异维A酸糖基衍生物的合成及其细胞毒活性研究

采用两种方法合成了2类新的异维A酸糖基衍生物(5a~5d, 6a, 10a~10c, 11a), 并进行了结构表征与确认. 采用MTT法测试了它们对肺癌细胞(A549)等的细胞毒活性. 结果显示, 含有糖苷结构的异维A酸衍生物明显比含有糖酯结构的异维A酸衍生物具有更好的细胞毒活性; 将糖环上的乙酰基脱去后, 相应的化合物活性有明显提高.     

Green and Efficient Synthesis of 4‐Heteryl‐Quinolines and Their Antibacterial Evaluations

A green and efficient synthesis of 4‐heteryl‐quinolines ( 9a , 9b , 9c , 9d ), ( 10a , 10b , 10c , 10d ) and ( 11a , 11b , 11c , 11d ) has been described using PEG‐600 as a green solvent. Initially, 4‐chloro‐2‐methylquinolines ( 5a , 5b , 5c , 5d ) on reaction with aromatic heterocyclic thiols ( 6 ), ( 7 ), and ( 8 ) using PEG‐600 at 100°C for 30–40 min resulted in ( 9 ), ( 10 ), and ( 11 ) in good yields. Alternatively, ( 9 ), ( 10 ), and ( 11 ) could also be prepared in dimethylformamide using K2CO3 as base and tetrabutylammonium bromide as phase transfer catalyst at 100°C for 1–2 h. All the compounds were synthesized and characterized by IR, NMR, mass spectroscopy, and 13C NMR analysis. All synthesized compounds were screened for their antibacterial activity against clinical strains that include Gram‐positive (Bacillus subtilis MTCC 121, staphylococcus aureus MLS‐16 MTCC 2940, Micrococcus lutes MTCC 2470, and Staphylococcus aureus MTCC 96) and Gram‐negative bacteria (Candida albicans MTCC 3017, Klebsiella planticola MTCC 530, Escherichia coli MTCC 739, and Pseudomonas aeruginosa MTCC 2453). The results revealed that compounds ( 9a , 9d , 10a , 10c , 11b , and 11d ) exhibited significant antibacterial activity almost equal to the standard drug, that is, Ciprofloxacin.     

Electron attachment and detachment, and the electron affinities of C5F5N and C5HF4N

Rate constants have been measured for electron attachment to C5F5N (297-433 K) and to 2, 3, 5, 6-C5HF4N (303 K) using a flowing-afterglow Langmuir-probe apparatus (at a He gas pressure of 133 Pa). In both cases only the parent anion was formed in the attachment process. The attachment rate constants measured at room temperature are 1.8 +/- 0.5 X 10(-7) and 7 +/- 3 X 10(-10) cm(-3) s(-1), respectively. Rate constants were also measured for thermal electron detachment from the parent anions of these molecules. For C5F5N- detachment is negligible at room temperature, but increases to 2530 +/- 890 s(-1) at 433 K. For 2, 3, 5, 6-C5HF4N-, the detachment rate at 303 K was 520 +/- 180 s(-1). The attachment/detachment equilibrium yielded experimental electron affinities EA(C5F5N)=0.70 +/- 0.05 eV and EA(2, 3, 5, 6-C5HF4N)=0.40 +/- 0.08 eV. Electronic structure calculations were carried out for these molecules and related C5HxF5-xN using density-functional theory and the G3(MP2)//B3LYP compound method. The EAs are found to decrease by 0.25 eV, on average, with each F substitution by H. The calculated EAs are in good agreement with the present experimental results.     

Differential pulse polarographic determination of ofloxacin in pharmaceuticals and biological fluids

A sensitive method is described for the determination of ofloxacin in its pure form, dosage forms and biological fluids. The proposed method depends upon the polarographic activity of ofloxacin in Britton Robinson buffers, whereby a well-defined cathodic wave is produced over the pH range 4.1-10.3. The wave was characterized as being irreversible, diffusion-controlled with limited adsorption properties. The current-concentration relationship was found to be rectilinear over the range 5x10(-5)-5x10(-4) M and 1x10(-5)-5x10(-4) M using the DC(t) and DPP modes respectively, with a minimum detectability (S/N=3) of 3x10(-7) M. The proposed method was successfully applied to the determination of ofloxacin in tablets and biological fluids. The results obtained were found to be in agreement with those obtained by a reference method.     

Separation and determination of the ingredients of a cold medicine by micellar electrokinetic chromatography with bile salts

The separation of fourteen active ingredients used in a cold medicine was investigated by micellar electrokinetic chromatography (EKC) employing bile salts. Basic drugs were also successfully separated by micellar EKC using bile salts with high theoretical plate numbers (2.0 x 10(5)-3.5 x 10(5)) within a relatively short time (ca. 20 min). The separation of these solutes by micellar EKC was not successful using sodium dodecyl sulphate. The effects of micellar concentration, pH and organic modifier content on migration times and selectivity were investigated. This technique was also applied to the determination of several active ingredients combined in commercial preparations by an internal standard method.     

Immobilizing single lipid and channel molecules in artificial lipid bilayers with annexin A5

The effects of annexin A5 on the lateral diffusion of single-molecule lipids and single-molecule proteins were studied in an artificial lipid bilayer membrane. Annexin A5 is a member of the annexin superfamily, which binds preferentially to anionic phospholipids in a Ca2+-dependent manner. In this report, we were able to directly monitor single BODIPY 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (DHPE) and ryanodine receptor type 2 (RyR2) labeled with Cy5 molecules in lipid bilayers containing phosphatidylserine (PS) by using fluorescence microscopy. The diffusion coefficients were calculated at various annexin A5 concentrations. The diffusion coefficients of BODIPY-DHPE and Cy5-RyR2 in the absence of annexin A5 were 4.81 x 10(-8) cm(2)/s and 2.13 x 10(-8) cm(2)/s, respectively. In the presence of 1 microM annexin A5, the diffusion coefficients of BODIPY-DHPE and Cy5-RyR2 were 2.2 x 10(-10) cm(2)/s and 9.5 x 10(-11) cm(2)/s, respectively. Overall, 1 microM of annexin A5 was sufficient to induce a 200-fold decrease in the lateral diffusion coefficient. Additionally, we performed electrophysiological examinations and determined that annexin A5 has little effect on the function of RyR2. This means that annexin A5 can be used to immobilize RyR2 in a lipid bilayer when imaging and analyzing RyR2.     

Determination of ascorbic acid in pharmaceuticals and urine by reverse flow injection.

Two reverse flow injection (FI) methods, using spectrophotometric detection, are proposed for the determination of ascorbic acid. Both methods are based on its reaction with the ethylenediaminetetraacetic acid-CoIII complex in a medium of 5% diethylamine. In the first method, using the peak-height FI technique, ascorbic acid is determined over the range from 2 x 10(-4) to 5 x 10(-3) mol dm-3 and in the second, using the peak-width FI method, the working range is extended (2 x 10(-3)-5 x 10(-2) mol dm-3). Both FI methods were applied to the determination of ascorbic acid in pharmaceuticals while the peak-height FI technique was also used to determine ascorbic acid in urine.     

Rapid and simultaneous determination of capecitabine and its metabolites in mouse plasma, mouse serum, and in rabbit bile by high-performance liquid chromatography

A rapid high-performance liquid chromatography method has been developed for simultaneous determination of capecitabine and its metabolites: 5'-deoxy-5-fluorocytidine (5'-DFCR), 5'-deoxy-5-fluorouridine (5'-DFUR) and 5-fluorouracil (5-FU). 5'-DFCR was synthesized by hydrolyzing capecitabine using commercially available carboxyl esterase (CES) and characterized by NMR, mass spectrometry and elemental analysis. Base-line separations between capecitabine, 5'-DFCR, 5'-DFUR and 5-FU were found with symmetrical peak shapes on a Discovery RP-amide C16 column using 10 mM ammonium acetate at pH 4.0 and methanol as the mobile phase. The retention times of capecitabine, 5'-DFCR, 5'-DFUR and 5-FU were 8.9, 5.0, 5.3 and 3.0 min, respectively. Linear calibration curves were obtained for each compound across a range from 1 to 500 microg ml(-1). The intra- and inter-day relative standard deviations (%RSD) were <5%. A single-step protein precipitation method was employed for separation of the analytes from bio-matrices. Greater than 85% recoveries were obtained for capecitabine, 5'-DFCR, 5'-DFUR and 5-FU from bio-fluids including mouse plasma, mouse serum and rabbit bile.     

Determination of Ionol by Voltammetry and Coulometric Titration

Procedures were developed for determining ionol by voltammetry and by coulometric titration with electrogenerated chlorine using the amperometric indication of the titration end point. Possible mechanisms of ionol oxidation with electrogenerated chlorine and its electrochemical oxidation at a glassy carbon and a gold electrode were discussed. Procedures were developed for determining ionol in mineral oil in analytical ranges from 1.0 × 10^–4 to 1.0 × 10^–2 M (RSD = 9%) and from 3.0 × 10^–5 to 4.0 × 10^–3 M (RSD = 9%) using a glassy carbon and a gold electrode, respectively. The detection limits for ionol at the glassy carbon and gold electrode were 2.8 × 10^–4 and 1.0 × 10^–5 M, respectively. The detection limit in coulometric titration was 20 g/mL.     

Polarographic study of acrolein and its determination by flow injection with amperometric detection at a mercury electrode

A study of the electrochemical behavior of acrolein at a dropping mercury electrode using different polarographic techniques is described. Theoretical studies of the reversibility of the wave of acrolein were carried out using two different polarographic techniques: direct current tast and differential pulse. Differential pulse polarography may be used to determine acrolein concentration in a Britton-Robinson buffer solution of pH 10 in the ranges 2 x 10(-7)10(-8) and 5 x 10(-8)-10(-4) mol dm(-3) and a coefficient of variation of 1.7% for a concentration of 10(-5)mol dm(-3). A flow injection method with amperometric detection at a potential of -1.4V using a mercury electrode is also described. Before each injection, any drop hanging from the tip of the capillary needs to be dislodged and a new electrode drop dispensed; three different drop sizes were tested. A linear relationship between peak intensity and acrolein concentration was obtained in the range 10(-5)-10(-7) mol dm(-3), with a detection limit of 9.8 x 10(-8) mol dm(-) 3 and a coefficient of variation of 2.9% for a 2 x 10(-7) mol dm(-3) concentration. Several organic and inorganic species were tested in order to ascertain whether they interfered with the signal for acrolein. The proposed methods were applied to the determination of acrolein in seawater samples.     

Peripherally metalated secoporphyrazines: a new generation of photoactive pigments

Base-catalyzed cross condensation of dipropylmaleonitrile 1 with bis(dimethylamino)maleonitrile 2 in an equimolar ratio afforded the porphyrazines 3a, 4a, 5a, 6a and 7a. Subsequent demetalation of 5a with TFA followed by remetalation with Zn(OAc)(2) gave ligand 5c in good yield. Compound 5c was, in turn, selectively oxidized and further peripherally functionalized using Pt(PhCN)(2)Cl(2) and PdCl(2) to yield the novel seco solitaire porphyrazines 10a and 10b. The photophysical profiles of the seco solitaire porphyrazines 10a and 10b were evaluated by means of absorption, emission, and transient absorption spectroscopy. The new pigments 10a and 10b were found to be photochemically more stable than the solitaire complexes 3d and 3e and mediated the generation of singlet oxygen with quantum yields of 0.59 and 0.45, respectively.     

Performance of throughout in-capillary derivatization capillary electrophoresis employing an on-line sample and run buffer loading device

We report on the effect on performance of varying the length of the capillary during throughout in-capillary derivatization (TICD) capillary electrophoresis (CE). Performance was evaluated by on-line coupling with a sample and CE runbuffer loading device that was newly introduced for this study. The device was assembled with a low cost using two 5 mm inner diameter (ID) disposable polyethylene syringes. First, a sequence was manually formed consisting of a 200 microL run buffer solution plug, a 100 microL sample plug and another 200 microL run buffer solution plug. Each plug was separated from its neighbor by a 100 microL air plug. When each plug reached the injection point where both a platinum-wire anode and the end of the separation capillary tube were located, 340 V/cm separation voltage (electrophoresis voltage) and 34 V/cm injection voltage were applied to the capillary for 3 s. Then the analytes were derivatized during migration in 50 microm ID capillaries filled with 2 mM o-phthalaldehyde (OPA)/N-acetylcysteine (NAC) in a 20 mM phosphate-borate buffer (pH 10), followed by separating and detecting of OPA derivatives by absorbance of 340 nm. Derivatization, separation, and detection were performed systematically using capillaries which varied in length from 5 to 80 cm. In the case of TICD-CE of a mixture containing 1 mM aspartic acid (Asp) and 20 mM m-nitorophenol (MNP) as a test solution, it was determined that peak area and peak width ratios of Asp to MNP did not depend on capillary length. Enantiomeric separations of DL-alanine (Ala) and Asp were examined using a run buffer consisting of a 45 microM beta-cyclodextrin (CD)-2 mM OPA/NAC-20 mM phosphate-borate buffer (pH 10). Even though the resolution of these enantiomeric pairs decreased with decreasing capillary length, as expected, the peaks corresponding to both enantiomeric amino acids were identified even when a 5 cm capillary was used. An 8-component amino acid mixture was also tested with 5 cm and 10 cm capillaries.     

A metallic cobalt electrode for the indirect potentiometric determination of calcium and magnesium in natural waters using flow injection analysis

A flow injection analysis of Ca(2+) and Mg(2+) using indirect potentiometric detection in natural waters is proposed, where Ca(2+) or Mg(2+) are injected into a buffer carrier containing phosphate, resulting in the formation of Ca(3)(PO(4))(2) or Mg(3)(PO(4))(2). The consequent reduction in free phosphate in the carrier solution is detected using a metallic cobalt wire electrode. Indirect electrode response was used and the experimental conditions affecting electrode response were optimized. Responses were linear in the concentration range 5x10(-4) to 5x10(-3) M with a detection limit of 1x10(-5) M in 20 mM phosphate buffer at pH 8.0. The relative standard derivation at 1 mM of Ca(2+) and Mg(2+) were 3.9 and 3.7% (n=10), respectively. EGTA and 8-hydroxyquinoline were used as the masking agents for Ca(2+) and Mg(2+), respectively. Concentrations of Ca(2+) and Mg(2+) in natural waters were successfully determined by the proposed method.     

高效液相色谱-质谱法测定比格犬血浆中的艾普拉唑及其药代动力学

运用高效液相色谱-电喷雾质谱(HPLC-ESI-MS)技术,建立了快速、简单、灵敏的比格犬静脉滴注艾普拉唑钠盐后血药浓度的检测方法。血浆样品采用蛋白沉淀法,以丁螺环酮作为内标,色谱柱为Teknokroma Kromasil C18(100 mm×2.1 mm, 5 μm),流动相为水-甲醇-乙腈(69:8:23, v/v/v)(含0.1%的甲酸),流速0.2 mL/min,采用电喷雾(ESI)离子源以正离子方式检测。绘制血药浓度-时间曲线,并采用DAS 2.0计算药代动力学参数。方法学实验结果表明内源性杂质不干扰艾普拉唑和内标的测定,线性范围为5～10000 μg/L (r=0.994),最低定量限为5 μg/L,精密度和准确度均符合生物样品测定的要求。低、中、高3个浓度的绝对回收率在106%左右,基质效应小于142.0%,表明该方法适合比格犬血浆中艾普拉唑浓度的测定及药代动力学研究。比格犬静脉滴注艾普拉唑钠盐3个剂量(0.2 mg/kg、0.8 mg/kg和3.2 mg/kg)后的药-时曲线下面积(AUC(0~∞))分别为(2.4×104±3×103)、(8.8×104±1.6×104)和(5.4×105±8×104) μg/L•min,呈线性药物代谢动力学过程。     

Condensed isoquinolines 28*. Synthesis and properties of 10a,15b-diazadibenzo[a,e]-pleiaden-11-ones

The reaction of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones with o-xylidene dibromide leads to 11-oxo-4bH,5H,10H,11H,16H-10a-aza-15b-azoniadibenzo[a,e]pleiadene bromides, which are converted to 11-oxo-10H,11H,16H-10a-aza-15b-azoniadibenzo[a,e]pleiadene salts upon oxidation using nitrobenzene. The reaction of these salts with benzylamine leads to 6-{2-[(benzylimino)methyl]phenyl}-7,12-dihydroisoquino[3,2-b][2]benzazepin-14(6H)-ones, which recyclize to 11-oxo-5H,10H,11H-10a-aza-15b-azoniadibenzo[a,e]pleiadene perchlorates upon the action of perchloric acid. The reactions of the 10a,15b-diazadibenzo[a,e]pleiadene salts obtained with NaBH₄ were studied and the structures of the reduction products were determined by spectral methods. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 280–292, February, 2008.     

Reaction of iminopropadienones with amines--formation of zwitterionic intermediates, ketenes, and ketenimines

Five aryliminopropadienones 4a- d have been synthesized by flash vacuum thermolysis (FVT) by using two different precursors in each case. These compounds were deposited at 50 K at a pressure of ca. 10(-6) mbar together with three different nucleophiles, namely, trimethylamine (TMA), dimethylamine (DMA), and diethylamine (DEA), in order to study their reactions as neat solids during warm-up by FTIR spectroscopy. The reaction with TMA showed that a zwitterionic species (5 and/or 6) was formed in all the cases. With DMA and DEA, an alpha-oxoketenimine and/or an imidoylketene (7 and 8 or 9 and 10) was formed as the final product. In addition, several bands were observed, which can be assigned to zwitterionic intermediates (11 or 12). Optimized structures and vibrational spectra for all products were calculated at the B3LYP/6-31G(d) level of theory by using the polarizable continuum model (epsilon = 5).     

Dielectrophoretic alignment of metal and metal oxide nanowires and nanotubes: a universal set of parameters for bridging prepatterned microelectrodes

Nanowires and nanotubes were synthesized from metals and metal oxides using templated cathodic electrodeposition. With templated electrodeposition, small structures are electrodeposited using a template that is the inverse of the final desired shape. Dielectrophoresis was used for the alignment of the as-formed nanowires and nanotubes between prepatterned electrodes. For reproducible nanowire alignment, a universal set of dielectrophoresis parameters to align any arbitrary nanowire material was determined. The parameters include peak-to-peak potential and frequency, thickness of the silicon oxide layer, grounding of the silicon substrate, and nature of the solvent medium used. It involves applying a field with a frequency >10(5) Hz, an insulating silicon oxide layer with a thickness of 2.5 μm or more, grounding of the underlying silicon substrate, and the use of a solvent medium with a low dielectric constant. In our experiments, we obtained good results by using a peak-to-peak potential of 2.1 V at a frequency of 1.2 × 10(5) Hz. Furthermore, an indirect alignment technique is proposed that prevents short circuiting of nanowires after contacting both electrodes. After alignment, a considerably lower resistivity was found for ZnO nanowires made by templated electrodeposition (2.2-3.4 × 10(-3) Ωm) compared to ZnO nanorods synthesized by electrodeposition (10 Ωm) or molecular beam epitaxy (MBE) (500 Ωm).     

Growth and characterization of sodium pentaborate [Na(H4B5O10)] single crystals

The bulk single crystals of sodium pentaborate [Na(H4B5O10)] were grown by slow evaporation solution growth technique using deionized water as solvent. The grown crystal was confirmed by single crystal X-ray diffraction studies. The structural perfection of the grown crystals has been analyzed by high resolution X-ray diffraction (HRXRD) studies by recording rocking curve. The photoluminescence (PL), UV-vis spectral studies were performed and the optical bandgap of the material was calculated. The presence of the functional groups was identified by FT-IR measurement. The factor group analysis was done on Na(H4B5O10) to reveal the vibrational optical modes. The thermal and mechanical properties of the grown crystal were studied by TG-DTA and Vickers microhardness tester, respectively. The dielectric behavior of Na(H4B5O10) was investigated with different frequencies and temperatures.     

Selective potentiometric determination of zolpidem hemitartrate in tablets and biological fluids by using polymeric membrane electrodes

The construction and electrochemical response characteristics of 4 polymeric membrane sensors were investigated for potentiometric determination of zolpidem hemitartrate. The construction of the 4 sensors was based on the formation of ion-pair complexes between the drug cation and ionic sites in the ratio of 1:2, respectively. Two of the sensors were constructed by using ammonium reineckate or ammonium tungstate as the fixed ionic site in a polymeric matrix of polyvinyl chloride (PVC) (sensors 1 and 2). Linear responses over the concentration range of 10(-5)-10(-3)M, with cationic slopes of 30 and 30.7 mV per concentration decade, were obtained by using sensors 1 and 2, respectively. The third sensor was fabricated by using PVC carboxylate (PVC-COOH). The dissociated COOH groups in the PVC-COOH act as a mediator and/or ionic site. A linear response was obtained over the concentration range of 10(-5)-10(-2)M with a cationic slope of 29 mV per concentration decade. Sensor 4 was fabricated by using 2,6-didodecyl-beta-cyclodextrin as the ionophore, polyurethane (Tecoflex) as a polymeric matrix, and potassium tetraphenyl borate as the ionic site; it showed a linear response over the concentration range of 10(-7)-10(-2)M with a cationic slope of 28.9 mV per concentration decade. The direct potentiometric determination of zolpidem hemitartrate in pure forms by using the 4 proposed sensors gave average recoveries of 98.5+/-0.7, 99.4 +/-0.2, 100.7+/-0.10, and 99.8+/-0.1% for sensors 1-4, respectively. The results obtained by the proposed procedures were statistically analyzed and compared with those obtained by using a reported method. The 4 proposed sensors were also applied successfully to the determination of the drug in tablets and in biological fluids. Average recoveries obtained by using sensors 1, 2, 3, and 4 for drug assay of tablets were 99.6+/-0.6, 100+/-0.7, 99.7+/-0.4, and 99.5+/-0.8%, respectively. The presence of tablet excipients did not interfere with the determination of the drug or with the accuracy and precision of the 4 proposed methods. The methods were also used to determine the drug in the presence of its degradates and thus could be used as stability-indicating methods.     

Separation and identification of zaleplon metabolites in human urine using capillary electrophoresis with laser-induced fluorescence detection and liquid chromatography-mass spectrometry

A capillary electrophoresis (CE) method using laser-induced fluorescence (LIF) detection for the determination of the hypnotic drug zaleplon and its metabolites in human urine could be developed using carboxymethyl-beta-cyclodextrin as a charged carrier. By the help of a complementary HPLC method coupled to mass spectrometry, three metabolites present in human urine could be identified as 5-oxozaleplon, 5-oxo-N-deethylzaleplon and 5-oxozaleplon glucuronide. N-Deethylzaleplon, a previously described zaleplon metabolite, as well as zaleplon itself could not be detected in human urine by the CE-LIF assay. The results were confirmed by spiking with reference compounds of the phase I metabolites. The metabolites differed very much concerning their fluorescence intensities, thus the 5-oxo metabolites present as lactam tautomer fluoresced tenfold lower than the unchanged drug zaleplon and its N-deethylated metabolite. The glucuronide of the 5-oxozaleplon, however, showed high fluorescence due to its lactim structure. Limits of quantification yielded by the CE-LIF assay including a ten-fold preconcentration step by solid-phase extraction were 10 ng/ml for zaleplon and N-deethylzaleplon and 100 ng/ml for 5-oxozaleplon and 5-oxo-N-deethylzaleplon.