Ion Trap Mass Spectrometer Research Articles

Surface assisted laser desorption/ionization mass spectrometry of lithium cationized lignans – A tool for rapid screening of plant extracts

Lignans are one of the most widespread classes of plant secondary metabolites possessing unique biological activities. The search for new sources of such compounds, their screening and identification in plant biomass is an urgent task, requiring the use of advanced analytical methods. In the present study, matrix-free surface assisted laser desorption/ionization (SALDI) mass spectrometry was proposed for its solution. The combination of carbon nanocoating sputtered on a target plate with lithium cationization allowed obtaining high-quality mass spectra of eight coniferous wood lignans with different bonds between aromatic units (secoisolariciresinol, matairesinol, 7-hydroxymatairesinol, nortrachelogenin, pinoresinol, guaiacylglycerol-β-guaiacyl ether, dehydrodihydrodiisoeugenol, and divanillin). Three types of fragmentation methods (post-source decay, high- and low-energy collision induced dissociation) for the first time were implemented on two types of MALDI instruments. Regardless of tandem mass spectrometry technique, lignans demonstrated the similar fragmentation patterns including the cleavage of bonds between aromatic units with the formation of mostly lithiated product ions. The low-energy collision induced dissociation in quadrupole ion trap provided the most informative tandem mass spectra and multi-stage fragmentation capabilities in structural studies. On this basis, an approach to rapid, high-throughput, and low-cost screening and tentative identification of lignans including isomeric compounds in plant biomass was developed and successfully tested on real samples of pine, fir, spruce, and larch knotwood extracts.

New piperazine and morpholine derivatives: Mass spectrometry characterization and evaluation of their antimicrobial activity

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain compounds with fewer side effects, at the same time effectively overcoming the problem of antimicrobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important support for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of Fourier transform-ion cyclotron resonance (FT-ICR) and Linear Trap Quadrupole (LTQ) mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribution and MSn spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds’ antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.

Electrodynamic manipulator for commercial fluorescence microscope

We have developed a simple electrodynamic manipulator extension for a commercial fluorescence microscope. This extension allows single charged nano- and microparticles to levitate being isolated in space. The proposed electrodynamic manipulator is based on the linear quadrupole Paul trap. We measured the luminescence spectrum of a single microparticle filled with semiconductor quantum dots to demonstrate the operation process of the electrodynamic manipulator. This paper reveals the manipulator design features and restrictions are imposed by microscopic equipment; the issues of optical spectra recording are also discussed. The electrodynamic manipulator is a cheap and robust tool that can be compatible with any commercial microscopes, and can be easily adapted and modified for various investigation needs.

Influence of the Capillary Design and Conditions upon the Transmission Efficiency of a Portable Ion Trap Mass Spectrometer

The capillary is a widely used atmospheric pressure interface in mass spectrometers that may be heated to enhance the desolvation of ions. In this study, the ion transmission efficiency of a portable ion trap mass spectrometer was investigated using capillaries with different inner diameters and temperatures, different vacuum pressures, and different ion optics designs. Due to the incomplete desolvation and the space charge effect inside the miniature ion funnel, the increase of ion intensities with the inner diameter of the capillary leveled off when the inner diameter of the capillary was larger than 0.37 mm. With the increase of capillary temperature, the ion intensities first increase due to better desolvation and then decrease due to greater diffusion loss. The optimal temperature of the capillary increases with the inner diameter of the capillary and the mass-to-charge ratio of ion. In addition, the pressures of different vacuum stages also exerted remarkable effects on the sensitivity of the portable mass spectrometer. From the perspective of instrument miniaturization, optimal transmission efficiency can be obtained when the first-stage vacuum pressure is maintained from 4 to 6 mbar. For a capillary with an inner diameter of 0.37 mm, the background of mass spectrum can be significantly reduced by replacing the pinhole behind the ion funnel with an off-axis skimmer.

Metabolite identification of salvianolic acid A in rat using post collision-induced dissociation energy-resolved mass spectrometry

BackgroundAs one of the most famous natural products, salvianolic acid A (SAA) is undergoing clinical trials for the treatments of angina pectoris and coronary heart disorders. However, the in vivo metabolites of SAA have only been tentatively identified, leading to a barrier for precise therapeutical drug monitoring.MethodsUltra-high performance liquid chromatography coupled with quadrupole time of flight tandem mass spectrometry (UPLC–Qtof-MS/MS) was firstly employed to acquire high-resolution MS1 and MS2 spectra for all metabolites. Through paying special attention onto the features of ester bond dissociation, metabolism sites were restricted at certain regions. To further determine the metabolism site, such as the monomethylated products (M23, M25, and M26), post collision-induced dissociation energy-resolved mass spectrometry (post-CID ER-MS) was proposed through programming progressive exciting energies to the second collision chamber of hybrid triple quadrupole-linear ion trap mass spectrometry (Qtrap-MS) device.ResultsAfter SAA oral administration, 29 metabolites (M1–M29), including five, thirteen, and sixteen ones in rat plasma, urine, and feces, respectively, were detected in rats. The metabolism route was initially determined by applying well-defined mass fragmentation pathways to those HR-m/z values of precursor and fragment ions. Metabolism site was limited to SAF- or DSS-unit based on the fragmentation patterns of ester functional group. Through matching the dissociation trajectories of concerned 1st-generation fragment ions with expected decomposition product anions using post-CID ER-MS strategy, M23 and M25 were unequivocally assigned as 3'-methyl-SAA and 3''-methyl-SAA, and M26 was identified as 2-methyl-SAA or 3-methyl-SAA. Hydrolysis, methylation, glucuronidation, sulfation, and oxidation were the primary metabolism channels being responsible for the metabolites' generation.ConclusionTogether, the metabolism regions and sites of SAA metabolites were sequentially identified based on the ester bond dissociation features and post-CID ER-MS strategy. Importantly, the present study provided a promising way to elevate the structural identification confidence of natural products and metabolites.Graphical abstract

Observing Variation in Whispering Gallery Mode Resonance of a Trapped and Levitated Dye Doped Microdrop.

Whispering gallery mode (WGM) resonance was created in a spherical micro drop. A gradual shift in the resonance were observed. For a 600 nm droplet radius, the blue shift were 1.5, 0.7, 3.7 nm. It was estimated that such a shift corresponds to a reduction in optical radius of the droplet by 1.3, 0.6, 3.3 nm respectively. The droplet was created from a solution of glycerol, methanol and rhodamine 6G dye, and was trapped and levitated in a modified Paul trap. The WGMs were created by optically exciting the dye material from an external 532 nm cw laser beam. A shift in the WGM was observed during a gradual increase in power of the excitation laser, and a reason for such a shift was thought to be thermal evaporation of the liquid. For a larger droplet an initial 0.1 nm thermal expansion was also estimated, preceding the volume contraction. Such an expansion was negligible for a smaller droplet. The rate of change of the blue shift depends upon initial radius of the droplet. For the smaller droplet the estimated rate of change of WGM with a change in optical radius, was 0.771. For larger droplet, this rate is lower.

Accurate and High-Resolution Particle Mass Measurement Using a Peak Filtering Algorithm.

Charge detection quadrupole ion trap mass spectrometry (CD-QIT MS) is an effective way of achieving the mass analysis of microparticles with ultrahigh mass. However, its mass accuracy and resolution are still poor. To enhance the performance of CD-QIT MS, the resolution Rpeak of each peak in the mass spectra resulting from an individual particle was assessed, and a peak filtering algorithm that can filter out particle adducts and clusters with a lower Rpeak was proposed. By using this strategy, more accurate mass information about the analyzed particles could be obtained, and the mass resolution of CD-QIT MS was improved by nearly 2-fold, which was demonstrated by using the polystyrene (PS) particle size standards and red blood cells (RBCs). Benefiting from these advantages of the peak filtering algorithm, the baseline separation and relative quantification of 3 and 4 μm PS particles were achieved. To prove the application value of this algorithm in a biological system, the mass of yeast cells harvested at different times was measured, and it was found that the mixed unbudded and budded yeast cells, which otherwise would not be differentiable, were distinguished and quantified with the algorithm.

Installation protocol for charge transfer dissociation mass spectrometry on ion trapping mass spectrometers.

Charge transfer dissociation (CTD) is a novel fragmentation technique that demonstrates enhanced structural characterization for a wide variety of molecules compared to standard fragmentation techniques like collision-induced dissociation (CID). Alternative fragmentation techniques, such as electron transfer dissociation, electron capture dissociation, and ultraviolet photodissociation, also overcome many of the shortfalls of CID, but none of them are a silver bullet that can adequately characterize a wide variety of structures and charge states of target compounds. Given the diversity of structural classes and their occasional obstinance towards certain activation techniques, alternative fragmentation techniques are required that rely on novel or alternative modes of activation. Herein, we present a step-by-step protocol for the installation of CTD on a quadrupole ion trap mass spectrometer and best practices for optimizing the signal-to-noise ratio and acquisition times for CTD mass spectra. In addition to two CTD installations in the Jackson laboratory, CTD has also been installed, and is currently in operation, on two 3D ion trap mass spectrometers in France: one in the laboratory of Dr. David Ropartz and Dr. Hélène Rogneaux at INRAE in Nantes, and the other in the laboratory of Dr. Jean-Yves Salpin at Université d'Évry Val-d'Essonne, part of the Paris-Saclay University system. Here, we provide a visual protocol to help others accomplish the instrument modification.

Improved Tensor Current Limit from ^{8}B β Decay Including New Recoil-Order Calculations.

A precision measurement of the β^{+} decay of ^{8}B was performed using the Beta-decay Paul Trap to determine the β-ν angular correlation coefficient a_{βν}. The experimental results were combined with new abinitio symmetry-adapted no-core shell-model calculations to yield the second-most precise measurement from Gamow-Teller decays, a_{βν}=-0.3345±0.0019_{stat}±0.0021_{syst}. This value agrees with the standard model value of -1/3 and improves uncertainties in ^{8}B by nearly a factor of 2. By combining results from ^{8}B and ^{8}Li, a tight limit on tensor current coupling to right-handed neutrinos was obtained. A recent global evaluation of all other precision β decay studies suggested a nonzero value for right-handed neutrino coupling in contradiction with the standard model at just above 3σ. The present results are of comparable sensitivity and do not support this finding.

Pseudotargeted metabolomics method and its application in erastin-stimulated gastric adenocarcinoma cells based on liquid chromatography with tandem mass spectrometry

Erastin, a classical ferroptosis inducer, exerts cytotoxicity in several types of cancer cells including gastric cancer cells. However, the mechanism of erastin in regulating metabolic pathways in gastric cancer remains largely unclear. To investigate the gastric cellular response to erastin therapy, a pseudotargeted metabolomics method was achieved on ultra-high performance liquid chromatography-hybrid triple quadrupole linear ion trap mass spectrometry (UHPLC-QTRAP MS), which was used to investigate metabolic changes between erastin-treated MGC-803 cells and the controls at different time points. We found that erastin induced tremendous impact on the metabolome of gastric cells by affecting key metabolic processes, such as cysteine and methionine metabolism, tryptophan metabolism, purine metabolism, glutathione biosynthesis, glycolysis and TCA cycle. Interestingly, S-adenosylmethionine, methionine, serine and cysteine were obviously increasing treads after erastin treatment, while S-adenosylhomocysteine and glutathione were always down-regulated up to 24 h. The results indicated that DNA methylation was activated and glutathione biosynthesis was blocked in erastin-treated MGC-803 gastric cells, highlighting the importance of erastin as a promising drug candidate for in vivo treatment of gastric tumor.

Gas-Phase Reactivity of Quinoline-Based Singlet Oxenium Cations.

Isomeric quinolyloxenium cations were generated in the gas phase in an ion trap mass spectrometer to explore their reactions. The structures of some products were identified via collision-activated dissociation experiments involving model compounds to demonstrate that they have the expected heavy atom connectivity. The lack of radical reactions suggests that the cations have closed-shell singlet electronic ground states. Calculations (CASPT2/CASSCF(16,14)/cc-pVTZ//CASSCF(16,14)/cc-pVTZ) predict that their closed-shell singlet (1A') ground states are lower in energy by ca. 25 kcal mol-1 than their lowest-lying excited states. All cations are reactive toward dimethyl disulfide, dimethyl sulfide, and allyl iodide and most toward water and moderately reactive toward cyclohexane, reflecting their strongly electrophilic nature. They form adducts with nucleophiles in exothermic reactions (ca. 50 kcal mol-1 for dimethyl sulfide) that can fragment or be stabilized via IR emission. Most water adducts spontaneously isomerize to lower-energy tautomers. The nucleophiles preferentially add to those carbon atoms in the benzene ring that have the greatest positive charge (but not the carbonyl carbon). The cations react with cyclohexane via hydride abstraction by the oxygen atom. This is the only reaction that initially involves the oxygen atom and hence reflects the formally positively charged, monovalent oxygen atom in these cations.

Dark resonance spectra of trapped ions under the influence of micromotion

We study the influence of micromotion on the spectrum of trapped ions with a lambda-type level scheme, leading to dark resonances due to coherent population trapping. We work with calcium ions trapped in a ring-shaped Paul trap, in which one can compensate excess micromotion for only one ion of the crystal. We observe that micromotion affects the shapes of the dark resonances and causes the appearance of “echoes” separated by intervals given by the drive frequency. We present a theoretical model that provides good fits to the measurements and can be used to estimate the amplitude of the micromotion modulation of the atomic motion. We estimate an effective temperature of the ions from the spectra and observe clear micromotion heating as well as impaired cooling for sufficiently large excess micromotion.

Ultrahigh Quality Factor of a Levitated Nanomechanical Oscillator.

A levitated nanomechanical oscillator under ultrahigh vacuum is highly isolated from its environment. It has been predicted that this isolation leads to very low mechanical dissipation rates. However, a gap persists between predictions and experimental data. Here, we levitate a silica nanoparticle in a linear Paul trap at room temperature, at pressures as low as 7×10^{-11} mbar. We measure a dissipation rate of 2π×69(22) nHz, corresponding to a quality factor exceeding 10^{10}, more than 2 orders of magnitude higher than previously shown. A study of the pressure dependence of the particle's damping and heating rates provides insight into the relevant dissipation mechanisms.

Calcium Ion as Quantum Bit in a Linear Paul Trap

يهدف هذا البحث الى دراسة ايون الكالسيوم كوحدة كمية في مصيدة بول الخطية، حيث يعتبر هذا الايون احد العناصر التي تستخدم في الكبت الكمي. اتبع البحث المنهج التجريبي وقسم الى مقدمة تعريفية بالموضوع واربعة مباحث وخاتمة، متناولا الاطار النظري والنموذج الحوسبي ومناقشة النتائج. أما الخاتمة فتضمنت النتائج ومن أهمها: تتحقق القيمة المثلى للدقة باختيار القيم المناسبة للمعلمات الفيزيائية، كما تتضمن هذه المعلمات زاوية سقوط الليزر مع محور المصيدة وترددها مع تردد مصيدة .Rabi

Plasma metabolomics identifies S-adenosylmethionine as a biomarker and potential therapeutic target for vascular aging in older adult males

Brachial-ankle pulse wave velocity (baPWV) is a noninvasive index of vascular aging. However, the metabolic profile underlying vascular aging has not yet been fully elucidated. The current study aimed to identify circulating markers of vascular aging as assessed by baPWV and to elucidate its mechanism from a metabolomic perspective in older adults. A total of 60 and 61 Chinese male participants aged ≥80 years were recruited to the metabolome and validation cohorts, respectively. The baPWV of participants was measured using an automatic waveform analyzer. Plasma metabolic profile was investigated using ultra-performance liquid chromatography coupled with triple quadrupole linear ion trap tandem mass spectrometry. Orthogonal partial least squares (OPLS) regression modeling established the association between metabolic profile and baPWV to determine important metabolites predictive of vascular aging. Additionally, an enzyme-linked immunosorbent assay was employed to validate the metabolites in plasma and culture media of vascular smooth muscle cells in vitro. OPLS modeling identified 14 and 22 metabolites inversely and positively associated with baPWV, respectively. These 36 biomarkers were significantly enriched in seven metabolite sets, especially in cysteine and methionine metabolism (p <0.05). Notably, among metabolites involved in cysteine and methionine metabolism, S-adenosylmethionine (SAM) level was inversely related to baPWV, with a significant correlation coefficient in the OPLS model (p <0.05). Furthermore, the relationship between SAM and vascular aging was reconfirmed in an independent cohort and at the cellular level in vitro. SAM was independently associated with baPWV after adjustments for clinical covariates (β = −0.448, p <0.001) in the validation cohort. In summary, plasma metabolomics identified an inverse correlation between SAM and baPWV in older males. SAM has the potential to be a novel biomarker and therapeutic target for vascular aging.

The Magnesium Dication and Water Synergistically Promote the Protonolysis of Two of the B-C Bonds in the Tetraphenylborate Anion.

Analytes are sampled from both solution phase and gas-phase environments during the ESI process, and thus, the mass spectrum that is measured can reflect both solution and gas-phase conditions. In the gas-phase regime, ion-molecule reactions can influence the types of ions that are observed. Herein, the synergistic effects of a Lewis acid (Mg2+) and background water are shown to lead to protonolysis of two of the B-C bonds of the tetraphenylborate ion in the gas phase, giving rise to different ions at different reaction times in ESI-MS/MS experiments in a linear ion trap mass spectrometer. At short reaction times (1 ms), the expected adduct [Mg(BPh4)]+ is observed. At 10 ms, [(HO)Mg(BPh3)]+ and [(HO)2Mg(BPh2)]+ are observed. At 100 ms, the water adducts [(HO)2Mg(BPh2)(H2O)]+ and [(HO)2Mg(BPh2)(H2O)2]+ appear, and these become the dominant ions at longer reaction times. DFT calculations provide a plausible explanation as to why only [(HO)Mg(BPh3)]+ and [(HO)2Mg(BPh2)]+ but not [(HO)3Mg(BPh)]+ are observed.

Liquid chromatography-mass spectrometry-based strategy for systematic profiling of chemical components and associated quantitative analysis of quality markers in Qi-Wei-Tong-Bi oral liquid.

Qi-Wei-Tong-Bi oral liquid (QWTB), a famous Chinese medicine preparation composed of seven crude drugs has a good therapeutic effect on rheumatoid arthritis and is widely used in China.However, its chemical composition and quality control have not been comprehensively and systematically investigated. In this study, high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was employed for its chemical profiling. As a result, 100 components were chemically characterized. Additionally, high-performance liquid chromatography coupled with a quadrupole linear ion trap mass spectrometry method was developed to simultaneously quantify nine bioactive components (hyperoside, ononin, quercetin, sinomenine, magnoflorine, gallic acid, protocatechuic acid, monotropein, and cyclo-(Pro-Tyr)) in multiple-reaction monitoring mode. After successful validation in terms of linearity, precision, repeatability, and recovery, the assay method was applied for the determination of 10 batches of QWTB. The results showed that QWTB was enriched in sinomenine and magnoflorine with the highest amount up to hundreds or even thousands of µg/mL, while quercetin, ononin, cyclo-(Pro-Tyr), and hyperoside were much lower with the lowest content below 10µg/mL. This study work would help to reveal the chemical profiling and provide a valuable and reliable approach for quality evaluation and even pharmacodynamic material basis studies of QWTB.

Survey of the multi-stage mass spectrometry of common ionic liquid cations and some polyfluorinated ions

Ionic liquids are useful for many applications and the structural diversity as a class is ever increasing. Knowledge of gas-phase dissociation pathways can inform analytical method development for the characterization of novel syntheses, degradation products, or environmental contaminants, and can inform our knowledge of the fate of ionic liquid species in the gas phase (e.g., after ejection by electrospray spacecraft thrusters). In this work, the N-heterocyclic (NHC) ions:1-butyl-1-methylpiperidinium (BMPi), 1-methyl-1-propylpiperidinium (MPPi), 1-butyl-1-methylpyrrolidinium (BMPyr), 1-ethyl-1-methylpyrrolidinium (EMPyr), 1-butylpyridinium (BPy), and 1-Butyl-1-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl) imidazolium (BFIm) were studied. An additional fluorinated anion, nonafluorobutanesulfonate (NFBS), was also studied. Collision-induced dissociation mass spectrometry (CID-MS), as MS2 and MS3 using an ion trap mass spectrometer and energy-resolved breakdown curves using a quadrupole time-of-flight mass spectrometer, were used to determine dissociation patterns. Assignment of proposed dissociation pathways were made based on the experimental results and complementary computational chemistry. It was observed that for aromatic NHCs, cleavage at the C–N bond was preferred, to generate alkene-based neutral losses. Non-aromatic NHCs typically generated both alkane- and alkene-based neutral losses. Breakdown curves, supported by theoretical thermodynamic calculations, suggest that the loss of the alkane is the favorable dissociation pathway. Additionally, some ring-opening and ring contraction reactions via C–C bond cleavage were observed in non-aromatic species, whereas the intact aromatic NHC is typically a stable terminal ion. The polyfluorinated imidazolium fragmented via the breaking of C–N, C–C, and C–F bonds. The fluorinated anion, NFBS, fragmented by C–C and C–S bond cleavage to generate fluoroalkene, sulfur dioxide, and sulfur trioxide neutral losses. Beyond these broad stroke findings, the dissociation pathways of the seven ionic liquid ions were mapped using evidence from MS3, breakdown curves, and computational chemistry together assigning product ions as either arising from competitive or sequential pathways and proposing tentative structures. Some of the ionic liquid ions showed class-based product ions which will be useful in analytical development for their characterization. Finally, these results were contextualized within previous literature reports on other ionic liquid species.

Measurement of the charge-to-mass ratio of particles trapped by the Paul trap for education

Paul traps are devices that confine particles using an alternating electric field and have been used in undergraduate experimental classes at universities. Owing to the requirement of a high voltage ( > 103 V), Paul traps are not used in middle and high schools. Therefore, we developed an all-in-one-type Paul trap, including a high-voltage transformer. The Paul trap can be equipped with two different types of electrode attachments, ring-type and linear-type, and the trap image can be observed using a built-in web camera. For example, the charge-to-mass ratio of particles was measured with different types of attachments, and reasonable values were obtained. These types of trap devices are currently used at several educational facilities in Japan.

Decarboxylation of fatty acids by ternary zinc cationic complexes studied by mass spectrometry and theoretical calculations

We have shown that fatty acids can be decarboxylated in the gas phase via collision-induced dissociation (CID) of ternary zinc complexes of the general formula [(L)Zn(OOCR)]+, where RC3H7, C6H13, C7H15, C17H35, C17H33, C17H31 and L = 1,10-phenanthroline or 2,2′:6′,2″-terpyridine. These complexes were formed by electrospray ionization of a solution mixture of zinc(II) salt, fatty acid, and the ligand. Two pathways were mapped for the resulting [(L)ZnR]+ organozinc ion: i) a gas-phase ion-molecule reaction with a neutral carboxylic acid R’COOH in the linear quadrupole ion trap resulted in the production of the alkane RH and formation of [(L)Zn(OOCR’)]+; ii) a second CID stage produced an alkene and the ion [(L)ZnH]+ which underwent a subsequent ion-molecule reaction with R’COOH to form [(L)Zn(OOCR’)]+ ion accompanied by the loss of H2. In the case of RR’ = C3H7 (butyric acid), both processes presented formal catalytic cycles with the overall equations C3H7COOHC3H8+ CO2 or C3H7COOHC3H6 + H2+ CO2. Theoretical DFT calculations provided the energetics of reactants/products as well as transition state energies and were in agreement with the experimental data. The work identifies Zn as a potential catalyst for deoxygenation of fatty acid with no fragmentation of the alkyl chain.