Structure rationalization and topology prediction of two-distinct-component organic crystals: the role of volume fraction and interface topology

We consider here small-length-scale crystal structures with two clearly different molecular components (e.g., hydrophobic and hydrophilic). Using a perspective developed by studies on large-length-scale block copolymers and liquid crystals, we focus on the crystalline interface between the two components. We examine four types of two-component crystals: aromatic ammonium carboxylates, aromatic oligo(ethylene oxides), cyclohexylammonium carboxylates, and ether-thioether compounds. Of the 111 crystal structures found in the Cambridge Structure Database (CSD), 108 adopt one of the five generic topologies found in diblock copolymers: spheres, columns, perforated layers, layers, and bicontinuous structures. As in diblock copolymers, a key factor controlling the interfacial topology is shown to be the volume ratio of the two components. When the volume fraction of one component is less than 30% of the whole, more than five-sixths of the examined crystal structures are of columnar or spherical type. For volume fractions between 40 and 50% more than three-quarters are of lamellar or bicontinuous type. We use this model to predict the topologies of small-length-scale two-component crystals. We predict the crystal topolgies of six new crystal structures: three are predicted to be columnar, and the other three, lamellar or bicontinuous. The crystal structures of these systems were then determined by single-crystal X-ray methods. Five of the structures form in topologies consistent with the predictions: three in columns and two in layers. The remaining one forms as a perforated layer instead of the predicted columnar structure. Such predictive accuracy is consistent with the statistics of the CSD investigation.     

Identification and quantitative investigation of the effects of intestinal microflora on the metabolism and pharmacokinetics of notoginsenoside Fc assayed by liquid chromatography with electrospray ionization tandem mass spectrometry

Notoginsenoside Fc, which is a protopanaxdiol‐type saponin isolated from the leaves of Panax notoginseng, exhibits an exceptional antiplatelet aggregatory effect. To study the modulating effect of gastrointestinal contents on the metabolic profile and pharmacokinetics, pseudo germ‐free rats were used to study the influence of the bacterial community structure on the metabolic profile. Glycosidase activities were measured using the spectrophotometric method. Biotransformations of notoginsenoside Fc in normal and pseudo germ‐free rat intestinal microflora were systematically investigated using ultra high performance liquid chromatography with tandem quadrupole/time‐of‐flight mass spectrometry. Moreover, a liquid chromatography with tandem mass spectrometry method was established for simultaneous determination of the notoginsenoside Fc prototype and its degradation products. Through an in vivo pharmacokinetic study, the pharmacokinetic characteristics were compared between normal rats and pseudo germ‐free rats. During the in vitro biotransformation, seven deglycosylated products were detected and identified after incubation in the intestinal bacteria of normal rats. In pseudo germ‐free rats, glycosidase activities were significantly decreased, and no obvious degradation occurred. In an in vivo study, the systemic exposure was significantly increased 40%, as evidenced by the area under the blood concentration–time curve from time zero to infinity value and half‐life value, which were prolonged more in the pseudo germ‐free group than in normal rats. The results demonstrate that patients who use intestinal bacteria‐metabolized herbs, such as panax notoginseng, should understand the profile of intestinal bacteria to ensure therapeutic efficacy.     

Simultaneous analysis of trans- and cis-isomers of 2-glucosyloxycinnamic acids and coumarin derivatives in Dendrobium thyrsiflorum by high-performance liquid chromatography (HPLC)-photodiode array detection (DAD)-electrospray ionization (ESI)-tandem mass spectrometry (MS)

A novel method has been developed for simultaneous analysis for three pairs of trans- and cis-isomers of 2-glucosyloxycinnamic acids, along with their biogenic metabolites (three coumarin derivatives including scopoletin, scoparone and ayapin) in a Chinese medicinal herb Dendrobium thyrsiflorum by using high-performance liquid chromatography (HPLC)-photodiode array detection (DAD)-electrospray ionization (ESI)-tandem mass spectrometry (MS). The method was carried out by using a Polaris C₁₈ column with a gradient solvent system of 0.5% acetic acid aqueous solution-acetonitrile. Seven target analytes including isodensifloside, isothyrsifloside, densifloside, thyrsifloside, scoparone, ayapin and scopoletin were exclusively identified by comparing their retention behaviors, UV and MS spectra with the authentic standards, and their contents in D. thyrsiflorum were simultaneous determined by employing UV detection at 342 nm. In addition, another pair of isomers of 2-glucosyloxycinnamic acids was putatively elucidated mainly based on the MS fragmentation. The method was validated and found to be satisfactorily linear, selective and robust. Recoveries ranged from 95.56 to 97.94% for all compounds at three different spiking levels. The limits of detection (LOD) and quantitation (LOQ) ranged, respectively, from 0.02 to 0.13 μg mL⁻¹ and 0.07 to 0.39 μg mL⁻¹ depending on various compounds. The established quality evaluation method was successfully used for evaluating the quality of D. thyrsiflorum samples of different organs and collections.     

Identification of metabolites of geniposide in rat urine using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry

Geniposide, an iridoid glycoside, is an important and characteristic compound in the fruits of Gardenia jasminoides Ellis, a commonly used medicinal herb in Chinese traditional and folk medicine for the treatment of inflammation and jaundice. However, few studies have been carried out on the metabolism of geniposide. In this study, we have established a rapid and sensitive method using ultra‐performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry (UPLC/ESI‐QTOF‐MS) for analysis of the metabolic profile of geniposide in rat urine after oral administration. A total of ten metabolites were detected and identified by comparing their fragmentation patterns with that of geniposide using Metabolynx? and MassFragment? software tools. The results revealed that the principal metabolism pathways of geniposide in rat occurred after deglycosylation of the irdoid glycoside take place and this is followed by glucuronidation and the pyran‐ring cleavages. The major metabolite, the glucuronic acid conjugate of genipin as observed in vivo, was further confirmed by the in vitro enzymatic study. The results of this work have demonstrated the feasibility of the UPLC/ESI‐QTOF‐MS approach for rapid and reliable characterization of metabolites from iridoid compounds. Copyright © 2011 John Wiley & Sons, Ltd.     

A Fused [5]Helicene Dimer with a Figure-Eight Topology: Synthesis,Chiral Resolution,and Electronic Properties

Chiral shape-persistent molecular nanocarbons are promising chiroptical materials; their synthesis, however, remains a big challenge. Herein, we report the facile synthesis and chiral resolution of a double-stranded figure-eight carbon nanobelt 1 in which two [5]helicene units are fused together. Two synthetic routes were developed, and, in particular, a strategy involving Suzuki coupling-mediated macrocyclization followed by Bi(OTf)₃-catalyzed cyclization of vinyl ether turned out to be the most efficient. The structure of 1 was confirmed by X-ray crystallographic analysis. The isolated (P,P)- and (M,M)- enantiomers show persistent chiroptical properties with relatively large dissymmetric factors (|g_abs|=5.4×10⁻³ and |g_lum|=1.0×10⁻²), which can be explained by the effective electron delocalization along the fully conjugated belt and the unique D₂ symmetry. 1 exhibits local aromatic character with a dominant structure containing eight Clar's aromatic sextet rings.     

Differentiating root and rhizome of panax notoginseng based on precursor ion scanning and multi heart-cutting two-dimensional liquid chromatography

Owing to increasing demand for Panax notoginseng-based medicines and health products, establishing a fast, simple, and reliable assay to analyze the chemical differences between its root and rhizome is important. Although previous studies showed that the chemical and biological differences between the root and rhizome of P. notoginseng seem to be small, efforts should be taken to investigate such differences to ensure the safety and efficacy of the products. This work describes a holistic approach that combines characteristic fingerprinting using ultra-high performance liquid chromatography-tandem mass spectrometry parent ion scanning with charged aerosol detection and targeted separation by online heart-cutting two-dimensional liquid chromatography, to identify and evaluate characteristic markers allowing differentiation of the root and rhizome. A total of five potential markers chikusetsusaponin L₅, ginsenoside Rb₂, stipuleanoside R_2, malonyl-ginsenoside Rb₁, and malonyl-ginsenoside Rd, were identified and confirmed by comparing chromatographic retention time, the accurate mass of molecular weight, and the fragments of secondary MS with the available reference materials. The results showed that all five markers were 2.8–7 times higher in content in the rhizome than in the root.