Chiral analyses of dextromethorphan/levomethorphan and their metabolites in rat and human samples using LC-MS/MS

In order to develop an analytical method for the discrimination of dextromethorphan (an antitussive medicine) from its enantiomer, levomethorphan (a narcotic) in biological samples, chiral analyses of these drugs and their O-demethyl and/or N-demethyl metabolites in rat plasma, urine, and hair were carried out using LC-MS/MS. After the i.p. administration of dextromethorphan or levomethorphan to pigmented hairy male DA rats (5 mg/kg/day, 10 days), the parent compounds and their three metabolites in plasma, urine and hair were determined using LC-MS/MS. Complete chiral separation was achieved in 12 min on a Chiral CD-Ph column in 0.1% formic acid–acetonitrile by a linear gradient program. Most of the metabolites were detected as being the corresponding O-demethyl and N, O-didemethyl metabolites in the rat plasma and urine after the hydrolysis of O-glucuronides, although obvious differences in the amounts of these metabolites were found between the dextro and levo forms. No racemation was observed through O- and/or N-demethylation. In the rat hair samples collected 4 weeks after the first administration, those differences were more clearly detected and the concentrations of the parent compounds, their O-demethyl, N-demethyl, and N, O-didemethyl metabolites were 63.4, 2.7, 25.1, and 0.7 ng/mg for the dextro forms and 24.5, 24.6, 2.6, and 0.5 ng/mg for the levo forms, respectively. In order to fully investigate the differences of their metabolic properties between dextromethorphan and levomethorphan, DA rat and human liver microsomes were studied. The results suggested that there might be an enantioselective metabolism of levomethorphan, especially with regard to the O-demethylation, not only in DA rat but human liver microsomes as well. The proposed chiral analyses might be applied to human samples and could be useful for discriminating dextromethorphan use from levomethorphan use in the field of forensic toxicology, although further studies should be carried out using authentic human samples.     

Biphenyl ether and biphenyl quinolizidine lactone alkaloids from Heimia salicifolia

Three new biphenyl ether quinolizidine lactone alkaloids (1–3) and 13 new biphenyl quinolizidine lactone alkaloids (4–16) were isolated from Heimia salicifolia (Lythraceae) together with seven known alkaloids. Their structures were determined by spectroscopic analyses and chemical conversions.     

Synthetic studies on macroviracin A: a rapid construction of C(42) macrocyclic dilactone corresponding to the core

The C(2)-symmetric macrodiolide core 2 of an antiviral agent, macroviracin A (1), was constructed in a single step by the intermolecular macrodimerization of C(22)-hydroxy carboxylic acid 3 with 2-chloro-1,3-dimethylimidazolinium chloride and DMAP in the presence of sodium hydride (NaH). The use of potassium hydride instead of NaH caused the intramolecular cyclization, predominantly providing the corresponding monomer 26. The acid 3 was synthesized through a series of reactions such as the coupling reaction of acetylene 5 and oxirane 6, stereoselective glycosidation with the trichloroacetimidate method, and Jones oxidation.     

Spectrophotometric determination of boron in natural waters and rocks after specific adsorption on sephadex gel

Borate ions are adsorbed on Sephadex G-25 gel from alkaline media and desorbed reversibly into acidic media; the adsorption is ascribed to complex formation between borate and glucose units in the gel matrix. The coexistence of large amounts of salts, e.g. sodium chloride, ammonium chloride, sodium sulfate, and sodium perchlorate, has little effect on the adsorption. The effect of cations which form complexes with borate can be eliminated by the addition of EDTA. Boron present, in natural waters and rocks at lowlevels can be selectively concentrated by means of a gel column and determined spectrophotometrically by the azomethine-H method.     

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.     

Nontrivial Eigenvalues of the Liouvillian of an Open Quantum System

We present methods of finding complex eigenvalues of the Liouvillian of an open quantum system. The goal is to find eigenvalues that cannot be predicted from the eigenvalues of the corresponding Hamiltonian. Our model is a T-type quantum dot with an infinitely long lead. We suggest the existence of the non-trivial eigenvalues of the Liouvillian in two ways: one way is to show that the original problem reduces to the problem of a two-particle Hamiltonian with a two-body interaction and the other way is to show that diagram expansion of the Green’s function has correlation between the bra state and the ket state. We also introduce the integral equations equivalent to the original eigenvalue problem.     

Simultaneous determination of N-benzylpiperazine and 1-(3-trifluoromethylphenyl)piperazine in rat plasma by HPLC-fluorescence detection and its application to monitoring of these drugs

An HPLC‐fluorescence detection method for simultaneous determination of N‐benzylpiperazine (BZP) and 1‐(3‐trifluoromethylphenyl)piperazine (TFMPP) labeled with 4‐(4,5‐diphenyl‐1 H‐imidazol‐2‐yl)benzoyl chloride (DIB‐Cl) was described. DIB‐BZP and ‐TFMPP were well separated within 13 min without interference of peaks from plasma components. The lower detection limits of BZP and TFMPP at a signal‐to‐noise ratio of 3 were 0.9 and 4.6 ng/mL, respectively. Precisions of the proposed method for intra‐ and inter‐day assays were less than 4.8 and 9.1% as %RSD (n = 5). Furthermore, the method could be successfully applied to monitor both compounds in plasma after their sole or co‐administration to rats (each dose, 2 mg/kg). Clearance of TFMPP was significantly different under the conditions (P = 0.047). Copyright © 2011 John Wiley & Sons, Ltd.     

Self-Assembled Graphene/MWCNT Bilayers as Platinum-Free Counter Electrode in Dye-Sensitized Solar Cells

We describe the preparation and properties of bilayers of graphene- and multi-walled carbon nanotubes (MWCNTs) as an alternative to conventionally used platinum-based counter electrode for dye-sensitized solar cells (DSSC). The counter electrodes were prepared by a simple and easy-to-implement double self-assembly process. The preparation allows for controlling the surface roughness of electrode in a layer-by-layer deposition. Annealing under N₂ atmosphere improves the electrode's conductivity and the catalytic activity of graphene and MWCNTs to reduce the I₃⁻ species within the electrolyte of the DSSC. The performance of different counter-electrodes is compared for ZnO photoanode-based DSSCs. Bilayer electrodes show higher power conversion efficiencies than monolayer graphene electrodes or monolayer MWCNTs electrodes. The bilayer graphene (bottom)/MWCNTs (top) counter electrode-based DSSC exhibits a maximum power conversion efficiency of 4.1 % exceeding the efficiency of a reference DSSC with a thin film platinum counter electrode (efficiency of 3.4 %). In addition, the double self-assembled counter electrodes are mechanically stable, which enables their recycling for DSSCs fabrication without significant loss of the solar cell performance.     

Synthesis and properties of π-extended fluoranthene derivatives from 1,2-diarylacenaphthylene derivatives

Acenaphthylene units work as a useful platform for the synthesis of polycyclic aromatic hydrocarbons (PAH). Three 1,2-diarylacenaphthylene derivatives (9-phenanthryl, 7-t-butyl-2-pyrenyl and 2-naphthyl) were prepared by Suzuki-Miyaura coupling of 1,2-dibromoacenaphthylene with the corresponding boronic acids and ester. The Scholl reaction of the phenanthryl derivative affords a donor-acceptor type fluoranthene derivative possessing a hemi-coronene structure by forming two CC bonds between phenanthryl groups. The reaction of the pyrenyl derivative allows one CC bond formation to give a helicene-type fluoranthene derivative. The reaction of the naphthyl derivative provides an asymmetric fluroranthene derivative having an anthracene unit accompanied with one CC bonding reaction, while a photochemical cyclization followed by dehydroaromatization reaction of the compound gives a symmetric fluoranthene derivative with a [5]helicene structure.