Lei Yue

Elimination of benzene from protonated N-benzylindoline: benzyl cation/proton transfer or direct proton transfer?

AbstractCollision-induced dissociation (CID) of protonated N-benzylindoline and its derivatives was investigated by electrospray ionization tandem mass spectrometry (ESI-MS/MS). Elimination of benzene was observed besides hydride transfer and electron transfer reactions. D-labeling experiments and accurate mass determinations of the product ions confirm that the external proton is retained in the fragment ion, and the elimination reaction was proposed to be initiated by benzyl cation transfer rather than proton transfer. Benzyl cation transfer from the nitrogen atom to one of the sp2-hybridized carbon atoms in the indoline core is the key step, and subsequent proton transfer reaction leads to the elimination of benzene. Density functional theory (DFT)-based calculations were performed and the computational results also support the benzyl cation/proton transfer mechanism.n Figureᅟ

Intriguing roles of reactive intermediates in dissociation chemistry of N-phenylcinnamides

In mass spectrometry of protonated N-phenylcinnamides, the carbonyl oxygen is the thermodynamically most favorable protonation site and the added proton is initially localized on it. Upon collisional activation, the proton transfers from the carbonyl oxygen to the dissociative protonation site at the amide nitrogen atom or the α-carbon atom, leading to the formation of important reactive intermediates. When the amide nitrogen atom is protonated, the amide bond is facile to rupture to form ion/neutral complex 1, [RC(6)H(4)CH=CHCO(+)/aniline]. Besides the dissociation of the complex, proton transfer reaction from the α-carbon atom to the nitrogen atom within the complex takes place, leading to the formation of protonated aniline. The presence of electron-withdrawing groups favored the proton transfer reaction, whereas electron-donating groups strongly favored the dissociation (aniline loss). When the proton transfers from the carbonyl oxygen to the α-carbon atom, the cleavage of the C(α)-CONHPh bond results in another ion/neutral complex 2, [PhNHCO(+)/RC(6)H(4)CH=CH(2)]. However, in this case, electron-donating groups expedited the proton transfer reaction from the charged to the neutral partner to eliminate phenyl isocyanate. Besides the cleavage of the C(α)-CONHPh bond, intramolecular nucleophilic substitution (a nucleophilic attack of the nitrogen atom at the β-carbon) and stepwise proton transfer reactions (two 1,2-H shifts) also take place when the α-carbon atom is protonated, resulting in the loss of ketene and RC(6)H(5), respectively. In addition, the H/D exchanges between the external deuterium and the amide hydrogen, vinyl hydrogens and the hydrogens of the phenyl rings were discovered by D-labeling experiments. Density functional theory-based (DFT) calculations were performed to shed light on the mechanisms for these reactions.

Intramolecular Halogen Transfer via Halonium Ion Intermediates in the Gas Phase.

AbstractThe fragmentation of halogen-substituted protonated amines and quaternary ammonium ions (R1R2R3N+CH2(CH2)nX, where X = F, Cl, Br, I, n = 1, 2, 3, 4) was studied by electrospray ionization tandem mass spectrometry. A characteristic fragment ion (R1R2R3N+X) resulting from halogen transfer was observed in collision-induced dissociation. A new mechanism for the intramolecular halogen transfer was proposed that involves a reactive intermediate, [amine/halonium ion]. A potential energy surface scan using DFT calculation for CH2–N bond cleavage process of protonated 2-bromo-N,N-dimethylethanamine supports the formation of this intermediate. The bromonium ion intermediate-involved halogen transfer mechanism is supported by an examination of the ion/molecule reaction between isolated ethylenebromonium ion and triethylamine, which generates the N-bromo-N,N,N-triethylammonium cation. For other halogens, Cl and I also can be involved in similar intramolecular halogen transfer, but F cannot be involved. With the elongation of the carbon chain between the halogen (bromine as a representative example) and amine, the migration ability of halogen decreases. When the carbon chain contains two or three CH2 units (n = 1, 2), formal bromine cation transfer can take place, and the transfer is easier when n = 1. When the carbon chain contains four or five CH2 units (n = 3, 4), formal bromine cation transfer does not occur, probably because the five- and six-membered cyclic bromonium ions are very stable and do not donate the bromine to the amine.n Graphical Abstractᅟ

Mass spectrometric studies on the interaction of cisplatin and insulin

The interaction of antitumor drug, cisplatin (cis-[PtCl2(NH3)2], CDDP) with insulin from porcine pancreas has been investigated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and high resolution hybrid ion trap/time-of-flight mass spectrometry (MALIDI-TOF/TOF–MS and ESI-IT/TOF MS). The MALDI-TOF/TOF–MS results demonstrated that the presence of cisplatin complex resulted in the reduction of the disulfide bond in porcine pancreas after the incubations of the two substances were performed in vitro. It indicated that the presence of cisplatin would destroy the native configuration of insulin, which may lead to the inactivation of insulin. High resolution mass values and the characteristic isotopic pattern of the platinated insulin ions allowed the analysis of platinated mono-, di- and triadducts of cisplatin and insulin in the incubations under different conditions. The laser-induced dissociation of the monoadduct obtained in MALDI source was carried out and one platinum was found to bind to insulin B chain was determined. The platinum binding sites were further identified to be the N terminus (B chain), cysteine 7 (B chain) and cysteine 19 (B chain) residues by electrospray ionization tandem mass spectrometry. The identification of the interaction between insulin and cisplatin broadens the horizon of the knowledge in the interaction of the proteins and metallodrugs.

Investigation of protonated and sodiated leucine-enkephalin by hydrogen–deuterium exchange and theoretical calculations

In this work, protonated and sodiated leucine-enkephalin (LE) were investigated by gas-phase hydrogen–deuterium exchange (HDX) performed on a linear ion trap time-of-flight mass spectrometer. It is found that more hydrogen atoms are exchanged in protonated LE than in sodiated LE, indicating the different conformations of the two peptide ions. To clarify further the experimental results, the conformations were calculated by using density functional theory, which shows that the terminal amino group is the most thermodynamically stable protonation site, while the sodium ion coordinated to four carbonyl oxygen atoms forms the most favourable sodium adduct. Limited HDX reactions of sodiated LE are explained by the rigid conformation and fewer exchangeable acidic hydrogen atoms from sodium coordination.

Enantioselectivity and catalysis improvements of Pseudomonas cepacia lipase with Tyr and Asp modification

A concise strategy to improve the p-NPP (p-nitrophenyl palmitate) catalytic activity and enantioselectivity towards secondary alcohols of Pseudomonas cepacia lipase (PcL) has been described. The PcL was modified by I3−, N-acetyl imidazole (NAI), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) and ethylenediamine (EDA) in the absence or presence of n-hexane, respectively. After being modified by the four modification reagents, the enantioselectivity (E value) of the PcL towards secondary alcohols was enhanced by 2- to 4-fold. The catalytic activity of EDA-PcL was increased by about 6-fold. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of modified PcL showed that Tyr4, Tyr29, Tyr45, Tyr95, Asp36 and Asp55 were the modified sites. When Tyr29 was modified, the E value of PcL towards secondary alcohols was largely improved. MALDI-TOF-MS characterization and molecular dynamics simulation of the lipase indicated that Tyr29 located inside the catalytic cavity had a significant impact on the E value. The strong steric hindrance of acetyl and iodine ion to the groups on the chiral center of the substrates is responsible for the improvement. In addition, the enhancement of hydrophobicity on the surface of the lipase due to the sidechain replacement of Asp with uncharged hydrophobic groups also improved the E value.

Optimization of Performance of Toroidal Ion Trap with Trianglar Electrode by Theoretical Simulation

Abstract Owing to the ion storage capacity far superior to that of three-dimensional ion trap of the same volume, toriodal ion trap is deemed to be another useful candidate of miniaturization of ion trap mass analyzer in recent years. To further optimize the performance of mass spectrometry of toriodal ion trap, especially the ion detection efficiency and the mass resolving power, a new toriodal ion trap built with triangular electrodes was proposed and investigated theoretically. The new toroidal ion trap was composed of two identical ring electrodes with triangular cross section and two cylindrical electrodes of different sizes. Ions were extracted from the ion trap through resonance excitation for mass analysis. The asymmetrical triangular electrode structure was obtained through theoretical simulation and optimization of ion detection efficiency and mass resolving power. The mass resolution ( M /Δ M ) of ∼1500 at m/z 609 was obtained for a toriodal ion trap with an optimal electrode structure.

Negative charge induced dissociation: fragmentation of deprotonated N-benzylidene-2-hydroxylanilines in electrospray ionization mass spectrometry

Unimolecular reactivities of different N-benzylidene-2-hydroxylaniline anions were investigated in gas phase by electrospray ionization tandem mass spectrometry. All the collision-induced dissociation spectra of N-benzylidene-2-hydroxylaniline anions show similar ions at phenyl anions, neutral loss of benzonitrile and benzoxazole anions, respectively. The possible fragmentation pathway was probed through deuterium labeling and various group substituents experiments. Computational results were applied to shed light on the mechanism of fragmentation patterns. The proton in the CH=N is reactive in the formation of the concerned ions. Its direct transfer to the oxygen results in 2-hydroxyphenyl anion. Proton abstraction between benzoxazole and phenyl anion leads to the formation of benzene and benzoxazole anion.

Competitive benzyl cation transfer and proton transfer: collision-induced mass spectrometric fragmentation of protonated N,N-dibenzylaniline: Competitive benzyl cation and proton transfer

Collision-induced dissociation of protonated N,N-dibenzylaniline was investigated by electrospray tandem mass spectrometry. Various fragmentation pathways were dominated by benzyl cation and proton transfer. Benzyl cation transfers from the initial site (nitrogen) to benzylic phenyl or aniline phenyl ring. The benzyl cations transfer to the two different sites, and both result in the benzene loss combined with 1,3-H shift. In addition, after the benzyl cation transfers to the benzylic phenyl ring, 1,2-H shift and 1,4-H shift proceed competitively to trigger the diphenylmethane loss and aniline loss, respectively. Deuterium labeling experiments, substituent labeling experiments and density functional theory calculations were performed to support the proposed benzyl cation and proton transfer mechanism. Overall, this study enriches the knowledge of fragmentation mechanisms of protonated N-benzyl compounds. Copyright

Ortho-hydroxyl effect and proton transfer via ion-neutral complex: the fragmentation study of protonated imine resveratrol analogues in mass spectrometry.

The fragmentation pathways of protonated imine resveratrol analogues in the gas-phase were investigated by electrospray ionization-tandem mass spectrometry. Benzyl cations were formed in the imine resveratrol analogues that had an ortho-hydroxyl group on the benzene ring A. The specific elimination of the quinomethane neutral, CH2 u2009=u2009C6 H4 u2009=u2009O, from the two isomeric ions [M1u2009+u2009H](+) and [M3u2009+u2009H](+) via the corresponding ion-neutral complexes was observed. The fragmentation pathway for the related meta-isomer, ion [M2u2009+u2009H](+) and the other congeners was not observed. Accurate mass measurements and additional experiments carried out with a chlorinated analogue and the trideuterated isotopolog of M1 supported the overall interpretation of the fragmentation phenomena observed. It is very helpful for understanding the intriguing roles of ortho-hydroxyl effect and ion-neutral complexes in fragmentation reactions and enriching the knowledge of the gas-phase chemistry of the benzyl cation. Copyright