Rapid and Sensitive Liquid Chromatography-Tandem Mass Spectrometry for Quantification of Glycyrrhetic Acid in Human Plasma

A simple, rapid and sensitive liquid chromatography-tandem mass spectrometry(LC-MS/MS) for the determination of glycyrrhetic acid in human plasma with ginsenoside Rh2 as internal standard was developed and validated. The plasma samples were prepared via liquid-liquid extraction with ethyl acetate. Chromatographic separation was accomplished on a Venusil MP-C18(50 mm×2.1 mm, 5 μm i.d.) column at 25 °C. The mobile phase consisted of acetonitrile/5 mmol?L-1 ammonium acetate(10:90, volume ratio) at a flow rate ...     

Self-Assembled Supramolecular Micellar Structures Based on Non-ionic Surfactants and Cyclodextrins

The complexation between non-ionic polyethylene oxide (PEO)-based surfactants (Triton X-45, Triton X-100, polyethylene glycol-1000-monostearate, and Brij 35) and cyclodextrins is studied. It is shown that the addition of surfactant solutions to the aqueous solution of alpha, beta-, and gamma-cyclodextrins affords poorly soluble crystalline precipitates. Parameters of crystalline structure and the composition of complexes are analogues to those obtained on the basis of polyethylene oxide. Using a method of surface tension it is shown that cyclodextrins favor the increase of the value of critical micelle concentration (CMC) of surfactants. The dependence of CMC from the molar ratio cyclodextrin/surfactant permits us to determine the composition of inclusion complexes in solution. For Triton X-100 and polyethylene glycol-1000-monostearate values of stoichiometric composition of complexes in solution and in condensed phase agree well. It is shown that in the presence of beta-cyclodextrin the destruction of micelles based on Triton X-100 occurs. UV-spectroscopy is used for the investigation of the microenvironment of a phenyl group in inclusion complexes based on alpha- and beta-cyclodextrins. The interaction of gamma-cyclodextrin with PEO surfactants results in the formation of novel double-tailed surfactants. The values of CMC registered in solutions of these complexes is lower than the corresponding value of Triton X-100 and polyethylene glycol-1000-monostearate. The stoichiometric composition of complexes in solution is established from the dependence of CMC versus the gamma-cyclodextrin/surfactant ratio. The composition of the complexes in solution and condensed phase agree well. The interaction of alpha- and gamma-cyclodextrins with Brij 35 results in the formation of nonstoichiometric complexes. The investigation of the dependences of CMC of modified surfactants from temperature shows that these supramolecular structures exist at high temperatures. Copyright 1999 Academic Press.     

Characterization of Rhodamine Self-Assembled Films Using Desorption Electrospray Ionization Mass Spectrometry

Growth process information and molecular structure identification are very important for characterization of self-assembled films. Here, we explore the possible application of desorption electrospray ionization mass spectrometry (DESI-MS) that provides the assembled information of rhodamine B (Rh B) and rhodamine 123 (Rh 123) films. With the help of lab-made DESI source, two characteristic ions [Rh B]⁺ and [Rh 123]⁺ are observed directly in the open environment. To evaluate the reliability of this technique, a comparative study of ultraviolet-visible (UV-vis) spectroscopy and our method is carried out, and the result shows good correlation. According to the signal intensity of characteristic ions, the layer-by-layer adsorption process of dyes can be monitored, and the thicknesses of multilayer films can also be comparatively determined. Combining the high sensitivity, selectivity, and speed of mass spectrometry, the selective adsorption of similar structure molecules under different pH is recognized easily from extracted ion chronograms. The variation trend of dyes signalling intensity with concentration of polyelectrolyte is studied as well, which reflects the effect of surface charge on dyes deposition. Additionally, the desorption area, surface morphology, and thicknesses of multilayer films are investigated using fluorescence microscope, scanning electron microscope (SEM), and atomic force microscopy (AFM), respectively. Because the desorption area was approximately as small as 2 mm², the distribution situation of organic dyes in an arbitrary position could be gained rapidly, which means DESI-MS has advantages on in situ analysis.

Analysis of Supramolecular Complexes of 3-Methylxanthine with Field Asymmetric Waveform Ion Mobility Spectrometry Combined with Mass Spectrometry

Miniaturised field asymmetric waveform ion mobility spectrometry (FAIMS), combined with mass spectrometry (MS), has been applied to the study of self-assembling, noncovalent supramolecular complexes of 3-methylxanthine (3-MX) in the gas phase. 3-MX forms stable tetrameric complexes around an alkali metal (Na⁺, K⁺) or ammonium cation, to generate a diverse array of complexes with single and multiple charge states. Complexes of (3-MX)_n observed include: singly charged complexes where n = 1–8 and 12 and doubly charged complexes where n = 12–24. The most intense ions are those associated with multiples of tetrameric units, where n = 4, 8, 12, 16, 20, 24. The effect of dispersion field on the ion intensities of the self-assembled complexes indicates some fragmentation of higher order complexes within the FAIMS electrodes (in-FAIMS dissociation), as well as in-source collision induced dissociation within the mass spectrometer. FAIMS-MS enables charge state separation of supramolecular complexes of 3-MX and is shown to be capable of separating species with overlapping mass-to-charge ratios. FAIMS selected transmission also results in an improvement in signal-to-noise ratio for low intensity complexes and enables the visualization of species undetectable without FAIMS.

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Application of Electrospray Mass Spectrometry for Characterizing Supramolecular Coordination Complexes

The Electrospray Mass Spectrometry (ES-MS) of eight different supramolecular complexes shows that the molecular peaks of the desolvated multiply charged cations can be recorded more easily than by Fast-Atom-Bom-bardment Mass Spectrometry (FAB-MS) measurements of similar compound. The preliminary application of the ES-MS technique to self-assembled helical complexes obtained from ligands L³ to L⁸ with various metal ions (Cu, Co, Eu, Tb) indicates that ES mass spectra qualitatively reflect the species present MeCN solution.     

The Characterization of Self-Assembled Monolayers on Copper Surfaces by Low-Temperature Plasma Mass Spectrometry

We describe direct analysis of self-assembled monolayers (SAMs) on copper surfaces by low temperature plasma (LTP) mass spectroscopy (MS). Two kinds of SAMs formed from n-dodecylmercaptan (NDM) and l-phenyl-5-mercaptotetrazole (PMTA) were prepared on copper by spontaneous chemisorption. With the LTP probe, desorption and ionization of the SAMs was easily achieved, and the ions produced were introduced into MS for analysis. Characteristic fragment ions from NDM SAMs, mainly [M + M - H](+) (M is the NDM molecule) and from PMTA SAMs, mainly [M + H - S](+) (M is the PMTA molecule), were both absent in the MS spectra of neat NDM and PMTA samples. This provided evidence of the formation of SAMs on copper. As a supplementary method, LTP-MS is helpful in obtaining information on the barrier properties of SAMs on copper, such as inhibitor efficiency (IE) and the surface adsorption concentration of corrosive electrolyte (Γ*) surrounding copper. Aiming for an evaluation of the reliability of LTP-MS, a comparative study of our method and the traditional method of cyclic voltammetry (CV) showed a correlation coefficient higher than 0.97. In addition, a rough, simple procedure for imaging of the distribution of the molecules adsorbed on copper surface was presented. The study supplied a rapid and simple method for direct investigation of SAMs on copper.     

L-抗坏血酸电喷雾串联质谱行为研究

采用电喷雾串联质谱(ESI-MSn)技术, 结合氢/氘交换方法, 研究了L-抗坏血酸在正、负离子模式下的质谱行为. 实验表明, 电喷雾质谱能够方便地观测到实验条件下L-抗坏血酸的特征裂解方式和相应碎片; 实验发现毛细管温度对L-抗坏血酸的裂解方式产生显著的影响, 从不同毛细管温度下的相应质谱信号强度变化能观察到L-抗坏血酸及其降解产物的热稳定性差异. 因此, 根据串联质谱所观测到的L-抗坏血酸特征碎片离子, 提出了L-抗坏血酸的结构变化及其降解反应的可能机理和基本规律, 为现代质谱技术快速测定复杂基体样品中的痕量抗坏血酸奠定了实验基础.     

Chromophoric Barbituric Acid Derivatives with Adjustable Hydrogen-Bonding Patterns as Component for Supramolecular Structures

Summary: The barbituric acid moiety of the presented dyes shows multifunctional properties like acidochromism, solvatochromism, and adjustable hydrogen-bonding pattern for molecular recognition. Hydrogen-bonding ability, acidity and solvatochromic effects are studied for a series of N-alkyl substituted 5-(4-nitrophenyl)-barbiturates. Solvatochromism and metal ion complexation are also investigated using chromophoric thiobarbituric acid derivatives.     

From Peptide Nucleic Acids to Supramolecular Structures of Nucleic Acid Derivatives

Nucleic acids play a pivotal role in life processes. The endeavours to shed light on the essential properties of these intriguing building blocks led us to the synthesis of different analogues and the investigation of their properties. First various peptide nucleic acid monomers and oligomers have been synthesized, using an Fmoc/acyl protecting group strategy, and their properties studied. The serendipitous discovery of a side reaction of coupling agents led us to the elaboration of a peptide sequencing method. The capricious behaviour of guanine derivatives spurred the determination of their substitution pattern using ¹³C, ¹⁵N NMR, and mass spectrometric methods. The properties of guanines initiated the logical transition to the study of supramolecular systems composed of purine analogues. Thus, xanthine and uracil derivatives have been obtained and their supramolecular self-assembly properties scrutinized in gas, solid, and liquid states and at solid-liquid interfaces.     

甘草次酸衍生物的合成及其抗癌活性

设计合成了6种甘草次酸衍生物,用元素分析、波谱分析鉴定了它们的结构,并比较了它们的体内、体外抗癌活性,均表现出较好的活性,尤其是化合物Ⅰa,Ⅰb口服效果比盐酸氮芥还好,表现出甘草次酸对氮芥有明显的增效应用。     

Synthesis and Hemolytic Properties of Glycyrrhetic Acid Glycosides

 The synthesis of monodesmosidic glycyrrhetic acid disaccharides via its diphenylmethyl ester is described. Their hemolytic activity is lower as compared to the corresponding oleanolic aciddisaccharides. The influence of the structure of the aglycon on the hemolytic activity is discussed.     

Characterization of Hydrogen-Bonded Supramolecular Assemblies by MALDI-TOF Mass Spectrometry after Ag+ Labeling

The high affinity of Ag ⁺ ions for aromatic π donors and cyano groups is exploited in a novel MALDI-TOF mass spectrometric method for the identification of hydrogen-bonded assemblies. The interaction with the Ag⁺ ions—which, for example, can be complexed by two phenyl groups in a sandwich-type manner (see drawing on the right)—provides positively charged assemblies in a nondestructive way.     

Synthesis and Hemolytic Properties of Glycyrrhetic Acid Glycosides

Summary.  The synthesis of monodesmosidic glycyrrhetic acid disaccharides via its diphenylmethyl ester is described. Their hemolytic activity is lower as compared to the corresponding oleanolic aciddisaccharides. The influence of the structure of the aglycon on the hemolytic activity is discussed. Received November 18, 1999. Accepted November 30, 1999     

Characterization of Nitro Arachidonic Acid and Nitro Linoleic Acid by Mass Spectrometry

Nitration of arachidonic and linoleic acids was performed with nitronium tetrafluroborate, nitrogen dioxide, and dinitrogen trioxide. The nitro compounds were separated on HPLC and characterized further on mass spectrometry. Formation of nitro arachidonic acid m/z 348 and nitro linoleic acid m/z 324 were observed with all the reagents. Interestingly, MS/MS of nitro AA and nitro LA showed specific ions m/z 142, m/z 193, and m/z 206 for nitro arachidonic and m/z 156 and m/z 196 for linoleic acid that were common in all three reactions.     

Synthesis of 2-Arylidene-3-Oxo-Derivatives of Glycyrrhetic Acid

Chemistry of Natural Compounds - Claisen–Schmidt reactions of 3-oxoglycyrrhetic acid with aromatic aldehydes in EtOH–NaOH (4N) synthesized 2-arylidene-3-oxo-derivatives in 65–70%...     

Quantifying Protein-Fatty Acid Interactions Using Electrospray Ionization Mass Spectrometry

The application of the direct electrospray ionization mass spectrometry (ESI-MS) assay to quantify interactions between bovine β-lactoglobulin (Lg) and a series of fatty acids (FA), CH₃(CH₂)_xCOOH, where x = 6 (caprylic acid, CpA), 8 (capric acid, CA), 10 (lauric acid, LA), 12 (myristic acid, MA), 14 (palmitic acid, PA) and 16 (stearic acid, SA), is described. Control ESI-MS binding measurements performed on the Lg-PA interaction revealed that both the protonated and deprotonated gas phase ions of the (Lg + PA) complex are prone to dissociate in the ion source, which leads to artificially small association constants (K _a ). The addition of imidazole, a stabilizing solution additive, at high concentration (10 mM) increased the relative abundance of (Lg + PA) complex measured by ESI-MS in both positive and negative ion modes. The K _a value measured in negative ion mode and using sampling conditions that minimize in-source dissociation is in good agreement with a value determined using a competitive fluorescence assay. The K _a values measured by ESI-MS for the Lg interactions with MA and SA are also consistent with values expected based on the fluorescence measurements. However, the K _a values measured using optimal sampling conditions in positive ion mode are significantly lower than those measured in negative ion mode for all of the FAs investigated. It is concluded that the protonated gaseous ions of the (Lg + FA) complexes are kinetically less stable than the deprotonated ions. In-source dissociation was significant for the complexes of Lg with the shorter FAs (CpA, CA, and LA) in both modes and, in the case of CpA, no binding could be detected by ESI-MS. The affinities of Lg for CpA, CA, and LA determined using the reference ligand ESI-MS assay, a method for quantifying labile protein–ligand complexes that are prone to in-source dissociation, were found to be in good agreement with reported values.