A Reflectron Time-of-Flight Mass Spectrometer with a Nano-Electrospray Ionization Source for Study of Metal Cluster Compounds

An experiment facility has been set up for the study of metal cluster compounds in our laboratory, which consists of a nano-electrospray ionization source, an ion transmission and focus system, and a reflectron time-of-fight mass spectrometer. Taking advantage of the nano-electrospray ionization source, polyvalent ions are usually produced in the ＂ionization＂ process and the obtained mass resolution of the equipment is over 8000. The molecular ion peaks of metal cluster compounds [Au20（PPhpy2）10Cl2]（SbF6）4, where PPhpy2=bis（2- pyridyl）phenylphosphine, and [AuaAg2（C）L6]（BF4）4, where L=2-（diphenylphosphino）-5- methylpyridine, are distinguished in the respective mass spectrum, accompanied by some fragment ion peaks. In addition, the mass-to-charge ratios of the parent ions are determi- nated. Preliminary results suggest that the device is a powerful tool for the study of metal cluster compounds. It turns out that the information obtained by the instrumentation serves as an essential supplement to single crystal X-ray diffraction for structure characterization of metal cluster compounds.

Offline two-dimensional liquid chromatography coupled with ion mobility-quadrupole time-of-flight mass spectrometry enabling fourdimensional separation and characterization of the multicomponents from white ginseng and red ginseng

Inherent complexity of plant metabolites necessitates the use of multi-dimensional information to accomplish comprehensive profiling and confirmative identification.A dimension-enhanced strategy,by offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry(2 D-LC/IM-QTOF-MS)enabling four-dimensional separations(2 D-LC,IM,and MS),is proposed.In combination with in-house database-driven automated peak annotation,this strategy was utilized to characterize ginsenosides simultaneously from white ginseng(WG)and red ginseng(RG).An offline 2 DLC system configuring an Xbridge Amide column and an HSS T3 column showed orthogonality 0.76 in the resolution of ginsenosides.Ginsenoside analysis was performed by data-independent high-definition MSE(HDMSE)in the negative ESI mode on a Vion?IMS-QTOF hybrid high-resolution mass spectrometer,which could better resolve ginsenosides than MSEand directly give the CCS information.An in-house ginsenoside database recording 504 known ginsenosides and 58 reference compounds,was established to assist the identification of ginsenosides.Streamlined workflows,by applying UNIFI?to automatedly annotate the HDMSEdata,were proposed.We could separate and characterize 323 ginsenosides(including 286 from WG and 306 from RG),and 125 thereof may have not been isolated from the Panax genus.The established 2 D-LC/IM-QTOF-HDMSEapproach could also act as a magnifier to probe differentiated components between WG and RG.Compared with conventional approaches,this dimensionenhanced strategy could better resolve coeluting herbal components and more efficiently,more reliably identify the multicomponents,which,we believe,offers more possibilities for the systematic exposure and confirmative identification of plant metabolites.

Modification of Reflectron Time-of-Flight Mass Spectrometer for Photodissociation of Mass-Selected Cluster lons

We introduce a modification of reflectron time-of-flight mass spectrometer for laser photodissociation of mass-selected ions. In our apparatus, the ions of interests were selected by a mass gate near the first space focus point and decelerated right after the mass gate, were then crossed by a laser beam for dissociation. The daughter ions and surviving parent ions were re-accelerated and analyzed by the reflectron time-of-flight mass spectrometer. Compared to the designs reported by other research groups, our selection-deceleration-dissociation-reacceleration approach has better daughter-parent-ions-separation, easier laser timing, and better overlapping between the ion beam and laser beam. We also conducted detailed cal- culations on the parent ion and daughter ion flight times, and provided a simplified formula for the calibration of daughter ion mass.

Dimension-Enhanced Ultra-High Performance Liquid Chromatography/Ion Mobility-Quadrupole Time-of-Flight Mass Spectrometry Combined with Intelligent Peak Annotation for the Rapid Characterization of the Multiple Components from Seeds of Descurainia sophia

The complex composition of herbal metabolites necessitates the development of powerful analytical techniques aimed to identify the bioactive components.The seeds of Descurainia sophia(SDS)are utilized in China as a cough and asthma relieving agent.Herein,a dimension-enhanced integral approach,by combining ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry(UHPLC/IMQTOF-MS)and intelligent peak annotation,was developed to rapidly characterize the multicomponents from SDS.Good chromatographic separation was achieved within 38 min on a UPLC CSH C18(2.1×100 mm,1.7μm)column which was eluted by 0.1%formic acid in water(water phase)and acetonitrile(organic phase).Collision-induced dissociation-MS^(2)data were acquired by the data-independent high-definition MS^(E)(HDMS^(E))in both the negative and positive electrospray ionization modes.A major components knockout strategy was applied to improve the characterization of those minor ingredients by enhancing the injection volume.Moreover,a self-built chemistry library was established,which could be matched by the UNIFI software enabling automatic peak annotation of the obtained HDMS^(E)data.As a result of applying the intelligent peak annotation workflows and further confirmation process,a total of 53 compounds were identified or tentatively characterized from the SDS,including 29 flavonoids,one uridine derivative,four glucosides,one lignin,one phenolic compound,and 17 others.Notably,four-dimensional information related to the structure(e.g.,retention time,collision cross section,MS^(1)and MS^(2)data)was obtained for each component by the developed integral approach,and the results would greatly benefit the quality control of SDS.

Studies on Fragmentation Regularity of 5-Methoxycarbonyl- 4-substituted-6-methyl-3,4-dihydropyrimidin-2(1H)-ones by Time-of-flight Mass Spectrometry

The electron impact time-of-flight(TOF) mass spectra of the title compounds were studied to establish their fragmentation processes. With the high resolution of the TOF instrument, the exact mass for each fragment was determined. These data were used to infer the molecular formulas and the elemental compositions for all the molecular ions and fragments through software interpretation. By further applying the fragmentation regularity, the majority of ions were fully assigned. The main fragmentation pathways of the title compounds include the formation of molecular ions by the loss of R 1 groups in the 4-position and the ester groups in the 5-position. The formed ion can be further fragmented by the elimination of MeOH.

Temporal and spatial study of differently charged ions emitted by ns-laser-produced tungsten plasmas using time-of-flight mass spectroscopy

Tungsten(W)is an important material in tokamak walls and divertors.The W ion charge state distribution and the dynamic behavior of ions play important roles in the investigation of plasma–wall interactions using laser-ablation-based diagnostics such as laser-induced breakdown spectroscopy and laser-induced ablation spectroscopy.In this work,we investigate the temporal and spatial evolutions of differently charged ions in a nanosecond-laser-produced W plasma in vacuum using time-of-flight mass spectroscopy.Ions with different charge states from 1 to 7(W+to W7+)are all observed.The temporal evolutions of the differently charged ions show that ions with higher charge states have higher velocities,indicating that space separation occurs between the differently charged ion groups.Spatially-resolved mass spectroscopy measurements further demonstrate the separation phenomenon.The temporal profile can be accurately fitted by a shifted Maxwell–Boltzmann distribution,and the velocities of the differently charged ions are also obtained from the fittings.It is found that the ion velocities increase continuously from the measured position of 0.75 cm to 2.25 cm away from the target surface,which indicates that the acceleration process lasts through the period of plasma expansion.The acceleration and space separation of the differently charged ions confirm that there is a dynamic plasma sheath in the laser-produced plasma,which provides essential information for the theoretical laser-ablation model with plasma formation and expansion.

The Development of Time-of-flight Mass Spectrometry( TOF-MS) and Its Applications in Screening Food Hazard Factors

The time-of-flight mass spectrometry(TOF-MS),one of the mass spectrometry techniques,has been widely applied in the field of rapid screening of food hazard factors as a superior analysis technique because of its wide mass range,high resolution and mass measurement accuracy,high sensitivity and high analysis speed.In this paper,research progresses of TOF-MS on the detection of food additives,food contaminants and residues,illegal additives,pesticide residues,veterinary drug residues and mycotoxin were reviewed,and its probable approaching applications were prospected.

MicrobMatcher: a microbial comparison software based on matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry

Matrix-assisted Laser Desorption/Ionization with Time-of-flight Mass Spectrometry (MALDI-TOFMS) was investigated as a method for the rapid identifica-tion of species. Current demand in microbial identi-fication is how to compare unknown strains to the known one quickly, semi-automatically and accurately. In this paper, we present a software tool that allows flexibly microbial matching in a user-friendly way, by letting the users to customize comparison parameters including: in vitro transcription enzyme, mass tolerance,minimum fragment length, intensity threshold and corresponding weights. We provide three spectral scoring functions to compute the affin-ity between the species. Therefore, the precision of microbial comparison increases. To test and verify this tool, we employed experimental spectral data based on MALDI-TOFMS and the gene sequences of E.coli and Salmonella. This software is written in Java for cross-platform intention.

Application of Liquid Chromatography-High Resolution Time-of-flight Mass Spectrometry in the Detection of Raw Milk and Dairy Products

Milk and dairy products are more and more popular with consumers due to their various nutrients, and their quality and safety issues have always been concerned. Therefore, the development of rapid, accurate and simple screening techniques is of great significance. Liquid chromatography-high resolution time-of-flight mass spectrometry has high-resolution and high-throughput detection functions, and has gradually begun to be applied in the detection of milk and dairy products. This paper summarized the application of milk and dairy products in liquid chromatography-high resolution time-of-flight mass spectrometry, laying a foundation for the development of new methods.

5-22 Design and Optimization of a Multi-re Time-of-flight Mass Analyzer for LPT

Multi-reflection time-of-flight mass spectrometer (MR-TOF-MS) is one of the new experimental devices developed in recent years. As the flight path extended several orders of magnitude as the analyzer is traversed many times by the ions, it allows achieving higher mass resolving power than the conventional time-of-flight mass spectrometry.

Time-of-Flight Mass Spectrometer with Transaxial Ion Reflector

Two variants of application of a transaxial mirror with stigmatic spatial time-of-flight focusing in the time-of-flight mass spectrometer have been considered. In the first variant, the transaxial mirror is used as an ion reflector in the ordinary scheme of the time-of-flight mass reflectron. In the second variant, the transaxial mirror simultaneously fulfills the function of the ion reflector and corrector of aberrations caused by the energy spread of ions in the package, formed by the ion source of the mass reflectron. The expressions defining the conditions of stigmatic spatial time-of-flight focusing in the transaxial mirror and the combined system consisting of an ion source and a mirror have been derived. The relationships between geometrical and electrical parameters of three- and four-electrode transaxial mirrors realizing these conditions have been obtained by numerical calculations.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry traces the geographical source of Biomphalaria pfeifferi and Bulinus forskali,involved in schistosomiasis transmission

Background Freshwater snails of the genera Bulinus spp.,Biomphalaria spp.,and Oncomelania spp.are the main intermediate hosts of human and animal schistosomiasis.Identification of these snails has long been based on mor-phological and/or genomic criteria,which have their limitations.These limitations include a lack of precision for the morphological tool and cost and time for the DNA-based approach.Recently,Matrix-Assisted Laser Desorp-tion/lonization Time-Of-Flight(MALDI-TOF)mass spectrometry,a new tool used which is routinely in clinical microbi-ology,has emerged in the field of malacology for the identification of freshwater snails.This study aimed to evaluate the ability of MALDI-TOF MS to identify Biomphalaria pfeifferi and Bulinus forskali snail populations according to their geographicalorigin.Methods This study was conducted on 101 Bi.pfeifferi and 81 Bu.forskali snails collected in three distinct geo-graphical areas of Senegal(the North-East,South-East and central part of the country),and supplemented with wild and laboratory strains.Specimens which had previously been morphologically described were identified by MALDl-TOF MS[identification log score values(LSV)≥1.7],after an initial blind test using the pre-existing database.After DNA-based identification,new reference spectra of Bi.pfeiferi(n=10)and Bu.forskali(n=5)from the geographical areas were added to the MALDI-TOF spectral database.The final blind test against this updated database was per-formed to assess identification at the geographic source level.Results MALDI-TOF MS correctly identified 92.1%of 101 Bi.pfeifferi snails and 98.8%of 81 Bu.forskali snails.At the final blind test,88%of 166 specimens were correctly identified according to both their species and sampling site,with LSVs ranging from 1.74 to 2.70.The geographical source was adequately identified in 90.1%of 91 Bi.pfeifferi and 85.3%of 75 Bu.forskalii samples.Conclusions Our findings demonstrate that MALDI-TOF MS can identify and differentiate snail populations according to geographical origin.It outperforms the current DNA-based approaches in discriminating laboratory from wild strains.This inexpensive high-throughput approach is likely to further revolutionise epidemiological studies in areas which are endemic for schistosomiasis.

Electrostatic-lenses position-sensitive TOF MCP detector for beam diagnostics and new scheme for mass measurements at HIAF

A foil–microchannel plate(MCP)detector,which uses electrostatic lenses and possesses both good position and timing resolutions,has been designed and simulated for beam diagnostics and mass measurements at the next-generation heavy-ion-beam facility HIAF in China.Characterized by low energy loss and good performances of timing and position measurements,it would be located at focal planes in fragment separator HFRS for position monitoring,beam turning,Bq measurement,and trajectory reconstruction.Moreover,it will benefit the building-up of a magnetic-rigidity–energy-loss–time-offlight(BqDETOF)method at HFRS for high-precision in-flight particle identification of radioactive isotope beams on an event-by-event basis.Most importantly,the detector can be utilized for in-ring TOF and position measurements,beam-line TOF measurements at two achromatic foci,and position measurements at a dispersive focus of HFRS,thus making it possible to use two complementary mass measurement methods[isochronous mass spectrometry at the storage ring SRing and magnetic-rigidity–time-of-flight(BqTOF)at the beam-line HFRS]in one single experimental run.

Screening and Identifying of Nephrotoxic Compounds in Lithospermum erythrorhizon Using Live-cell Fluorescence Imaging and Liquid Chromatography Coupled with Tandem Mass Spectrometry

In order to identify the potential nephrotoxic compounds in traditional Chinese medicine Lithospermum erythrorhizon,it was separated into serial fractions according to their polarities.An in vitro method was utilized to determine the nephrotoxicity of these fractions with the help of fluorescence image analysis.As a result,the primary fraction A05 and its secondary fractions C06 ＂C09 and C12 ＂C14 were found to have significant toxicity to LLC-PK1 cell line,as determined by the survive rate less than 20% after they were treated with these fractions.These potential nephrotoxic fractions were further analyzed by multistage and high resolution mass spectrometry.The main compounds in these fractions were tentatively identified to be acetylshikonin,isobutyrylshikonin,β,β＇-dimethyla-cryloylshikonin,and isovalerylshikonin,which may bring nephrotoxicity.

Improved preparation and identification of aristolochic acid-DNA adducts by solid-phase extraction with liquid chromatography-tandem mass spectrometry

Aristolochic acid （AA） is a known nephrotoxin and potential carcinogen, which can form covalent DNA adducts after metabolic activation in vivo and in vitro. A simple method for preparation and characterization of aristolochic acid-DNA adducts was developed. Four AA-adducts were synthesized by a direct reaction of AAI/AAII with 2′-deoxynucleosides. The reaction mixture was first cleaned-up and pre-concentrated using solid phase extraction （SPE）, and further purified by a reversed-phase high performance liquid chromatography （HPLC）. By the application of developed SPE procedure, matrices and byproducts in reaction mixture could be greatly reduced and adducts of high purity （more than 94% as indicated by HPLC） were obtained. The purified AA-DNA adducts were identified and characterized with liquid-electrospray ionization-quadrupole-time of flight-mass spectrometry （LC-ESI-Q-TOF-MS/MS） and LC-Diode array detector-fluorescence （LC-DAD-FL） analysis. This work provides a robust tool for possible large-scale preparation of AA-DNA adduct standards, which can promote the further studies on carcinogenic and mutagenic mechanism of aristolochic acids.

Mass Spectrometric Studies on Metal-hexafluorobenzene Anionic Complexes(M=Ag, Au, Pd, Pt, Pb and Bi)

The anionic products from the reactions between metal（M=Ag, Au, Pd, Pt, Pb and Bi） vapour produced by laser ablation and hexafluorobenzene seeded in carrier gas（Ar） were studied by means of a homemade reflectron time-of-flight mass spectrometry（RTOF-MS）. Experimental results show that the dominant products were [MmC6F6]^- complexes for the reactions ofAg, Au, Pd and Pt with C6F6, while the dominant products were [MmC6F5]^- complexes for the reactions of Pb and Bi with C6F6. The formation mechanisms of the products, including the adsorption of metal cluster anions on hexafluorobenzene and the C--F cleavage induced by metal cluster anions, were discussed.

Characterization of 4-Aryl-5-ethoxycarbonyl-6-methyl-3,4-dihydro-pyrimidin-2(1H)-thiones by EI-TOF Mass Spectrometry

The electron impact （EI） time-of-flight mass spectra （TOFMS） of the title compounds （ thioxo-Biginelli compounds） were studied to establish their fragmentation pathways. With a TOF instrument of high resolution, the exact mass for each fragment was determined. These data were used to infer the molecular formulas and the ionic elemental compositions for all the compounds through interpretation by software. By further applying chemical intuition, majority of the fragmentation ions were fully assigned. All the compounds give strong signals（ average 76% ） for their molecular ions in the El spectra. Two kinds of characteristic fragmentation pathways from the molecular ion were observed. One is related to the loss of the ester group, forming a resonance stabilized ion with a moderate abundance（ average 40% ）. The other concerns the loss of the aromatic-ring radical, forming another resonance stabilized ion at m/z 199 with a high abundance（ average 79% ）, from which further important fragmentations including the formation of an ion at m/z 171 （average 24% ） by the loss of C2H2 （via the McLafferty rearrangement）, and an ion at m/z 153（ average 10% ） by the elimination of a water molecule preceed. In addition, ion [ M - Et ]^＋ with a high abundance（average 62% ） is a characteristic for the Biginelli compounds with an ethoxycarbonyl group. Differences and similarities among the fragmentations observed from the EI-TOFMS of oxo-Biginelli compounds are discussed.

Analysis of Pharmacodynamic Substance Basis of Fufang Changtai in Treating Colorectal Cancer by UPLC-Q-TOF-MS Combined with Network Pharmacology

[Objectives] To systematically study the main active components of Fufang Changtai(FFCT) in the treatment of colorectal cancer(CRC), and to explore its mechanism of action. [Methods] The main chemical components of FFCT were analyzed by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) combined with automatic analysis platform, and the main pharmacodynamic substances of FFCT were studied by network pharmacology method and its mechanism of action was explored. The binding degree between the active components and the core targets were verified by molecular docking technology. [Results] A total of 86 compounds were identified from FFCT, among which 26 compounds were Ginsenoside Rg3, Ginsenoside Rb1, Astragaloside III, etc. The key target pathway enrichment analysis showed that FFCT played its role in the treatment of CRC mainly through the PI3K-Akt signaling pathway and MAPK signaling pathway. [Conclusions] This study comprehensively identified the FFCT components. Supplemented by network pharmacology and molecular docking technology, it is expected to provide a scientific theoretical basis and an important reference for FFCT therapeutic components identification, key target verification and mechanism of action in the treatment of CRC.

Ion-Pair Photodissociation of Trichloromonofluoromethane

fragments, F- and Cl- including two isotope species 35Cl- and 37Cl-, are observed in the photoexcitations of CFC13. The ion-pair anion efficiency spectra of 35Cl- and 37Cl- are recorded in the photon energy range of 7.75-22.00 eV. The threshold of ion-pair dissociation CFCl3-CFC12＋＋Cl- is experimentally determined to be 7.944-0.04 eV. With the references of the high-resolution photoabsorption spectra reported in the literatures, we make tentative assignments of the electron valence-to-Rydberg transitions. Furthermore, the multibody ion-pair fragmentation processes to Cl- are discussed by comparison between the calculated thermochemical thresholds and the experimental efficiency spectrum.