Gas chromatographic analysis of isomeric organic mononitrates in plasma.

A specific, sensitive and precise capillary gas chromatographic method using electron-capture detection was developed for the determination of four isomeric vasodilating organic mononitrates, viz. L-isoidide mononitrate (L-IIMN), isosorbide-2-mononitrate (IS-2-MN), isomannide mononitrate (IMMN) and isosorbide-5-mononitrate (IS-5-MN), in rat plasma. With a sample size of 100 microliters of rat plasma, the detection limits were found to be between 0.5 and 2 ng/ml for these mononitrates, and the absolute recovery was found to range from 83 to 90%. The within-day coefficients of variation for the assay of the four isomers were less than 5%, while the between-day coefficients of variation were less than 10%. Because of the short retention times of these isomers in this assay, routine analyses of about sixty plasma samples per day can be carried out. The possibility of in vivo interconversion among these four isomers in rats was investigated after individual administration of each isomer. No interconversion was found based on examination of plasma samples. The gas chromatographic method was applied to the pharmacokinetic studies of these four isomers in rats; at an intravenous dose of 2 mg/kg, the biological half-lives of L-IIMN, IMMN, IS-2-MN and IS-5-MN were found to be 13.2, 25.2, 54.6 and 112 min, respectively.     

Synthesis of Coumarin Derivatives as Inhibitors of Platelet Aggregation

In a search for the inhibitors of platelet aggregation, certain coumarin derivatives were synthesized and evaluated for antiplatelet activity against thrombin(Thr)-, arachidonic acid(AA)-, collagen(Col)-, and platelet-activating-factor(PAF)-induced aggregation in washed rabbit platelets. These compounds were synthesized from 4-hydroxycoumarin ( 1 ) or naphthalen-1-ol via alkylation and Reformatsky-type condensation (Schemes 1–3). Among them, 4-[(2,3,4,5-tetrahydro-4-methylidene-5-oxo-2-phenylfuran-2-yl)methoxy]-2H-1-benzopyran-2-one ( 6b ) showed potent antiplatelet effects on AA- and PAF-induced aggregation with IC₅₀ values of 8.21 and 103.67 m?M , respectively (see Tables 1 and 2). The antiplatelet potency of 6b against PAF-induced aggregation could be further improved by introducing a proper substituent at the 2-phenyl group of the lactone ring.     

Synthesis and antibacterial activity of 1-(substituted-benzyl)-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acids and their 6,8-difluoro analogs

Alkylation of 6,7-difluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester with substituted-benzyl chlorides gave 1-(substituted-benzyl)-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid ethyl esters. Their treatment with piperazine or N-methylpiperazine in pyridine yielded 1-(substituted-benzyl)-6-fluoro-1,4-dihydro-4-oxo-7-(l-piperazinyl)quinoline-3-carboxylic acid ethyl esters which were hydrolyzed with aqueous sodium hydroxide and then acidified with hydrochloric acid afforded the desired 1-(substituted-benzyl)-6-fluoro-1,4-dihydro-4-oxo-7-(1-iperazinyl)quinoline-3-carboxylic acids. The 6,8-difluoro analogs were prepared similarly using 6,7,8-trifluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester as a starting material. Some of these quinolones demonstrated fairly good antibacterial activities. Among them, 6-fluoro-1-(4-fluorophenylmethyl)-1,4-dihydro-7-(1-iperazinyl)-4-oxoquinoline-3-carboxylic acid ( 7d ) and 6,8-difluoro-1-(3-fluorophenylmethyl)-1,4-dihydro-7-(1-piperazinyl)-4-oxoquinoline-3-carboxylic acid ( 8c ) are two of the best.     

Plastic microchip electrophoresis for genetic screening: the analysis of polymerase chain reactions products of fragile X (CGG)n alleles

Clinical screening of abnormal chromosomes associated with fragile X syndrome (FXS) demands a high-throughput method including DNA sizing and detection of the amplified products. This study is to explore the use of polymer microchip electrophoresis for the analysis of polymerase chain reaction (PCR) products of fragile X (CGG)n alleles to facilitate a fast exclusion test of FXS. The sequences flanking the CGG-repeat of FMR1 gene was amplified by betaine-PCR and the amplified products were desalted and then analyzed by microchips which were fabricated on poly(methyl methacrylate) (PMMA) substrate. The PCR bands with more than six CGG-repeats in difference could be clearly distinguished in less than 3 min by microchip electrophoresis with a separation length of 6 cm. It was found that the signal was greatly enhanced with the use of both covalent (Cy5) and intercalating dye (TORRO-3), which has never been demonstrated before. We tested the method by reanalysis of twelve samples from males and six samples from females. For female samples with less than six repeat differences, Southern blotting method was performed to confirm or exclude the findings from microchips. It was found that the test results from all male and female samples show a 100% correlation between the microchip electrophoresis and the existing methods.     

Role of the F spin-orbit excited state in the F+HD reaction: contributions to the dynamical resonance

We report quantum mechanical calculations of excitation functions (relative reaction cross sections) for the F+HD reaction. We include three potential energy surfaces and an accurate treatment of all couplings (non-adiabatic, spin-orbit, and Coriolis). Comparison with experimental results [Dong, Lee, and Liu, J. Chem. Phys., 113, 3633 (2000)] show excellent agreement for the DF product channel and an improved but not perfect agreement for the HF product channel. In the former case, when weighted by the (16%) fractional population of the spin-orbit excited state (F(*)) in the beam, the overall reactivity of the F(*) is small (approximately 5%). For the HF product channel and with the same (16%) fractional weight, F(*) reactivity makes a contribution of approximately 12% in the high-energy tail of the resonance peak. As a result, averaging over the population of F spin-orbit states in the beam changes the shape of the resonance. The greater the fraction of F(*) in the beam, the less pronounced will be the resonance modulation of the reaction excitation function.     

A luminescent supermolecule with gold(I) quinoline-8-thiolate: crystal structure,spectroscopic and photophysical properties

The trinuclear complex [(8-QNS)(2)Au(AuPPh(3))(2)].BF(4) (8-QNS = quinoline-8-thiolate), with intramolecular gold(I)...gold(I) distances of 3.0952(4) and 3.0526(3) A, is aggregated to form a novel hexanuclear supermolecule, ([(8-QNS)2(Au(AuPPh3)2])2.(BF4)2, via a close intermolecular gold(I)...gold(I) contact of 3.1135(3) A. The beautiful hexanuclear supermolecule has an inversion center, and the six metal centers can be viewed as roughly coplanar. Six gold(I) ions are embedded in an ellipse and surrounded by 4 quinoline and 12 phenyl rings. The title compound shows interesting spectroscopic and luminescence properties dependent on the solvent polarity; i.e., it emits at ca. 440 and 636 nm in CH(2)Cl(2) and only at ca. 450 nm in CH(3)CN. The long-lived emission at ca. 636 nm (16.2 micros) in CH(2)Cl(2) is quenched by polar solvents such as CH(3)CN and CH(3)OH with quenching constants as 1.00 x 10(5) and 3.03 x 10(4) s(-1) M(-1), respectively, which is suggested to be related to the presence or absence of gold(I)...gold(I) interactions due to scrambling of the [AuPPh(3)]+ units, isolobal to H+.     

Supramolecular assembly and solvochromic luminescence of a Au(I) complex containing di(4-pyridylmethyl)aminedithiocarbamate

The di(4-pyridylmethyl)aminedithiocarbamate (DPMACS₂) ligand was used to react with (Me₂S)AuCl to give a dinuclear complex, [Au(DPMACS₂)]₂, which shows both intramolecular Au(I)⋅⋅⋅Au(I) distances of 2.741(9)–2.788(1) Å and intermolecular Au(I)···Au(I) contacts of 2.917(5)–3.047(7) Å, leading to 1-D Au(I) chains in the solid state. In addition, complex [Au(DPMACS₂)]₂ shows the luminescence at 555 nm at room temperature while excited, and almost no energy shift for the luminescence at 553 nm upon grinding has been observed. In this regard, we further examined the solvochromic luminescence upon grinding with various solvents, and the luminescence is within 549–572 nm. It is noted that the solvochromic luminescence for dichloromethane (566 nm) and 1,2-dichloroethane (572 nm) has been observed, and the original luminescence at 555 nm can be restored upon solvent loss. Indeed, such red-shifts for the solvochromic luminescence are most likely due to a decrease in intermolecular Au(I)⋅⋅⋅Au(I) contacts while solvents entering into crystal lattices upon grinding and it is a reversible process upon solvent loss.     

Simultaneous determination of myo-inositol and scyllo-inositol by MEKC as a rapid monitoring tool for inositol levels

A simple and rapid MEKC method was developed for the simultaneous determination of myo-inositol, scyllo-inositol, and glucose. Prior to electrophoretic separation, the nonfluorescent inositols and glucose were derivatized by N-methylisatoic anhydride at 25 degrees C for 10 min so that they could be detected by a fluorescence detector during separation. The good separation with high efficiency by MEKC was achieved in 13 min with a glycine buffer containing SDS and PEG 4000. Several parameters affecting the separation were studied, including the pH of BGE, the concentrations of glycine, SDS, and PEG 4000, and the applied voltage. Using glycerol as an internal standard, the linear ranges of the method for myo-inositol, scyllo-inositol, and glucose were 0.03-10, 0.01-5, and 0.05-20 mM; the concentration LODs of myo-inositol, scyllo-inositol, and glucose were 0.020, 0.0078, and 0.026 mM, respectively. The method was applied to analyze extracellular myo-inositol and glucose in the microdialysates from rat brain cortex of ischemia animal model and intracellular myo-inositol and scyllo-inositol in the rat brain extract.     

Mass-analyzed Threshold Ionization Spectroscopy of Rotamers of p-ethoxyphenol Cations and Configuration Effect

Two-color resonant two-photon mass-analyzed threshold ionization （MATI） spectroscopy was used to record the vibrationally resolved cation spectra of the selected rotamers of p- ethoxyphenol. The adiabatic ionization energies of the trans and cis rotamers are determined to be 61565±5 and 61670±5 cm^-1, which are less than that of p-methoxyphenol by 645 and 643 cm^-1, respectively. Analysis on the MATI spectra of the selected rotamers of p-ethoxyphenol cation shows that the relative orientation of the ethoxy group has little effect on the in-plane ring vibrations. The low-frequency OC2H5 bending vibrations appear to be active for both forms of the cation.