. Thus, the two mechanisms would compete and coexist to affect the SEY characteristics in Cu doped carbon films.

Study on the effects of various incubation conditions on aggregation of SOD1 variants: disulfide bond reduction and demetallation synergistically promote generation of non-amyloid amorphous aggregates from SOD1 mutants

Study on the effects of various incubation conditions on aggregation of SOD1 variants: disulfide bond reduction and demetallation synergistically promote generation of non-amyloid amorphous aggregates from SOD1 mutants

Numerical investigation of flexural behaviours of precast segmental concrete beams internally post-tensioned with unbonded FRP tendons under monotonic loading

This study numerically examines the prospects of replacing steel tendons with fibre reinforced polymer (FRP) tendons in precast segmental concrete girders/beams (PSCBs) for mitigating the corrosion damage to precast structures using finite element (FE) software Abaqus. This is the first study in the published literature that successfully builds an experimentally-verified 3D FE model of dry-joined PSCBs internally prestressed with unbonded FRP tendons to thoroughly investigate the beam’s flexural behaviour. The effect of segments’ interface imperfection on the initial stiffness of PSCBs was successfully captured in this study. The distinguished working mechanisms between monolithic and segmental beams, and between FRP and steel tendons in both tension- and compression-governed cases were comprehensively discussed. An intensive parametric study was also conducted to examine the effect of primary parameters (effective prestressing stress, prestressing reinforcement amount, span-to-depth ratio and different types of FRP tendons) on the flexural response of PSCBs. The results have proven that commonly available CFRP tendons (Young’s modulus Ep = 145 GPa) can well replace steel tendons in PSCBs while high-modulus CFRP tendons (Ep = 200 GPa) should be used with caution to ensure the PSCBs can achieve sufficient deformability. Moreover, among some existing models, ACI 440.4R-04′s model gave the most accurate predictions of the ultimate stress of unbonded FRP tendons (fpu) in PSCBs compared to the numerical results but its estimation was slightly unconservative and scattered. A new bond reduction factor was, hence, proposed for better prediction of fpu of FRP tendons in PSCBs. The ultimate stress of unbonded FRP tendons in PSCBs should be limited to 75% of the tensile strength of the tendon in design to account for the deformation concentration at the joints and the brittle failure characteristics of FRP tendons.

Enantioselective Synthesis of Isoflavanones and Pterocarpans through a RuII‐Catalyzed ATH‐DKR of Isoflavones

AbstractNoyori‐Ikariya RuII complexes promoted the one‐pot C=C/C=O bonds reduction of isoflavones using sodium formate as the hydrogen source through Asymmetric Transfer Hydrogenation‐Dynamic Kinetic Resolution (ATH‐DKR). Due to the neutral conditions employed, isoflavones with different substituents at the 2’‐position of B‐ring (H, OH, OMe and Br) were successfully reduced. Ten cis‐3‐phenylchroman‐4‐ols were selectively obtained (>20 : 1 dr) in good yields (up to 86 %) and excellent enantioselectivities (up to >99 : 1 er). The synthetic applications of these chiral compounds were also demonstrated. Enantioenriched isoflavanones were obtained under mild metal‐free oxidation of the cis‐3‐phenylchroman‐4‐ols while pterocarpans were synthesized by two strategies: an acid‐catalyzed cyclization and a novel approach based on a Pd‐catalyzed C−O intramolecular cross‐coupling reaction.

Amplified electrochemical sensor employing Ag NPs functionalized graphene paper electrode for high sensitive analysis of Sudan I

In this study, a high-performance flexible reduced graphene oxide (rGO) paper electrode composed of silver nanoparticles (Ag NPs) for the detection of Sudan I was fabricated. Ag NPs were doped with rGO nanoheets by self-assemble and assembled into a paper electrode with layer-by-layer structure via vacuum filtration. Thanks to the highly efficient electrocatalysis of Ag NPs towards reduction of azo bond, the as-prepared hybrid paper can be used alone as a flexible sensor for the detection of Sudan I in chili powder, with the high sensitivity (22.93 μA μmol/L) and the low detection limit (41.3 nmol/L). The sensor also expressed good selectivity, repeatability, reproducibility, stability and recovery between 96.1% and 101.8% (RSD < 6%). With the advantages of low-cost and scalable production capacity, such Ag NPs/rGO functional papers can be used as flexible disposable sensors for electrochemical detection of Sudan I.

Broader than expected tolerance for substitutions in the WCGPCK catalytic motif of yeast thioredoxin 2

Thioredoxins constitute a key class of oxidant defense enzymes that facilitate disulfide bond reduction in oxidized substrate proteins. While thioredoxin's WCGPCK active site motif is highly conserved in traditional model organisms, predicted thioredoxins from newly sequenced genomes show variability in this motif, making ascertaining which genes encode functional thioredoxins with robust activity a challenge. To address this problem, we generated a semi-saturation mutagenesis library of approximately 70 thioredoxin variants harboring mutations adjacent to their catalytic cysteines, making substitutions in the Saccharomyces cerevisiae thioredoxin Trx2. Using this library, we determined how such substitutions impact oxidant defense in yeast along with how they influence disulfide reduction and interaction with binding partners in vivo. The majority of thioredoxin variants screened rescued the slow growth phenotype that accompanies deletion of the yeast cytosolic thioredoxins; however, the ability of these mutant proteins to protect against H2O2-mediated toxicity, facilitate disulfide reduction, and interact with redox partners varied widely, depending on the site being mutated and the substitution made. We report that thioredoxin is less tolerant of substitutions at its conserved tryptophan and proline in the active site motif, while it is more amenable to substitutions at the conserved glycine and lysine. Our work highlights a noteworthy plasticity within the active site of this critical oxidant defense enzyme.

From Magic Bullet to Magic Bomb: Reductive Bioactivation of Antiparasitic Agents.

Paul Ehrlich coined the term "magic bullet" to describe how a drug kills the parasite inside its human host without harming the host itself. Ehrlich concluded that the drug must have a greater affinity to the parasite than to human cells. Today, the specificity of drug action is understood in terms of the drug target. An ideal target is a protein that is essential for the proliferation of the pathogen but absent in human cells. Examples are the enzymes of folate synthesis or of the nonmevalonate pathway in the malaria parasites. However, there are other ways how a drug can kill selectively. Of particular relevance is the specific activation of a prodrug inside the pathogen but not in the host, as this is how the current frontrunners of parasite chemotherapy work. Artemisinins for malaria, fexinidazole for human African trypanosomiasis, benznidazole for Chagas' disease, metronidazole for intestinal protozoa: these molecules are "magic bombs" that are triggered selectively. They are prodrugs that need to be activated by chemical reduction, i.e., the acquisition of an electron, which occurs in the parasite. Such a mode of action is shared by the novel antimalarial peroxides arterolane and artefenomel, which are activated by reduction of the endoperoxide bond with ferrous heme as the likely electron donor, a metabolic end-product of Plasmodium falciparum. Here we provide an overview on the molecular basis of selectivity of antiparasitic drug action with particular reference to the ozonides, the new generation of antimalarial peroxides designed by Jonathan Vennerstrom.

High Pressure Behavior of Mascagnite from Single Crystal Synchrotron X-ray Diffraction Data

High-pressure synchrotron X-ray diffraction was carried out on a single crystal of mascagnite, compressed in a diamond anvil cell. The sample maintained its crystal structure up to ~18 GPa. The volume–pressure data were fitted by a third-order Birch–Murnaghan equation of state (BM3-EOS) yielding K0 = 20.4(7) GPa, K’0 = 6.1(2), and V0 = 499(1) Å3, as suggested by the F-f plot. The axial compressibilities, calculated with BM3-EOS, were K0a = 35(3), K’0a = 7.7(7), K0b = 10(3), K’0b = 7(1), K0c = 25(1), and K’0c = 4.3(2) The axial moduli measured using a BM2-EOS and fixing K’0 equal to 4, were K0a = 52(2), K0b = 20 (1), and K0c = 29.6(4) GPa, and the anisotropic ratio of K0a:K0b:K0c = 1:0.4:0.5. The evolution of crystal lattice and geometrical parameters indicated no phase transition until 17.6 GPa. Sulphate polyhedra were incompressible and the density increase of 30% compared to investigated pressure should be attributed to the reduction of weaker hydrogen bonds. In contrast, some of them, directed along [100], were very short at room temperature, below 2 Å, and showed a very low compressibility. This configuration explains the anisotropic compressional behavior and the lowest compressibility of the a axis.