Dual-Polarity Ion Trap Mass Spectrometry: Dynamic Monitoring and Controlling Gas-phase Ion–Ion Reactions

A dual-polarity linear ion trap (LIT) mass spectrometer was developed in this study, and the method for simultaneously controlling and detecting cations and anions was proposed and realized in the LIT. With the application of an additional dipolar DC field on the ejection electrodes of an LIT, dual-polarity mass spectra could be obtained, which include both the mass-to-charge (m/z) ratio and charge polarity information of an ion. Compared with conventional method, the ion ejection and detection efficiency could also be improved by about one-fold. Furthermore, ion–ion reactions within the LIT could be dynamically controlled and monitored by manipulating the distributions of ions with opposite charge polarities. This method was then used to control and study the reaction kinetics of ion–ion reactions, including electron transfer dissociation (ETD) and charge inversion reactions. A dual-polarity collision-induced dissociation (CID) experiment was proposed and performed to enhance the sequence coverage of a peptide ion. Ion trajectory simulations were also carried out for concept validation and system optimization.

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Identification of the Phenol Functionality in Deprotonated Monomeric and Dimeric Lignin Degradation Products via Tandem Mass Spectrometry Based on Ion–Molecule Reactions with Diethylmethoxyborane

Conversion of lignin into smaller molecules provides a promising alternate and sustainable source for the valuable chemicals currently derived from crude oil. Better understanding of the chemical composition of the resulting product mixtures is essential for the optimization of such conversion processes. However, these mixtures are complex and contain isomeric molecules with a wide variety of functionalities, which makes their characterization challenging. Tandem mass spectrometry based on ion–molecule reactions has proven to be a powerful tool in functional group identification and isomer differentiation for previously unknown compounds. This study demonstrates that the identification of the phenol functionality, the most commonly observed functionality in lignin degradation products, can be achieved via ion–molecule reactions between diethylmethoxyborane (DEMB) and the deprotonated analyte in the absence of strongly electron-withdrawing substituents in the ortho- and para-positions. Either a stable DEMB adduct or an adduct that has lost a methanol molecule (DEMB adduct-MeOH) is formed for these ions. Deprotonated phenols with an adjacent phenol or hydroxymethyl functionality or a conjugated carboxylic acid functionality can be identified based on the formation of DEMB adduct-MeOH. Deprotonated compounds not containing the phenol functionality and phenols containing an electron-withdrawing ortho- or para-substituent were found to be unreactive toward diethylmethoxyborane. Hence, certain deprotonated isomeric compounds with phenol and carboxylic acid, aldehyde, carboxylic acid ester, or nitro functionalities can be differentiated via these reactions. The above mass spectrometry method was successfully coupled with high-performance liquid chromatography for the analysis of a complex biomass degradation mixture.

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Ab Initio Chemical Kinetics for the Thermal Decomposition of SiH4 + Ion and Related Reverse Ion–Molecule Reactions of Interest to PECVD of a-Si:H Films

Plasma Chemistry and Plasma Processing - The thermal unimolecular decomposition of SiH4 + ion and its related reverse reactions, SiH3 + + H and SiH2 + + H2, have...     

Gas Chromatographic-Ion Trap Mass Spectrometric Analysis of Volatile Organic Compounds by Ion–Molecule Reactions Using the Electron-Deficient Reagent Ion CCl<Stack><Subscript>3</Subscript><Superscript>+</Superscript></Stack>

When using tetrachloromethane as the reagent gas in gas chromatography-ion trap mass spectrometry equipped with hybrid ionization source, the cation CCl₃⁺ was generated in high abundance and further gas-phase experiments showed that such an electron-deficient reagent ion CCl₃⁺ could undergo interesting ion–molecule reactions with various volatile organic compounds, which not only present some informative gas-phase reactions, but also facilitate qualitative analysis of diverse volatile compounds by providing unique mass spectral data that are characteristic of particular chemical structures. The ion–molecule reactions of the reagent ion CCl₃⁺ with different types of compounds were studied, and results showed that such reactions could give rise to structurally diagnostic ions, such as [M + CCl₃ – HCl]⁺ for aromatic hydrocarbons, [M – OH]⁺ for saturated cyclic ether, ketone, and alcoholic compounds, [M – H]⁺ ion for monoterpenes, M^·+ for sesquiterpenes, [M – CH₃CO]⁺ for esters, as well as the further fragment ions. The mechanisms of ion–molecule reactions of aromatic hydrocarbons, aliphatic ketones and alcoholic compounds with the reagent ion CCl₃⁺ were investigated and proposed according to the information provided by MS/MS experiments and theoretical calculations. Then, this method was applied to study volatile organic compounds in Dendranthema indicum var. aromaticum and 20 compounds, including monoterpenes and their oxygen-containing derivatives, aromatic hydrocarbon and sesquiterpenes were identified using such ion–molecule reactions. This study offers a perspective and an alternative tool for the analysis and identification of various volatile compounds.     

Characterization of Phosphatidylethanolamine Molecular Species in Human Blood by On-Line High Performance Liquid Chroma-tography/Quadrupole-Linear Ion Trap Mass Spectrometry

Asanimportantconstituentinthebiomem branes ,phospholipids (PL)areacomplexmixtureofmolecularspeciescontainingavarietyoffattya cylandhead groupcompositions .Inadditiontotheirstructuralrole ,somephospholipidsalsopar ticipateinbiologicalprocessesinvariousways…     

Characterization of Phosphatidylethanolamine Molecular Species in Human Blood by On-Line High Performance Liquid Chromatography/Quadrupole-Linear Ion Trap Mass Spectrometry

As an important constituent in the biomembranes, phospholipids (PL) are a complex mixture of molecular species containing a variety of fatty acyl and head group compositions. In addition to their structural role, some phospholipids also participate in biological processes in various     

Identification of Carboxylate,Phosphate, and Phenoxide Functionalities in Deprotonated Molecules Related to Drug Metabolites via Ion–Molecule Reactions with water and Diethylhydroxyborane

Tandem mass spectrometry based on ion–molecule reactions has emerged as a powerful tool for structural elucidation of ionized analytes. However, most currently used reagents were designed to react with protonated analytes, making them suboptimal for acidic analytes that are preferentially detected in negative ion mode. In this work we demonstrate that the phenoxide, carboxylate, and phosphate functionalities can be identified in deprotonated molecules by use of a combination of two reagents, diethylmethoxyborane (DEMB) and water. A novel reagent introduction setup that allowed DEMB and water to be separately introduced into the ion trap region of the mass spectrometer was developed to facilitate fundamental studies of this reaction. A new reagent, diethylhydroxyborane (DEHB), was generated inside the ion trap by hydrolysis of DEMB on introduction of water. Most carboxylates and phenoxides formed a DEHB adduct, followed by addition of one water molecule and subsequent ethane elimination (DEHB adduct +H₂O ? CH₃CH₃) as the major product ion. Phenoxides with a hydroxy group adjacent to the deprotonation site and phosphates formed a DEHB adduct, followed by ethane elimination (DEHB adduct ? CH₃CH₃). Deprotonated molecules with strong intramolecular hydrogen bonds or without the aforementioned functionalities, including sulfates, were unreactive toward DEHB/H₂O. Reaction mechanisms were explored via isotope labeling experiments and quantum chemical calculations. The mass spectrometry method allowed the differentiation of phenoxide-, carboxylate-, phosphate-, and sulfate-containing analytes. Finally, it was successfully coupled with high-performance liquid chromatography for the analysis of a mixture containing hymecromone, a biliary spasm drug, and its three possible metabolites.

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Selective Determination of Fourteen Nitroimidazoles in Honey by High-Performance Liquid Chromatography–Tandem Mass Spectrometry

A selective method for the determination of fourteen nitroimidazoles and their hydroxy-metabolites in honey was developed based on improved molecularly imprinted solid-phase extraction followed by liquid chromatography–tandem mass spectrometry. The separation of analytes was performed on a C₁₈ column using a mobile phase of 0.1% formic acid in acetonitrile and 0.1% formic acid in water with gradient elution. The method was suitable for metronidazole, hydroxymetronidazole, dimetridazole, ronidazole, hydroxydimetridazole, ipronidazole, hydroxyipronidazole, carnidazole, menidazole, nimorazole, ornidazole, secnidazole, ternidazole, and tinidazole. The procedure was evaluated according to EU Commission Decision 2002/657/EC requirements by determining linearity, specificity, recovery, repeatability, within-laboratory reproducibility, decision limit, detection capability, matrix effects, and stability. The method determined nitroimidazoles and their hydroxy-metabolites below the recommended concentration level of 3 µg kg^?1. The decision limits and detection capabilities ranged from 0.110 µg kg^?1 to 0.387 µg kg^?1 and from 0.179 µg kg^?1 to 0.508 µg kg^?1, respectively. The results from stability tests indicated that all analyzed nitroimidazoles were stable in honey stored at 4°C for at least 28 weeks and that elevated temperature and exposure to light exposure accelerated their degradation. The method was successfully applied to the analysis of a wide variety of honey samples.     

Application of the Reversed-phase Liquid Chromatography Coupled to Ion Trap Mass Spectrometry with Principal Components Analysis for Metabonomics Studies of Scutellarin in Rat Urine

Recently, much attention has been paid to metabonomics and great growth in it as a novel systemic approach to study metabolic profile accelerate the process of drug development1-5. Traditional Chinese Medicine (TCM) is an emerging field for medical and ph…     

Mapping Protein–Ligand Interactions in the Gas Phase Using a Functional Group Replacement Strategy. Comparison of CID and BIRD Activation Methods

Intermolecular interactions in the gaseous ions of two protein–ligand complexes, a single chain antibody (scFv) and its trisaccharide ligand (α-D-Galp-(1→2)-[α-D-Abep-(1→3)]-α-Manp-OCH_3, L1) and streptavidin homotetramer (S₄) and biotin (B), were investigated using a collision-induced dissociation (CID)-functional group replacement (FGR) strategy. CID was performed on protonated ions of a series of structurally related complexes based on the (scFv + L1) and (S₄?+?4B) complexes, at the +10 and +13 charge states, respectively. Intermolecular interactions were identified from decreases in the collision energy required to dissociate 50 % of the reactant ion (Ec₅₀) upon modification of protein residues or ligand functional groups. For the (scFv + L1)¹⁰⁺ ion, it was found that deoxygenation of L1 (at Gal C3 and C6 and Man C4 and C6) or mutation of His101 (to Ala) resulted in a decrease in Ec₅₀ values. These results suggest that the four hydroxyl groups and His101 participate in intermolecular H-bonds. These findings agree with those obtained using the blackbody infrared radiative dissociation (BIRD)-FGR method. However, the CID-FGR method failed to reveal the relative strengths of the intermolecular interactions or establish Man C4 OH and His101 as an H-bond donor/acceptor pair. The CID-FGR method correctly identified Tyr43, but not Ser27, Trp79, and Trp120, as a stabilizing contact in the (S₄?+?4B)¹³⁺ ion. In fact, mutation of Trp79 and Trp120 led to an increase in the Ec₅₀ value. Taken together, these results suggest that the CID-FGR method, as implemented here, does not represent a reliable approach for identifying interactions in the gaseous protein–ligand complexes.      

Theoretical Study on the Mass Transfer of Metal Ions in Ion Exchange Process

The kinetics of ion exchange between Ca2 , Mg2 , Co(Ⅱ), Cu(Ⅱ),Ni(Ⅱ), Fe(Ⅲ), y3 or Sm3 , respectively, in 0.50 mol/L HC1 and H on macrorecticular sulfonic ion exchange resin and the kinetics of the same reactions (M -H exchange) when Mn(Ⅱ) coexisted in resin phase as accelerating ion were studied. The accelerating effect manifested and its rule are consistent with the accelerating effect theory based on the concept concerned with adsorption electrical double layer which has been suggested in a previous paper published.     

Theoretical Study of the Sensitivity-Improvement Effect of Phosphoryl Group in Mass Spectrometry of Small Peptides

Mass spectrometry plays an important role in peptide sequencing since the invention of soft ionization techniques, such as fast atom bombardment (FAB), electrospray (ESI) and matrix-assisted laser desorption/ionization (MALDI). In our previous work, it was found that phosphorylation on the N-terminal of small peptides could enormously improve their sensitivity in FAB-MS1.To understand the sensitivity-improvement effect of phosphoryl group, the energies for the protonation of glycylglycin…     

Comparison of Different Sorbents in the QuEChERS Method for the Determination of Pesticide Residues in Strawberries by LC–MS/MS

A comparison of sample preparation based on the quick, easy, cheap, effective, rugged and safe (QuEChERS) method for analysis of pesticide residues in strawberries by LC–MS/MS was made using different sorbents in the clean-up by dispersive solid-phase extraction (d-SPE). Some sorbents were laboratory-made, prepared by depositing poly(methyloctadecylsiloxane) (PMODS), poly(methyloctylsiloxane) (PMOS), aminopropyl-terminated poly(dimethylsiloxane) (APPS) and copolymer of (52–48 %)dimethyl-(48–52 %)methylphenyl-siloxane (DMMPS) onto silica supports. The commercial sorbent primary–secondary amine (PSA) and mixtures of two sorbents, primary–secondary amine and poly(methyloctadecylsiloxane), were also used in the experiments. The performances of the sorbents were evaluated by parameters such as color of the final extract, gravimetric measurement, recovery and matrix effect at the fortification level of 100 ng g^?1 of the pesticide mixture in strawberries. The recoveries were in the range 70–120 %, and the RSD values were lower than 20 % for most of the pesticides using the modified QuEChERS method with different sorbents in the clean-up step. The strawberry extracts were cleaned more efficiently with the use of primary–secondary amine sorbent, which has the function of removing sugars, organic acids and especially pigments. The sample preparation method was efficient, and LC–MS/MS determination was optimal because of high selectivity and good detectivity for the multiresidue analyses.     

Desymmetrization of Perylenediimide Bay Regions Using Selective Suzuki–Miyaura Reactions from Dinitro Substituted Derivatives

Bay decoration of perylenediimide (PDI) is an attractive approach for tuning the optoelectronic properties of the dye as well as breaking backbone planarity, which provides the possibility of preventing the undesired formation of aggregates. This is usually performed through successive bis-bromination of PDI and pallado-catalyzed cross-coupling, which leads to symmetric triads. We now describe an efficient synthetic strategy for desymmetrization of the accepting PDI core by starting from its bis-nitration. To this end, Suzuki–Miyaura Couplings (SMC) were carried out on a mixture of 1,6- and 1,7-dinitroPDI regioisomers to add triphenylamine donating moieties and obtain donor–acceptor–donor triads. Investigation of the reactivity of dinitro PDI derivatives toward SMC has allowed us to access unprecedented asymmetric π-conjugated PDI-centered triads. These 1,6- and 1,7-PDI based triads, prepared as regioisomeric mixtures, were successfully separated and their spectroscopic, crystallographic and optoelectronic differences are reported.     

Photochemical Reactions in the Synthesis of Protein–Drug Conjugates

The ability to modify biologically active molecules such as antibodies with drug molecules, fluorophores or radionuclides is crucial in drug discovery and target identification. Classic chemistry used for protein functionalisation relies almost exclusively on thermochemically mediated reactions. Our recent experiments have begun to explore the use of photochemistry to effect rapid and efficient protein functionalisation. This article introduces some of the principles and objectives of using photochemically activated reagents for protein ligation. The concept of simultaneous photoradiosynthesis of radiolabelled antibodies for use in molecular imaging is introduced as a working example. Notably, the goal of producing functionalised proteins in the absence of pre-association (non-covalent ligand-protein binding) introduces requirements that are distinct from the more regular use of photoactive groups in photoaffinity labelling. With this in mind, the chemistry of thirteen different classes of photoactivatable reagents that react through the formation of intermediate carbenes, electrophiles, dienes, or radicals, is assessed.     

Selective Arylation of β-Cyclodextrin with an Ethylenediamino Group and Characteristics of Arylated β-Cyclodextrin Derivatives in Host–Guest Complexation

Mono-3-deoxy-(N-benzoyl-ethylenediamino)--CD, mono-3-deoxy-(N-benzylidene-ethylenediamino)--CD and mono-3-deoxy-(N-salicylidene-ethylenediamino)--CD, each having a flexible chain that bonds the aryl moiety on the secondary side of -CD, were prepared. The reaction processes might involve the formation of mono-(2,3-manno-epoxide)--CD as an intermediate under our reaction conditions. Further experiments showed that the aryl moiety which was bonded as a functional group on the primary side of -CD or on the secondary side of -CD with or without an ethylenediamino chain show remarkably different complexation properties in the complexation with small molecular guests such as alkanes, cycloketones etc.     

Effect of the Allyl Group in Reactions of Allyl Alcohol and Its Derivatives with ε-Caprolactam

Unlike saturated alcohols, allyl alcohol reacts with -caprolactam under considerably milder conditions. Allyl esters react with -caprolactam to give the corresponding allyl -acylaminocaproates. The yield of the latter decreases in going from formyl to acetyl and propionyl derivatives. The observed effect of the allyl group is explained in terms of possible allylic rearrangement in the transition state.     

Characterization of the Ion Beam Focusing in a Mass Spectrometer Using an IonCCD™ Detector

A position sensitive pixel-based detector array, referred to as the IonCCD, has been employed to characterize the ion optics and ion beam focusing in a custom built mass spectrometer designed for soft and reactive landing of mass-selected ions onto surfaces. The IonCCD was placed at several stages along the path of the ion beam to determine the focusing capabilities of the various ion optics, which include an electrodynamic ion funnel, two radiofrequency (rf)-only collision quadrupoles, a mass resolving quadrupole, a quadrupole bender, and two einzel lens assemblies. The focusing capabilities of the rf-only collision quadrupoles and einzel lenses are demonstrated by large decreases in the diameter of the ion beam. In contrast, the mass resolving quadrupole is shown to significantly defocus the mass-selected ion beam resulting in an expansion of the measured ion beam diameter. Combined with SIMION simulations, we demonstrate that the IonCCD can identify minor errors in the alignment of charged-particle optics that result in erratic trajectories and significant deflections of the ion beam. This information may be used to facilitate the design, assembly, and maintenance of custom-built mass spectrometry instrumentation.