Identification of a novel cannabimimetic phenylacetylindole, cannabipiperidiethanone, as a designer drug in a herbal product and its affinity for cannabinoid CB₁ and CB₂ receptors

A new cannabimimetic phenylacetylindole (cannabipiperidiethanone, 1) has been found as an adulterant in a herbal product which contains two other known synthetic cannabinoids, JWH-122 and JWH-081, and which is distributed illegally in Japan. The identification was based on analyses using GC-MS, LC-MS, high-resolution MS and NMR. Accurate mass spectrum measurement showed the protonated molecular ion peak of 1 at m/z 377.2233 [M+H]? and the molecular formula of 1 was C??H??N?O?. Both mass and NMR spectrometric data revealed that 1 was 2-(2-methoxyphenyl)-1-{1-[(1-methylpiperidin-2-yl)methyl]-1H-indol-3-yl}ethanone. Compound 1 has a mixed structure of known cannabimimetic compounds: JWH-250 and AM-2233. Namely, the moiety of phenylacetyl indole and N-methylpiperidin-2-yl-methyl correspond to the structure of JWH-250 and AM-2233, respectively. However, no synthetic, chemical or biological information about 1 has been reported. A binding assay of compound 1 to cannabinoid receptors revealed that 1 has affinity for the CB? and CB? (IC??=591, 968 nM, respectively) receptors, and shows 2.3- and 9.4-fold lower affinities than those of JWH-250. This is the first report to identify cannabimimetic compound (1) as a designer drug and to show its binding affinity to cannabinoid receptors.     

Charge‐Transfer Mechanism in Pt/KTa(Zr)O3 Photocatalysts Modified with Porphyrinoids for Water Splitting

The mechanism of photocatalytic splitting of H₂O into H₂ and O₂ on Pt/KTa(Zr)O₃ modified with various porphyrinoids was investigated. The photocatalytic activity of KTaO₃ catalysts is improved by dye modification. Cyanocobalamin (vitamin B₁₂) is the most effective for improving water‐splitting activity, and the formation rates of H₂ and O₂ achieved values of 575 and 280 μmol g_cat.^?1 h^?1, respectively. X‐ray photoelectron spectroscopy spectra of KTa(Zr)O₃ photocatalysts showed that Pt loaded onto dye‐modified KTaO₃ was slightly oxidized and had low catalytic activity for the H₂ oxidation reaction. Photoluminescence (PL) spectra of KTaO₃ catalysts suggested that excitation energy was transferred between KTaO₃, tetraphenylporphyrinatochromium(III) (Cr–TPP), and the Pt cocatalyst. The wavelength dependence of the activity of dye‐modified KTa(Zr)O₃ photocatalysts indicated that excitation of both KTa(Zr)O₃ and the dye was essential for achieving increased photocatalytic activity. This result suggests that two‐step excitation occurred in the dye‐modified KTa(Zr)O₃ photocatalysts. Because the lifetime of the charge‐separated state increased, this study reveals that modification with porphyrinoids is effective for increasing water‐splitting activity.     

Simultaneous determination of nitrite, nitrate, thiocyanate and uric acid in human saliva by capillary zone electrophoresis and its application to the study of daily variations

Simultaneous determination of nitrite (NO2-), nitrate (NO3-), thiocyanate (SCN-) and uric acid in human saliva was performed by capillary zone electrophoresis using a coated capillary with reversed electroosmotic flow (EOF), using a 100 mM sodium phosphate buffer at pH 6.5 as a running buffer. Saliva samples were deproteinized with acetonitrile and filtered through a membrane filter. The important advantages of the reported method are: simple operation, short analysis time, minimal sample pre-treatment and sample dilution. In order to evaluate the daily variations of the anionic components, the concentrations were determined in the human saliva of four healthy volunteers upon waking and at 2qh intervals during a day.     

A new series of estrogen receptor modulators: effect of alkyl substituents on receptor-binding affinity

New types of selective estrogen receptor modulators (SERMs) were synthesized and evaluated for their binding affinity and biological effect on reproductive cells. A proposed lead structure (B) was derivatized to provide compounds 30 and 44, which showed good estrogen-receptor binding affinity (K(i) values: 6.3 and 10 nM, respectively), as well as minimal impact on mammary and uterine carcinoma cells. Introduction of an alkyl group in the core structure considerably enhanced receptor-binding affinity of the compounds tested. Synthesis and structure-activity relationships of these compounds are described.     

Electrochemical preparation of graphite intercalation compounds containing a cyclic amide, [CF2(CF2SO2)2N]

Graphite intercalation compounds (GICs) containing the cyclo-hexafluoropropane-1,3-bis(sulfonyl)amide anion, [CF₂(CF₂SO₂)₂N]⁻, are prepared for the first time. Stages 2 and 3 GICs are obtained by electrochemical oxidation of graphite in a nitromethane electrolyte. Gallery heights of 0.85-0.86 nm are determined by powder X-ray diffraction, and the intercalate anion orientation within the intercalate galleries is modeled using an energy minimized anion structure. GIC compositions are determined by thermogravimetric, fluorine and nitrogen analyses. The chemical preparation and bifluoride displacement reactions are compared with a GIC containing the linear bis(trifluoromethanesulfonyl)amide anion, [(CF₃SO₂)₂N]⁻.     

Temperature-induced transformations of peroxide radicals formed in polytetrafluoroethylene with γ-ray irradiation

At 200°C, temperature-induced transformations of peroxide radicals from ? CF₂CF(OO·)CF₂? (radical I) to ? CF₂CFCF₂? (radical 1) and ? CF₂CF₂OO· (radical II) to ? CF₂CF₂ (radical 2) in vacuo, and from I to II in oxygen atmosphere were observed. In these thermal transformations, the evolution of CO₂ with a small amount of CO and CF₂O was observed. Further, measurements of the heat of crystallization of the treated polytetrafluoroethylene suggest that a reduction of polymer molecular weight occurs during the transformations from I to 1 and I to II.     

Effect of acetylene on the γ-radiation-induced polymerization of ethylene

The effects of acetylene on the γ-radiation-induced polymerization of ethylene were studied from the viewpoint of the gaseous products and polymer structure. The experiments were carried out under a pressure of 400 kg/cm²; the temperature was 30°C; the does rate was 1.1 × 10⁵ rad/hr; and the acetylene content was 0–20%. The solid polymer was obtained in the polymerization of ethylene containing 2.2% acetylene, while the monomer containing 19.7% acetylene gave a yellowish viscous oil. The polymer yield and molecular weight decreased remarkably with acetylene content. The main gaseous product was hydrogen, and trace amounts of butane, butene-1, butadiene-1,3, and benzene and its derivatives were also observed. The rate of formation of hydrogen was almost independent of acetylene content and there was no difference in acetylene contents before and after the irradiation was found. The infrared spectra of the polymers showed the presence of vinylidene, trans-vinylene, and terminal vinyl unsaturations, 1,4-disubstituted benzene, and carbonyl groups. The contents of trans-vinylene, terminal vinyl, and methyl groups increased with acetylene content, and that of vinylidene was independent of acetylene content. The monomer reactivity ratios of ethylene and acetylene were evaluated as 45.5 and 66.0, respectively. On the basis of the results, the effects of acetylene on the γ-radiation-induced polymerization of ethylene were discussed.     

SmI2-induced reductive cyclization of optically active β-alkoxyvinyl sulfoxides with aldehyde

SmI₂-induced reductive cyclization of optically active (E)- and (Z)-β-alkoxyvinyl sulfoxides with aldehyde was developed for the construction of several stereoisomers of tetrahydropyran derivatives.