Systematic screening and characterization of novel bufadienolides from toad skin using ultra‐performance liquid chromatography/electrospray ionization quadrupole time‐of‐flight mass spectrometry

During the discovery process of novel compounds, it is of significant importance to differentiate novel from known compounds in crude extracts before starting the time‐consuming process of purification. Bufadienolides are the main active components of the skin of the toad Bufo bufo gargarizans Cantor (toad skin), an important traditional Chinese medicine. The fragmentation behavior and mass spectra profiles of bufadienolides standards were investigated using ultra‐performance liquid chromatography/electrospray ionization quadrupole time‐of‐flight mass spectrometry (UPLC/ESI‐Q‐TOFMS). Several fragmentation rules were summarized and applied to characterize novel and known bufadienolides in toad skin. Characteristic substituent groups could be identified by both diagnostic ions and their relative abundance. Bufadienolide stereoisomers could be differentiated from positional isomers by comparing fragment abundance profiles. This was used to characterize new stereoisomers for known bufadienolides. A total of 39 bufadienolides were screened out using a systematic method developed in our laboratory. In addition to 19 known bufadienolides, 20 putative novel compounds, including 8 stereoisomers, were characterized. UPLC/Q‐TOFMS was demonstrated to be a powerful tool for the characterization of low‐abundance bufadienolides in complex samples. This study provides guidelines for the targeted isolation of novel bufadienolides from natural products. Copyright © 2010 John Wiley & Sons, Ltd.     

Study of the effect of Wuzhi tablet (Schisandra sphenanthera extract) on tacrolimus tissue distribution in rat by liquid chromatography tandem mass spectrometry method

A liquid chromatography/tandem mass spectrometry (LC‐MS/MS) method was developed and validated for determining tacrolimus (FK506) in rat tissues to study the effect of Schisandra sphenanthera extract on FK506 tissue distribution. After a liquid–liquid extraction with ethyl acetate, FK506 and ascomycin (IS) were subjected to LC‐MS/MS analysis using positive electrospray ionization under multiple reactions monitoring mode. Chromatographic separation of FK506 and ascomycin was achieved on a Hypersil BDS C₁₈ column with a mobile phase consisting of methanol‐water (containing 2 mM ammonium acetate, 95 : 5, v/v). The intra‐ and inter‐batch precision of the method were less than 8.8 and 9.8%, respectively. The intra‐ and inter‐batch accuracies ranged from 97.5 to 104.0%. The lowest limit of quantification for FK506 was 0.5 ng/mL. The method was applied to a FK506 tissue distribution study with or without a dose of Wuzhi (WZ) tablet. Most of the FK506 tissue concentrations were slightly increased after a concomitant WZ tablet dose, but the whole blood concentration of FK506 was dramatically increased 3‐fold after a concomitant WZ tablet dose. These results indicated that the LC‐MS/MS method was rapid and sensitive enough to quantify FK506 in different rat tissues, and strict drug monitoring is recommended when co‐administering WZ tablet in clinical use. Copyright © 2009 John Wiley & Sons, Ltd.     

A convergence of photo‐bergman cyclization and intramolecular chain collapse towards polymeric nanoparticles

Employing enediynes as crosslinking precursors, a novel yet efficient strategy, namely photo‐triggered Bergman cyclization, was integrated with intramolecular chain collapse to yield polymeric nanoparticles with the size regime below 20 nm. Enediyne motif was designed delicately to possess a high photo‐reactivity, with the double bond locked in a methyl benzoate ring while triple bonds substituted with phenyls. Single electron transfer‐living radical polymerization was conducted to provide linear acrylate copolymers with controlled molecular weights and narrow polydispersities. Poly(butylarylate‐co‐ 5 ) went through UV‐irradiation with a concurrent Bergman cyclization, resulting in well‐defined ultrafine polymeric nanoparticles. Results from NMR, Raman scattering, photoluminescence and UV‐vis spectra corroborated the presence of conjugative structures in the polymeric nanoparticles, indicating the occurrence of photo‐induced Bergman cyclization. A series of other acrylate‐based nanoparticles were investigated to confirm the applicability of such a unique strategy in thermal sensitive but UV‐stable polymeric structures, making photo‐Bergman cyclization a promising tool towards polymeric nanoparticles. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Chiral crystal of a C2v‐symmetric 1,3‐diazaaulene derivative showing efficient optical second harmonic generation

Achiral nonlinear optical (NLO) chromophores 1,3‐diazaazulene derivatives, 2‐(4′‐aminophenyl)‐6‐nitro‐1,3‐diazaazulene (APNA) and 2‐(4′‐N,N‐diphenylaminophenyl)‐6‐nitro‐1,3‐diazaazulene (DPAPNA), were synthesized with high yield. Despite the moderate static first hyperpolarizabilities (β₀) for both APNA [(136 ± 5) × 10^?30 esu] and DPAPNA [(263 ± 20) × 10^?30 esu], only APNA crystal shows a powder efficiency of second harmonic generation (SHG) of 23 times that of urea. It is shown that the APNA crystallization driven cooperatively by the strong H‐bonding network and the dipolar electrostatic interactions falls into the noncentrosymmetric P2₁2₁2₁ space group, and that the helical supramolecular assembly is solely responsible for the efficient SHG response. To the contrary, the DPAPNA crystal with centrosymmetric P‐1 space group is packed with antiparalleling dimmers, and is therefore completely SHG‐inactive. 1,3‐Diazaazulene derivatives are suggested to be potent building blocks for SHG‐active chiral crystals, which are advantageous in high thermal stability, excellent near‐infrared transparency and high degree of designing flexibility. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011     

用固体石蜡山梨酸碳糊电极电位法测定食品中山梨酸

制备了一种以山梨酸根与乙基紫形成的缔合物为电活性物的固体石蜡山梨酸碳糊电极,并对其性能做了测定。结果显示该电极对山梨酸有较好的能斯特响应。山梨酸的线性范围为2.2×10-5～1.0×10-1mol.L-1,检出限为1.6×10-5mol.L-1。该电极用于食品中山梨酸根的测定,结果与分光光度法结果相符。     

A metabonomic analysis of urine from rats treated with rhizoma alismatis using ultra‐performance liquid chromatography/mass spectrometry

A metabonomic approach based on ultra‐performance liquid chromatography coupled to mass spectrometry (UPLC/MS) was used to study the nephrotoxicity of rhizoma alismatis (RA) in rats. Potential biomarkers of RA toxicity were identified and the toxicological mechanism is discussed. Urine samples were collected from control and treated rats at various stages and analyzed by UPLC/MS in positive ionization mode. Histopathological analysis was used to evaluate renal function. The differences in the metabolic profiles of the control and treated rats were clearly distinguishable with principal components analysis (PCA) of the chromatographic data, and significant changes in 13 metabolite biomarkers were detected in the urine. This metabonomic method combined with PCA could discriminate the treated rats from the control rats on days 60, 120, and 180 after treatment, before serious organic renal damage was apparent on day 180 with histopathology. This research indicates that UPLC/MS‐based metabonomic analysis of urine samples can be used to predict the chronic nephrotoxicity induced by rhizoma alismatis. Copyright © 2011 John Wiley & Sons, Ltd.     

Hydrolytic Ring Opening Reactions of Pyromellitic Dianhydride for Divalent Transition Metal Carboxylate Complexes

The hydrolytic ring opening reactions of pyromellitic dianhydride is an effective method to prepare transition metal carboxylate complexes. In this paper, two dinuclear complexes [Ni₂(2,2′‐bipy)₂(btec)(H₂O)₆] · 2H₂O ( 1 ) and [Cd₂ (phen)₄(H₂O)₂(H₂btec)] · H₂btec · 2H₂O ( 2 ) (H₄btec = 1,2,4,5‐benzenetetracarboxylic acid, phen = 1,10‐phenanthroline, and 2,2′‐bipy = 2,2′‐bipyridine) were synthesized by slow diffusion methods and their structures were determined byX‐ray structure analysis. In both structures metal atoms are in distorted octahedral environments and they are linked by bis‐monodentately coordinated 1,2,4,5‐benzentetracarboxylate ligands as bridging units. The crystalline compounds, which are insoluble in water as well as common organic solvents, have been characterized in the solid‐state by elemental analysis, thermogravimetric analysis, IR, and diffuse reflectance UV/Visspectroscopy. Moreover, the study of the physical properties of complex 2 demonstrates that it exhibits blue fluorescence emission in the solid state at room temperature.