Influence of a ring substituent on the tendency to form H(2)O adducts to Ag(+) complexes with phenylalanine analogues in an ion trap mass spectrometer

In a previous report we showed that certain binary Ag(+)-amino acid complexes formed adduct ions by the attachment of a single water and methanol molecule when stored in an ion trap mass spectrometer: complexes with aliphatic amino acids and with 4-fluorophenylalanine formed the adduct ions whereas complexes with phenylalanine and tryptophan did not. In this study we compared the tendency of the Ag(+) complexes derived from phenylalanine, 4-fluorophenylalanine, 4-hydroxyphenylalanine (tyrosine), 4-bromophenylalanine, 4-nitrophenylalanine and aminocyclohexanepropionic acid to form water adducts when stored, without further activation, in the ion trap for times ranging from 1 to 500 ms. Because the donation of pi electron density to the Ag(+) ion is a likely determining factor in complex reactivity, our aim in the present study was to determine qualitatively the influence of para-position substituents on the aromatic ring on the formation of the water adducts. Our results show that the reactivity of the complexes is influenced significantly by the presence of the various substituents. Decreases in [M + Ag](+) ion abundance, and increases in adduct ion abundance, both measured as a function of storage time, follow the trend -NO(2) > -Br > -F > -OH > -H. The complex of Ag(+) with 4-nitrophenylalanine was nearly as reactive towards water as the Ag(+) complex with aminocyclohexanepropionic acid, the last being an amino acid devoid of pi character in the ring system. Collision induced dissociation of the [M + Ag](+) species derived from the amino acids produces, among other products, Ag(+) complexes with a para-substituted phenylacetaldehyde: complexes that also form adduct species when stored in the ion trap. The trends in adduct ion formation exhibited by the aldehyde-Ag(+) complex ions were similar to those observed for the precursor complexes of Ag(+) and the amino acids, confirming the influence of the ring substituent.     

Ethylenediamine as a liquid chemical reagent to probe hydrogen bonding and host-guest interactions with crown ethers in an ion trap tandem mass spectrometer

Ethylenediamine (EDA) was used as a novel liquid chemical reagent to probe hydrogen bonding and host-guest interactions with crown ether derivatives in an ion trap mass spectrometer (ITMS). Selective ion/molecule reaction product ions were generated by reactions of EDA with oxygenated and aza-crown ethers. For the oxygenated crown ethers, glycols and dimethylglycols, ion/molecule reactions led to the formation of the protonated molecules ([M+H](+)) and adduct ions including [M+30](+), [M+44](+) and [M+61](+). The aza-crown ethers produced [M+H](+), [M+13](+) and [M+27](+) ions. Collisionally activated dissociation (CAD) experiments were applied to probe the binding strength of these ion/molecule reaction products. CAD results indicated that all these hydrogen-bonding complexes are weakly bound except for the [M+44](+) ion of 18-crown-6, since all the complexes dissociate to the protonated polyether and/or protonated EDA. Fragmentation of the [M+H](+) ions under CAD conditions indicates the extensive covalent bond cleavage of the protonated crown ether skeleton.     

Cationization of simple organic molecules by singly-charged Ag<Stack><Subscript>3</Subscript><Superscript>+</Superscript></Stack> cluster ions in matrix-assisted laser desorption/ionization mass spectrometry: Metal cluster-molecule interactions

It was found earlier that under matrix-assisted laser desorption/ionization (MALDI) conditions several organic compounds which produce adduct with silver ions, are also capable of forming adducts with Ag(3)(+) cluster ions under appropriate conditions. The Ag(3)(+) cluster ion can be in situ generated under the MALDI analysis conditions from silver trifluoroacetate cationization agent in the presence of organic MALDI matrices. In this article the fragmentation of a commercial plasticizer, a peracetylated isoflavone glycoside and a pyrazolylphenyl disulfide derivative cationized with silver ions and Ag(3)(+) cluster ions are compared. It was observed that the complexes of Ag(3)(+) are less fragmented than the corresponding adduct ions with Ag(+). The presumable fragmentation channel of [M + Ag(3)(+)] is the elimination of Ag(2) units from these complexes. No significant dissociation of [M + Ag(3)(+)], into M and Ag(3)(+) takes place, indicating a tight connection between the corresponding molecule and Ag(3)(+) cluster ion. However, with a compound carrying very labile groups, such as the pyrazolylphenyl disulfide derivative, intramolecular cleavages can occur prior to significant dissociation of the Ag(3)(+) cluster ion.     

Enantiomeric differentiation of β‐amino alcohols under electrospray ionization mass spectrometric conditions

The enantiomeric differentiation of a series of chiral β‐amino alcohols (A) is attempted, for the first time, by applying the kinetic method using L‐proline, L‐tryptophan, 4‐iodo‐L‐phenylalanine or 3, 5‐diiodo‐L‐tyrosine as the chiral references (Ref) and Cu²⁺ or Ni²⁺ ion (M) as the central metal ion. The trimeric diastereomeric adduct ions, [M+(Ref)₂+A‐H]⁺, formed under electrospray ionization conditions, are subjected for collision‐induced dissociation (CID) experiments. The products ions, formed by the loss of either a reference or an analyte, detected in the CID spectra are evaluated for the enantiomeric differentiation. All the references showed enantiomeric differentiation and the R_chiral values are better for the aromatic alcohols than for aliphatic alcohols. Notably, the R_chiral values of the aliphatic amino alcohols enhanced when Ni²⁺ is used as the central metal ion. The experimental results are well supported by computational studies carried out on the diastereomeric dimeric complexes. The computational data of amino alcohols is correlated with that of amino acids to understand the structural interaction of amino alcohols with reference molecule and central metal ion and their role on the stabilization of the dimeric complexes. Application of flow injection MS/MS method is also demonstrated for the enantiomeric differentiation of the amino alcohols. Copyright © 2014 John Wiley & Sons, Ltd.     

Elucidation of the collision induced dissociation pathways of water and alcohol coordinated complexes containing the uranyl cation

Multiple-stage tandem mass spectrometry was used to characterize the dissociation pathways for complexes composed of (1) the uranyl ion, (2) nitrate or hydroxide, and (3) water or alcohol. The complex ions were derived from electrospray ionization (ESI) of solutions of uranyl nitrate in H2O or mixtures of H2O and alcohol. In general, collisional induced dissociation (CID) of the uranyl complexes resulted in elimination of coordinating water and alcohol ligands. For undercoordinated complexes containing nitrate and one or two coordinating alcohol molecules, the elimination of nitric acid was observed, leaving an ion pair composed of the uranyl cation and an alkoxide. For complexes with coordinating water molecules, MS(n) led to the generation of either [UO2(2+)OH-] or [UO2(2+)NO3(-)]. Subsequent CID of [UO2(2+)OH-] produced UO2(+). The base peak in the spectrum generated by the dissociation of [UO2(2+)NO3(-)], however, was an H2O adduct to UO2(+). The abundance of the species was greater than expected based on previous experimental measurements of the (slow) hydration rate for UO2(+) when stored in the ion trap. To account for the production of the hydrated product, a reductive elimination reaction involving reactive collisions with water in the ion trap is proposed.     

Lithium and transition metal ions enable low energy collision-induced dissociation of polyglycols in electrospray ionization mass spectrometry

Electrospray ionization tandem mass spectrometry has the potential to be widely used as a tool for polymer structural characterization. However, the backbones or molecular chains of many industrial polymers including functional polyglycols are often difficult to dissociate in tandem mass spectrometers using low energy collision-induced dissociation (CID). We present a method that uses Li+ and transition metal ions such as Ag+ as the cationization reagents for electrospray ionization in an ion trap mass spectrometer. It is shown that lithium and transition metal polyglycol adduct ions can be readily fragmented with low energy CID. Comparative results from different cationization reagents in their abilities of producing both MS spectra and CID spectra are shown. This method opens the possibility of using conventional and readily available low energy CID tandem MS to study polyglycol structures.     

Gas phase ion–molecule reactions in a modified ion trap: H/D exchange of non-covalent complexes and coordinatively unsaturated platinum complexes

A commercially available electrospray ionization ion trap mass spectrometer has been modified to carry out gas phase ion–molecule reactions. The ability to study gas phase ion–molecule reactions in conjunction with collision induced dissociation (CID) based methods and the multistage trapping capabilities of the ion trap have been exploited in two ways: (i) gas phase H/D exchange reactions inside the ion trap, coupled with CID tandem mass spectrometry have been used to provide insights into the reactivity of non covalent complexes of amino acids and simple peptides, and (ii) CID prior to performing ion–molecule reactions has been used to synthesize and examine the reactivity of coordinatively unsaturated platinum complexes. © 1998 John Wiley & Sons, Ltd.     

Selective ion-molecule reactions of lactams with dimethyl ether ions

The ion-molecule reactions of dimethyl ether ions CH₃OCH₃ ⁺ and (CH₃OCH₃)H⁺, and four- to seven-membered ring lactams with methyl substituents in various positions were characterized by using a quadrupole ion trap mass spectrometer and a triple-quadrupole mass spectrometer. In both instruments, the lactams were protonated by dimethyl ether ions and formed various combinations of [M + 13] ⁺, [M + 15] ⁺, and [M + 45] ⁺ adduct ions, as well as unusual [M + 3] ⁺ and [M + 16] ⁺ adduct ions. An additional [M + 47] ⁺ adduct ion was formed in the conventional chemical ionization source of the triple-quadrupole mass spectrometer. The product ions were isolated and collisionally activated in the quadrupole ion trap to understand formation pathways, structures, and characteristic dissociation pathways. Sequential activation experiments were performed to elucidate fragment ion structures and stepwise dissociation sequences. Protonated lactams dissociate by loss of water, ammonia, or methylamine; ammonia and carbon monoxide; and water and ammonia or methylamine. The [M + 16] ⁺ products, which are identified as protonated lactone structures, are only formed by those lactams that do not have an N-methyl substituent. The ion-molecule reactions of dimethyl ether ions with lactams were compared with those of analogous amides and lactones.     

Chiral discrimination of alpha-amino acids by DNA tetranucleotides under electrospray ionization conditions

A set of DNA tetranucleotides, which are 3'- or 5'-end extended versions of GCA, was used as chiral selectors for the discrimination of enantiomers of alpha-amino acids. The [X+Y-2H](2-) ions of the 1:1 complexes were generated by electrospraying a mixture of tetranucleotide (X) and amino acid (Y) solution. Chiral discrimination was achieved by studying the collision-induced dissociation spectra of the [X+Y-2H](2-) ion and the ratio of relative abundance of precursor ion to that of the product ion was used to measure the extent of discrimination. Among the tetranucleotides used, GCAA and GGCA exhibited better discrimination, in which GCAA showed D-selectivity and GGCA showed L-selectivity for the studied amino acids. In addition, binding constants were measured for the 1:1 complexes of phenylalanine enantiomers with GCAA and GGCA. Ltd.     

Cation-pi interactions with a model for the side chain of tryptophan: structures and absolute binding energies of alkali metal cation-indole complexes

Threshold collision-induced dissociation techniques are employed to determine bond dissociation energies (BDEs) of mono- and bis-complexes of alkali metal cations, Li+, Na+, K+, Rb+, and Cs+, with indole, C8H7N. The primary and lowest energy dissociation pathway in all cases is endothermic loss of an intact indole ligand. Sequential loss of a second indole ligand is observed at elevated energies for the bis-complexes. Density functional theory calculations at the B3LYP/6-31G level of theory are used to determine the structures, vibrational frequencies, and rotational constants of these complexes. Theoretical BDEs are determined from single point energy calculations at the MP2(full)/6-311+G(2d,2p) level using the B3LYP/6-31G* geometries. The agreement between theory and experiment is very good for all complexes except Li+ (C8H7N), where theory underestimates the strength of the binding. The trends in the BDEs of these alkali metal cation-indole complexes are compared with the analogous benzene and naphthalene complexes to examine the influence of the extended pi network and heteroatom on the strength of the cation-pi interaction. The Na+ and K+ binding affinities of benzene, phenol, and indole are also compared to those of the aromatic amino acids, phenylalanine, tyrosine, and tryptophan to elucidate the factors that contribute to the binding in complexes to the aromatic amino acids. The nature of the binding and trends in the BDEs of cation-pi complexes between alkali metal cations and benzene, phenol, and indole are examined to help understand nature's preference for engaging tryptophan over phenylalanine and tyrosine in cation-pi interactions in biological systems.     

电喷雾质谱法研究谷胱甘肽与L型芳香性氨基酸非共价复合物

为探索谷胱甘肽和L型芳香性氨基酸的非共价相互作用, 将一定化学剂量比的还原型γ-谷胱甘肽分别与L型芳香性氨基酸(包括苯丙氨酸、酪氨酸和色氨酸)在室温和生理pH条件下混合后, 温育1 h, 生成非共价复合物, 并使反应完全. 电喷雾质谱测量结果揭示谷胱甘肽和L型芳香性氨基酸反应可以生成非共价复合物. 在二级串级质谱MS2测得的复合物碎片离子峰中, 除芳香性氨基酸离子峰外, 还包括谷胱甘肽及其它再次碎裂产生的b2和y2碎片离子, 进一步确认了非共价复合物的形成. 紫外光谱也证实了电喷雾质谱的实验结果. 为避免严重的离子化效率差异和质谱信号的相互抑制作用, 定量评估了谷胱甘肽和酪氨酸的相互作用, 结果显示反应物的初始浓度应该选择在5×10-5~3.00×10-4 mol/L范围内. 用质谱滴定法测定了谷胱甘肽与3个芳香性氨基酸非共价复合物的解离常数, 结果表明, 谷胱甘肽复合物的稳定性按Tyr, Trp和Phe次序依次增大.     

Experimental and theoretical study on gas-phase ion/molecule reactions of silver trimer cation, Ag3+, with 12-crown-4

The reaction mechanisms of silver trimer cation, Ag3+, with 12-crown-4 (12C4) were studied experimentally and theoretically. Using a cylindrical ion trap time-of-flight mass spectrometer, gas-phase ion/molecule reactions of Ag3+ with 12C4 were observed. Metal-ligand complexes of [Ag(12C4)]+, [Ag3(12C4)]+ and [Ag3(12C4)2]+, and of [Ag(12C4)2]+ and [Ag3(12C4)3]+, were observed as the reaction intermediates and terminal products, respectively. The formations of the [Ag12C4]+ and [Ag(12C4)2]+ complexes indicated that the neutral dimer (Ag2) had been eliminated from the trimer cation. From the results of ab initio calculations at the HF/LanL2DZ level of theory and the experiments, it is suggested that three 12C4 molecules can attach to Ag3+ through consecutive reactions and that neutral Ag2 can be easily eliminated from [Ag3(12C4)]+.     

Chemical ionization of substituted naphthalenes using tetrahydrofuran as a reagent in gas chromatography with ion trap mass spectrometry

The ion/molecule reactions of nine monosubstituted naphthalene compounds in chemical ionization mass spectrometry (CI-MS) were studied using tetrahydrofuran (THF) as CI reagent. Proton affinity factors, substituent effects and the preferred site of adduct ion attachment were examined. Good correlation was observed between proton affinity and the formation of [M](+*) and [M+H](+) ions. The influence of substituents on protonation and site-specific adduct [M+13](+) and [M+41](+) ion formation is also observed, with the cyano substituent showing the most stable [M+41](+) ion. Collision-activated dissociation experiments were used to characterize the variety of adducts formed under CI conditions, and provided insight into product ion structures and mechanisms of dissociation and condensation during CI-MS/MS.     

Determination of polycyclic aromatic hydrocarbons by liquid chromatography-electrospray ionization mass spectrometry using silver nitrate as a post-column reagent

Liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) using silver nitrate as a post-column reagent has been used for the determination of 10 polycyclic aromatic hydrocarbons (PAHs) in river water. In this method, after all the PAHs were separated by reversed-phase liquid chromatography, analytes formed complexes with silver cation by mixing with silver nitrate solution. The complexes then transfer the molecular ion, [M]+, of the PAHs by charge transfer using in source collision-induced dissociation. The positive ion ESI mass spectra of all PAHs tested in this study showed [M]+ as the base peak and abundant [M+Ag]+, [2M+Ag]- with very weak or no [2M+Ag]+. For the sample extraction, several solid-phase extraction parameters using the blue-chitin column were optimized. The limits of detection (S/N=3) of all PAHs for the spiked river water sample ranged from 0.001 to 0.03 ng/ml, and the detector responses were linear up to I ng/ml (correlation coefficients > or =0.0998). Repeatability and reproducibility were in the range from 4.3 to 6.8% and from 6.2 to 9.5%, respectively.     

Evaluation of the α‐phenylvinyl cation as a chemical ionization reagent for the differentiation of isomeric substituted phenols in an ITMS

Ion–molecule reactions between the α‐phenylvinyl cation and isomeric naturally occurring phenols were investigated using a quadruple ion trap mass spectrometer. The α‐phenylvinyl cation m/z 103, generated by chemical ionization from phenylacetylene, reacts with neutral aromatic compounds to form the characteristic species: [M + 103]⁺ adduct ions and the trans‐vinylating product ions [M + 25]⁺, which correspond to [M + 103]⁺ adduct after the loss of benzene. Isomeric differentiation of several ring‐substituted phenols was achieved by using collision‐induced dissociation of the [M + 103]⁺ adduct ions. This method also showed to be effective in the differentiation of 4‐ethylguaiacol from one of its structural isomers that displays identical EI and EI/MS/MS spectra. The effects of gas‐phase alkylation with phenylvinyl cation on the dissociation behavior were examined using mass spectrometryⁿ and labeled derivatives. Copyright © 2015 John Wiley & Sons, Ltd.     

Application of liquid chromatography-ion trap mass spectrometry to the characterization of the 16-membered ring macrolide josamycin propionate

Coupled liquid chromatography and ion trap mass spectrometry (LC/MS) was used for the characterization of the semi-synthetic 16-membered ring macrolide josamycin propionate. On-line identification of impurities in this antibiotic complex was performed with an ion trap mass spectrometer without recourse to time-consuming isolation and purification procedures. Ion trap mass spectrometry is ideally suited to identification of impurities because it provides MSn capability, enabling multiple stages of mass spectrometry to obtain the maximum amount of structural information for a given molecule. The ion trap was used with an electrospray ionization source operated in the positive ion mode or with an atmospheric pressure chemical ionization source operated in the negative ion mode. The identity of the unknown compounds was deduced using the MS/MS and MSn collision-induced dissociation spectra of reference substances or structural analogs as interpretative templates, combined with knowledge about the nature of functional group fragmentation behavior. Given the importance attached to the identification of impurities of unknown identity in pharmaceutical substances, this study is useful for companies producing josamycin propionate. The knowledge of the fragmentation behavior is also of importance in further research on other 16-membered macrolides.     

The use of paraquat as an NMR.- and charge-transfer-probe for solvent-exposed aromatic amino-acid side-chains

The purpose of this investigation was to find new and more potent charge-transfer probes for the study of certain aspects of polypeptide and protein conformation, especially of solvent-exposure of aromatic amino-acid side chains. N,N′-dimethyl-4,4′-dipyridylium ion (paraquat) was shown by NMR. to complex specifically with tryptophan, tyrosine, and phenylalanine. The long-wavelength absorption (electronic transitions) typical of charge-transfer complexes was detectable with tryptophan and tyrosine, not with phenylalanine. Paraquat forms slightly stronger complexes than N(1)-methyl-nicotinamidium ion, and appears to have different steric requirements. Im human calcitonin and human calcitonin-(11–32)-dokosipeptide all the aromatic amino-acid side-chains (Phe, Tyr) are accessible to paraquat in solution. This is true also for at least one of the two tyrosines and the tryptopha of ACTH-(1–24)-tetrakosipeptide, and for Trp (62) of chicken egg-white lysozyme. Paraquat is of special interest, because it generates a CT.-absorption band not only with tryptophan, but also with tyrosine, and because of its strong diamagnetic shielding effect.     

Adduction of solvent molecules by ions isolated within an ion trap mass spectrometer under atmospheric pressure ionisation conditions

Benzylpyridine and papaverine, an alkyl quinoline, both produce product ions containing an azepinium ring during atmospheric pressure chemical ionisation or electrospray multistage mass spectrometry. By controlling the trapping conditions, an isolated azepinium ion was held within the trap for an extended period of time without excitation. A subsequent analytical scan revealed a mass spectrum containing ions at two mass-to-charge (m/z) ratios, the first at the m/z of the isolated product ion and the second at an m/z ratio corresponding to the adduction of a molecule of solvent. Isolation and resonance excitation of the adduct ion remove the solvent molecule, resulting in recovery of the azepinium ion at the same signal intensity as the adduct ion. Isolating and trapping the ion for a further period allowed the solvent adduct ion to be re-formed. Modulation of the solvent flowing into the source while the ion was trapped allowed variation in the solvent molecule adducted to the trapped ion. The proportion of the ion current due to the adduct ion depends on the nature of the isolated ion, the proton affinity of the solvent and the length of time for which the ion was trapped. Adduct ion formation, deliberately maximised in this study, can occur to a significant extent under standard ion trap operating conditions, reducing the ion current of product ions of interest and, ultimately, the response in tandem mass spectrometric assays.     

Mass spectrometric investigation of N-sulfonylated purine nucleic bases and nucleosides

The gas/phase behaviour of N-sulfonylated purine nucleic bases and nucleosides towards electron impact (EI) and matrix-assisted laser desorption/ionization (MALDI) occurring in a ion trap of a Fourier transform ion cyclotron resonance mass spectrometer is investigated. The influence of the storage time on the protonated molecule ([M+H](+)) abundance under EI conditions confirms that the formation of these ions proceeds through ion/molecule reactions. Using stored-waveform inverse Fourier transform (SWIFT) selective isolation of M(+.) or H(3)O(+), self-chemical ionization, M(+.)/M, and chemical ionization, H(3)O(+)/M, are detected. Investigation of specific EI expulsion of SO(2), SO(2)H and/or SO(2)H(2) from M(+.) and/or [M+H](+) shows that oxygen protonation in bond;SO(2)bond; proceeds faster than nitrogen protonation. Expulsion of SO(2) from molecular ions is not observed in MALDI mass spectra of nucleosides.     

Solvation of acylium fragment ions in electrospray ionization quadrupole ion trap and Fourier transform ion cyclotron resonance mass spectrometry

In electrospray ionization (ESI) quadrupole ion trap and Fourier transform ion cyclotron resonance mass spectrometry, certain fragment ions (e.g. acylium ions) generated either during the ion transportation process (in the source interface region) or in the ion trap are found to undergo ion--molecule reactions with ESI solvent molecules (water, acetonitrile and aliphatic alcohols) to form adduct species. These unexpected solvated fragment ions severely complicate the interpretation of mass spectrometic data. High-resolution accurate mass measurements are important in establishing the elemental compositions of these adduct species and preventing erroneous data interpretation.