Structure determination of a sildenafil analogue contained in commercial herb drinks

It was found from HPLC analysis that a commercial herb drink contains a putative sildenafil analog. In order to identify the sildenafil-like compound, separation and purification were carried out. The structure determination was performed based on routine 1D and 2D NMR experiments. Unlike sildenafil, the compound contains an ethylpiperazine instead of a methylpiperazine group. In addition, the piperazine and phenyl groups are connected through an acetyl group instead of the sulfonyl group of sildenafil.     

Decomposition of oxalate by hydrogen peroxide in aqueous solution

The decomposition rate of oxalate by hydrogen peroxide has been investigated by a KMnO₄ titration method. The rate equation for decomposition of hydrogen peroxide in the aqueous phase is 1n([H₂O₂]/[H₂O₂]₀)=?k₁·t, where k₁=0.2, for [H⁺]<2M, k₁=0.2+0.34([H⁺]?2), for [H⁺]>2M. As the acidity increases over 2M, an acid catalysis effect appeard. The new rate equation proposed for the decomposition of oxalate by hydrogen peroxide is $$ - \frac{d}{{dt}}X_{[OX]} = k_2 [H_2 O_2 ]_0 (1 - X_{[OX]} )(e^{ - k_1 t} - \frac{{[OX]_0 }}{{[H_2 O_2 ]_0 }}X_{[OX]} )$$ The rate constant for decomposition of oxalate, k₂, increased with nitric acid concentration and the effect of hydrogen ion concentration was expressed as k₂=a[H⁺]ⁿ, where the values fora andn were a=1.54, n=0.3 at [H⁺]<2M, a=0.31, n=2.5 at [H⁺]>2M, respectively.     

Exploiting poly(dimethylsiloxane)-modified tips to evaluate frictional behavior by friction force microscopy

With the aim of investigating the effect of the surface properties on the friction behavior of self-assembled monolayers, we have modified tipless atomic force microscopy (AFM) cantilevers with a poly(dimethylsiloxane) (PDMS) lens. The friction coefficient using the silicon tip is strongly influenced by the mechanical properties of the substrate monolayer because hard, sharp silicon tips penetrate the surface of organic monolayers. However, the friction coefficient obtained for the PDMS-modified AFM cantilever is mostly due to the surface properties of the monolayer functional end group, rather than the viscoelastic deformation of the monolayer. The use of the PDMS tip was demonstrated as a novel means to investigate the effect of surface properties on the frictional behavior of self-assembled monolayers with various functional groups with less mechanical deformation.     

Blockade of translationally controlled tumor protein attenuated the aggressiveness of fibroblast-like synoviocytes and ameliorated collagen-induced arthritis

Histamine releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses, but the role of HRF/TCTP in rheumatoid arthritis (RA) remains undefined. In this study, we explored the pathogenic significance of HRF/TCTP and evaluated the therapeutic effects of HRF/TCTP blockade in RA. HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine the experimental phenotypes of RA. HRF/TCTP levels in the sera of RA patients were measured and compared to those from patients with osteoarthritis (OA), ankylosing spondylitis, Behçet’s disease, and healthy controls. HRF/TCTP expression was also assessed in the synovium and fibroblast-like synoviocytes (FLSs) obtained from RA or OA patients. Finally, we assessed the effects of HRF/TCTP and dimerized HRF/TCTP-binding peptide-2 (dTBP2), an HRF/TCTP inhibitor, in RA-FLSs and CIA mice. Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were increased in HRF/TCTP TG mice and decreased in KD mice compared to wild-type littermates. HRF/TCTP levels in the sera, synovial fluid, synovium, and FLSs were higher in patients with RA than in control groups. Serum levels of HRF/TCTP correlated well with RA disease activity. The tumor-like aggressiveness of RA-FLSs was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice and had no detrimental effects in a murine tuberculosis model. Our results indicate that HRF/TCTP is a novel biomarker and therapeutic target for the diagnosis and treatment of RA.Subject terms: Translational research, Autoimmunity     

High-throughput screening of inhibitory potential of nine cytochrome P450 enzymes in vitro using liquid chromatography/tandem mass spectrometry

The early detection of potential drug-drug interactions is an important issue of drug discovery that has led to the development of high-throughput screening (HTS) methods for potential drug interactions. We developed a HTS method for potential interactions of inhibitory drugs for nine human P450 enzymes using cocktail incubation and tandem mass spectrometry in vitro. This new method involves incubation of two cocktail doses and single cassette analysis. The two cocktail doses in vitro were developed to minimize solvent effects and mutual drug interactions among substrates: cocktail A was composed of phenacetin for CYP1A2, coumarin for CYP2A6, paclitaxel for CYP2C8, S-mephenytoin for CYP2C19, dextromethorphan for CYP2D6, and midazolam for CYP3A4; and cocktail B was composed of three substrates including bupropion for CYP2B6, tolbutamide for CYP2C9, and chlorzoxazone for CYP2E1. In the incubation study of these cocktails, the reaction mixtures were pooled and simultaneously analyzed using liquid chromatography/tandem mass spectrometry employing a fast gradient. The method was validated by comparing the inhibition data obtained from the incubation of each individual probe substrate alone with data from the new method. The IC50 value of each inhibitor in the cocktail agreed well with that of the individual probe drug as well as with values previously reported in the literature. As a HTS method for potential interactions of the inhibition of these nine P450 enzymes, this new method will be useful in the drug discovery process and for the mechanistic understanding of drug interactions.     

Solvent effects on the singlet - triplet equilibrium and reactivity of a ground triplet state arylalkyl carbene

Results from intramolecular singlet and triplet specific reactivity in solvents of different Polarity suggest that the spin state equilibrium of 1,2-diphenyl-1-butylidene, a triplet ground state carbene. is largely susceptible to solvent polarity. The results are consistent with stabilization of the zwitterionic singlet state in solvents of high polarity.     

Column chromatographic prefractionation leads to the detection of 543 different gene products in human fetal brain

In a previous publication a large series of proteins were identified in fetal human brain by the use of two-dimensional electrophoresis (2-DE) with subsequent matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and MALDI-tandem time-of-flight (TOF/TOF) analysis. Further identification of many more different spots by traditional 2-DE without additional step such as narrow immobilized ph gradient (IPG) strips or prefractionation seems unlikely and we therefore decided to separate extracted brain proteins by ion-exchange chromatography using a TSK gel DEAE-5PW column followed by 2-DE of individual fractions and analysis by MALDI-TOF/TOF with LIFT technology in fetal brain of the early second trimester. About 1880 protein spots corresponding to 543 different gene products were identified. These proteins included housekeeping, signaling, cytoskeletal, metabolic, antioxidant, and neuron/synaptosomal specific proteins. Among these, 314 gene products (314/543, 57.8%), which have never been detected in traditional 2-DE of human fetal brain, were observed by this method. This updated map of fetal brain proteins may serve as data base and reference map for fetal brain proteins, and the methodology applied may be used as a valuable analytical tool for the basis of protein expressional studies in health and disease.     

Simultaneous vibrational and rotational transitions in hydrogen + argon at high collision velocities: Collisions at nonzero impact parameters

The problem of vibrationally and rotationally inelastic scattering processes in H₂ + Ar for nonzero impact parameter b has been investigated in the collision velocity range of 10⁶–10⁷ cm/sec by use of the sudden approximation. The simultaneous vibrational (0 → 1) and rotational (00 → 00, 20, or 40) transitions were studied. For υ > 3 x 10⁶ cm/sec, the probabilities for b/l = 1.0 are found to be very large compared with those for b = 0, where l is the hard-sphere collision diameter; for b/l > 1.0, the probabilities decrease very rapidly with increasing b. The results show that nonzero-b collisions must be included in the calculation of simultaneous transition processes in H₂ + Ar at higher collision velocities.     

Vibrational relaxation of hydrogen fluorides: HF(ν = 1) + F → HF(ν = 0) + F

The deexcitation rate constant of HF(ν = 1) + F → HF(ν = 0) + F is calculated over the temperature range 100–3000 K based on the collision model of FH + F in an operator calculus approach. At temperatures above 1500 K, the rate constant is very large with the magnitude of 10¹³ cm³/mol s. From 100 to 1500 K, the rate constant increases by two orders of magnitude.     

Study of the effect of stabilizer on the degradation of poly(vinyl chloride) by pyrolysis–gas chromatography

The effect of stabilizer on the thermal degradation of poly(vinyl chloride) was studied by means of pyrolysis–gas chromatography. The stabilizers used in this study were dibutyltin dilaurate, dibutyltin bis(n-dodecyl mercaptide), barium stearate, and zinc stearate. PVC containing these stabilizers was degraded in a stream of nitrogen at temperatures ranging from 350 to 570°C. It was found that observed drastic reduction of benzene yield from the PVC containing zinc stearate had a close correlation with the formation of crosslinking structures.