bluuebunny/crossref_metadata_2025 huggingface dataset:
Configurational effects on internal proton transfers and ion–neutral complex formation in stereoisomeric 1,4‐di(alkoxymethyl)cyclohexanes on chemical ionization
Authors: Denekamp C. , Mandelbaum A.
Published: May 2005

Cis‐ and trans‐1,4‐dimethyl‐1‐d3‐methoxymethyl‐4‐(2‐methoxy‐2‐propyl)cyclohexane (3a‐c and 3a‐t), the isomeric 1,4‐dimethyl‐1‐methoxymethyl‐4‐(2‐d3‐methoxy‐2‐propyl)cyclohexanes (3b‐c and 3b‐t) and 1,4‐dimethyl‐1‐methoxymethyl‐4‐(2‐d3‐methoxy‐2‐propyl)cyclohexanes (3b‐c and 3b‐t) and 1,4‐dimethyl‐1‐ethoxymethyl‐4‐(2‐methoxy‐2‐propyl)cyclohexanes (3c‐c and 3c‐t) give rise to different isobutane chemical ionization (CI) mass spectra. The cis isomers exhibit abundant [MHROH]+ ions (100%, ROH originating from the tertiary alkoxy group), while no MH+ or [MHR′OH]+ ions (R′OH originating from the primary alkoxyl) were detected in the mass spectra. This behaviour indicates an efficient proton transfer between the two ether functions in the transient MH+ ions of the cis isomers, resulting in the total and exclusive elimination of methanol from the tertiary position. In contrast to the cis diethers, the trans isomers 3a‐t, 3b‐t and 3c‐t afford relatively abundant [MHROH]+ and [MHR′OH]+ ions. This behaviour is consistent with protonation on each of the two distant non‐interacting ether groups, resulting in two isomeric MH+ ions, each of which eliminates the corresponding alcohol. The highly stereospecific behaviour of the cis and trans diethers 3c and 3t is dependent on the presence of the methyl substituents at positions 1 and 4: identical mass spectra were obtained for cis‐ and trans‐1‐ alkoxymethyl‐4‐(2‐alkoxy‐2‐propyl)cyclohexanes (4‐c and 4‐t) (four pairs with different 1‐ and 4‐alkoxy groups), and both stereoisomers exhibit exclusive elimination of ROH originating from the tertiary methoxy group in each pair. The absence of [MHR′OH]+ and MH+ ions in the isobutane CI mass spectra of 4‐t requires proton transfer from the primary OR′ to the tertiary OR group prior to the elimination of ROH, despite the large distance between them in the trans configuration. These results indicate isomerization of the fragmenting MH+ ions of 4‐t to structures which allow a facile proton transfer from the primary the tertiary alkoxyl. The similarity of the mass spectra of 4‐c and 4‐t suggests trans → cis isomerization, which may occur via an ion–neutral complex.
Tandem mass spectrometry of peptides. III—differentiation between leucine and isoleucine based on neutral losses
Authors: Squire Nicole L. , Beranová Šárka , Wesdemiotis Chrys
Published: May 2005

The neutral species generated during the collisionally activated dissociation (CAD) of the protonated dipeptides Ala–Leu, Ala–Ile, Leu–Ala and Ile–Ala are post‐ionized by collision and detected in neutral fragment‐reionization (+NfR+) mass spectra. These spectra are dominated by fragment ions diagnostic for the C‐terminal amino acid, as confirmed by comparison with reference collision‐induced dissociative ionization (CIDI) mass spectra of authentic Ala, Leu and Ile. CIDI of Leu and Ile yields distinct and structurally indicative products. These are also observed upon +NfR+ of [Ala–Leu]H+ and [Ala–Ile]H+, respectively, thus allowing one to deduce the correct sequence. In contrast, [Leu–Ala]H+ and [Ile–Ala]H+, which possess identical C‐termini, form no differentiating neutral losses upon CAD.
Selective enhancement of ion signal of charged surfactant in fast atom bombardment mass spectrometry
Authors: Chen Yu‐Chie , Shiea Jentaie
Published: May 2005

The addition of sodium dodecylsulfate (SDS) to a glycerol solution containing equal concentrations of a series of quaternary amines has been found to have a significant effect on the relative fast atom bombardment (FAB) response factors for each analyte. The relative FAB signals of quaternary amines with different alkly chain length were found to be either enhanced or degraded under different SDS concentrations. The effect observed can be correlated with the difference in the rate of ion‐pair precipitate formation between negatively charged dodecylsulfate and positively charged quaternary amine. It is also demonstrated that, in much the same way, SDS can be used to enhance the response of the less surface‐active component in an industrial dye by FAB analysis.
Origin of [M + H]+ ions in electron impact mass spectra of tertiary nitrosonitriles
Authors: Grela Karol , Konopski Leszek
Published: May 2005

The presence of [M + H]+ ions was observed in the electron impact mass spectra of the series of dimers of aliphatic tertiary β‐, γ‐ and δ‐nitrosonitriles. Neither M+· nor [M + H]+ ions are observed in the spectra of α‐nitrosonitriles or after introduction of voluminous substituents into the molecule, so the geometric factor is very important. It was found that this effect was probably due to the rearrangement of the hydrogen atom in the fragmentation pattern of the dimer molecular ions 2M+· of β‐ and δ‐nitrosonitriles. Aliphatic nitrosocompounds exist even in the gas phase in equilibrium with their dimers. The existence of dimers was confirmed by the presence of the [2M + H]+· ion in the liquid secondary ion mass spectrum of a γ‐nitrosonitrile. Using deuterium labelling, as distinct to the nitrosoketones and esters, it was unexpectedly found that the origin of hydrogen in the [M + H]+ ions was the methyl groups in the position vicinal to the tertiary nitroso group (CH3)2C(NO)R.
Stable isotope labelling and quantitative determination of enalaprilate in human plasma by GC–NICI–MS
Authors: Leis H. J. , Gleispach H. , Windischhofer W.
Published: May 2005

A method for the quantitative determination of enalaprilate, the active metabolite of the angiotensin‐converting enzyme inhibitor enalapril, is presented. The asay is based on gas chromatography–negative ion chemical ionization–mass spectrometry. The preparation of 18O4‐labelled enalaprilate for use as an internal standard is described. The method involves solid phase extraction and derivation to the pentafluorobenzyl diester–trifluoroacetamide derivatives. The detection limit was found to be 0.5 pg, and a lower limit of quantitation was reached down to 40 pg ml−1 plasma. The method was applied to pharmacokinetics of the metabolite in humans.
Thermospray liquid chromatography–mass spectrometry of the DNA adducts formed between 2′‐deoxynucleosides and bisphenol A diglycidyl ether
Authors: Vanhoutte K. , Joos P. , Lemière F. , Van Dongen W. , Esmans E. L. , Claeys M. , Van den Eeckhout E.
Published: May 2005

The adducts formed between 2′‐deoxyadenosine (dAdo), 2′‐deoxycytidine (dCyd), 2′‐deoxycytidine (dUrd), 2′‐deoxyguanosine (dGuo) and bisphenol A diglycidyl ether (BPADGE) were analysed by high‐performance liquid chromatography (HPLC) and thermospray liquid chromatography–mass spectrometry. An HPLC method was developed using a 5RP8 select B column (125 × 4 mm i.d.) and a mobile phase of MeOH/0.1 M NH4OAc at a flow‐rate of 0.8 ml min−1. A sample enrichment procedure using solid phase extraction was developed and was found to result in an enrichment factor with a mean value of 9. Mono‐adducts were characterized by intense [BH + H]+, [BH + Na]+ and [S]+ ion signals. Imidazole ring opening was observed for the BPADGE/dGuo adduct indicating that the alkylation occurs at N‐7. The alkylation site in the BPADGE/dCyd adduct was assigned to N‐3 because a hydrolytic deamination reaction was observed leading to the BPADGE/dUrd adduct. Crosslinking was not observed.
Matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) of membrane proteins and non‐covalent complexes
Authors: Rosinke Burkhard , Strupat Kerstin , Hillenkamp Franz , Rosenbusch Jürg , Dencher Norbert , Krüger Ulrike , Galla Hans‐Joachim
Published: May 2005

Matrix‐assisted laser desorption/ionization (MALDI) mass spectra and methods to improve their quality are reported for three hydrophobic, membrane‐bound proteins: porin from Escherichia coli, bacteriorhodopsin from Halobacterium salinarium and cholesterolesterase from Pseudomonas fluorescens. Several commonly used UV and IR matrices have been tested. In addition, the susceptibility of MALDI mass spectrometry to various neutral and ionic detergents, known usually to degrade the quality of MALDI mass spectra, has been tested systematically. For porin, consisting of three identical non‐covalently bound subunits, a new sample preparation is reported, resulting in the desorption of the intact quaternary protein structure. This leads to a better understanding of the way a given analyte is embedded into the host matrix crystals.
Simultaneous quantification of cyclosporin A and its major metabolites by time‐of‐flight secondary‐ion mass spectrometry and matrix‐assisted laser desorption/ionization mass spectrometry utilizing data analysis techniques: Comparison with high‐performance liquid chromatography
Authors: Muddiman David C. , Gusev Arkady I. , Karl‐Stoppek‐Langner  , Proctor Andrew , Hercules David M. , Tata Prasad , Venkataramanan Raman , Diven Warren
Published: May 2005

Simultaneous quantification of cyclosporin A (CsA) and its major metabolite (AM1) in blood has been achieved using time‐of‐flight secondary‐ion mass spectrometry (TOF‐SIMS) and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI/TOF‐MS). Previous investigations indicated that spectral interferences exist in the analysis of CsA blood samples by the above methods. In TOF‐SIMS, interference is caused by overlap of the Ag‐cationized internal standard, cyclosporin D (CsD), with the Ag‐cationized metabolite, AM1. To resolve this interference and obtain quantitative information, cross‐correlation analysis was applied to the TOF‐SIMS data. Application of damped non‐linear least squares curve‐fitting was carried out to resolve an interference in the MALDI/TOF‐MS data due to multiple cationization products (i.e. Na and K). Measurement of standard samples indicates that the minimum accuracy (95% confidence level) of the TOF‐SIMS method was better than 9% for CsA and 13% for AM1 using only one standard curve'. Similarly, the minimum accuracy of the MALDI/TOF‐MS method was determined to be 14% for CsA and better than 25% for AM1. Blood samples obtained from transplant patients receiving CsA were analyzed by polyclonal fluorescence polarization immunoassay, high‐performance liquid chromatography (HPLC), and by both TOF‐MS methods. Both TOF‐MS results for CsA and mono‐hydroxylated CsA are in good agreement with the HPLC results.
Electron capture negative chemical ionization mass spectrometry and tandem mass spectrometry analysis of β‐carotene, α‐tocopherol and their oxidation products
Authors: McClure Thomas D. , Liebler Daniel C.
Published: May 2005

The biological antioxidants α‐tocopherol, 1, and β‐carotene, 4, and products of their antioxidant reactions are potentially important indicators of biological antioxidant status and functions. Electron capture by compounds 1 and 4 and their oxidation products yields intense molecular anions with little fragmentation. Collision‐induced dissociation of the molecular anions was studied by linked‐scaning (B/E = constant) on a reverse‐geometry magnetic‐sector mass spectrometer. Both 1 and 4 and their products undergo extensive diagnostic cleavages of their hydrocarbon chains, apparently via charge‐remote fragmentation. Electron capture negative chemical ionization mass spectrometry appears uniquely suited to structure identification studies of antioxidants and their oxidation products. This methodology is used to identify oxidation products of 1 and 4 from a model biological membrane system subjected to peroxyl radical attack.
Liquid chromatography/fast atom bombardment and electrospray ionization mass spectrometry of gibberellin A3 1,2‐trans‐glycosyl esters
Authors: Schneider Gernot , Schmidt Jürgen , Moritz Thomas
Published: May 2005

The glucosyl ester (2b), the galactosyl ester (3b), the xylosyl ester (4b) and the arabinosyl ester (5b) of gibberellin A3 (GA3) as well as the glucosyl ester (7b) and the xylosyl ester (8b) of isoGA3 were synthesized and their structures confirmed especially by 1H nuclear magnetic resonance. In order to identify such conjugates in nature, the glycosyl esters 2b, 3b, 4b, 5b, 7b and 8b were subjected to mass spectrometry analysis using fast atom bombardment and electrospray ionization techniques. The spectra obtained from both negative and positive ions were compared and interpreted on the basis of tandem mass spectrometry experiments. The differences between the fragmentation of GA3 glycosyl ester and that of isoGA3 glucosyl ester are discussed. Diagnostic ions were evaluated, which should be useful for the identification of these conjugates by liquid chromatography/mass spectrometry.
Mass spectrometric and theoretical determination of polynuclear aromatic hydrocarbon proton affinities
Authors: Trouk‐Pointet Karine , Milliet Arielle , Renou‐Gonnord Marie‐France
Published: May 2005

Proton affinities (PAs) in the gas phase have been calculated for a series of polynuclear aromatic hydrocarbons by MOPAC 6.0 using AM1 and PM3 Hamiltonians and compared to the experimental values published in the literature. A correlation between PAs and the reactional competition leading to the respective formation of the molecular ion and the protonated molecular ion under ammonia positive‐ion chemical ionization (PICI) has been demonstrated. A method for estimating PAs from ion abundances in the ammonia PICI mass spectra is proposed.
Characterization of metabolites of Δ8,9‐dehydroestrone in dogs
Authors: Chandrasekaran A. , Osman M. , Raveendranath P. , Chan K. , Scatina J. A. , Sisenwine S. F.
Published: May 2005

Δ8,9‐Dehydroestrone is the fifth most abundant component in the conjugated equine estrogen preparation Premarin®, representing about 2 to 6% of the total steroids in the tablet. The metabolism of this estrogen has been determined in female beagle dogs after acute peroral administration. 17β‐Dihydro‐Δ8,9‐dehydroestrone(17β‐Δ8,9‐dehydroestradiol) and 17α‐dihydro‐Δ8,9dehydroestrone(17α‐Δ8,9‐dehydroestradiol) have been identified as the major metabolites in plasma and urine. These metabolites, along with the unchanged drug, were isolated and purified by ether extraction and thin‐layer chromatography of the urine samples after enzyme hydrolysis. The trimethylsilyl ether derivatives of the isolated metabolites were characterized by comparison of their mass spectra and chromatographic properties with those of synthetic reference standards.
Special feature: Tutorial. Principles and instrumentation in time‐of‐flight mass spectrometry. Physical and instrumental concepts
Authors: Guilhaus Michael
Published: May 2005

The principles of time‐of‐flight mass spectrometry (TOFMS) are described with a view to understanding the strengths and weaknesses of this method of mass analysis in the context of current applications of mass spectrometry and the more familiar scanning instruments. Fundamental and instrumental factors affecting resolving power, sensitivity and speed are examined. Methods of gating ion populations and the special requirements in the detection and digitisation of the signals in the TOFMS experiment are discussed.
The role of the CC double bond in alcohol elimination from MH+ ions of unsaturated bicyclic esters upon chemical ionization
Authors: Khaselev N. , Mandelbaum A.
Published: May 2005

Methyl and ethyl endo‐ and exo‐bicyclo [2.2.2] oct‐5‐ene‐2‐carboxylates exhibit different mass spectral behaviour under i‐Bu‐chemical ionization (CI) conditions and upon collision‐induced dissociation (CID) of their MH+ IONS. The endo‐esters exhibit m/z 135 [MH  MeOH]+ and [MH  EtOH]+ ions, which are absent in the i‐Bu‐CI mass spectra of the exo‐isomers. This stereospecific behavior is explained in terms of the proton bridging requirement in the alcohol elimination from MH+ ions of esters. Such proton bridging between the alkoxycarbonyl group and the double bond is possible in the endo‐esters, but not in the exo‐isomers. Hydrogen‐deuterium exchange processes, observed in the CID spectra of the MD+ ion of the endo‐esters, support the proposed mechanistic pathway. Hydrogen bridging with the double bond also plays a role in the alcohol elimination processes of stereoisomeric bicyclo [2.2.2] oct‐5‐ene‐2,3‐dicarboxylates.
Energy resolved mass spectrometry of diethyl alkyl phosphonates with an atmospheric pressure ionization tandem mass spectrometer
Authors: Wensing Michael W. , Snyder A. Peter , Harden Charles S.
Published: May 2005

Energy resolved mass spectrometry (ERMS) was used to characterize the dissociation processes of four diethyl alkyl phosphonates where the alkyl R group attached to the central phosphorus atom ranged from methyl to n‐butyl. An atmospheric pressure ionization triple quadrupole mass spectrometer was used in the analyses. Dissociation of the MH+ and further dissociation of the resulting progeny ions was induced between the atmospheric—vacuum sampling orifice and the first ion focusing RF‐only quadrupole, Q0, instead of the central Q2 quadrupole. The major dissociation pathways of the four phosphonates could be characterized by two sequential McLafferty rearrangements yielding an alkyl phosphonic acid. This acid further dissociated losing H2O followed by ROH to produce PO+, or the same process occurred but in the reverse order, i.e. first losing ROH followed by H2O to yield PO+. The latter process was the energetically favored process. The alkyl group attached to the phosphorus atom of the protonated alkyl phosphonic acid was observed to have a significant influence on the stability of the protonated alkyl phosphonic acid. As the R group increased in size with a concomitant increase in electron‐donating power, the alkyl phosphonic acid was less prone to dissociation than other alkyl phosphonic acids which possessed smaller R groups. A significant difference was also noted in the alkyl phosphonic acid dissociation processes; methyl phosphonic acid dissociated predominantly via H2O loss unlike the other acids which favored the loss of ROH over H2O.
Liquid chromatography–electrospray tandem mass spectrometry of dansylated polyamines and basic amino acids
Authors: Feistner Gottfried J.
Published: May 2005

Liquid chromatogrpahy‐electrospray tandem mass spectrometry allows identification of dansylated basic amino acids and polyamines with a high degree of specificity, including unambiguous acid and 2 hydroxycadaverine, and N1‐ and N8‐acetylspermidine. In favorable cases, characteristic fragmentation mechanisms permit identification even in the absence of authentic reference compounds. The method readily identified acetyldiaminopropane, citrul‐line, and diacetylspermine as metabolic products of Erwinia amylovora.
The isomers of ionized dimethyl sulfoxide (C2H6OS+·) and their CH3OS+ fragments. An ab initio and multiple‐stage mass spectrometric (MSn) study
Authors: Gozzo Fábio Cesar , Eberlin Marcos N.
Published: May 2005

The relative stabilities, isomerizations and dissociations of ionized dimethyl sulfoxide (DMSO), its three C2H6OS+· isomers and of all their 14 conceivable CH3OS+ fragments (1–14), have been investigated by ab initio calculations at the MP2/6–31G(d,p)//6–31G(d,p) + ZPE and G2 levels of theory, and by multiple‐stage two‐ and three‐dimensional mass spectrometry performed in a pentaquadrupole instrument. The ab initio relative energies of the isomers, their connecting transition states, and their dissociation thresholds were used to elaborate potential energy surface diagrams that precisely corroborate and unify several previously divergent experimental observations on these systems. The most kinetically favorable isomerization of (CH3)2SO+· (I) to its aci‐form CH2S(OH)CH (II) displays a transition state considerably lower in energy than the threshold for its direct dissociation by CH3⋅ loss. Therefore, low‐energy, long‐lived metastable ions I are predicted to isomerize to II, and to dissociate in turn to CH2S+OH (2) upon CH3⋅ loss. Ions I excited a few electronvolts above the threshold are, on the other hand, predicted to dissociate directly to CH3S+O (1). Isomerization of I to the most stable C2H6OS+· ion, that is CH3SOCH (III), displays the most energetic transition state and should be negligible, whereas III is predicted to dissociate by CH3⋅ loss preferentially to 1 rather than 5 (CH3OS+). Nine CH3OS+ isomers, that is 1, 2, (HCS…OH2)+ (3), +CH2S(O)H (4), 5, HC(SH)OH+ (9), CH2OSH+ (10), CH2+OSH (11), and (HCO…SH2)+ (14), were found as true minima on the RHF/6–31G(d,p) potential‐energy surface, and some of their isomerization barriers and dissociation thresholds were estimated. Tandem and multiple‐stage (MS3) mass spectrometric experiments show that non‐dissociating DMSO+· ions produce, upon collision‐induced dissociation (CID), a mixture of approximately 40% of 1 and 60% of 2, whereas the CID chemistry of 1 and 2 is affected considerably by the collision energies employed. Both the experimental and theoretical results on 1 and 2 allow a detailed interpretation of their complex dissociation chemistry, which clarifies the nature of most of their indirect fragments. Such fragments are proposed to be formed via the common isomerization/dissociation sequences 1 → 2 → 9 ⇌ 3 → HCS+ (m/z 45) + H2O, and 1 → 2 → [7, HOCH2S+] → S + CH2OH+ (m/z 31). These processes are favored at lower collision energies, whereas direct dissociation of 1 to CH3+ (m/z 15) and SO+· (m/z 48), and of 2 to CH2S+· (m/z 46) occurs to greater extents at higher collision energies.
A method for counting disulfide bridges in small proteins by reduction with mercaptoethanol and electrospray mass spectrometry
Authors: Svoboda M. , Meister W. , Vetter W.
Published: May 2005

A simple and rapid method for counting the number of internal disulfide bridges in a protein by incubation with 2‐mercaptoethanol and electrospray mass spectrometry analysis of the products was developed. 2‐Mercaptoethanol yields intermediate mixed disulfides during reduction of a protein. This results in a molecular weight increase of the protein by 78 Da per disulfide bond, which can easily be determined by electrospray mass spectrometry (ESMS). The number of mercaptoethanol adducts observed by ESMS reveals the number of disulfide bridges in the peptide or protein. Since the protein–mercaptoethanol–disulfide bonds are themselves further reduced by excess mercaptoethanol, the course of the reaction has to be followed in order to detect the maximum number of intermediates. Owing to the volatility of mercaptoethanol, samples can be taken out of the reaction solution for MS analysis without prior purification. Successful experiments were carried out using proteins with one, two, four or six SS‐bonds, covering a mass range from about 1 to over 23 kDa.
Electron impact ionization and fast atom bombardment mass spectrometry of some 3,3‐dimethyl‐1‐(isoxazol‐3‐yl)triazenes, a new class of potential anticancer agents
Authors: Orsatti Laura , Seraglia Roberta , Traldi Pietro , Diamantini Giuseppe , Tarzia Giorgio , Tontini Andrea
Published: May 2005

A series of 3,3‐dimethyl‐1‐(isoxazol‐3‐yl)triazenes, potential anticancer agents, were studied by electron impact (EI) ionization and fast atom bombardment mass spectrometry. Their behaviour was compared with that of dacarbazine, 5‐(3,3‐dimethyl‐1‐triazenyl)‐(1H)‐imidazole‐4‐carboxamide, which is employed in the treatment of several neoplastic conditions. An interesting EI‐generated decomposition pathway was observed, consisting in the primary formation of [NH2CH3]+ cations, involved in the metabolic pathway of triazenes, as the alkylating agent responsible for the anticancer properties of the drug. A higher thermodynamic stability of the examined compounds than decarbazine was observed, which reasonably reflects the higher chemical stability.
Negative‐ion mass spectrometry of sulfonylurea herbicides
Authors: Winnik Witold , Brumley William , Betowski Leon
Published: May 2005

Sulfonylurea herbicides have been studied using negative‐ion desorption chemical ionization (DCI) mass spectrometry (MS) and DCI‐MS/MS techniques. Both [M  H]− and M−· ions were observed in the DCI mass spectra. The collisionally activated dissociation (CAD) spectra were characteristic of the structure of the herbicides examined. The fragmentation pattern was established based on the tandem mass spectra of the in situ deuterated sulfonylureas and on the comparison of the CAD spectra of sulfonylurea fragment ions with the CAD spectra of the ions derived from saccharin (o‐benzoic sulfimide) and methyl 2‐(aminosulfonyl)benzoate.
Investigation of doubly charged organic cations by electrospray ion cyclotron resonance mass spectrometry
Authors: Katritzky Alan R. , Shipkova Petia A. , Burton Richard D. , Allin Steven M. , Watson Clifford H. , Eyler John R.
Published: May 2005

The production and detection of doubly charged organic cations were studied using a previously unreported approach—electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry. Owing to its ultra‐high mass resolution, accurate and stable mass calibration, multiple stages of collisionally activated dissociation (CAD) allowing tandem mass spectrometry and extremely long ion storage times (> 1 min), this technique has proven to be a powerful method for the detection and study of doubly charged organic compounds. CAD studies were used for the identification of ion–molecule reactions and for the investigation of the propensity towards gas‐phase SN1 and SN2 reaction pathways. To date exclusively SN1‐type reactions in the gas phase have been detected. Three doubly charged pyridinium salts were chosen as model compounds for this study.
A micromethod for the measurement of deuterium bound to carbon‐6 of glucose to quantify gluconeogenesis in vivo
Authors: Kalhan Satish C. , Trivedi Roopa , Singh Sheila , Chandramouli Visvanathan , Schumann William C. , Landau Bernard R.
Published: May 2005

A method to measure the enrichment of deuterium in the hydrogens bound to C‐6 of glucose has been refined and taken to the micro‐scale. Glucose (≤0.2 mg) in small quantities of plasma samples is oxidized with sodium periodate. The formaldehyde formed contains the two hydrogens bound to C‐6 of glucose. The formaldehyde is condensed with ammonia to form hexamethylenetetramine (HMT), which can be directly determined by gas chromatography/mass spectrometry. All of the 12 hydrogens of HMT are from the formaldehyde and therefore deuterium enrichment as low as 0.1% on hydrogens bound to C‐6 of glucose can be measured with a coefficient of variation of less than 3%. The method can be used to quantify gluconeogenesis in vivo in humans by administering [2H2]O at an enrichment in total body water of only 0.5%, resulting in reproducibly measurable labeling of the hydrogens bound to C‐6 of glucose. The method is presented because of its potential value for the measurement of gluconeogenesis in humans in vivo at safe and acceptable doses of [2H2]O.
Linearized dipolar excitation and detection and quadrupolarized axialization in a cylindrical ion cyclotron resonance ion trap
Authors: Guan Shenheng , Huang Yulin , Marshall Alan G.
Published: May 2005

Although cylindrical Penning ion traps are commonly used in atomic physics and in Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICRMS or FTMS), such traps offer far from ideal dipolar excitation/detection and azimuthal quadrupolar axialization performance. Here it is shown that by applying r.f. voltages of just two (± V0) or three (0, ± V0) different amplitudes to appropriately spaced electrode segments, a cylindrical trap can produce nearly linear dipolar excitation/detection and nearly azimuthal quadrupolar excitation for ion axialization. Moreover, voltages are applied directly, rather than through a complex resistive or capacitive voltage dividing network as in prior designs. Advantages of the present design are confirmed by potential simulations and signal harmonic analysis.
Isolation and mass spectrometric characterization of an oxidized form of vasostatin I, an N‐terminal chromogranin A‐derived protein, from bovine chromaffin cells
Authors: Dillen L. , Zhang X. Y. , Claeys M. , Liang F. , De Potter W. P. , Van Dongen W. , Esmans E. L.
Published: May 2005

An N‐terminal proteolytic processing product of chromogranin A was obtained from bovine chromaffin granules using two steps of C18 solid‐phase extraction and reversed‐phase high‐performance liquid chromatography. Electrospray mass spectrometry revealed a protein with a molecular mass of 8632.0 for the fraction showing immunoreactivity against the N‐terminus of chromogranin A, which differed by 48 u from that of the N‐terminal processing product, vasostatin I (CGA1−76). Derivatization with mercaptoethanol showed that the peptide had an intact SS bridge, which is a key structural feature of vasostatin I. Peptide mapping experiments involving reduction/alkylation with vinylpyridine and trypsin digestion were consistent with oxidation of the three methionine residues of vasostatin I to their sulphoxide forms. The oxidation of the methionine residues was found to occur during the C18 solid‐phase extraction procedure. The use of freshly prepared Tris–HCl buffer and eluents and flushing the buffer and eluents with nitrogen were shown to result in the isolation of the non‐oxidized form of vasostatin I.
Gas‐phase complexes of amino acids with Cu(II) and diimine ligands. Part I. Aliphatic and aromatic amino acids
Authors: Gatlin Christine L. , Tureček František , Vaisar Tomáš
Published: May 2005

Gas‐phase complexes of Cu(II) with aliphatic and aromatic α‐amino acids (AA) and diimine ligands, 2,2′‐bipyridyl (bpy) and phenanthroline (phen) are obtained by electrospray ionization of their aqueous‐methanol solutions. The amino acids are found to bind to Cu(II) by their COO− and amino groups in the gas‐phase complexes. The [Cu(II)(AA – H)(bpy)]+· complexes (M+·) show distinct dissociations upon collisional activation. Decarboxylation produces stable (M – CO2)+· ions containing α‐amino alkyl residues coordinated to copper. Further dissociations of radicals derived from aliphatic amino acids involve fission of the CβCγ bond in the alkyl chain that reveals its branching. Leucine and isoleucine are readily distinguished by their different dissociation products. Complexes of aromatic amino acids undergo facile amine group transfer on to copper. Electron distributions in several copper complexes were obtained by ab initio calculations and used to discuss the dissociation products formed from gas‐phase [Cu(II)(AA – H)(bpy)]+· ions.
Gas‐phase complexes of amino acids with Cu(II) and diimine ligands. Part II. Amino acids with O, N and S functional groups in the side‐chain
Authors: Gatlin Christine L. , Tureček Frantiček , Vaisar Tomáš
Published: May 2005

Ternary complexes of amino acids, Cu(II) and diimine ligand 2,2′‐bipyridyl (bpy) are obtained in the gas phase by electrospray ionization (ESI). The amino acids are found to bind to Cu(II) by their deprotonated carboxylate groups in the gas‐phase complexes. Collisionally activated dissociations at low ion kinetic energies of the [Cu(II)(AA – H)(bpy)]+· complexes show decarboxylation followed by cleavages of the amino acid side‐chains that reveal interactions with the Cu atom of the side‐chain functional groups. Hydroxy, sulfide and disulfide groups are transferred on to the Cu atom following collisional activation, but do not displace the bpy ligand. The side‐chain functional groups and the CβH2CαHNH2 fragment are found to compete for coordination to Cu(bpy)+ in the products. The ε‐amino group in lysine and the guanidyl group in arginine displace the bpy ligand following decarboxylation. The fragmentations of the gas‐phase [Cu(II)(AA – H)(bpy)]+· complexes are highly specific for the amino acid residues. Arginine and lysine also form doubly charged ions by ESI that distinguish lysine from the isobaric glutamine.
Negative‐ion fast atom bombardment and tandem mass spectrometric investigation of phenylpropanoid glycosides isolated from Polygonum pensylvanicum L.
Authors: Sneden A. T. , Zimmermann M. L. , Sumpter T. L.
Published: May 2005

Investigation of the novel phenylpropanoid sucrose esters vanicoside A, vanicoside B and hydropiperoside, derived from Polygonum pensylvanicum L., by negative‐ion fast atom bombardment and tandem mass spectrometry has elucidated collision‐induced decomposition pathways and identified common trends of fragmentation for this class of compounds. The constant neutral loss spectrum of the crude extract of P. pensylvanicum, monitoring the loss of a p‐coumaryl ketene fragment, can be used to identify homologues in the mixture for further investigation. This information can be used to characterize mixtures of this type of compound without the need for derivatization and prior to chromatographic separation, providing a method for guiding the isolation of similar compounds from crude extracts of other plants in the Polygonaceae family.
Gas‐phase nucleophilic displacement reactions
Authors: Olmstead William N. , Brauman John I.
Published: May 2005

Displacement reactions of each of a variety of anionic nucleophiles reacting with each of a variety of neutrals have been studied by pulsed ion cyclotron resonance (ICR) spectroscopy. Rate constants for these reactions are interpreted in terms of a three‐step reaction sequence. RRKM calculations are used to obtain information about the energy of transition states. The origin of the barrier to reaction in solution is discussed.
Assignment of the ions in the electrospray ionization mass spectra of the tryptic digest of the non‐derivatized globin, covering the whole sequence of α‐ and β‐chains: A rapid diagnosis for haemoglobinopathy
Authors: Nakanishi Toyofumi , Kishikawa Masahiko , Shimizu Akira , Hayashi Akira , Inoue Fumio
Published: May 2005

For the rapid and simple identification of haemoglobin variants, tryptic peptides prepared by digestion of the mixture of normal and variant subunits were analysed by electrospray ionization mass spectrometry (ESI‐MS). The globin was not reduced and alkylated. In a single spectrum from the ESI analysis of tryptic digests from normal adult globin, nearly 90 significant peaks were observed. Many of these peaks had the right mass and yielded tandem mass spectra of sufficient quality to define the sequence. Some ion peaks were assigned mainly by mass values with additional indirect evidence. A series of multiply charged ions were observed and these ions were valuable for making the assignments. Ion peaks which were assigned with some degree of certainty covered whole sequence from α‐and β‐subunits. In addition to the normal ion peaks, variant ion peaks were observed in the analysis of tryptic peptides of the non‐derivatized globin mixture from Hb SC double heterozygote and from Hb MBoston heterozygote. This approach will offer routine methods in clinical laboratories.
Simultaneous determination of thromboxane B2, prostaglandin E2 and leukotriene B4 in whole blood by liquid chromatography/mass spectrometry
Authors: Oda Yoshiya , Mano Nariyasu , Asakawa Naoki
Published: May 2005

Thromboxane B2, prostaglandin E2 and leukotriene B4 were simultaneously extracted from human whole blood without any time‐consuming evaporation or derivatization process, and directly determined by liquid chromatography/ionspray mass spectrometry. In order to obtain high sensitivity and specificity, the chromatographic and mass spectrometric conditions were optimized. Use of the turbo ionspray method plus a microbore column gave excellent sensitivity. A special column‐switching technique allowed the injection of large sample volumes with minimum band broadening. The calibration graphs were linear from a few tens of pg ml−1 to 10 ng ml−1. This simple and rapid method was validated using human whole blood samples to which known amounts of standards had been added. Because the levels of these mediators in biological samples are elevated in some diseases or owing to stimulants, this method is very useful for determining them in such cases.
Site‐specific analysis of the N‐glycans on murine polymeric immunoglobulin A using liquid chromatography/electrospray mass spectrometry
Authors: Kragten Eddy A. , Bergwerff Aldert A. , van Oostrum Jan , Müller Dieter R. , Richter Wilhelm J.
Published: May 2005

The site‐specific distribution of oligosaccharides on murine polymeric immunoglobulin A (pIgA) consisting of two or more immunoglobulin A (IgA) antibodies connected through J‐chain was analysed by liquid chromatography/electrospray mass spectrometry. Glycopeptides from pIgA were localized in a reversed‐phase tryptic peptide chromatogram by collision excitation scanning and their amino acid sequences determined by electrospray tandem mass spectrometry and Edman degradation. Two glycosylation sites on IgA and a single glycosylation site on J‐chain were identified. Using biosynthetic constraints on carbohydrate structures, molecular mass information on the glycan moieties of the glycopeptides was translated into specific carbohydrate structure proposals. The glycopeptide incorporating the single glycosylation site at Asn49 in J‐chain carried fucosylated and non‐fucosylated di‐and triantennary N‐acetyllactosamine type carbohydrate chains terminated by N‐acetyl‐ and/or N‐glycolylneuraminic acid residues. The glycosylation site in the IgA heavy chain at Asn446 contained two oligomannose‐type carbohydrate chains, one carrying five and the other six mannose residues. To the other glycosylation site in the IgA heavy chain at Asn155 one oligomannose structure, hybrid structures with the lactosamine branch terminated by either an additional galactose residue, N‐glycolylneuraminic acid or N‐acetylneuraminic acid, and non‐fucosylated N‐acetyllactosamine‐type structures carrying the same terminating residues were attached. This glycosylation site was present in two separate glycopeptides differing only in their degree of carboxymethylation and yielding identical oligosaccharide distributions, thus providing additional confidence in the assignment method.
A gas chromatographic/electron impact mass spectrometric method for the isolation and derivatization of plasma taurine for use in stable isotope tracer kinetic studies
Authors: Marks L. , Iglicki F. , Rakotoambinina B. , Thuillier F. , Messing B.
Published: May 2005

To aid in the understanding of the human requirement for 2‐aminoethanesulphonic acid (taurine), a method was developed for the analysis of plasma taurine and used for preliminary studies of the kinetics of plasma taurine in three healthy adult volunteers. A gas chromatographic/electron impact mass spectrometric (GC/EIMS) stable isotope ratio method was developed for the measurement of enrichment of the tracer [1,2‐13C2] taurine in plasma. Natural abundance taurine and [1,2‐13C2] taurine were analysed as their N‐pentafluorobenzoyldi‐n‐butylamide (PFB‐dBA) derivatives by GC/EIMS. With the addition of an internal standard, methyltaurine, the taurine concentration could also be measured. After an overnight fast, three healthy adult human subjects were given an intravenous priming dose of [1,2‐13C2] taurine (3 μmol kg−1), which was immediately followed by a continuous infusion of the tracer (3 μmol kg−1 h−1) for 6 h. The mean plasma plateau enrichment was 8.07 ± 0.46 mol% excess (RSD = 5.67%) and a rate of appearance of 34 ± 2.23 μmol kg−1 h−1 was calculated. The plasma taurine concentration was found to be 56 ± 14 μmol l−1. This technique for the assessment of plasma taurine kinetics should enhance the understanding of taurine metabolism as it could be a conditionally essential amino acid in man.
Combined experimental and computational study of the double ionization of ethylamine, propylamine and butylamine to triplet electronic states of their dications
Authors: Andrews Stuart R. , Parry David E. , Harris Frank M.
Published: May 2005

Vertical double‐ionization energies of ethylamine, propylamine and butylamine molecules to triplet electronic states of their dications were measured by double‐charge‐transfer spectroscopy. The energies to the lowest states of the dications were calculated using an ab initio method with four basis sets. The calculated values predicted fairly well the reduction in the lowest energy observed when the length of the substituted alkyl group increased. Double‐ionization energies to the lowest and higher lying triplet states of the dications were calculated by application of a semi‐empirical form of the multiple scattering Xα method. Even though several spectral peaks may only be identified with transitions to groups of closely lying states, the calculated data gave an insight into the electronic transitions which take place to give the double‐charge‐transfer spectra.
Electron impact‐promoted fragmentation of some substituted 4‐quinazolones
Authors: Badr M. Z. A. , Hammerum Steen , Duffield A. M.
Published: May 2005

Low‐resolution mass spectra, and where appropriate complete high‐resolution mass spectra, were recorded for 29 2,3‐disubstituted 4‐quinazolones. Rationalizations are presented for the principal fragmentation modes of this series of aromatic compounds. Four of the 4‐quinazolones which contain a vinyl‐2‐furanyl group attached to C‐2 of the heterocyclic ring exhibited an unusual loss of C3H2O from their respective molecular ions.
Determination of O‐(chloroacetylcarbamoyl)fumagillol (TNP‐470; AGM‐1470) and two metabolites in plasma by high‐performance liquid chromatography/mass spectrometry with atmospheric pressure chemical ionization
Authors: Moore Jeff D. , Sommadossi Jean‐Pierre
Published: May 2005

High performance liquid chromatography/mass spectrometry using a heat nebulizer atmospheric pressure chemical ionization interface was investigated as a sensitive and selective technique for the chromatographic separation and quantitation of the anti‐angiogenic drug TNP‐470 and its polar metabolites MII and MIV. Upon extraction from plasma, the analytes were measured using selected‐ion monitoring in the positive ionization mode and single quadrapole mass spectrometric detection. A trideuterated 13C‐labeled analog of TNP‐470 was used as an internal standard. Two plasma extraction procedures were evaluated. An acetonitrile precipitation method resulted in a recovery of 65.9% and 44.4% for MIV and TNP‐470, respectively, and a limit of quantitation of 2.5 ng ml−1 with a limit of detection of 0.63 ng ml−1 for both analytes. In contrast, a solid‐phase extraction method led to a higher recovery of 92.9% and 111.0% for MIV and TNP‐470, respectively, and a limit of quantitation of 0.63 ng ml−1 with a limit of detection of 0.16 ng ml−1 for both analytes. Intra‐day and inter‐day precisions were <10% and <18% for both analytes. The solid‐phase extraction, by decreasing plasma interferences present within the column capacity, also allowed the detection and quantitation of MII, a highly polar metabolite of TNP‐470. The recovery of MII in plasma was 77.4% with a limit of quantitation and detection of 2.5 and 1.25 ng ml−1, respectively. Intra‐day and inter‐day precisions were 6.19% and 2.99%. Quantitative analysis of plasma samples from a patient receiving 10 mg m−2 of TNP‐470 by a 1 h intravenous infusion is reported.
Liquid chromatography/thermospray mass spectrometry of mustard and its metabolites
Authors: Munavalli S. , Jakubowski E. M. , Durst H. D.
Published: May 2005

There is considerable interest in the detection and analysis of chemical warfare agents. Since thermospray provides soft ionization and interesting fragmentation patterns under discharge conditions, the liquid chromatographic/thermospray mass spectrometric behavior of bis(2‐chloroethyl) sulfide and its metabolites was investigated. All of the metabolites except mustard sulfone and thiodiglycol sulfone indicated the presence of a three‐membered cyclic sulfonium ion intermediate or its equivalent in their mass spectra. Other observed reactions of the above substrates include polymerizations and nucleophilic substitution reactions.
Direct analysis by electrospray ionization and matrix‐assisted laser desorption ionization mass spectrometry of standard and urinary acylcarnitines. Comparison with fast atom bombardment and gas chromatography chemical ionization mass spectrometry
Authors: Briand Gilbert , Fontaine Monique , Schubert Ralf , Ricart Guy , Degand Pierre , Vamecq Joseph
Published: May 2005

A simple method using matrix‐assisted laser desorption ionization mass spectrometry (MALDI‐MS) is described for the characterization of acylcarnitines in standard solutions and urinary samples from controls and patients with β‐oxidation deficiency disorders. This mass spectrometric approach is compared with other techniques currently utilized for studying acylcarnitines: fast atom bombardment mass spectrometry (FABMS), gas chromatography/chemical ionization mass spectrometry (GC/CIMS) and electrospray ionization mass spectrometry (ESI‐MS). MALDI‐MS was found to compare favourably with the recently described ESI‐MS analysis of acylcarnitines. Both ESI‐MS and MALDI‐MS share the following advantages: (i) non‐requirement of a derivatization step; (ii) easy detection of acylcarnitine esters in standard preparations and urinary samples from human subjects; (iii) detection of fatty acid oxidation disorders from the urinary acylcarnitine profiles in patients suffering from medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD), multiple acyl‐CoA dehydrogenase deficiency (MADD) and mitochondrial carnitine palmitoyltransferase type II (CPT II) deficiency; (iv) sensitivity comparable to FABMS and GC/CIMS, the two reference methods most widely utilized for routine detection of acylcarnitines; and (v) ability (like FABMS but in contrast with GC/CIMS) to detect long‐chain acylcarnitines, suggesting that these esters might have been previously underestimated in body fluids from patients with β‐oxidation deficiency disorders. MALDI‐MS, like ESI‐MS, provides a fast and sensitive method for determining carnitine and its esters, with the potential for routine application in neonatal screening for inherited metabolic disorders involving acylcarnitine metabolism.
Decomposition channels alternative to remote‐charge fragmentations observed in mass spectrometry of alkyltrimethylammonium cations
Authors: Bambagiotti‐Alberti Massimo , Coran Silvia A. , Benvenuti Fabrizio , Lonostro Piero , Catinella Silvia , Favretto Donata , Traldi Pietro
Published: May 2005

A series of alkyltrimethylammonium cations, generated by fast atom bombardment from 1‐dodecanaminium‐, 1‐tetradecanaminium‐ and 1‐hexadecanaminium‐N,N,N‐trimethyl bromides, were studied by high‐energy collisions and comparison with N,N,N‐trimethyl‐d9 labelled analogues. The results show that, together with remote‐charge fragmentation processes, alkyltrimethylammonium cations exhibit further decomposition pathways which may be explained by interaction between the alkyl chain and the methyl group linked to the nitrogen atom. The sharp interruption of remote‐charge fragmentation at the C‐5 atom was observed for all compounds and explained as due to the formation of an energetically favoured six‐membered cyclic structure.
Regiospecific addition of CH2O at the radical site of the ˙CH2CH2OHCH3+ distonic ion
Authors: Troude V. , Leblanc D. , Mourgues P. , Audier H. E.
Published: May 2005

The reaction of the ˙CH2CH2OHCH3+ distonic ion with CH2O was studied by Fourier transform ion cyclotron resonance spectrometry. The process is induced by an initial regiospecific attack of the carbon CH2O at the radical site of the distonic ion, leading to an intermediate adduct ion which loses water. The mechanism was demonstrated by labelling, by studying the structure of the product ion and by examining independently the behaviour of the putative intermediate radical cation.