High-resolution Electron Impact Mass Spectrometry Research Articles

Synthesis, biological evaluation and in silico molecular modelling studies of chloro substituted bis-indole containing benzohydrazide analogues as potential anti-diabetic and anti-Alzheimer's agents

Fifteen bis-indolylmethane analogues were synthesized, characterized through NMR (1H, 13C) and high-resolution electron-impact mass spectrometry (HREI-MS), and tested against α-glucosidase, α-amylase, acetylcholinesterase, and butyrylcholinesterase inhibitory potentials. All analogues exhibited different inhibitory potentials, with IC50 values ranging between 7.5 ± 0.92 to 58.4 ± 0.07 μM (α-glucosidase), and 0.80 ± 0.05 to 15.30 ± 0.10 μM (α-amylase) as compared to the standard drug acarbose (IC50 = 38.45 ± 0.80 and 8.90 ± 0.10 μM). Out of fifteen analogues, nine showed an excellent inhibitory potency that was manyfold better than standard drugs. A slight increase or decrease in inhibition was observed due to substituents attached at imine site. In the case of α-amylase inhibition, two analogues such as 2 and 11, showed excellent inhibitory potential with IC50 values of 0.80 ± 0.05 and 0.90 ± 0.10 μM while all other analogues showed good potency. All analogues were also tested against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory potentials, and they showed good potentials ranging from 1.40 ± 0.20 to 16.20 ± 0.50 μM (AChE) and 3.20 ± 0.10 to 19.60 ± 0.20 μM (BuChE) as compared to the standard drug Donepezil (IC50 = 2.16 ± 0.12 μM and 4.5 ± 0.11 μM). In the case of AChE, analogue 3 is the most potent, and in the case of BuChE, analogue 9 is the most potent among the series. The structure-activity relationship was carried out, mainly associated with the nature, number, and position and the electron-donating and electron-withdrawing effects of the substituent(s) on the phenyl ring. The binding modes as well as binding free energy for α-glucosidase and α-amylase inhibitors were determined through docking studies.

Ammonium Salts as a Source of Small Molecules Observed with High-Resolution Electron-Impact Ionization Mass Spectrometry.

Recent high-resolution in situ mass spectrometry at comet 67P/Churyumov-Gerasimenko visited by European Space Agency's Rosetta spacecraft raised the question, if sublimating ammonium salts can unequivocally be detected in the cometary coma. In laboratory experiments with the twin model of the space instrument, two prototypic ammonium salts NH4B, namely, ammonium chloride (B = Cl-) and ammonium formate (B = HCOO-) (as well as methodologically relevant isotopologues), were allowed to sublimate in vacuum while mass spectra were collected. High-resolution electron-impact ionization mass spectrometry provides an outstanding experimental tool to investigate the complex physicochemical processes occurring during the sublimation of ammonium salts. Sublimation of ammonium chloride led to the observation of the ammonium cation NH4+ and the chloramide molecule NH2Cl in the neutral gas mode of the instrument. These observations could be jointly interpreted as indirect evidence for the existence of a neutral gaseous parent species (either as the molecular complex NH3···HB or the double-ionic species NH4+···B-). However, the qualitative fragmentation pattern we present for 13C15N-ammonium formate suggests an alternative route of NH4+ production within the ionization region of the instrument, namely, by protonation/hydrogenation. Besides NH4+, other species were observed that were formed in protonation/hydrogenation reactions. Moreover, together with the two major species from the decomposition of the salt, ammonia and formic acid, three minor species also contributed to the fragmentation pattern: HCN/HNC, HOCN/HNCO, and CH3NO. Like chloramide, formamide (CH3NO) also is a secondary species probably formed in a pseudo-intramolecular chemical reaction while ammonia and the respective acid are in a state of association. HCN/HNC and HOCN/HNCO are ternary products coming out of formamide decomposition reactions. We discuss our experimental findings, summarized in a tentative chemical reaction network, in light of the available theoretical literature and highlight their relevance for the interpretation of in situ measurements in space research.

Synthesis of 4-substituted ethers of benzophenone and their antileishmanial activities.

Leishmaniasis is a vector-borne protozoan disease; it mainly originates from the bite of sandfly and initiated when parasite is transmitted to human at metacyclic flagellated promastigote form. In the current study, a synthesis of a series of 4-substituted benzophenone ethers 1–20 was carried out in good yields and their in vitro antileishmanial activities were also screened. Among synthetic derivatives, 15 compounds 1, 3, 5–12, 15 and 17–20 showed antileishmanial activities against promastigotes of Leishmania major with IC50 values in the range of 1.19–82.30 µg ml−1, and the values were compared with those of the standard pentamidine (IC50 = 5.09 ± 0.09 µg ml−1). Our study identified a series of new antileishmanial molecules as potential leads. Structures of these synthetic compounds were deduced by different spectroscopic techniques, such as 1H and 13C nuclear magnetic resonance, electron impact and high-resolution electron impact mass spectrometry and IR.

Antioxidant xanthones and anthraquinones isolated from a marine-derived fungus Aspergillus versicolor

Chemical examination of an EtOAc extract of cultured Aspergillus versicolor fungus from deep-sea sediments resulted in the isolation of four xanthones, eight anthraquinones and five alkaloids, including a new xanthone, oxisterigmatocystin D (1) and a new alkaloid, aspergillusine A (13). High resolution electron impact mass spectrometry (HR-EI-MS), FT-IR spectroscopy, and NMR techniques were used to elucidate the structures of these compounds, and the absolute configuration of compound 1 was established by its NMR features and coupling constant. Furthermore, the biosynthesis pathway of these xanthones and anthraquinones were deduced, and their antioxidant activity and cytotoxicity in human cancer cell lines (HTC-8, Bel-7420, BGC-823, A549, and A2780) were evaluated. The trolox equivalent antioxidant capacity (TEAC) assay indicated most of the xanthones and anthraquinones possessing moderate antioxidant activities. The Nrf2-dependent luciferase reporter gene assay revealed that compounds 6, 7, 9, and 12 potentially activated the expression of Nrf2-regulated gene. In addition, compounds 5 and 11 showed weak cytotoxicity on A549 with the IC50 values of 25.97 and 25.60 μmol·L−1, respectively.

New apoptosis-inducing sesquiterpenoids from the mycelial culture of Chinese edible fungus Pleurotus cystidiosus.

Two new bisabolane-type sesquiterpenoids, pleuroton A (1) and pleuroton B (2), and three clitocybulol derivatives, clitocybulol D (3), clitocybulol E (4), and clitocybulol F (5), were obtained from the mycelial culture of edible fungus Pleurotus cystidiosus O. K. Mill by repeated column chromatography over RP-18, Sephadex LH-20, and silica gel. Their structures were determined according to nuclear magnetic resonance data, high-resolution electron impact mass spectrometry, and circular dichroism spectra. These new sesquiterpenoids exhibited significant cytotoxicity against two human prostate cancer DU-145 and C42B cells in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The median inhibitory concentration (IC50) of compounds 1, 2, 3, 4, and 5 was 174, 28, 233, 162, and 179 nM, respectively, against the DU-145 cell and was 104, 52, 163, 120, and 119 nM, respectively, against the C42B cell. Especially, pleuroton B (2) exhibited the strongest cytotoxity among these sesquiterpenoids, which was confirmed by the colony formation assay. Furthermore, pleuroton B (2) could trigger the apoptosis of DU-145 cells through the detection of apoptosis cells using annexin V-FITC staining by flow cytometry, the observation of condensed nuclei in the apoptosis cells, and the western blot analysis for the expression of apoptosis-related proteins Bcl-2, Bak, and Bax. Analysis of structure-activity relationships of these sesquiterpenoids revealed that the unusual functional moiety of pleuroton B should contribute to its significant bioactivity. These results display the pharmacological potential of P. cystidiosus.

Feeding deterrents from the tubers of Boschniakia himalaica against the red flour beetle, Tribolium castaneum

In our screening program for new agrochemicals from Chinese medicinal herbs and local wild plants, MeOH/CHCl3 extract of the tubers of Boschniakia himalaica was found to possess strong feeding deterrent activity against the red flour beetle, Tribolium castaneum. From the MeOH/CHCl3 extract, three feeding deterrents were isolated by bioassay-guided fractionation. The constituent compounds were isolated and identified as 3β-acetoxyurs-12-en-28-oic acid (1), 3β-acetoxyurs-28,13-olide (2) and (+)-pinoresinol monoglucoside (3) based on high-resolution electron impact mass spectrometry and nuclear magnetic resonance. Compounds 1, 2 and 3 exhibited feeding deterrent activity against T. castaneumadults with ED50 values of 378, 940 and 609 ppm, respectively. Key words: Boschniakia himalaica, Tribolium castaneum, feeding deterrent.

Mosquito larvicidal activity of alkaloids and limonoids derived from Evodia rutaecarpa unripe fruits against Aedes albopictus (Diptera: Culicidae)

In recent years, uses of environment friendly and biodegradable natural insecticides of plant origin have received renewed attention as agents for vector control. During a screening program for new agrochemicals from Chinese medicinal herbs and local wild plants, the ethanol extract of Evodia rutaecarpa Hook f. et Thomas (Rutaceae) unripe fruits was found to possess larvicidal activity against the mosquitoes. The aim of this research was to determine larvicidal activity of the ethanol extract of E. rutaecarpa unripe fruits and the isolated constituents against the larvae of the Culicidae mosquito Aedes albopictus. The powder, 5 kg of the fruit material, was extracted with 30 l of 95 % ethanol, filtered, and evaporated to dryness in a rotary vacuum evaporator. The crude extract was then partitioned between methanol-water and n-hexane. The n-hexane fraction was evaporated off to given n-hexane extract. The aqueous layer was repartitioned with chloroform to provide chloroform extract after evaporation of the solvent. Further partitioning with ethyl acetate gave a residue after evaporation of the solvent. Bioactivity-directed chromatographic separation of chloroform extract on repeated silica gel columns led to the isolation of three alkaloids (evodiamine, rutaecarpine, and wuchuyuamide I) and two limonoids (evodol and limonin). The structures of the constituent compounds were elucidated based on high-resolution electron impact mass spectrometry and nuclear magnetic resonance. Evodiamine, rutaecarpine, and wuchuyuamide I exhibited strong larvicidal activity against the early fourth instar larvae of A. albopictus with LC(50) values of 12.51, 17.02, and 26.16 μg/ml, respectively. Limonin and evodol also possessed larvicidal activity against the Asian tiger mosquitoes with LC(50) values of 32.43 and 52.22 μg/ml, respectively, while the ethanol extract had a LC(50) value of 43.21 μg/ml. The results indicated that the ethanol extract of E. rutaecarpa and the five isolated constituents have a good potential as a source for natural larvicides.

All-Nitrogen Coordinated Amidinato/Imido Complexes of Molybdenum and Tungsten: Syntheses and Characterization

The first all-nitrogen coordinated bis(alkylamidinato)/bis(alkylimido) complexes of molybdenum and tungsten, [Mo(NtBu)(2){(iPrN)(2)CMe}(2)]and [W(NtBu)(2){(iPrN)(2)CMe}(2)], have been synthesized and fully characterized by (1)H and (13)C NMR spectroscopy, elemental analyses, high-resolution electron impact mass spectrometry, and Fourier transform infrared spectroscopy. Density functional theory calculations of the tungsten complex allow for geometry optimization and structural characterization by assignment of the NMR data, in particular a comparison of the experimental (13)C NMR signals with the calculated ones. Both compounds sublime without decomposition at 130 °C and 1 mTorr and show rapid decomposition above 250 °C, hence representing promising vapor-phase deposition routes for metal nitride based thin-film materials.

Lignans from the Tuber-barks of Colocasia antiquorum var. esculenta and Their Antimelanogenic Activity

Colocasia antiquorum var. esculenta , a variant of C. antiquorum , commonly known as "Imperial Taro", is an edible vegetable in many tropical and subtropical regions of the world. This study with the aim of evaluating the potential of C. antiquorum var. esculenta as a functional food with a depigmenting effect resulted in the identification of a new sesquilignan, named colocasinol A (1), and a new acyclic phenylpropane lignanamide, named cis-grossamide K (2), together with 10 known compounds (3-12). The identification and structural elucidation of these compounds were based on 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data analysis as well as high-resolution fast atom bombardment mass spectrometry (FABMS) and electron impact mass spectrometry (EIMS). Quantitation of the melanin contents and cell viability in murine melanocyte melan-a cells was used to assess the antimelanogenic activities of the isolated compounds. Among them, cis-grossamide K (2), isoamericanol A (3), americanol A (4), 2-hydroxy-3,2'-dimethoxy-4'-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-1-propenyl)biphenyl (5), and (-)-pinoresinol (6) showed inhibitory effects on melanin production. Compounds 2, 5, and 6 exerted a particularly strong antimelanogenic activity on the cells without high cell toxicity (IC(50) = 54.24, 53.49, and 56.26 microM, and LD(50) = 163.60, 110.23, and >500 microM, respectively).

Structure elucidation and NMR assignments for two xanthone derivatives from a mangrove endophytic fungus (No. ZH19)

The structure elucidations and complete (1)H and (13)C NMR assignments are reported for two new xanthone derivatives: 1,7-dihydroxy-2-methoxy-3-(3-methylbut-2-enyl)-9H-xanthen-9-one (1) and 1-hydroxy-4,7-dimethoxy-6-(3-oxobutyl)-9H-xanthen-9-one (2). Both of these secondary metabolites were isolated from the fermentation medium of a mangrove endophytic fungus (No. ZH19). High-resolution electron impact mass spectrometry (HREIMS), Fourier transform infrared (FT-IR) absorption spectrometry, and NMR experiments including gCOSY, gHMQC, and gHMBC were used for the determination of the structures and NMR spectral assignments. Preliminary pharmacological test showed that compounds (1) and (2) inhibited KB cells with IC(50) values of 20 and 35 micromol/ml, and KB(V)200 cells with IC(50) values of 30 and 41 micromol/ml, respectively.

Structure elucidation and NMR assignments for two amide alkaloids from a Mangrove endophytic Fungus (No. ZZF‐22)

The structure elucidations and complete (1)H and (13)C NMR assignments are reported for two new natural products: 3-benzylidene-8,8a-dihydroxy-2-methyl-hexahydro-pyrrolo[1,2-a]pyrazine-1,4-dione(1) and 4-hydroxy-6-(hydroxy-phenyl-methyl)-N-(3-methyl-butyryl)-nicotinamide (2). Both of these secondary metabolites were isolated from the fermentation medium of a Mangrove endophytic fungus. High resolution electron impact mass spectrometry (HREIMS), FT-IR Spectroscopy and NMR experiments including gCOSY, gHMQC, gHMBC and NOE were used for determination of the structures and assignments of the amide alkaloids.

Ozonation By-products and Determination of Extracellular Release in Freshwater Algae and Cyanobacteria

This work identifies the cyanobacterial and algal extracellular products (ECPs) and their derived byproducts during preozonation. Laboratory experiments were performed on two cyanobacterial species (Oscillatoria tenuisa and Microcystis aeruginosa) and one algal species (Chlorella sp.) dominating eutrophic reservoirs. Gas chromatography, coupled with high-resolution electron-impact mass spectrometry (GC/EI-MS), and high-performance anion-exchange chromatography (HPAEC) was adopted. Over 20 compounds were detected in the mass spectra analyses of the cyanobacterial and algal extracts (including cells and filtrates). The main identified ECPs were classified as monosaccharides, fatty acids, hydrocarbons, and aldehydes. Odor-causing substances were also present in the cyanobacteria, such as trans-1,10-dimethyl-trans-9-decalol (geosmin) and 2-methylisoborneol (2-MIB). The results from ozonated cyanobacteria and algae indicated that the dissolved organic carbon (DOC) content of culture suspensions increased during ozonation. Most of the additional DOC is produced by the increased liberation of ECPs to the bulk phase. Several byproducts were present in the ozonated cyanobacterial and algal cultures: a total of 22 different organic compounds were detected—mostly aldehydes and phthalates.

Evaluation of extracellular products and mutagenicity in cyanobacteria cultures separated from a eutrophic reservoir

The algal extracellular products (ECPs) in three cultures of cyanobacteria species (Anabaena, Microcystis, and Oscillatoria) dominating the eutrophic reservoir populations and their toxins have been investigated in the present work. Using gas chromatography coupled with high-resolution electron-impact mass spectrometry (GC/EI-MS) and high performance anion-exchange chromatography (HPAEC) techniques, more than 20 compounds were found in the algal culture (including cells and filtrates) extracts. The main identified ECPs were classified to polysaccharides, hydrocarbons, and aldehydes. Odor causing substances such as trans-1,10-dimethyl-trans-9-decalol (geosmin) and 2-methylisoborneol (2-MIB)were also found in the algal cultures. The potential mutagenicity of the algal suspensions was also studied with the Ames test. The organic extracts of the algal suspension from the axenic cultures were mutagenicity in TA98 without S9 mix and in TA100 with and without S9 mix. The results indicate that the ECPs of three algae species dominating the eutrophic reservoir were mutagenic clearly in the bacterial test.

Novel Rearranged Abietane Diterpenoids from the Roots ofSalvia sahendica

Two naphthoquinone diterpenoids, 1 and 2, one tricyclic, and one tetracyclic rearranged abietane ('4,5-seco-10,5-friedo-abietane') diterpenoids, 3 and 4, respectively, together with horminone (5) have been isolated from the roots of Salvia sahendica. Compounds 2 and 3 are new, and the 13C-NMR assignment for compound 4 was modified using ' Heteronuclear Multiple-Bond Correlation' (HMBC) spectroscopic data. The structures of the compounds have been established by using different spectral data including 1D- and 2D-NMR, IR, UV, and MS. The elemental composition for the major peaks of 3 and 4 were determined by ' High-Resolution Electron Impact Mass Spectrometry' (HR-EI-MS). The relative configurations of the new compounds were determined by 1H-NMR and 'Rotating-Frame NOES' (ROESY) spectroscopy. Compounds 1, 2, and 5 showed antifungal activities when tested on Blakeslea trispora. Lapachol, a prelynated naphthoquinone, was used as a positive control. The biological activities of the related naphthoquinones and abietane diterpenoids were discussed.

Two New 5‐Deoxyflavonoids from Calliandra inermis

AbstractFor Abstract see ChemInform Abstract in Full Text.

Usnic Acid, Metabolite from Neuropogon Sp., An Antarctic Lichen Isolation, Structure Elucidation and Biological Activity

ABSTRACTFrom the lichen Neuropogon sp., collected in the region Livingston Island, Antarctica was isolated secondary metabolite, identical to (-) usnic acid (C18H16O7, MW. 344) with antibiotic activity. The structure was settled on the basis of high-resolution electron impact mass spectrometry(HREI-MS) and one and two dimensional NMR spectroscopy(1H, 13C, DEPT, COSY, HSQC and HMBC). The usnic acid was investigated for antimicrobial activity against pathogenic Gram-positive and Gram-negative bacteria as Streptococcus pyogenes 15346, Staphilococcus epidermidis 1093, Bacillus cereus 157, Listeria monocytogenes 981, Yersinia enterocolitica 013, Klebsiella pneumoniae 52145 and Salmonella thyphimurium.

Two new 5-deoxyflavonoids from Calliandra inermis.

Two new 5-deoxyflavonoids, 7,2',3',4'-tetramethoxyflavone (1) and 7,2',3',4'-tetramethoxyflavanone (2) together with a known flavone 7,4'-dimethoxy-3'-hydroxyflavone (3) were isolated from the whole plant of Calliandra inermis. The structures of these new compounds were elucidated by high resolution electron impact mass spectrometry (HR-EI-MS) and 1D and 2D-NMR spectral studies including 1H-1H correlation spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond connectivity (HMBC) and nuclear Overhauser enhancement spectroscopy (NOESY).

Biosynthesis of diaporthin and orthosporin by Aspergillus ochraceus

Diaporthin and orthosporin were characterised from the fungus Aspergillus ochraceus D2306. Diaporthin was identified by high-resolution electron impact mass spectrometry and 1H and 13C NMR spectroscopy, from which new spectroscopic assignments were made. Orthosporin was also identified by mass spectrometry and both fungal metabolites are reported for the first time as co-metabolites and also as products of A. ochraceus. The methylation inhibitor ethionine affected production of both diaporthin and orthosporin in spite of no obvious methylation step in the biosynthesis of orthosporin, implying that extracellular orthosporin may arise by de-O-methylation of diaporthin. The biosynthetic origin of diaporthin was demonstrated by incorporation of [1-14C]acetate and [methyl-14C]methionine administered in early idiophase.

On-line acquisition, analysis, and e-mailing of high-resolution exact-mass electron impact/chemical ionization mass spectrometry data acquired using an automated direct probe

A complete automation package has been developed for data acquisition, processing, interpreting, and e-mailing of high-resolution exact-mass electron impact (EI) and chemical ionization (CI) mass spectrometry data. A commercial high performance magnetic sector mass spectrometer equipped with a commercial programmable robotic direct probe was used. The software package contains a series of modules that automatically performs all the functions necessary for data reduction and reporting. In sequential order, these functions include downloading of sample information from a corporate database, creation of a sample list, acquisition of high-resolution exact-mass data, processing of the data, generation of an exact-mass report, e-mailing of the results to the requesting chemists, and finally shutting down of the instrument. The performance of the system was evaluated with nearly 500 samples. The system was found to be reliable and robust with a small average systematic mass error of −0.47 mmu and a standard deviation of 1.61 mmu.

Identification of New Ozone Disinfection Byproducts in Drinking Water

Using a combination of spectral identification techniquesgas chromatography coupled with low- and high-resolution electron-impact mass spectrometry (GC/EI-MS), low- and high-resolution chemical ionization mass spectrometry (GC/CI-MS), and infrared spectroscopy (GC/IR)we identified many drinking water disinfection byproducts (DBPs) formed by ozone and combinations of ozone with chlorine and chloramine. Many of these DBPs have not been previously reported. In addition to conventional XAD resin extraction, both pentafluorobenzylhydroxylamine (PFBHA) and methylation derivatizations were used to aid in identifying some of the more polar DBPs. Many of the byproducts identified were not present in spectral library databases. The vast majority of the ozone DBPs identified contained oxygen in their structures, with no halogenated DBPs observed except when chlorine or chloramine was applied as a secondary disinfectant. In comparing byproducts formed by secondary treatment of chlorine or chloramine, chloramine appeared to form the same types of halogenated DBPs as chlorine, but they were generally fewer in number and lower in concentration. Most of the halogenated DBPs that were formed by ozone−chlorine and ozone−chloramine treatments were also observed in samples treated with chlorine or chloramine only. A few DBPs, however, were formed at higher levels in the ozone−chlorine and ozone−chloramine samples, indicating that the combination of ozone and chlorine or chloramine is important in their formation. These DBPs included dichloroacetaldehyde and 1,1-dichloropropanone.