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A series of three new Mo-Sn clusters containing a [Mo3OS3Sn](super 6+) core are prepared by the reaction of [Mo(sub 3)(mu3-O)(mu-S)3](super 4+) type cluster complexes with SnCl2. Different configurations are observed according to the peripheral ligands.

Research is presented describing the stereospecific hydration of alpha,beta-unsaturated acyl-CoA thiolesters catalyzed by enoyl-CoA hydratase. The absolute stereospecificity for the enzyme-catalyzed reaction is calculated.

Geminal acylation of the acetal of isophorone by 1, 2-bisubstituted cyclobutene in the presence of borontrifluoride etharate yields angular triquinane plus or minus pentalenene. The spiro (4.4) nonane system, required for the formation of the final central ring, was obtained through ring cleavage and reclosure. Reduction of the double bond and ketone and dehydration after cyclization to the enone completed the synthesis.

A molecular model of the dimer of the equine infectious anemia virus proteinase (EIAV PR) in complex with a peptide substrate was constructed based on the Rouse sarcoma virus and human immunodeficiency virus (HIV-1) proteinases. Many similarities were observed between the molecular structures of EIAV PR and HIV-1 PR. A major difference, however, was the presence of 6 more residues near the tip of the flap believed to be important in interactions with substrate. In addition, a single residue deletion in the beta b' strand was found at a position corresponding to HIV-1 PR residue 60. The conformation of the residues leading to the flap were also modeled.

The structure of the tandem zinc-finger region of human ZHX1 protein related to the occurrence of certain cancers was determined to understand the function and structure of the individual ZHX domains. The results showed that both zinc-fingers (ZNF1 and ZNF2) adopted canonical [beta][beta][alpha]-folds in which a zinc ion is coordinated by two cysteine and two histidine residues while the C-terminal extension to ZNF2 forms two [beta]-strands to form a [beta]-sheet with the [beta]-strands of this zinc-finger.

By taking advantage of certain features in piperidine 4, we developed a novel series of cyclohexylamine- and piperidine-based benzenesulfonamides as potent and selective Nav1.7 inhibitors. However, compound 24, one of the early analogs, failed to reduce phase 2 flinching in the mouse formalin test even at a dose of 100 mpk PO due to insufficient dorsal root ganglion (DRG) exposure attributed to poor membrane permeability. Two analogs with improved membrane permeability showed much increased DRG concentrations at doses of 30 mpk PO, but, confoundingly, only one of these was effective in the formalin test. More data are needed to understand the disconnect between efficacy and exposure relationships. [ABSTRACT FROM AUTHOR]

Transcriptional control of c-myc oncogene is an important strategy for antitumor drug design. G-quadruplexes in the promoter region have been proven to be the transcriptional down-regulator of this gene. The transcriptional factor NM23-H2 can reactivate c-myc transcription by unwinding the G-quadruplex structure. Thus, down-regulation of c-myc transcription via disrupting G-quadruplex-NM23-H2 interaction might be a potential approach for cancer therapy. Here, a series of new isaindigotone derivatives were designed and synthesized based on our previous study. The abilities of these derivatives on interacting with G-quadruplexes or NM23-H2, and disrupting G-quadruplex-NM23-H2 interaction were evaluated. Among these derivatives, 19d and 22d showed remarkable abilities on disrupting G-quadruplex-NM23-H2 interaction. They exhibited significant effects on c-myc-relating processes in SiHa cells, including inhibiting the transcription and translation, inhibiting cellular proliferation, inducing apoptosis, and regulating cell cycle. Our findings provided the basis for the anticancer strategy based on c-myc transcriptional regulation via small molecules disrupting G-quadruplex-protein interaction. [ABSTRACT FROM AUTHOR]

Truncation of the S3 substituent of the biaryl aminothiazine 2, a potent BACE1 inhibitor, led to a low molecular weight aminothiazine 5 with moderate activity. Despite its moderate activity, compound 5 demonstrated significant brain Aβ reduction in rodents. The metabolic instability of 5 was overcome by the replacement of the 6-dimethylisoxazole, a metabolic soft spot, with a pyrimidine ring. Thus, truncation of the S3 substituent represents a viable approach to the discovery of orally bioavailable, brain-penetrant BACE1 inhibitors. [ABSTRACT FROM AUTHOR]

Negative Poisson's ratio (NPR) materials have drawn significant interest because the enhanced toughness, shear resistance, and vibration absorption that typically are seen in auxetic materials may enable a range of novel applications. In this work, we report that single-layer graphene exhibits an intrinsic NPR, which is robust and independent of its size and temperature. The NPR arises due to the interplay between two intrinsic deformation pathways (one with positive Poisson's ratio, the other with NPR), which correspond to the bond stretching and angle bending interactions in graphene. We propose an energy-based deformation pathway criteria, which predicts that the pathway with NPR has lower energy and thus becomes the dominant deformation mode when graphene is stretched by a strain above 6%, resulting in the NPR phenomenon. [ABSTRACT FROM AUTHOR]

Michael addition of thiourea to enones with subsequent intramolecular aminal ether formation provided easy access to furo[2,3-d]thiazinamines and pyrano[2,3-d][1,3]thiazin-2-amines. These amines served as versatile intermediates to a variety of beta-amyloid cleaving enzyme-1 (BACE1) inhibitors. [ABSTRACT FROM AUTHOR]

The chemical synthesis of paeoniflorin, the alpha-glucoside of paeoniflorigenin, and of plus- or minus-paeoniflorigenin has been accomplished. Paeoniflorin is a unique complex terpenoid from the roots of Paeonia lactiflora, the Chinese paeony, commonly employed in conventional Chinese medicine. It has been associated with intriguing neuromuscular, antiinflammatory, sedative and anticoagulant activities.

By coating polydimethylsiloxane (PDMS) relief structures with a layer of opaque metal such as gold, the incident light is strictly allowed to pass through the nanoscopic apertures at the sidewalls of PDMS reliefs to expose underlying photoresist at nanoscale regions, thus producing subwavelength nanopatterns covering centimeter-scale areas. It was found that the sidewalls were a little oblique, which was the key to form the nanoscale apertures. Two-sided and one-sided subwavelength apertures can be constructed by employing vertical and oblique metal evaporation directions, respectively. Consequently, two-line and one-line subwavelength nanopatterns with programmable feature shapes, sizes, and periodicities could be produced using the obtained photomasks. The smallest aperture size and line width of 80 nm were achieved. In contrast to the generation of raised positive photoresist nanopatterns in phase shifting photolithography, the recessed positive photoresist nanopatterns produced in this study provide a convenient route to transfer the resist nanopatterns to metal nanopatterns. This nanolithography methodology possesses the distinctive advantages of simplicity, low cost, high throughput, and nanoscale feature size and shape controllability, making it a potent nanofabrication technique to enable functional nanostructures for various potential applications. [ABSTRACT FROM AUTHOR]

A dogma for DNA polymerase catalysis is that the enzyme binds DNA first, followed by MgdNTP. This mechanism contributes to the selection of correct dNTP by Watson–Crick base pairing, but it cannot explain how low-fidelity DNA polymerases overcome Watson–Crick base pairing to catalyze non-Watson–Crick dNTP incorporation. DNA polymerase X from the deadly African swine fever virus (Pol X) is a half-sized repair polymerase that catalyzes efficient dG:dGTP incorporation in addition to correct repair. Here we report the use of solution structures of Pol X in the free, binary (Pol X:MgdGTP), and ternary (Pol X:DNA:MgdGTP with dG:dGTP non-Watson–Crick pairing) forms, along with functional analyses, to show that Pol X uses multiple unprecedented strategies to achieve the mutagenic dG:dGTP incorporation. Unlike high fidelity polymerases, Pol X can prebind purine MgdNTP tightly and undergo a specific conformational change in the absence of DNA. The prebound MgdGTP assumes an unusual syn conformation stabilized by partial ring stacking with His115. Upon binding of a gapped DNA, also with a unique mechanism involving primarily helix aE, the prebound syn-dGTP forms a Hoogsteen base pair with the template anti-dG. Interestingly, while Pol X prebinds MgdCTP weakly, the correct dG:dCTP ternary complex is readily formed in the presence of DNA. H115A mutation disrupted MgdGTP binding and dG:dGTP ternary complex formation but not dG:dCTP ternary complex formation. The results demonstrate the first solution structural view of DNA polymerase catalysis, a unique DNA binding mode, and a novel mechanism for non-Watson–Crick incorporation by a low-fidelity DNA polymerase. [ABSTRACT FROM AUTHOR]

Weperform molecular dynamics simulations to investigate the reductionof the thermal conductivity by kinks in silicon nanowires. The reductionpercentage can be as high as 70% at room temperature. The temperaturedependence of the reduction is also calculated. By calculating phononpolarization vectors, two mechanisms are found to be responsible forthe reduced thermal conductivity: (1) the interchanging effect betweenthe longitudinal and transverse phonon modes and (2) the pinchingeffect, that is, a new type of localization, for the twisting andtransverse phonon modes in the kinked silicon nanowires. Our workdemonstrates that the phonon interchanging and pinching effects, inducedby kinking, are brand-new and effective ways in modulating heat transferin nanowires, which enables the kinked silicon nanowires to be a promisingcandidate for thermoelectric materials. [ABSTRACT FROM AUTHOR]

The rapid and convenient method for identification of all kinds of G-quadruplex is highly desirable. In the present study, a novel colorimetric indicator for a vast variety of G-quadruplex was designed and synthesized on the basis of thiazole orange and isaindigotone skeleton. Its distinct color change enables label-free visual detection of G-quadruplexes, which is due to the disassembly of dye H-aggregates to monomers. This specific detection of G-quadruplex arises from its end-stacking interaction with G-quartet. On the basis of this universal indicator, a facile approach for large-scale identification of G-quadruplex was developed. [ABSTRACT FROM AUTHOR]

A novel route for preparing multidoped FePO4, an excellent starting material for synthesis of multidoped LiFePO4cathode materials for lithium ion batteries, by using converter steel slag as raw material is proposed in this study. The processes included selectively reclaiming Fe, Mn, Cr, and P from the slag in the form of a ferroalloy through a carbothermic process, reacting the ferroalloy with phosphoric acid and hydrogen peroxide solution to produce a precursor, and calcining the precursor to finally obtain the single-phase multidoped FePO4. Effects of the pH value of the reactive system on the constituents and structures of products are determined by XRF, XRD, and SEM analysis. The single-phase hexagonal multidoped FePO4doped with 1.5–3.3 atom % (Mn) was obtained at pH = 3.0–4.0, where the molar ratios of (Fe㉿) to P were tested to be close to 1. About 80 wt % Fe and Cr in the slag could be recovered and directly turned into the multidoped FePO4, and the control on recovery rate of Mn could be performed by adjusting the pH value of the precipitation system according to constituent demand of the final product. The results indicate that a feasible route for utilizing converter steel slag as substitutes for chemical reagents to prepare multidoped FePO4has been offered. [ABSTRACT FROM AUTHOR]

This paper describes the development of a high-throughput method for the analysis of cytochrome P450 (CYP) inhibition assay incubation samples using laser diode thermal desorption interfaced with atmospheric pressure chemical ionization mass spectrometry (LDTD-APCI-MS). Data for the CYP isoforms 3A4, 2D6, 2C9, and 1A2 from competitive inhibition assays are shown. The potential for inhibition of the CYP isoforms was measured by monitoring the level of the metabolites 6β-hydroxytestosterone (3A4), dextrorphan (2D6), 4′-hydroxydiclofenac (2C9), and acetaminophen (1A2) formed in the presence of drug candidates using an eight-point titration. The analytical method involves plating of the inhibition samples on specially designed 96-well plates with stainless steel bottoms, followed by direct analysis using the LDTD source. Validation of the LDTD-MS method was performed by testing for interferences, reproducibility, dynamic range, ion suppression, and the ability of the source to produce comparable results to previously validated LC-MS methods. IC50 values for each CYP isoform using 33 different test compounds showed excellent agreement between LDTD-APCI-MS and LC-MS methods and literature values where available. Assay analysis time using the LDTD-APCI source is reduced to less than 30 min for a single 96-well plate compared to greater than 10 h using the LC-MS method. The LDTD-APCI-MS and LC-MS methods and results are compared and limitations and future potential for LDTD-APCI-MS are discussed. [ABSTRACT FROM AUTHOR]

A triple quadrupole mass spectrometer capable of ion trapping experiments has been adapted for ion/ion reaction studies. The instrument is based on a commercially available linear ion trap (LIT) tandem mass spectrometer (i.e., an MDS SCIEX 2000 Q TRAP) that has been modified by mounting an atmospheric sampling glow discharge ionization (ASGDI) source to the side of the vacuum manifold for production of singly charged anions. The ASGDI source is located line of sight to the side of the third quadrupole of the triple quadrupole assembly (Q3). Anions are focused into the side of the rod array (i.e., anion injection occurs orthogonal to the normal ion flight path). A transmission mode method to perform ion/ion reactions has been developed whereby positive ions are transmitted through the pressurized collision quadrupole (Q2) while anions are stored in Q2. The Q2 LIT is used to trap negative ions whereas the Q3 LIT is used to accumulate positive ions transmitted from Q2. Anions are injected to Q3 and transferred to Q2, where they are stored and collisionally cooled. Multiply charged protein/peptide ions, formed by electrospray, are then mass selected by the first quadrupole assembly (Q1) operated in the rf/dc mode and injected into Q2. The positive ions, including the residual precursor ions and the product ions arising from ion/ion proton-transfer reactions, are accumulated in Q3 until they are analyzed via mass-selective axial ejection for mass analysis. The parameters that affect ion/ion reactions are discussed, including pressure, nature of the gas in Q2, and operation of Q2 as a linear accelerator. Ion/ion reactions in this mode can be readily utilized to separate ions with the same m/z but largely different mass and charge, e.g., +1 bradykinin and +16 myoglobin, in the gas phase. [ABSTRACT FROM AUTHOR]

Describes the role of antiapoptotic Cdc42 mutants on cellular transformation. Conservation of aspartic residues; Induction of cellular transformation; Stimulation of GDP-GTP exchange reaction.

Examines the use of electrospray ionization combined with ion/ion reaction in a quadruple ion trap for analysis of oligonucleotide mixtures. Issues on the ion polarity combination; Derivation of anions from perfluorocarbons; Conditions in forming positive oligonucleotide ions devoid of adducts.

Examines the protonated ubiquitin ions by using ion trap tandem mass spectrometry. Purification process of ubiquitin protein; Use of electrospray ionization for protein identification; Fragmentation reaction of protein ions.

This paper describes a visible-light-mediated oxidative cyclization of 2-aminobenzyl alcohols and secondary alcohols to produce quinolines at room temperature. This photocatalytic method employed anthraquinone as an organic small-molecule catalyst and DMSO as an oxidant. According to this present procedure, a series of quinolines were prepared in satisfactory yields.

Transcriptional control of c-myc oncogene is an important strategy for antitumor drug design. G-quadruplexes in the promoter region have been proven to be the transcriptional down-regulator of this gene. The transcriptional factor NM23-H2 can reactivate c-myc transcription by unwinding the G-quadruplex structure. Thus, down-regulation of c-myc transcription via disrupting G-quadruplex-NM23-H2 interaction might be a potential approach for cancer therapy. Here, a series of new isaindigotone derivatives were designed and synthesized based on our previous study. The abilities of these derivatives on interacting with G-quadruplexes or NM23-H2, and disrupting G-quadruplex-NM23-H2 interaction were evaluated. Among these derivatives, 19d and 22d showed remarkable abilities on disrupting G-quadruplex-NM23-H2 interaction. They exhibited significant effects on c-myc-relating processes in SiHa cells, including inhibiting the transcription and translation, inhibiting cellular proliferation, inducing apoptosis, and regulating cell cycle. Our findings provided the basis for the anticancer strategy based on c-myc transcriptional regulation via small molecules disrupting G-quadruplex-protein interaction.

Negative Poisson's ratio (NPR) materials have drawn significant interest because the enhanced toughness, shear resistance, and vibration absorption that typically are seen in auxetic materials may enable a range of novel applications. In this work, we report that single-layer graphene exhibits an intrinsic NPR, which is robust and independent of its size and temperature. The NPR arises due to the interplay between two intrinsic deformation pathways (one with positive Poisson's ratio, the other with NPR), which correspond to the bond stretching and angle bending interactions in graphene. We propose an energy-based deformation pathway criteria, which predicts that the pathway with NPR has lower energy and thus becomes the dominant deformation mode when graphene is stretched by a strain above 6%, resulting in the NPR phenomenon.

The Poisson's ratio characterizes the resultant strain in the lateral direction for a material under longitudinal deformation. Though negative Poisson's ratios (NPR) are theoretically possible within continuum elasticity, they are most frequently observed in engineered materials and structures, as they are not intrinsic to many materials. In this work, we report NPR in single-layer graphene ribbons, which results from the compressive edge stress induced warping of the edges. The effect is robust, as the NPR is observed for graphene ribbons with widths smaller than about 10 nm, and for tensile strains smaller than about 0.5% with NPR values reaching as large as -1.51. The NPR is explained analytically using an inclined plate model, which is able to predict the Poisson's ratio for graphene sheets of arbitrary size. The inclined plate model demonstrates that the NPR is governed by the interplay between the width (a bulk property), and the warping amplitude of the edge (an edge property), which eventually yields a phase diagram determining the sign of the Poisson's ratio as a function of the graphene geometry.