Gas-phase ion-molecule reactions using regioselectively generated radical cations to model oxidative damage and probe radical sites in peptides

Collision induced dissociation (CID) of sodiated peptide derivatives containing a nitrate ester functionality was used to regiospecifically generate three isomeric radicals of the model peptide Bz-Ala-Gly-OMe corresponding to radicals formed at: C(α) of the alanine residue [4+Na](+); C(α) of the glycine residue [5+Na](+); and the side chain of alanine [6+Na](+). The ion-molecule reactions of these peptide radicals were examined to model oxidative damage to peptides and to probe whether the radical sites maintain their integrity or whether they isomerise via intramolecular hydrogen atom transfer (HAT). Only [6+Na](+) is reactive towards O(2), forming the peroxyl radical [7+Na](+), which loses O(2), HO˙ and HO(2)˙ under CID. The radical ion [7 + Na](+) abstracts a hydrogen atom from 4-fluorothiophenol to form the hydroperoxide [8+Na](+), which upon CID fragments via the combined loss of HO˙ and CH(2)O. In contrast, all three of the isomeric sodiated radicals react with NO˙ and NO(2)˙ to form adducts. CID of the NO adducts only regenerates the radicals via NO˙ loss, thus providing no structural information. In contrast, CID of the NO(2) adducts gives rise to a range of product ions and the spectra are different for each of the three adducts, suggesting that the isomeric radicals [4+Na](+), [5+Na](+) and [6+Na](+) are produced as discrete species. Finally, CID of the NO(2) adducts was used to probe the rearrangement of the radicals [4+Na](+), [5+Na](+) and [6+Na](+) prior to their reaction with NO(2)˙: [6 + Na](+) rearranges to a mixture of [4+Na](+) and [5+Na](+) while [5+Na](+) rearranges to [4+Na](+).     

Formation of metal complex ions from amino acid in the presence of Li+, Na+ and K+ by electrospray ionization: metal replacement of hydrogen in the ligands

Alkali metal cations easily form complexes with proteins in biological systems; understanding amino acid clusters with these cations can provide useful insight into their behaviors at the molecular level including diagnosis and therapy of related diseases. For the purpose of characterization of basic interaction between amino acids and alkali metal, each of the 20 naturally occurring amino acids were ionized in the presence of lithium, sodium and potassium cations by electrospray ionization, and the resulting product ions were analyzed. We focus our attention on the gas phase alkali metal ion-proton exchanged complexes in current study, specifically complexes with serine, threonine, asparagine and glutamine, which share characteristic pattern unlike other amino acids. All amino acids generated [M + H](+) and [M + Na](+) ions, where M stands for the neutral amino acid. Serine, threonine, asparagine and glutamine generated cluster ions of [nM - nH + (n + 1)Na](+) and [nM - (n - 1)H + (n - 1)Na + K](+) , where n = 1-7. While the (M - H + Li) and (M - H + K) species were not observed, the neutral (M - H + Na) species formed by proton-sodium cation exchange had a highly stable cyclic structure with ketone and amine ligand sites, suggesting that (M - H + Na) serves as a building block in cluster ion formation. Cluster ion intensity distributions of [nM - nH + (n + 1)Na](+) and [nM - (n - 1)H + (n - 1)Na + K](+) showed a magic number at n = 3 and 4, respectively. Extensive B3LYP-DFT quantum mechanical calculations were carried out to elucidate the geometry and energy of the cluster ions, and they provided a reasonable explanation for the stability and structure of the cluster ions.     

Matrix-free laser desorption/ionization of ions landed on plasma-treated metal surfaces

We report new experiments in which laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF-MS) was applied to detection and characterization of gramicidin S and IgG pentapeptide (DSDPR) that were reactively landed on plasma-treated stainless steel surfaces. The distributions of [M + H](+), [M + Na](+) and [M + K](+) ion species in LDI-TOF for gramicidin S and IgG pentapeptide (DSDPR) were found to be markedly different from those in conventional MALDI-TOF spectra of the same samples. LDI-TOF mass spectra showed a strong preference for [M + K](+) adducts even in the presence of a large excess of sodium cations, or following surface treatment with trifluoroacetic acid. Alkali metal cations (K(+) and Cs(+)) can be exchanged in reactively landed peptide samples to provide the corresponding cationized peptide ions by LDI. Multiple charged trypsin cations were reactively landed into a layer of 2-(4-hydroxyphenylazo)benzoic acid and ionized by LDI. The ionization mechanisms for LDI of surface-deposited peptides are briefly discussed. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Collision-induced dissociation of MCl(+) adducts (M = Mg, Mn, Zn, Co, Ni and Cu) and Cu(+) and Ag(+) adducts of dithioalkyl ketene acetals

Electrospray ionization mass spectra of equimolar solutions of dithioalkyl ketene acetals 1 and 2 and metal chlorides (MgCl(2), MnCl(2), ZnCl(2), CoCl(2), NiCl(2) and CuCl(2)) produced abundant ligated metal ion adducts [1 + MCl](+) and [2 + MCl](+). In addition, CuCl(2) also gave rise to Cu(+) adducts. The ligated metal ion adducts upon collision-induced dissociation (CID) showed characteristic fragmentation pathways reflecting the favoured site of coordination. The results show that MgCl(+) prefers oxygen over sulfur, whereas the reverse is true for ZnCl(+) adducts, exemplified by the preferred fragmentation of [1 + MgCl](+) as elimination of MgCl(OH), while that of [1 + ZnCl](+) is expulsion of ZnCl(SCH(3)). Co and Ni chloride adducts tend to give stable metal coordinated species. Cleavage of the dithiolane ring followed by elimination of C(2)H(4)S is the preferred pathway during the CID of [2 + MCl](+) adducts. The CuCl(+) adducts of 1 and 2 showed reduction of Cu((I)) to Cu((0)) resulting in the M(+)(*)ions of 1 and 2. Abstraction of *CH(3) resulting in elimination of CuCH(3) was observed during CID of Cu(+) adducts of 1 and 2. A comparative study of the corresponding Ag(+) adducts revealed a similar behaviour.     

Fragmentation study of salinomycin and monensin A antibiotics using electrospray quadrupole time-of-flight mass spectrometry

The fragmentation pathways of two selected ionophore antibiotics, salinomycin and monensin A, were studied using electrospray (ES) orthogonal acceleration quadrupole time-of-flight mass spectrometry in positive-ion mode. The identity of fragment ions was determined by accurate-mass measurements. In ES mass spectra, ion signals of relatively high intensity were observed for [M+Na](+) and [M-H+2Na](+) for each antibiotic. Each of the ion species [M+Na](+) and [M-H+2Na](+) for salinomycin and [M-H+2Na](+) for monensin A were isolated in turn and subjected to fragmentation. In the fragmentation of [M+Na](+) and [M-H+2Na](+) from salinomycin, only Cbond;C single bond cleavage and dehydration were observed. Product ion mass spectra obtained from [M-H+2Na](+) of monensin A showed that ether ring opening, Cbond;C single bond cleavage and dehydration fragmentations had occurred. Fragment ions containing two sodium atoms were observed in the product ion mass spectrum of [M-H+2Na](+) from salinomycin, but not from monensin A. Both type A (containing the terminal carboxyl group) and type F (containing the terminal hydroxyl group) fragment ions were observed in the product ion mass spectra of sodium adduct ions of salinomycin and monensin A.     

Differentiation of a pair of diastereomeric tertiarybutoxycarbonylprolylproline ethyl esters by collision-induced dissociation of sodium adduct ions in electrospray ionization mass spectrometry and evidence for chiral recognition by ab initio molecular orbital calculations

The fragmentation of the sodium adduct ions for tert-butoxycarbonyl-L-prolyl-L-proline ethyl ester (Boc-L-Pro-L-Pro-OEt) was compared with that for Boc-D-Pro-L-Pro-OEt in positive-ion electrospray ionization (ESI) mass spectrometry. In the collision-induced dissociation (CID) mass spectra of the [M + Na](+) ions, the abundance of the [M + Na - C(CH(3))(3) + H](+) ion, which is due to the loss of a tert-butyl group from the [M + Na](+) ion for Boc-D-Pro-L-Pro-OEt, was about eight times higher than that for Boc-L-Pro-L-Pro-OEt. In addition, in the CID spectra of the sodium adduct fragment ion ([M + Na - Boc + H](+)), the abundance of the [M + Na - Boc - prolylresidue + H](+) ion, which is due to the loss of prolyl residue from the [M + Na - Boc + H](+) ion for Boc-L-Pro-L-Pro-OEt, was about five times higher than that for Boc-D-Pro-L-Pro-OEt. These results indicate that Boc-L-Pro-L-Pro-OEt was distinguished from Boc-D-Pro-L-Pro-OEt by the CID mass spectra of the sodium adduct ions in ESI mass spectrometry. The optimized geometries of the [M + Na](+) and the [M + Na - Boc + H](+) ions calculated by ab initio molecular orbital calculations suggest that the chiral recognition of these diastereomers was due to the difference of the orientation of a sodium ion to the oxygen and nitrogen atoms in dipeptide derivatives, and to the difference of the total energies between them.     

Studies on high-energy collision-induced dissociation of endogenous cannabinoids: 2-arachidonoylglycerol and n-arachidonoylethanolamide in FAB-mass spectrometry.

Analysis of 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamide (anandamide) via alkali or alkaline earth metal-adduct high-energy collision-induced dissociation (CID) in fast-atom bombardment (FAB) ionization-mass spectrometry (MS) is described. The CID-MS/MS of the [2-AG+Li](+) or [2-AG+Na](+) ion undergoes charge-remote fragmentation (CRF), which is useful for the determination of the double-bond positions in the hydrocarbon chain, while the CID-MS/MS of the [2-AG-H+Cat](+) (Cat = Mg(2+), Ca(2+), Ba(2+)) ion provides an abundant fragment ion of the cationized arachidonic acid species, which is derived from cleaving the ester bond via a McLafferty-type rearrangement in addition to structurally informative CRF ions in small amounts. On the other hand, the CID-MS/MS spectra of anandamide cationized with both alkali metal (Li(+) or Na(+)) and alkaline earth metal (Mg(2+), Ca(2+), or Ba(2+)) show CRF patterns: the spectra obtained in lithium or sodium adduct are more clearly visible than those in magnesium, calcium, or barium adduct. The McLafferty rearrangement is not observed with metal-adduct anandamide. The characteristics in each mass spectrum are useful for the detection of these endogenous ligands. m-Nitrobenzyl alcohol (m-NBA) is the most suitable matrix. A lithium-adduct [2-AG+Li](+) or [anandamide+Li](+) ion is observed to be the most abundant in each mass spectrum, since the affinity of lithium for m-NBA is lower than that for other matrices examined.     

Elimination of isocyanate and isothiocyanate molecules at the electrospray ionization ion trap, electrospray ionization quadrupole time-of-flight and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry fragmentation of sodium cationized brassitin, brassinin and their glycosides

Fragmentation mechanisms of phytoalexin analogs, including brassitin and brassinin and their glucosylated analogs, have been studied by electrospray (ESI) ion trap (IT) multistage (MS(n), n = 1-4) mass spectrometry, matrix-assisted laser desorption/ionization time-of-flight (MALDI ToF/ToF) and ESI-Q/ToF tandem mass spectrometry techniques. At the fragmentation of sodium adducts a hitherto not described process has been elucidated The proposed mechanism of this process includes cyclization of the brassitin and brassinin cationized adducts through a six-membered cycle of the molecules and the elimination of isocyanate or isothiocyanate from the thio- or dithiocarbamate moiety, giving rise to [M + Na - 43](+) or [M + Na - 59](+) adducts. The elimination of NH=C=O or NH=C=S molecules has been confirmed by the high resolution measurement of the elemental composition of the ions produced and quantum-chemical calculations of the six-membered transition state. Other fragmentation routes include cleavage of an alkane linker, while numerous characteristic hexopyranose pathways are taking place in the glucosylated compounds. The presented theoretical data on the ESI and MALDI behavior of the saccharidic, as well as of the indole aglycon parts, can facilitate structural elucidation of the analogous compounds.     

Heavier alkali metal complexes of 2-phenylamidopyridine: an X-ray crystallographic and theoretical study of a structurally diverse series of crown ether adducts

Complexes of the anion of the secondary amine 2-phenylaminopyridine (LH) with the heavier alkali metals Na-Cs have been prepared in the presence of various macrocyclic polyether crowns [12-crown-4 (12C4), 15-crown-5 (15C5), and 18-crown-6 (18C6)], which coordinate to the metal ions in all cases. Depending on the combination of alkali metal and crown, the products include separated ion pairs [(crown)(2)M](+)L(-)(12C4/Na, 15C5/K, 15C5/Rb, 15C5/Cs) and contact-ion-pair neutral molecules [(crown)ML](15C5/Na, 18C6/Na, 18C6/K, 18C6/Rb) in which L(-) acts as a bidentate ligand. [((12C4)KL)(2)] is a dimer in which the amido and pyridine N atoms of two ligands bridge the metal ions, while [((18C6)KL(2)K)([infinity])] is a chain polymer with crown O and pyridyl N atoms acting as bridges in corner-sharing KOKN four-membered rings and may be regarded as a potassium potassate complex. [((18C6)Cs(2)L(2))([infinity])] is also polymeric, with a basic arrangement like that of [((12C4)KL)(2)], but with each 18C6 ligand mu-kappa6:kappa6 to two metal centres, generating the polymer. Although most of the [(crown)(2)M](+) sandwich cations have essentially parallel crown ligands, [(12C4)(2)Rb](+) is markedly bent, both in the complex incorporating THF as an additional ligand and in the THF-free complex, where two of these cations form a centrosymmetric dimer through two bridging oxygen atoms; DFT calculations indicate that the bending is inherent, thus enabling the coordination by an extra oxygen atom rather than being a consequence of this coordination. Attempts to isolate the caesium 12C4 derivative were unsuccessful. The compounds have been characterized by NMR spectroscopy, CHN microanalysis and, in most cases, X-ray crystallography.     

How alkali metal ion binding alters the conformation preferences of gramicidin A: a molecular dynamics and ion mobility study

Here, we present a systematic study combing electrospray ionization-ion mobility experiments and an enhanced sampling molecular dynamics, specifically integrated tempering sampling molecular dynamics simulations (ITS-MDS), to explore the conformations of alkali metal ion (Na, K, and Cs) adducts of gramicidin A (GA) in vacuo. Folding simulation is performed to obtain inherent conformational preferences of neutral GA to provide insights about how the binding of metal ions influences the intrinsic conformations of GA. The comparison between conformations of neutral GA and alkali metal ion adducts reveals a high degree of structural similarity, especially between neutral GA and [GA + Na](+); however, the structural similarities decrease as ionic radius of the metal increases. Collision cross section (CCS) profiles for [GA + Na](+) and [GA + Cs](+) ions obtained from by ITS-MDS compare favorably with the experimental CCS, but there are significant differences from CCS profiles for [GA + K](+) ions. Such discrepancies between the calculated and measured CCS profiles for [GA + K](+) are discussed in terms of limitations in the simulation force field as well as possible size-dependent coordination of the [GA + K](+) ion complex.     

Development of cation/anion "interaction" scales for ionic liquids through ESI-MS measurements

Electrospray ionization mass spectrometry applied to ionic liquids allowed the study of loosely bonded supramolecules, originating from these organic salts. Based on the observation that ionic liquids formed cationic [C(q+1)X(q)](+) and anionic [C(q)X(q+1)](-) supramolecular aggregates, we have investigated mixed networks, formed by different cations coordinated to a selected anion or by different anions bonded to a given cation, i.e., [C1...X...C2](+) and [X1...C...X2](-), with the aim to build a scale of the cation-anion interaction strength. The qualitative order of intrinsic bond strength to Br- was found to be the following: [emim](+) > [bmim](+) > [mor1,2](+) > [hmim]+ > [omim](+) > [mor1,4](+) > [bupy](+) > [bpyrr](+) > [picol](+) > [bm(2)im](+) > [TBA](+). Similarly, the interaction energies to 1-butyl-3-methylimidazolium (bmim) species envisaged two classes of anions: species tightly coordinated to the cationic moiety that include CF3COO(-), Br(-), N(CN)2(-), and BF4(-) and anions loosely interacting with the alkylimidazolium species such as OTf(-), PF6(-), and Tf2N(-).     

碱金属阳离子对铁卟啉电催化CO2还原的影响

电催化CO2还原反应(CO2RR)可以有效地将温室气体转化为燃料或高附加值的化学品,从而缓解目前人类所面临的环境问题和能源危机,其中开发高效的电催化剂是至关重要的环节.近年来,研究者设计了多种高效的过渡金属配合物(包括Mn,Fe,Co,Ni和Cu)用作CO2RR分子电催化剂,并研究了其中的构效关系,例如,在分子内修饰质子给体取代基或电荷取代基可以显著提高CO2RR的催化效率.而电催化CO2RR的实际应用要在含有碱金属阳离子(例如,Na+和K+)的电解质水溶液中进行,但在已有报道中,很少有关于碱金属阳离子对CO2RR的影响.在众多的分子催化剂中,铁卟啉可以以较高的催化活性和选择性实现CO2到CO的转化.重要的是,卟啉环的刚性结构、稳定的配位环境及其骨架上官能团的易于修饰性成为研究CO2RR的构效关系的理想分子模型.基于以上考虑,本文以铁卟啉配合物为分子模型,研究了碱金属阳离子Na+和K+对电催化CO2RR的影响.首先,本文合成了简单的A4型铁卟啉化合物四-(3,4,5-三甲氧基苯基)-铁卟啉(FeP).并采用核磁共振、质谱分析、单晶衍射等表征手段对化合物进行了表征,在含有电解质的DMF溶液中测试其电催化CO2还原性能.实验结果表明,FeP可以实现高效的电催化CO2还原,催化电流随FeP的浓度呈线性增加,说明催化反应速率与催化剂浓度呈一级反应速率关系.较长时间的恒电压电解实验以及电解前后化合物的紫外-可见光谱证实了FeP的稳定性.通过气相色谱对产物进行分析,CO为主要产物,法拉第效率为95％.以上结果均表明,FeP是一个优良的分子催化剂.在此基础上,本文还发现加入Na+和K+均可以显著提升催化活性,而K+的加入使催化电流的提升更加显著,这可能是由于K+在溶液中的迁移速度比Na+更快.基于此实验现象,本文通过在FeP的第二配位层修饰1-氨-18-冠-6-醚官能团(N18C6),合成了N18C6-FeP化合物.结果表明,由于N18C6与Na+/K+之间的配位作用,使得N18C6-FeP比FeP具有更好的电催化CO2RR活性.研究表明,催化活性的提升归因于碱金属阳离子能够通过静电相互作用稳定Fe-CO2中间体.1H NMR谱证实了N18C6基团的确能够螯合碱金属阳离子.本文研究证明了碱金属阳离子对改善电催化CO2RR的积极作用,对于进一步深入了解CO2RR催化反应机理和未来合理的设计高效催化剂也都具有重要意义.     

Gas phase ion chemistry of charged silver(I) adenine ions via multistage mass spectrometry experiments and DFT calculations

Electrospray ionization (ESI) of solutions containing adenine and AgNO(3) yields polymeric [Ad(x)+ Ag(y)-zH]((y-z)+) species. Density functional theory (DFT) calculations have been used to examine potential structures for several of the smaller ions while multistage mass spectrometry experiments have been used to probe their unimolecular reactivity (via collision-induced dissociation (CID)) and bimolecular reactivity (via ion-molecule reactions with the neutral reagents acetonitrile, methanol, butylamine and pyridine). DFT calculations of neutral adenine tautomers and their silver ion adducts provide insights into the binding modes of adenine. We find that the most stable [Ad + Ag](+) ion does not correspond to the most stable neutral adenine tautomer, consistent with previous studies that have shown that transition metal ions can stabilize rare tautomeric forms of nucleobases. Both the charge and the stoichiometry of the [Ad(x)+ Ag(y)-zH]((y-z)+) complexes play pivotal roles in directing the types of fragmentation and ion-molecule reactions observed. Thus, [Ad(2)+ Ag(2)](2+) is observed to dissociate to [Ad + Ag](+) and to react with butylamine via proton transfer, while [Ad(2)+ Ag(2)- H](+) fragments via loss of neutral adenine to form the [Ad + Ag(2)- H](+) ion and does not undergo proton transfer to butylamine. DFT calculations on several isomeric [Ad(2)+ Ag(2)](2+) ions suggest that planar centrosymmetric cations, in which two adjacent silver atoms are bridged by two N7H adenine tautomers via N(3),N(9)-bidentate interactions, are the most stable. The [Ad + Ag(2)-H](+) ion adds two neutral reagents in ion-molecule reactions, consistent with the presence of two vacant coordination sites. It undergoes a silver atom loss to form the [Ad + Ag - H](+) radical cation, which in turn fragments quite differently to the even electron [Ad + Ag](+) ion. Several other pairs of radical cation/even electron adenine-silver complexes were also found to undergo different fragmentation reactions.     

Differentiation of the diastereomeric synthetic precursors of isofebrifugine and febrifugine by electrospray ionization tandem mass spectrometry

Febrifugine is an alkaloid with potent antimalarial activity isolated from Dichroa febrifuga and Hydrangea umbellate, and it exists naturally with its diastereomeric component, isofebrifugine. Here we report the differentiation of diastereomeric synthetic precursors of isofebrifugine (1, cis) and febrifugine (2, trans) and a structurally similar model diastereomeric pair without a halogen substituent (3 and 4) by electrospray ionization (ESI) tandem mass spectrometry. Compounds 1-4 contain a tert-butoxycarbonyl (BOC) substituent, and the collision-induced dissociation (CID) spectra of the [M+H](+), [M+Na](+) and [M+Li](+) ions of 1-4 include the expected product ions corresponding to the loss of C(4)H(8) (isobutene) and of C(5)H(8)O(2) (BOC-H). Loss of C(5)H(8)O(2) is dominant in cis isomers (1 and 3) and/or loss of C(4)H(8) ions is dominant in trans isomers (2 and 4). The decomposition of [M+H](+) ions shows stereoselectivity in the formation of the [M+H-(BOC-H)-C(3)H(5)OBr](+) and [M+H-(BOC-H)-C(6)H(5)CH(2)OH](+) ions. The [M+Cat](+) ions (where Cat = Na or Li) additionally show loss of NaBr and HBr from [M+Cat-(BOC-H)](+), and these product ions are constantly more abundant in cis isomers than in trans isomers. The stereoselectivity for the product ion corresponding to the loss of [(BOC-H)+C(3)H(5)OBr] from [M+H](+) ions differs from that from [M+Cat](+) ions.     

Tandem electrospray mass spectrometric studies of proton and sodium ion adducts of neutral peptides with modified N- and C-termini: synthetic model peptides and microheterogeneous peptaibol antibiotics

The fragmentations of [M+H]+ and [M+Na]+ adducts of neutral peptides with blocked N- and C-termini have been investigated using electrospray ion trap mass spectrometry. The N-termini of these synthetically designed peptides are blocked with a tertiarybutyloxycarbonyl (Boc) group, and the C-termini are esterified. These peptides do not possess side chains that are capable of complexation and hence the backbone amide units are the sole sites of protonation and metallation. The cleavage patterns of the protonated peptides are strikingly different from those of sodium ion adducts. While the loss of the N-terminal blocking group occurs quite readily in the case of MS/MS of [M+Na]+, the cleavage of the C-terminal methoxy group seems to be a facile process in the case of MS/MS of [M+H]+ * Fragmentation of the protonated adducts yields only bn ions, while yn and a(n) ions are predominantly formed from the fragmentation of sodium ion adducts. The a(n) ions arising from the fragmentation of [M+Na](+) lack the N-terminal Boc group (and are here termed a(n)* ions). MS/MS of [M+Na]+ species also yields b(n) ions of substantially lower intensities that lack the N-terminal Boc group (b(n)*). A similar distinction between the fragmentation patterns of proton and sodium ion adducts is observed in the case of peptides possessing an N-terminal acetyl group. An example of the fragmentation of the H+ and Na+ adducts of a naturally occurring peptaibol from a Trichoderma species confirms that fragmentation of these two ionized species yields complementary information, useful in sequencing natural peptides. Inspection of the isotopic pattern of b(n) ions derived from [M+H]+ adducts of peptaibols provided insights into the sequences of microheterogeneous samples. This study reveals that the combined use of protonated and sodium ion adducts should prove useful in de novo sequencing of peptides, particularly of naturally occurring neutral peptides with modified N- and C-termini, for example, peptaibols.     

Electrospray ionization mass spectrometry of ginsenosides

Ginsenosides R(b1), R(b2), R(c), R(d), R(e), R(f), R(g1), R(g2) and F(11) were studied systematically by electrospray ionization mass spectrometry in positive- and negative-ion modes with a mobile-phase additive, ammonium acetate. In general, ion sensitivities for the ginsenosides were greater in the negative-ion mode, but more structural information on the ginsenosides was obtained in the positive-ion mode. [M + H](+), [M + NH(4)](+), [M + Na](+) and [M + K](+) ions were observed for all of the ginsenosides studied, with the exception of R(f) and F(11), for which [M + NH(4)](+) ions were not observed. The signal intensities of [M + H](+), [M + NH(4)](+), [M + Na](+) and [M + K](+) ions varied with the cone voltage. The highest signal intensities for [M + H](+) and [M + NH(4)](+) ions were obtained at low cone voltage (15-30 V), whereas those for [M + Na](+) and [M + K](+) ions were obtained at relatively high cone voltage (70-90 V). Collision-induced dissociation yielded characteristic positively charged fragment ions at m/z 407, 425 and 443 for (20S)-protopanaxadiol, m/z 405, 423 and 441 for (20S)-protopanaxatriol and m/z 421, 439, 457 and 475 for (24R)-pseudoginsenoside F(11). Ginsenoside types were identified by these characteristic ions and the charged saccharide groups. Glycosidic bond cleavage and elimination of H(2)O were the two major fragmentation pathways observed in the product ion mass spectra of [M + H](+) and [M + NH(4)](+). In the product ion mass spectra of [M - H](-), the major fragmentation route observed was glycosidic bond cleavage. Adduct ions [M + 2AcO + Na](-), [M + AcO](-), [M - CH(2)O + AcO](-), [M + 2AcO](2-), [M - H + AcO](2-) and [M - 2H](2-) were observed at low cone voltage (15-30 V) only.     

Differentiation of diasteromeric α-sulfanyl-β-amino acid derivatives by electrospray ionization tandem mass spectrometry

A set of diastereomeric α-sulfanyl-β-amino acid derivatives, which are important building blocks for pharmaceuticals with potent biological activity, are studied by electrospray ionization tandem mass spectrometry. The collision induced dissociation (CID) spectra of [M+H](+), [M+NH(4)](+), [M+Na](+) and [M+Li](+) of the diastereomers were studied, among them the CID of [M+Na](+) and [M+Li](+) showed consistent differences in the relative abundance of characteristic ions that enabled distinction of the anti isomers from syn isomers. The decomposition pathways for the diagnostic ions were arrived at based on high-resolution mass spectrometry data, multiple mass spectrometry data, deuterium labeling experiments and the mass shift in accordance with the substituents located at different places. Loss of (R(1)-C(6)H(4)-CH=NH) and (Cat-NH-SO(2)R(2)) from [M+Cat](+), where Cat=Na and Li, and the product ions as a results of McLafferty rearrangement involving either >S=O or >C=O group were found to be diagnostic. The McLafferty rearrangement product ions involving >S=O group were more abundant in syn isomers while those involving >C=O group were more abundant in anti isomer. The selectivity observed in the decomposition of [M+Li](+) ions was found to be similar to that of [M+Na](+) ions, but in few cases the differences are marginal in the decomposition [M+Li](+) ions.     

Application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to the structure determination of medium and large macrocycles formed by palladium(0)-catalyzed allylation of arenesulfonamides, sulfamide, and cyanamide

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry allowed the direct determination of the extent of macrocyclic and linear oligomer formation in the palladium(0)-catalyzed allylation of highly acidic and non-nucleophilic arenesulfonamides, sulfamide, and cyanamide. Palladium-containing 15-membered-ring macrocyclic compounds gave unusual [M - H](+) ions besides [M + Na](+) and [M + K](+) adducts. Copyright 1999 John Wiley & Sons, Ltd.     

Analysis of triacetone triperoxide (TATP) and TATP synthetic intermediates by electrospray ionization mass spectrometry

The explosive triacetone triperoxide (TATP) has been analyzed by electrospray ionization mass spectrometry (ESI-MS) on a linear quadrupole instrument, giving a 62.5 ng limit of detection in full scan positive ion mode. In the ESI interface with no applied fragmentor voltage the m/z 245 [TATP + Na](+) ion was observed along with m/z 215 [TATP + Na - C(2)H(6)](+) and 81 [(CH(3))(2)CO + Na](+). When TATP was ionized by ESI with an applied fragmentor voltage of 75 V, ions at m/z 141 [C(4)H(6)O(4) + Na](+) and 172 [C(5)H(9)O(5) + Na](+) were also observed. When the precipitates formed in the synthesis of TATP were analyzed before the reaction was complete, a new series of ions was observed in which the ions were separated by 74 m/z units, with ions occurring at m/z 205, 279, 353, 427, 501, 575, 649 and 723. The series of evenly spaced ions is accounted for as oligomeric acetone carbonyl oxides terminated as hydroperoxides, [HOOC(CH(3))(2){OOC(CH(3))(2)}(n)OOH + Na](+) (n = 1, 2 ... 8). The ESI-MS spectra for this homologous series of oligoperoxides have previously been observed from the ozonolysis of tetramethylethylene at low temperatures. Precipitates from the incomplete reaction mixture, under an applied fragmentor voltage of 100 V in ESI, produced an additional ion observed at m/z 99 [C(2)H(4)O(3) + Na](+), and a set of ions separated by 74 m/z units occurring at m/z 173, 247, 321, 395, 469 and 543, proposed to correspond to [CH(3)CO{OOC(CH(3))(2)}(n)OOH + Na](+) (n = 1,2 ... 5). Support for the assigned structures was obtained through the analysis of both protiated and perdeuterated TATP samples.     

Structural analysis of phosphatidylcholines by post-source decay matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

The utility of post-source decay (PSD) matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was investigated for the structural analysis of phosphatidylcholine (PC). PC did not produce detectable negative molecular ion from MALDI, but positive ions were observed as both [PC+H](+) and [PC+Na](+). The PSD spectra of the protonated PC species contained only one fragment corresponding to the head group (m/z 184), while the sodiated precursors produced many fragment ions, including those derived from the loss of fatty acids. The loss of fatty acid from the C-1 position (sn-1) of the glycerol backbone was favored over the loss of fatty acid from the C-2 position (sn-2). Ions emanating from the fragmentation of the head group (phosphocholine) included [PC+Na-59](+), [PC+Na-183](+) and [PC+Na-205](+), which corresponded to the loss of trimethylamine (TMA), non-sodiated choline phosphate and sodiated choline phosphate, respectively. Other fragments reflecting the structure of the head group were observed at m/z 183, 146 and 86. The difference in the fragmentation patterns for the PSD of [PC+Na](+) compared to [PC+H](+) is attributed to difference in the binding of Na(+) and H(+). While the proton binds to a negatively charged oxygen of the phosphate group, the sodium ion can be associated with several regions of the PC molecule. Hence, in the sodiated PC, intermolecular interaction of the negatively charged oxygen of the phosphate group, along with sodium association at multiple sites, can lead to a complex and characteristic ion fragmentation pattern. The preferential loss of sn-1 fatty acid group could be explained by the formation of an energetically favorable six-member ring intermediate, as apposed to the five-member ring intermediate formed prior to the loss of sn-2 fatty acid group.