Low temperature radiolysis of fullerene C<Subscript>60</Subscript> and its solutions in isopropylbenzene and <Emphasis Type="Italic">N</Emphasis>-vinylpyrrolidone

Low-temperature (77 K) radiolysis of solid fullerene C₆₀ and its glassy solutions in isopropylbenzene (IPB) and N-vinylpyrrolidone (N-VP) has been investigated with the use of ESR spectroscopy. Radiationchemical yields for the formation of paramagnetic centers (G _PMC, 1/100 eV) have been determined to be ∼0.001 for pure fullerene and 0.3 and 0.7 for its solutions in IPB and N-VP, respectively. The low value of G _PMC for fullerene indicates a high stability of this form of carbon. The increase in G _PMC in solutions as compared to the pure solvents (0.15 for IPB and 0.3 for N-VP) indicates the sensitizing effect of C₆₀.     

Pharmacokinetics of methyl salicylate‐2‐O‐β‐D‐lactoside,a novel salicylic acid analog isolated from Gaultheria yunnanensis,in dogs

Methyl salicylate‐2‐O‐β‐D‐lactoside (MSL), a natural salicylate derivative of Gaultheria yunnanensis (Franch.) Rehder (G. yunnanensis), has been shown to provide a beneficial anti‐inflammatory effect in animal models. Studies on the pharmacokinetics and bioavailability of MSL can provide both a substantial foundation for understanding its mechanism and empirical evidence to support its use in clinical practice. A simple and sensitive high‐performance liquid chromatography (HPLC) method, coupled with ultraviolet analyte detection, was developed for determining the concentration of MSL and its metabolite in beagle plasma. Chromatographic separation was achieved on a Agilent Zorbax SB‐C₁₈ column (5 μm ,4.6 × 250 mm). The mobile phase consisted of aqueous solution containing 0.1% phosphoric acid and acetonitrile (82:90, v/v), at a flow rate of 1 mL/min. Validation of the assay demonstrated that the developed HPLC method was sensitive, accurate and selective for the determination of MSL and its metabolite in dog plasma. After orally administering three doses of MSL, it could no longer be detected in dog plasma and its metabolite, salicylic acid, was detected. Salicylic acid showed a single peak in the plasma concentration–time curves and linear pharmacokinetics following the three oral doses (r² > 0.99). In contrast, only MSL was detected in plasma following intravenous administration. These results will aid in understanding the pharmacological significance of MSL. The developed method was successfully used for evaluation of the oral and intravenous pharmacokinetic profile of MSL in dogs. Copyright © 2013 John Wiley & Sons, Ltd.     

Dérivés du C-méthyl-3-xylofurannose

3-C-Methylxylofuranose Derivatives 3′-C-methyladenosine has been known for almost ten years whereas its 3′-epimer is still to be prepared, because of the difficulty of synthesizing the 3-C-methylxylo-furanose. In this communication, the synthesis of 1,2-O-isoproypylidene acetal 9 and its derivatives is described. Vicinal dihydroxylation of 5-O-benzoyl-3-deoxy-1,2-O-isopryopylidene-3-C-methylidene-α-D -erythro-pentofuranose ( 6 ) led to the branchedchain sugar derivative 7 which was selectively tosylated to 8 whose reduction gave 9 . These reactions, as well as the derivatizations of 7 , 8 and 9 , took place with good to excellent yields.     

Highly Diastereoselective,Biogenetically Patterned Synthesis of (+)‐(1S,6R)‐Volvatellin (=(+)‐(4R,5S)‐5‐Hydroxy‐4‐(5‐methyl‐1‐methylenehex‐4‐en‐2‐ynyl)cyclohex‐1‐ene‐1‐carbaldehyde)

The synthesis of volvatellin ( 4a ), previously isolated from a herbivorous marine mollusk, was achieved with high diastereoselectivity from putative dietary oxytoxin‐1 ( 2 ). A biogenetically patterned carbonyl‐ene route was chosen, proceeding from 2 predominantly via the trans cyclization product 3 without the use of enzymes. This challenges the involvement of enzymes in the formation of 4a in nature. The optical purity and absolute configuration (1S,4S,6R), assigned to 3 from high‐field ¹H‐NMR examination of its Mosher (MTPA) esters 6 , was retained on its chemical conversion to (+)‐(1S,6R)‐configured 4a and is consistent with the (4S) configuration previously established for caulerpenyne ( 1 ).     

Immobilization and direct electrochemistry of cytochrome <Emphasis Type="BoldItalic">c</Emphasis> at a single-walled carbon nanotube-modified electrode

A single-walled carbon nanotube (SWNT)-modified electrode was fabricated and characterized by SEM and ac impedance techniques. The direct electrochemistry of cytochrome c (Cyt c), which was adsorbed on the surface of the SWNT, was studied by cyclic voltammetry. The results from cyclic voltammetry and infrared spectroscopy indicated that Cyt c remained in its original structure and did not undergo structural change after its immobilization on the SWNT. Further results demonstrated that the SWNT had promotional effects on the direct electron transfer of Cyt c and also indicated that the immobilized Cyt c retained its electrocatalytic activity to the reduction of H₂O₂. This modified electrode might be used in development of new biosensors and the biofuel cells.     

A first <Emphasis Type="Italic">P,N</Emphasis>-bidentate phosphite with a chiral ketimine fragment. Catalytic properties of its Rh<Superscript>I</Superscript> and Pd<Superscript>II</Superscript> complexes in comparison with those of phosphine analogs

A chiral P,N-bidentate aryl phosphite ligand containing peripheral (R)-(+)-camphor-derived ketimine and its rhodium(I) and palladium(II) chelate complexes were synthesized for the first time. These compounds were found to be suitable for asymmetric allylic substitution. The Pd-catalyzed sulfonylation of 1,3-diphenylallyl acetate with sodium p-toluenesulfinate gave the product in 73% ee; in the alkylation of the same substrate with dimethyl malonate, the ee was 94%. These ee values are higher than the enantioselectivity achieved with the known phosphine analogs.Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1942–1945, September, 2004.     

Rethinking Cysteine Protective Groups: S‐Alkylsulfonyl‐l‐Cysteines for Chemoselective Disulfide Formation

The ability to reversibly cross‐link proteins and peptides grants the amino acid cysteine its unique role in nature as well as in peptide chemistry. We report a novel class of S‐alkylsulfonyl‐l ‐cysteines and N‐carboxy anhydrides (NCA) thereof for peptide synthesis. The S‐alkylsulfonyl group is stable against amines and thus enables its use under Fmoc chemistry conditions and the controlled polymerization of the corresponding NCAs yielding well‐defined homo‐ as well as block co‐polymers. Yet, thiols react immediately with the S‐alkylsulfonyl group forming asymmetric disulfides. Therefore, we introduce the first reactive cysteine derivative for efficient and chemoselective disulfide formation in synthetic polypeptides, thus bypassing additional protective group cleavage steps.     

Prediction of electron-ionization mass spectra of <Emphasis Type="Italic">O</Emphasis>-Alkyl-<Emphasis Type="Italic">N,N</Emphasis>-dialkylphosphoramido cyanidates

A method is proposed for the prediction of electron-ionization mass spectra of highly toxic O-alkyl-N,N-dialkylphosphoramido cyanidates. The approach is based on the fact that the compounds can be divided into three groups by the type of fragmentation. The main group (O-alkyl, O-methyl, O-ethyl) containing almost all compounds of this class (61440 of 61460), in its turn, can be divided into ten subgroups characterized by different combinations of two N-alkyl radicals. Each subgroup possesses its specific generalized spectral image, i.e., a set of peaks characterized by mass numbers and relative intensities. A spectrum of an individual O-alkyl-N,N-dialkylphosphoramido cyanidate is considered as a sum of the generalized spectral image of a corresponding subgroup and a spectrum of an alkene with a carbon chain identical to the O-alkyl group of the molecule.     

Action de nucléophiles sur des sucres ramifiés cyanovinylidéniques: Addition conjuguée,stéréomutation,migration de doubles liaisons. Communication préliminaire

When treated with a series of nucleophiles cis-3-cyanomethylene-3-deocy-1,2:5,6-di-O-isopropylidene-α-D-ribo-hexofurannose ( 1 ) may yield its trans isomer, a product of allylic isomerization or a product of conjugate addition, depending on the nature of the nucleophile. The configuration of the starting material is also important as shown by the differences in reactivity between 1 and its trans-xylo isomer 8 .     

Simultaneous quantification and rat pharmacokinetics of formononetin‐7‐O‐β‐d‐glucoside and its metabolite formononetin by high‐performance liquid chromatography–tandem mass spectrometry

Formononetin‐7‐O‐β‐d ‐glucoside has been proved to have significant anti‐inflammatory effect. To evaluate its rat pharmacokinetics, a rapid, sensitive, and specific liquid chromatography–tandem mass spectrometry method has been developed and validated for the quantification of formononetin‐7‐O‐β‐d ‐glucoside and its main metabolite formononetin in rat plasma. Samples were pretreated using a simple protein precipitation and the chromatographic separation was performed on a C₁₈ column by a gradient elution using a mobile phase consisting of water and acetonitrile both containing 0.1% formic acid. Both analytes were detected using a tandem mass spectrometer in positive multiple reaction monitoring mode. The assay showed wide linear dynamic ranges of both 0.10–100 ng/mL, with acceptable intra‐ and inter‐batch accuracy and precision. The lower limits of quantification were both 0.10 ng/mL using 50 μL of rat plasma for two analytes. The method has been successfully used to investigate the oral pharmacokinetic profiles of both analytes in rats. After oral administration of formononetin‐7‐O‐β‐d ‐glucoside at the dose of 50 mg/kg, it was rapidly absorbed in vivo and metabolized to its metabolite formononetin. The plasma concentration‐time profiles both showed double‐peak phenomena, which would be attributed to the strong enterohepatic circulation of formononetin‐7‐O‐β‐d ‐glucoside.     

A new cyclic peptide from the marine fungal strain <Emphasis Type="Italic">Aspergillus</Emphasis> sp<Emphasis Type="Italic">.</Emphasis> AF119

A new cyclic heptapeptide containing γ-aminobutyric acid in the ring, namely unguisin E (1), was isolated from the fermentation culture of Aspergillus sp. AF119. The structure was elucidated by spectroscopic analyses, including 1D and 2D NMR experiments, and HR ESI-Q-TOF mass spectrometry, and by comparison with those reported. Compound 1 was evaluated for its antimicrobial activities by the paper diffusion method.     

Screening free radical scavengers in Xiexin Tang by HPLC‐ABTS‐DAD‐Q‐TOF/MS

Xiexin Tang (XXT) is a traditional Chinese medicine (TCM) that has been used in herbal clinics for more than 1800 years. Many studies have shown that XXT has therapeutic effects on patients with arteriosclerosis owing to its antioxidant activity. However, there is little information about the relationship between the chemical composition of XXT and its antioxidant activity. In this study, the HPLC‐ABTS‐DAD‐Q‐TOF/MS method, which can simultaneously identify individual components and rapidly screen for antioxidant compounds, was used to screen and identify antioxidant components in XXT. The 15 compounds identified were gluco‐syringic acid, adenine, gallic acid, biflorin, cularine, 6‐C ‐arabinose‐8‐C ‐glucose‐chrysin, 6‐C ‐glucose‐8‐C ‐arabinose–chrysin, baicalin, rhein‐8‐O‐β ‐d ‐glucopyranoside, coptisine, epiberberine, jatrorrhizine, norwogonin, 5,7,2′‐trihydroxy‐6‐ methoxyflavone and baicalein. In addition, the data showed that the antioxidant activity of peaks 4, 6, and 11 was lower in XXT than in its constituent herbs, while the activity of peaks 1, 2, 3, 5, 7, 8, 10, 12, 13, 14 and 15 was higher in XXT. Compound 5 had the strongest antioxidant activity in XXT, while compound 1 showed the strongest antioxidant activity among its constituent herb. The differences between antioxidant activities of major components of XXT and those of its constituent herbs might be due to the interaction of crude drugs that changes the solubility of active components during the decoction process. The results show that the HPLC‐ABTS‐DAD‐Q‐TOF/MS method can successfully combine on‐line mass spectrometry with activity detection system. It is a useful tool for the rapid detection and identification of antioxidants, and for quantitative analysis of individual antioxidants in complex mixtures such as plant extracts. Furthermore, this method does not require extensive extract purification and fraction collection.     

Synthesis of 8‐Desoxythunberginol A and (±)‐8‐Desoxy‐3,4‐Dihydrothunberginol A

A two step synthesis of title isocoumarin isolated from Homalium longifolium and its conversion into corresponding 3,4‐dihydroisocoumarin has been described. 3,4‐Dimethoxybenzoyl chloride on condensation with homophthalic acid afforded 3‐(3′,4′‐dimethoxyphenyl)isocoumarin which was demethylated to furnish the 8‐desoxythunberginol A, whereas its sequential saponification, reduction and demethylation yielded the (±)‐8‐desoxy‐3,4‐dihydrothunberginol A. The synthesized compounds were examined in vitro for antibacterial activity.     

Excited‐State Proton‐Relay Dynamics of 7‐Hydroxyquinoline Embedded in a Solid Matrix of Poly(2‐hydroxyethyl methacrylate)

Excited 7‐hydroxyquinoline embedded in a solid matrix of poly(2‐hydroxyethyl methacrylate) undergoes a proton‐relay reaction efficiently to form its keto tautomer. However, the reaction mechanism depends on the torsional conformation and the microscopic environment of the molecule at the moment of excitation. Whereas the bridged cis‐enol form undergoes proton relay immediately on absorption of a photon to produce its tautomeric keto species, the unbridged cis form requires 120 ps for bridge formation via solvent reorganization prior to proton relay. Furthermore, the trans form needs 1000 ps for tautomerization because it requires an activated (11 kJ mol^?1) torsional motion to change into its cis form prior to bridge formation and proton relay. Torsional motion rather than solvent reorganization determines the proton relay rate of the trans‐form of the molecule.     

Refolding of urea‐denatured α‐chymotrypsin by protein‐folding liquid chromatography

An approach for re‐folding denatured proteins during proteome research by protein folding liquid chromatography (PFLC) is presented. Standard protein, α‐chymotrypsin (α‐Chy), was selected as a model protein and hydrophobic interaction chromatography was performed as a typical PFLC; the three different α‐Chy states – urea‐denatured (U state), its folded intermediates (M state) and nature state (N state) – were studied during protein folding. Based on the test by matrix‐assisted laser desorption/ionization time of flight mass spectrometry and bioactivity, only one stable M state of the α‐Chy was identified and then it was prepared for further investigation. The specific bioactivity of the refolded α‐Chy was found to be higher than that of commercial α‐Chy as the urea concentration in the sample solution ranged from 1.0 to 3.0 m ; the highest specific bioactivity at urea concentration was 1.0 m , indicating the possibility for re‐folding some proteins that have partially or completely lost their bioactivity, as a dilute urea solution was employed for dissolving the sample. The experiment showed that the peak height of its M state increased with increasing urea concentration, and correspondingly decreased in the amount of the refolded α‐Chy. When the urea concentration reached 6.0 m , the unfolded α‐Chy could not be refolded at all. Copyright © 2012 John Wiley & Sons, Ltd.     

sp‐9‐Acetyl­fluorene,the initial acetyl­ation product of 9‐fluorenyl­lithium

The reaction of 9‐fluorenyl­lithium with acetyl chloride (tetra­hydro­furan, 213 K, under argon) provided four products which we have isolated and whose structures we have unequivocally identified for the first time. That of the initially formed component, 9‐acetyl­fluorene (C₁₅H₁₂O), described here, shows it to be exclusively the sp rotamer in its crystalline form. The acetyl C—C=O plane is essentially perpendicular to the planar fluorene ring and there is no indication of rotational restriction. In contrast, related 9‐pivaloyl­fluorene, which we reported previously, is rotationally restricted and exists exclusively as its ap rotamer, in which the pivaloyl C—C=O plane is also almost perpendicular to the fluorene ring.     

Enhanced <Emphasis Type="SmallCaps">l</Emphasis><Emphasis Type="Italic">-</Emphasis>(+)-Lactic Acid Production by an Adapted Strain of <Emphasis Type="Italic">Rhizopus oryzae</Emphasis> using Corncob Hydrolysate

Corncob is an economic feedstock and more than 20 million tons of corncobs are produced annually in China. Abundant xylose can be potentially converted from the large amount of hemicellulosic materials in corncobs, which makes the crop residue an attractive alternative substrate for a value-added production of a variety of bioproducts. Lactic acid can be used as a precursor for poly-lactic acid production. Although current industrial lactic acid is produced by lactic acid bacteria using enriched medium, production by Rhizopus oryzae is preferred due to its exclusive formation of the l-isomer and a simple nutrition requirement by the fungus. Production of l-(+)-lactic acid by R. oryzae using xylose has been reported; however, its yield and conversion rate are poor compared with that of using glucose. In this study, we report an adapted R. oryzae strain HZS6 that significantly improved efficiency of substrate utilization and enhanced production of l-(+)-lactic acid from corncob hydrolysate. It increased l-(+)-lactic acid final concentration, yield, and volumetric productivity more than twofold compared with its parental strain. The optimized growth and fermentation conditions for Strain HZS6 were defined.     

Composition and Antimicrobial Activity of <Emphasis Type="Italic">Helichrysum italicum</Emphasis> Essential Oil and Its Terpene and Terpenoid Fractions

The essential oil of Helichrysum italicum (Roth) G. Don from Croatia has been fractionated into terpene and terpenoid fractions and analyzed using GC/MS. Fifty-two compounds were identified. The main hydrocarbons of the oil were α-pinene (10.2%), α-cedrene (9.6%) aromadendrene (4.4%), β-caryophyllene (4.2%), and limonene (3.8%), while the main oxygen-containing compounds were neryl acetate (11.5%), 2-methylcyclohexyl pentanoate (8.3%), 2-methylcyclohexyl octanoate (4.8%), and geranyl acetate (4.7%). The essential oil and its terpene and terpenoid fractions were evaluated for antibacterial and antifungal activities. The screening of antimicrobial activity was conducted by a disc diffusion test and the minimum inhibitory concentration was determined against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. The essential oil and its terpenoid fraction exhibited higher antimicrobial activity with respect to the terpene fraction. The antimicrobial activities of the oil and its terpenoid fraction were more pronounced against Staphylococcus aureus and Candida albicans.__________Published in Khimiya Prirodnykh Soedinenii, No. 1, pp. 29–32, January–February, 2005.     

A Cerberus‐Inspired Anti‐Infective Multicomponent Gatekeeper Hydrogel against Infections with the Emerging “Superbug” Yeast Candida auris

The pathogenic yeast Candida auris has received increasing attention due to its ability to cause fatal infections, its resistance toward important fungicides, and its ability to persist on surfaces including medical devices in hospitals. To brace health care systems for this considerable risk, alternative therapeutic approaches such as antifungal peptides are urgently needed. In clinical wound care, a significant focus has been directed toward novel surgical (wound) dressings as first defense lines against C. auris. Inspired by Cerberus the Greek mythological “hound of Hades” that prevents the living from entering and the dead from leaving hell, the preparation of a gatekeeper hybrid hydrogel is reported featuring lectin‐mediated high‐affinity immobilization of C. auris cells from a collagen gel as a model substratum in combination with a release of an antifungal peptide drug to kill the trapped cells. The vision is an efficient and safe two‐layer medical composite hydrogel for the treatment of severe wound infections that typically occur in hospitals. Providing this new armament to the repertoire of possibilities for wound care in critical (intensive care) units may open new routes to shield and defend patients from infections and clinical facilities from spreading and invasion of C. auris and probably other fungal pathogens.     

A triclinic polymorph of 1,3‐thia­zolidine‐2‐thione (2‐mercaptothia­zoline)

A planar conformation of 1,3‐thia­zolidine‐2‐thione (TZDTH), C₃H₅NS₂, was crystallized for the first time. The new triclinic polymorph (P) obtained was compared in terms of its intra‐ and inter­molecular geometry with three previous reports of a monoclinic polymorph (P2₁/n). The packing is based on centrosymmetric dimers of TZDTH, linked by N—H⋯S hydrogen bonds.