bluuebunny/crossref_metadata_2025 huggingface dataset:
Doubly charged positive ions of chromium hexacarbonyl and molybdenum hexacarbonyl: Calculated and measured electronic‐state energies
Authors: Harris F. M. , Jackson P. J. , Rontree J. A. , Andrews S. R. , Parry D. E.
Published: May 2005

Double‐charge‐transfer spectroscopy was used to measure the double‐ionization energies of chromium hexacarbonyl and molybdenum hexacarbonyl molecules to triplet electronic states of the corresponding dications. The spectra were interpreted using data calculated using a modified MSXα method. The measured double‐ionization energy to the ground triplet state is 22.8 ± 0.5 eV for Cr(CO)6 and 22.4 ± 0.5 eV for Mo(CO)6; both values match, within experimental error, an earlier measurement of 22.8 ± 0.5 eV for W(CO)6. The spectra for the three hexacarbonyls are remarkably similar, probably reflecting that the electronic structures of the three molecules are almost identical in the valence region. The similarity is reflected in the calculated data; the Coulomb repulsions between the two positive holes which characterize the dictations' states are 4.54, 4.44 and 4.45 eV for Cr(CO), Mo(CO) and W(CO), respectively. These values correspond to the repulsive energy for two single charges separated by just over 3 Å, this separation being consistent with the size of the molecules.
High‐performance liquid chromatography/thermospray mass spectrometry of some prostaglandins of the F series
Authors: Abián J. , Gelpí E.
Published: May 2005

Thermospray (TSP) mass spectra and chromatographic characteristics of the prostanoids PGF2α, 6‐keto‐PGF1α, 2,3‐dinor‐6‐keto‐PGF1α, and their methyl esters and methoximes are reported. The spectra of these compounds are dominated by ions of the type [M + H +xNH3 ‐ nH2O]+ in the positive‐ion mode and [M ‐ H + xAcOH – nH2O]− in the negative‐ion mode (n ranges from 0–4 and x is 0 or 1). The relative abundances of these ions depend on the particular structure, source and interface temperatures and eluent composition. In addition, these compounds show losses of 44 mass units, mainly due to the loss of the C‐10–C‐11 moiety, as demonstrated by deuterium labelling of PGF2α. Methoximated derivatives of 6‐keto‐PGF1α also show low‐abundance ions due to fragmentation in the position α to the methoxime group. The liquid‐phase equilibria of tautomers of 2,3‐dinor‐6‐keto‐PGF1α or products thereof which direct its particular chromatographic behavior, can be effectively blocked by methoximation of the keto group thus improving its detectability. Detection limits of 20 ng on‐column may be obtained for this derivative. Adsorption and hydrolysis in the interface are the principal factors responsible for this relatively high detection limit.
Mass spectrometric evidence for the formation of silaethene accompanying the fragmentation of a non‐ester silicon‐containing pyrethroid insecticide
Authors: Fleet Ian A. , Tetler Lee W. , Monaghan John J.
Published: May 2005

The non‐ester silicon‐containing pyrethroid SSI‐116 and its carbon analogue (ethofenprox, MTI‐500) were investigated using a tandem quadrupole mass spectrometer incorporating a hexapole collision cell under positive‐ion electron impact ionization conditions. Conventional mass spectrometry using the first quadrupole analyser only and tandem mass spectrometry on selected precursor ions and product ions, and also constant neutral loss scan experiments, were used. Accurate mass measurements on key ions were made using a high‐resolution double‐focusing mass spectrometer. Based on the experimental observations, mechanisms have been proposed to explain the major fragmentation pathways of SSI‐116 and ethofenprox. The novel expulsion of silaethene, CH2SiH2, as a neutral species from the silicon‐containing insecticide and the formation of an ion at m/z 135, isomeric with the fragment ion, [C9H11O]+, observed in the spectrum of its carbon analogue, have also been rationalized. Minor fragmentation pathways, found only in the silicon‐containing analogue, are also discussed.
Selective ion–molecule reactions of ether reagent ions with nucleoside antibiotics in a quadrupole ion trap
Authors: Alvarez Erwin J. , Brodbelt Jennifer S.
Published: May 2005

The analysis of a targeted group of nucleoside antibiotics has been accomplished through the use of selective ion‐molecule reactions and collision‐activated dissociation (CAD) techniques in a quadrupole ion trap. A series of homologous ether reagent ions generated from dimethyl ether, di‐n‐butyl ether and 2‐methoxyethanol were used as chemical ionization reagents. Because chemical ionization with dimethyl ether and di‐n‐butyl ether reagent ions did not provide selectivity and signal enhancement for the analysis of these biopharmaceuticals, a chemical ionization reagent with special hydrogen‐bonding capabilities was used. The reagent ion that showed the greatest promise is a product of 2‐methoxyethanol, CH3OCH2CH2OCH2 +. This highly reactive species, which reacts selectively with nitrogen‐containing compounds, can undergo both nucleophilic attack and anchoring via hydrogen bond formation between the methoxy oxygen and an acidic hydrogen of the nucleoside substrate. The reaction of the CH3OCH2CH2OCH2+ ion with each of the nucleoside antibiotics resulted in formation of [M + 13]+ and [M + 89]+ products. The CAD spectra indicated that the adducts are covalently bound species and that the nucleotide moiety dominates both the reactive and dissociative behavior of the nucleoside antibiotics.
Radical cation adduct formation between dihydroxybenzenes and ammonia under CI conditions
Authors: Madhusudanan K. P.
Published: May 2005

Under ammonia chemical ionization conditions, instead of the expected [M + H]+, and [M + NH4]+ and [M + N2H7]+ ions, hydroquinone gives rise to M+·, [M + NH3]+· and [M + 2NH3]+· ions, whereas resorcinol gives both series of ions. Catechol shows M+·, [M + NH3]+·, [M + NH4]+ and [M + N2H7]+ ions. The favourable ionization energy difference between ammonia and the dihydroxybenzenes leads to charge exchange and the resulting radical cations, being highly acidic, form clusters with the NH3. The effect of ion source parameters and mass‐analysed ion kinetic energy (MIKE) and collisional activation spectra confirm proton‐bound structures for [M + NH3]+· and [M + 2NH3]+ ions. Because of the proximity of the two OH groups, NH4+ attachment is favoured in catechol. The MIKE spectra of [M + H + Et2O]+ ions show that resorcinol has the highest proton affinity among the dihydroxybenzenes.
Identification of new metabolites of ifosfamide in rat urine using ion cluster technique
Authors: Wang Jeff J.‐H. , Chan Kenneth K.
Published: May 2005

Metabolism of the anticancer drug ifosfamide was investigated in Sprague‐Dawley rats. Along with four known metabolites, namely N2‐dechloroethylifosfamide, N3‐dechloroethylifosfamide, alcoifosfamide and isophosphoramide mustard, four new urinary metabolites were identified utilizing combined techniques of chemical modification/derivatization, capillary gas chromatography/chemical ionization mass spectrometry (ammonia), deuterium‐labeling/ion cluster analysis and chemical synthesis. Secondary metabolites of N2‐dechloroethyl and N3‐dechloroethylifosfamide formed by 4‐hydroxylation, i.e. 4‐hydroxy‐N2‐dechloroethylifosfamide and 4‐hydroxy‐N3‐dechloroethylifosfamide, respectively, and their subsequent decomposition product, N‐dechloroethyliso‐phosphoramide mustard, were identified. Secondary dealkylation pathways of N2‐dechloroethylifosfamide and/or N3‐dechloroethylifosfamide were also demonstrated through characterization of N2,3‐didechloroethyl ifosfamide. The key active metabolite of ifosfamide, 4‐hydroxyifosfamide, was characterized as a cyanohydrin adduct for the first time.
Negative‐ion fast atom bombardment mass spectrometry of anionic ruthenium carbonyl cluster complexes
Authors: Chihara Teiji , Yang Lanping , Esumi Yasuaki , Wakatsuki Yasuo
Published: May 2005

Bis(triphenylphosphine)iminium salts of a series of high‐nuclear and anionic ruthenium carbonyl cluster complexes were characterized by use of the negative‐ion fast atom bombardment mass spectrometry. With a m‐nitrobenzyl alcohol matrix, all of the monoanionic cluster complexes gave relatively intense intact anion peaks [A]− and all of the dianionic cluster complexes examined gave protonated monoanion peaks [HA]−. In some cases weak adduct ions were observed, which arose from the reaction of the cluster anions with the matrix during the bombardment process. The predominant fragmentation process of intact ions was found to be sequential loss of CO ligands and no loss of methyl, allyl or iodo ligand was observed. However, dissociation of bromo ligand from [Ru6C(CO)16Br]− and fragmentation of acetyl groups in [Ru5C(CO)13I2(COMe)]− and 6C(CO)16(COMe)− were noted. Degradation of cluster metal frameworks of [HRu10C(CO)24]− and [Ru10C(CO)24]2− into [HRu6C(CO)16]− was observed. These fragmentation and degradation patterns are comparable to their reactions in solution.
Determination of plasma levels of exemestane (FCE 24304), a new irreversible aromatase inhibitor, using liquid chromatography/thermospray mass spectrometry
Authors: Allievi C. , Zugnoni P. , Benedetti M. Strolin , Dostert P.
Published: May 2005

A high performance liquid chromatographic mass spectrometric method with thermospray ionization for the determination of concentrations of exemestane (6‐methylenandrosta‐1,4‐diene‐3,17‐dione, FCE 24304) in human plasma has been developed. The sensitivity of the method allowed the determination of exemestane concentrations as low as 1 ng ml−1. A suitable internal standard was used for quantification. The intra‐day precision (relative standard deviation, R.S.D.) ranged from 16.3% near to the lower limit of quantification to 0.3% close to the upper end of the calibration graph. The mean accuracy of the method was found to be 97.8% (R.S.D.=7%). Unlike a previously developed gas chromatographic/mass spectrometic method, the new method proved to be suitable for the determination of unchanged drug plasma levels in exemestane‐treated subjects.
Determination of various steroids in normal adrenal glands and adrenocortical tumours by liquid chromatography/atmospheric pressure ionization mass spectrometry
Authors: Komatsu Funito , Morioka Masaaki , Fujita Yukitoshi , Sugahara Kazunori , Kodama Hiroyuki
Published: May 2005

Seven steroids in normal adrenal gland and those of patients with aldosteronoma or Cushing's adenoma were measured by liquid chromatography/mass spectrometry with an atmospheric pressure ionization interface system. Using this system, quasi‐molecular ions [M + H]+ of standard cortisol, corticosterone, 17α‐hydroxyprogesterone, 11β‐hydroxyandrostenedione and Δ4‐androstenedione and [(M + H) − H2O]+ ions of aldosterone and dehydroe‐piandrosterone were observed as their base peaks, and quasi‐molecular ions [M + H]+ and [(M + H) − H2O]+ ions of seven steroids were clearly observed in chromatograms of biological samples. The ratio of glucocorticoid (cortisol) to mineralocorticoid (corticosterone) content was measured, and found to be significantly lower for aldosteronomas and higher for Cushing's adenomas than for normal adrenals. These findings indicate that the method had suffficient sensitivity for the identification and simultaneous measurement of a variety of adrenal gland steroids.
Alkali metal cationization and its effect on the collision‐induced decomposition of taxol
Authors: Madhusudanan K. P.
Published: May 2005

The effect of alkali metal cationization on the collision‐induced decomposition of taxol is discussed. The facile elimination of H2O observed from the [M + H]+ ion does not occur from the corresponding [M + Met]+ ion. Some of the major decomposition pathways appear to be charge‐remote fragmentations involving eliminations of the functional groups on the taxane ring or the cleavage of the side‐chain with retention of the metal ion on either the side‐chain or the taxane ring. The collision‐induced decompositions of the lithiated side‐chain reflect multi‐site binding of the lithium ion with the basic centres in the side‐chain.
Recognition of cell‐wall peptide ligands by vancomycin group antibiotics: Studies using ion spray mass spectrometry
Authors: Lim Heng‐Keang , Hsieh Yin Liang , Ganem Bruce , Henion Jack
Published: May 2005

Non‐covalent binding of antibiotics to their target ligands represents a form of molecular recognition which is of considerable contemporary interest in bioorganic and bioanalytical chemistry. The vancomycin antibiotics, including vancomycin and ristocetin, are a family of complex glycopeptides which bind specifically to the C‐terminal sequence X‐D‐Ala‐D‐Ala, where × is L‐lysine, L‐diaminopimelic acid, L‐alanine or L‐homoserine. It is shown that non‐covalent complexation of vancomycin and ristocetin with peptide ligands in solution, a key molecular recognition phenomenon in antibacterial chemotherapy, can be detected and analyzed in the gas phase by ionspray mass spectrometry. Using Nα,Nϵ‐diacetyl‐L‐Lys‐D‐Ala‐D‐Ala (Ac2KAA) as a representative ligand, it is further demonstrated that correlations of relative ion abundance with ligand concentrations in solution afford a direct method for measuring the binding constants of vancomycin and ristocetin complexes with target peptide sequences in bacterial cell wall. Results for ristocetin‐Ac2KAA (Ka = 6.25 × 105 l mol−1) and vancomycin‐Ac2KAA (Ka = 7.33 × 105 l mol−1, are in reasonable agreement with previously values [Ka = 5.9 × 105] and 1.5 × 106 l mol−1, respectively).
Reactions in the mass spectrometry of a hydride meisenheimer complex of 2,4,6‐trinitrotoluene (TNT)
Authors: Yinon Jehuda , Johnson Jodie V. , Bernier Ulrich R. , Yost Richard A. , Mayfield Howard T. , Mahone William C. , Vorbeck Claudia
Published: May 2005

A hydride Meisenheimer complex of 2,4,6‐trinitrotoluene (TNT) (TNTH−) was synthesized using tetramethylammonium octahydroborate. TNT and TNTH− (as the tetramethylammonium salt) were analyzed by direct exposure probe mass spectrometry using electron impact (EI), chemical ionization (CI) and negative‐ion chemical ionization (NCI). For further identification, the ions of the mass spectra were investigated using tandem mass spectrometry with collision‐induced dissociation (CID). Although the EI mass spectra of both compounds were similar, the CID mass spectra of the ions at m/z 227 (M+ of TNT) of the two compounds showed large differences in daughter ion abundances. A major difference between the two compounds also appeared in their CI methane mass spectra. Two abundant ions, at m/z 183 and 198, appeared only in the CI mass spectrum of TNNH−. CID parent ion scans showed that the origin of these two ions was not the m/z 227 ion. We suggest that these ions are formed by chemical reactions of the complex on the surface of the heated probe tip, followed by ionization. These reactions, probably a reduction process forming m/z 198 and hydrolysis forming m/z 183, occur preferentially in TNTH−, the already reduced form of TNT. Formation of the ions at m/z 183 and 198 was also observed in the liquid chromatography particle beam CI mass spectrum of TNTH−.
Reactivity of [C3H8N]+ ions: A combined Fourier transform ion cyclotron resonance and molecular orbital approach
Authors: Bouchoux G. , Penaud‐Berruyer F. , Tortajada J.
Published: May 2005

The unimolecular dissociations of the two isomeric ions, [CH3 CH2 CHNH2]+, 1, and [CH3 CH2 NHCH2]+, 2, were re‐examined. Molecular orbital calculations (MP2/6–311 + G**//HF/6–31G* + ZPE level) were used to characterize the corresponding potential energy profiles and, in order to understand the various kinetic effects observed, RRKM calculations were also undertaken. The experimental picture was completed by a Fourier transform ion cyclotron resonance mass spectrometry investigation on the system [CH2CHCH2]+ + NH3. A prominent result is that the elimination of an ethene molecule from metastable ions 1 and 2 occurs via two ion‐neutral complexes involving [CH2 NH2]+ and C2H4 species. In the former case, this intermediate structure looks like a corner protonated cyclopropylamine. In the latter, the data confirm the earlier proposal of Bowen et al. that the reaction is mediated by a proton‐bound complex [C2H4 …︁H…︁NHCH2]+.
Gas‐phase nucleophilic reactions in tetraalkoxysilanes
Authors: da Silva Maria Lucia Pereira , Riveros José M.
Published: May 2005

The gas‐phase reactions of F−, OH−·, OH−, EtO−, NH and EtNH− with Si(OEt)4 were investigated by Fourier transform ion cyclotron resonance in order to probe the intrinsic reactivity of substrates used in plasma chemical vapour deposition. Isotopic data and the nature of the product ions suggest that reactions proceed primarily by attack of the nucleophile on the silicon centre. The ensuing chemistry can be explained by the fragmentation pathways available to the [XSi(OR)4]− intermediate, which includes alkoxide displacement, internal nucleophilic displacement and cyclic elimination of ethylene in the ethoxy case. Pentacoordinated adducts are observed in the reactions with F− and in the symmetric alkoxide/tetraalkoxysilane reactions. The reaction of F− with Si(OMe)4 is also shown to produce a perplexing ion of unknown structure and identified as [FSi(OMe)2(OCH2)]−.
Electron impact mass spectrometry of monocyclic and spirocyclic oxyphosphorane compounds
Authors: Chen Xin , Zhao Yufen , Fu Hua , Wang Jingzun
Published: May 2005

The electron impact ionizatio (EI) mass spectral (EIMS) fragmentations of a series of monocyclic and spirocyclic oxyphosphorane compounds were investigated. The results showed that the EIMS of such compounds exhibited very characteristic fragmentation patterns, which could provide a useful tool for the structural assignment of other pentacovalent phosphorus compounds.
Generation and fragmentation of didehydronaphthalene radical cations under electron impact
Authors: Bromfield Sean M. , Dyall Leonard K.
Published: May 2005

The electron impact mass spectra of disubstituted naphthalenes (chloronitro, acetylnitro, dibromo and dinitro derivatives) and of two naphthalenedicarboxylic anhydrides were studied under high resolution and by means of linked (B/E) scans. They all generate didehydronaphthalene radical cation, C10H, in most cases with a very high abundance, so that a convenient route to these interesting species is provided. These isomeric ions were all seen to lose the same fragments, namely C2H2, C2H4, C3H3, C4H2, or C2H2 + C2H2. In three instances, mass‐analysed ion kinetic energy spectrometric (MIKES) and collisional activation/MIKES experiments were carried out and no differences in fragmentation behaviour were detected. Hence these isomeric C10H6+˙ ions achieve some common structure either before or during the fragmentation.
Dissociation of meta‐stable ions in mass spectrometers with release of internal energy
Authors: Beynon J. H. , Saunders R. A. , Williams A. E.
Published: May 2005

Certain of the “meta‐stable peaks” in mass spectra are abnormally wide. This extra width is shown to be associated with release of kinetic energy during fragmentation. Methods are presented for measuring this energy release and values are given for various transitions in the spectra of aromatic nitro compounds.
Collisional activation spectra of organic ions
Authors: McLafferty F. W. , Bente P. F. , Kornfeld Richard , Tsai Shih‐Chuan , Howe Ian
Published: May 2005

Collision with neutral molecules is shown to provide a convenient method of adding internal energy to ions in a field‐free drift region of the mass spectrometer. The effects on this process of ion accelerating potential, target gas pressure and identity, and precursor ion internal energy and mass have been investigated to optimize experimental conditions. Such collisions cause ion decompositions whose activation energies cover a broad range; for a particular ion such decompositions can be viewed as its “collisional activation (CA) spectrum.” CA spectra, which can be obtained for each ion in the normal mass spectrum, and which appear to follow the predictions of the quasi equilibrium theory, show many more of the possible unimolecular ion decomposition reactions for an ion than do unimolecular metastables, and thus provide valuable information for ion reaction mechanisms and molecular structure determination. Collisional activation can sometimes yield ion energies which are relatively inaccessible by electron impact. The precursor ion internal energy has a negligible effect on the ion's CA spectrum except for product ions formed through the processes of lowest activation energy. Thus, CA spectra should also be valuable for the characterization of ion structures.
Relative carbonyl isocyanate cation [OCNCO]+ affinities of pyridines determined by the kinetic method using multiple‐stage (MS3) mass spectrometry
Authors: Yang Sheng Sheng , Chen Guodong , Ma Shuguang , Cooks R. Graham , Gozzo Fabio C. , Eberlin Marcos N.
Published: May 2005

Ion‐molecule reactions in a pentaquadrupole mass spectrometer are used to generate cluster ions in which neutral pyridine molecules are bound to a linear polyatomic cation, [OCNCO]+. The dimeric adduct, viz. Py1[OCNCO]+Py2 where Py1 and Py2 represent substituted pyridines, formed upon reaction of mass‐selected [OCNCO]+ with a mixture of pyridines, has a loosely bound structure, as suggested by triple stage mass spectrometric (MS3) experiments. Dimeric adducts comprised of meta‐ and/or para‐substituted pyridines (unhindered pyridines) display an excellent linear correlation between the fragment ion abundance ratio ln [Py1[OCNCO]+/Py2[OCNCO]+] and the proton affinity difference of the pyridines. On the assumption that the effective temperature of the [OCNCO]+ ‐bound dimers is similar to that of the corresponding Cl+‐bound dimers, [OCNCO]+ affinities of the substituted pyridines relative to pyridine are estimated to be 3‐MePy 2.3, 4‐MePy 3.2, 3‐EtPy 3.5, 4‐EtPy 4.1, 3,5‐diMePy 4.9 and 3,4‐diMePy 5.6 kcal mol−1 (1 kcal = 4.184 kJ). A linear relationship between the relative [OCNCO]+ cation affinity and the relative proton affinity (PA) is derived as relative [OCNCO]+ affinity (kcal mol−1) = 0.96 ΔPA, using the assumed effective temperature of 555 K. Dimers consisting of ortho‐substituted pyridines display substantial steric effects between the ortho‐substituted alkyl group and the central [OCNCO]+ cation. A set of gas‐phase steric parameters (Sk) is determined and steric effects are ordered 2‐MePy (‐1.39) <2,5‐diMePy (‐3.02) < 2,4‐diMePy (‐3.15) < 2,3‐diMePy ( −3.29) < 2,6‐diMePy (‐5.09) < 2,4,6‐triMe (‐6.13). A greater steric effect is experienced in the [OCNCO]+ system than in the corresponding Cl+ system, owing to the larger central ion in Py[OCNCO]+ Py. Structural and electronic information regarding the bond angles, bond lengths and charge density distributions in [OCNCO]+, Py[OCNCO]+ and Py[OCNCO]Py+ was obtained from ab initio calculations. The calculations show that [OCNCO]+ is linear with high positive charge densities on the carbon atoms. The calculations also reveal that the Py[OCNCO]+ monomer is a planar ion with the nitrogen atom of pyridine bound to a carbon atom of the [OCNCO]+ cation, and that the Py[OCNCO]Py+ dimer is a symmetrical ion in which the nitrogen atoms on the pyridine molecules bind to the carbon atoms of the central cluster ion, [OCNCO]+.
In vivo metabolism of substance P in rat striatum utilizing microdialysis/liquid chromatography/micro‐electrospray mass spectrometry
Authors: Andrén Per E. , Caprioli Richard M.
Published: May 2005

In vivo microdialysis in combination with liquid chromatography/micro‐electrospray mass spectrometry was used to study the metabolism of substance P in rat brain. A microdialysis probe was used both to introduce substance P into the brain and to collect metabolic products. Unilateral infusions of 25 and 50 pmol μl−1 substance P, or isotopically labeled [D8‐Phe8] substance P, at flow rates of 0.3 μl min−1, were made through the microdialysis probe implanted in the striatum of anesthetized rats. The metabolic products were analyzed by on‐line mass spectrometry and the results showed that substance P, an 11 amino acid residue polypeptide, was metabolized in the striatum to form N‐terminal fragments 1–9, 1–8 and 1–7; C‐terminal fragments 3–11, 5–11, 6–11, 7–11 and 8–11; and internal fragments 4–8, 6–10 and 7–10. The concentrations of these metabolites in dialysates were measured in order to compare the relative importance of several possible metabolic degradative pathways.
Ultrahigh‐resolution matrix‐assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectra of peptides
Authors: Paša‐Tolić Ljiljana , Huang Yulin , Guan Shenheng , Kim Hyun Sik , Marshall Alan G.
Published: May 2005

Quasimolecular peptide [M + H]+ions are generated by matrix‐assisted (2,5‐dihydroxybenzoic acid/D‐fructose) laser desorption/ionization (frequency‐tripled Nd: YAG at 355 nm) from leucine enkephalin, bradykinin, the non‐apeptide Arg–Leu–Cys–Ile–Phe–Ser–Cys–Phe–Arg, angiotensin I, bovine insulin chain B and some of their deuterated derivatives. The ions are cooled and axialized by azimuthal quadrupolar irradiation in the presence of argon collision gas in the ‘source’ compartment of a dual cubic Penning trap. Following ion transfer to the low‐pressure ‘analyzer’ trap, ultrahigh FT‐ICR mass resolving power is obtained for protonated oligopeptide quasimolecular [M + H]+ions: e.g.m/Δm50%≈ 1 500 000 for bradykinin (m/z≈ 1060) after frequency drift correction and 100 000 for insulin B‐chain, in which Δm50%is the magnitude‐mode peak full width at half‐maximum peak height. These results constitute the highest mass resolving power yet demonstrated for internally‐generated MALDI ions at 3 T, and compare favorably with results obtained at much higher‐magnetic field with externally‐generated ions. High mass resolution is important for resolving adducts and chemical modifications of a peptide or protein and (as demonstrated here) for facile determination of the degree of deuteration from an H/D exchange experiment. Limitations to FT‐ICR mass resolving power by Coulombic ion–ion interactions at high ion density in the trap are demonstrated experimentally and discussed.
Ion–molecule reactions of C60Rh+ with CH3X, C6H5X(X = Cl, Br, I) and CH2I2
Authors: Kan Steven Z. , Xu Young C. , Byun Yong G. , Freiser Ben S.
Published: May 2005

The gas‐phase ion‐molecule chemistry of exohedrally bound C60Rh+ with CH3X, C6H5X (X = Cl, Br, and I) and CH2I2 is studied using Fourier transform ion cyclotron resonance mass spectrometry. Reactions with CH3I and CH2I2 yield the buckminsterfullerene derivatives, C60CH3+ and C60CH2+, respectively. Energy resolved collisional activation experiments on these two product ions indicate that the methylene group is more strongly bound to C60 than the methyl group. This is consistent with methylene being bound by two carbon‐carbon bonds to C60, while methyl is bound by a single carbon‐carbon bond. Unlike CH3I, CH3Cl and CH3Br react with C60Rh+ in a stepwise fashion to yield C60Rh(CH2)n+ (n = 1 − 3). Interestingly, C60Rh(CH2)2,3+ are shown to be isomers of C60RhX+ (X = ethene, propene), possibly with a carbon‐carbon bond formed with C60. Products containing more than three CH2 moieties were not observed. Reactions of C60Rh+ with C6H5X(X = Cl, Br, and I) yield C60Rh(C6H4)n+ (n = 1, 2), in a stepwise fashion via losses of HX. C60Rh(C6H4)2+ is unreactive with C6H5X. Again, indirect evidence for CC bond formation to C60 is obtained. Consistent with previous observations on C60Fe+ C60Co+, the Rh+–C60 bond energy is found to fall between those of Rh+–propene and Rh+–benzene, due to the alkene behavior of C60.
Space‐charge effects and ion distribution in plasma source mass spectrometry
Authors: Li Gangqiang , Duan Yixiang , Hieftje Gary M.
Published: May 2005

Space‐charge effects appear to be key in understanding ion‐transport processes in plasma‐source mass spectrometry. Both theoretical calculations and experimental measurements demonstrate that space charge influences ion transport between the plasma source and mass analyzer. In a theoretical analysis, both drift space and accelerating space in the interface have been considered and preliminary conclusions have been drawn concerning space‐charge repulsion and ion‐beam divergence in those regions. In the experimental work, spatial patterns of sample deposition on the third stage vacuum orifice plate were recorded while using a microwave plasma source. To measure these patterns, a stainless‐steel target was used to cover the orifice and both x‐ray fluorescence microanalysis and scanning electron microscopy (SEM) were used to examine the sample material deposited on it. The resulting spatial maps show that analyte deposition is somewhat element‐dependent in a way that is correlated with analyte atomic mass. These findings can be explained on the basis of space‐charge theory.
Simultaneous measurement of fluphenazine and [2H4]fluphenazine in plasma using solids probe tandem mass spectrometry
Authors: Hadad S. , Edom R. , McKay G. , Hawes E. M. , Midha K. K.
Published: May 2005

A procedure which utilizes the specificity of tandem mass spectrometry was developed for the simultaneous quantification of fluphenazine and its stable isotopomer, [2H4] fluphenazine, in 1 ml plasma samples, after low oral doses of this antipsychotic agent. The unlabeled and the deuterium labeled‐drug were isolated by a selective extraction procedure, derivatized and analyzed under electron impact ionization via the direct insertion probe of a tandem mass spectrometer. Selected reaction monitoring of the low‐energy collision‐induced dissociation of analogous major fragment ions to their respective product ions conferred the necessary specificity to allow direct analysis of plasma extracts without the need for a chromatographic separation step. Calibration graphs constructed from spiked blank plasma were linear over the range 25–1000 pg ml−1 for each isotopomer, with an overall coefficient of variation of 4.82% and 4.72% for fluphenazine and [2H4] fluphenazine, respectively. The limit of detection was 5 pg ml−1 when 1 ml of plasma was used. The described procedure provided sufficient sensitivity and selectivity such that plasma concentrations of fluphenazine and [2H4] fluphenazine could be followed in schizophrenic patients for 24 h after the simultaneous administration of single oral doses that contain 5 mg each of fluphenazine dihydrochloride and its deuterated isotopomer, [2H4] fluphenazine dihydrochloride. Endogeneous plasma constituents and known metabolites of fluphenazine did not interfere in the assay. Virtually superimposable plasma concentration versus time profiles were obtained, demonstrating that the deuterated isotopomer has no significant isotopic effect.
Comparison of thermospray and electrospray for the analysis of the conjugates of androgen receptor antagonist zanoterone
Authors: Stack Robert F. , Rudewicz Patrick J.
Published: May 2005

The use of both pneumatically‐assisted ionspray (IS) and thermospray (TS) in liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the determination of the biotransformation pathways of zanoterone in humans is described. After administration of a single oral dose of [14C] zanoterone, 16% of the dose was excreted as four metabolites in urine. Initially TS LC‐MS/MS analysis indicated the presence of monohydroxylated metabolites; however, their high‐performance liquid chromatographic (HPLC) retention times indicated more polar structures. These conflicting results led to IS experiments, in which abundant molecular ions were obtained for all four metabolites, identifying them as either glucuronide or sulfate conjugates. A contour plot of the data from an IS neutral loss experiment revealed the presence of a minor metabolite not observed in either HPLC–flow scintillation or TS LC‐MS experiments. These data demonstrate the advantages of IS LC‐MS/MS for the analysis of drug conjugates.
Studies on the distribution of oligodeoxynucleotide charge states in the gas phase by ion spray mass spectrometry
Authors: Tong Xinchun , Henion Jack , Ganem Bruce
Published: May 2005

The naturally occurring purine and pyrimidine heterocycles found in nucleic acids differ significantly in their basicity. To investigate whether such differences may provide useful mass spectrometric information about nucleic acid sequence and/or composition, the distribution of charge states in a series of oligodeoxynucleotide gas‐phase ions was studied by ion spray mass spectrometry (MS). Hexadeoxynucleotides of adenosine, cytidine, guanosine and thymidine were evaluated over the pH range 2.6–7.0 using negative‐ion MS. A significant reduction in the maximum charge state was noted for d(pA)6, d(pC)6 and d(G)6 at low pH, while the maximum charge state observed for d(pT)6 was independent of pH. These effects displayed a good correlation with the pKa values of the respective nucleoside bases. The findings suggest that charge‐state reduction probably resulted from internal charge neutrazation by gas‐phase protonation of the nucleoside base.
Structural characterization of naturally occurring pteridines by laser desorption Fourier transform mass spectrometry
Authors: Hettich Robert L. , Jacobson K. Bruce
Published: May 2005

Detailed structural information can be obtained without derivatization for a variety of naturally occurring pteridines by using laser desorption Fourier transform mass spectrometry. Laser desorption provides a soft ionization technique for these non‐volatile compounds and generates characteristic positive and negative ions. The positive‐ion spectra usually consist of [M + Na]+ and [M + K]+ ions, whereas the negative‐ion spectra reveal [M – H]− ions and fragment ions. Collison‐induced dissociation experiments were used to probe the fragmentation pathways of these negative ions. The fragmentation observed for negative ions supports known resonance structures and provides detailed structural information which can be used to differentiate isomers, such as L‐sepiapterin, L‐biopterin, and L‐primapterin (sometimes referred to as 7‐biopterin). However, optical isomers, such as monapterin and neopterin, cannot be resolved by differences in fragmentation alone. Twenty‐three compounds that are pterins or related structures were characterized.
Regioselectivity of dechlorination of DDT and its metabolites in mass spectrometry
Authors: Lépine François L. , Milot Sylvain , Mamer Orval A.
Published: May 2005

DDT and several of its metabolites were synthesized with their aromatic chlorines enriched with 37Cl. The mass spectra of these compounds were recorded under electron impact and under methane positive‐ion and electroncapture negative‐ion chemical ionization. The regioselectivity of the dechlorination reactions was determined by measurement of the relative proportions of the unlabeled aliphatic versus the labeled aromatic chlorines in the various fragment ions observed. For all the α,β‐unsaturated compounds studied under electron impact ionization, the regioslectivity is small, as both the aromatic and the aliphatic chlorines are lost. Under positive‐ion chemical ionization, the dechlorination is highly regioselective, the aliphatic chlorines being almost exclusively lost. Under electron‐capture negative‐ion chemical ionization, the regioselectivity is also very high and the reactivity of the various chlorines is often controlled by the position of the aromatic chlorines.
Analysis of benzannelated thiophene derivatives by negative‐ion chemical ionization using oxygen as a reagent gas
Authors: Drabner G. , Budzikiewicz H.
Published: May 2005

Under the conditions of negative‐ion chemical ionization with O2 as a reagent gas [NCI(O2)], thiophene derivatives suffer surface‐catalysed oxidative degradation with subsequent ionization of the resulting species. These degradation reactions are to some extent structure specific and thus may be used for the localization of rings and/or substituents. It is advisable, however, to combine NCI(O2) with either electron impact ionization or positive ion CI. The latter ionization methods yield abundant M+· ions but hardly any structure‐specific fragments, whereas with NCI(O2) the determination of the molecular mass may be difficult owing to the competing oxidation reactions.
Determination of N‐terminal myristoylation of proteins using a combined gas chromatographic/mass spectrometric assay of derived myristoylglycine: Electron impact‐induced fragmentation of acylglycine derivatives
Authors: McIlhinney R. A. Jeffrey , Harvey David J.
Published: May 2005

A method based on gas chromatography/mass spectrometry is described for the detection of N‐terminal myristoylation of proteins. Myristoylglycine, derivatized as its trimethylsily (TMS) ester, gave an electron impact mass spectrum containing abundant molecular and and [M  CH3]+ ions, together with several ions diagnostic of the acyl glycine moiety, namely at m/z 145, 158, 172 and 189. The compositions of these ions and the mechanisms that produced them were investigated by high‐resolution mass measurements, deuterium labelling and the preparation of analogous compounds. As these were present in the spectra of all acylglycines examined, they could be used as markers for these compounds. A selected‐ion monitoring method for the detection of myristoylglycine was set up using the above ions and was used to confirm the presence of N‐terminal myristoylation in three reference peptides. A series of ions produced by radical‐induced cleavage of the alkyl chain following TMS group migration and elimination of carbon dioxide gave information on the structure of the chain and could be used to determine the structure of other potential acylglycines such as those with unsaturated acyl chains. Thus the derivatives could be used not only to detect myristoylation of protein, but also to detect and determine the structures of other acyl substituents.
Determination of β‐agonist residues in human plasma using liquid chromatography/atmospheric pressure chemical ionization mass spectrometry and tandem mass spectrometry
Authors: Doerge D. R. , Bajic S. , Blankenship L. R. , Preece S. W. , Churchwell M. I.
Published: May 2005

A multi‐residue gradient liquid chromatographic (LC) separation was developed for five β‐agonists (fenoterol, metaproterenol, terbutaline, salbutamol and clenbuterol) in human plasma and detection was made using LC/atmospheric pressure chemical ionization mass spectrometry (LC/APCI‐MS) in the selected‐ion monitoring (SIM) mode. Detection limits for the protonated molecules of the β‐agonists were <2.5 ppb in plasma or 100 pg on‐column and responses were highly linear over the range 2.5–50 ppb. A solid‐phase extraction (SPE) procedure, yielding recoveries of 67–104% from plasma spiked at 5 ppb with the five analytes, was also developed. In‐source collision‐induced dissociation was used to produce mass spectra containing diagnostic fragment ions and a common mechanism of fragmentation for all the β‐agonists was identified. The LC/APCI‐MS method was unable to determine salbutamol at levels <10 ppb in spiked plasma. To determine whether this resulted from low SPE efficiency or matrix interference, LC/APCI‐MS/MS was performed in the multiple reaction monitoring (MRM) mode to enhance the selectivity of the analysis. The MRM results showed that high recoveries were obtained for salbutamol, confirming the detrimental effect of co‐eluting interferences in the LC/MS analysis. This study demonstrates the feasibility of using SPE, gradient LC separation and highly sensitive/selective detection using LC/APCI‐MS and MS/MS for the multi‐residue analysis of β‐agonists at low ppb levels in a biological matrix.
Special feature: Perspective. Host–guest chemistry in the mass spectrometer
Authors: Vincenti Marco
Published: May 2005

The study of host–guest chemistry in the gas phase has been pursued systematically only in the last 5 years, after sporadic interest in the 1980s, despite extensive investigation of this chemistry in the condensed phase and the success encountered in several fields of application. Most gas‐phase studies have been performed under the controlled conditions that can be achieved inside a mass spectrometer, where solvent effects are not present. At this point, the first evaluation of the achievements and knowledge emerging from these mass spectrometric investigations can be attempted. At the same time, it is possible to evaluate the most promising subjects for future research. This review undertakes these tasks, by presenting (i) applications where mass spectrometry was used to investigate condensed phase equilibria and, more extensively, (ii) experiments where host–guest complexes were formed directly in the gas phase. The latter processes are discussed in detail in relation to the structural and electronic effects, the energetic requirements and the dependence on size, rigidity, spatial geometry and functional groups of both hosts and guests. All these effects combined are likely to contribute to the strength and multiplicity of the non‐covalent bonds that allow the complex to be formed. The macro(poly)cyclic hosts considered include crown ethers, cryptands, cyclodextrins, calixarenes, cryptophanes, cavitands, carcerands and macrolides. The guests are either metal cations or organic molecules and ions.
Distinguishing isobaric amino acids in sequence analysis of cyclosporins by fast atom bombardment and linked‐scan mass spectrometry
Authors: Havlíček Vladimír , Jegorov Alexandr , Sedmera Petr , Wagner‐Redeker Winfried , Ryska Miroslav
Published: May 2005

An analytical protocol suggested previously for the mass spectrometric sequence analysis of cyclosporins was extended by addition of methods for discrimination among isobaric amino acids differing either in the nature of the side‐chain or N‐substitution. The former goal was achieved by comparison of B/E linked‐scan mass spectra of corresponding collisionally activated immonium ions with those of standard amino acids and the latter by comparison of B/E fragment ion spectra of [M + H]+ and [Md + 2H]+ ions. The use of the improved protocol is illustrated by the structure elucidation of a novel natural cyclosporin, [Leu9]CS.
Gas chromatographic–mass spectrometric identification of chlorinated octadecanoic acids in eel lipids
Authors: Wesén Clas , Mu Huiling , Sundin Peter , Frøyen Paul , Skramstad Jan , Odham Göran
Published: May 2005

Gas chromatographic (GC) studies with halogen‐selective electrolytic conductivity detection (ELCD) showed that chlorinated carboxylic acids are major organochlorine compounds in lipids of eel (Anguilla anguilla) from the receiving waters of a chlorine bleaching sulphite pulp mill. To facilitate the recording of full mass spectra, chlorinated carboxylic acid methyl esters were cold‐trapped after capillary GC separation monitored with ELCD. Methyl dichlorooctadecanoate was identified using GC/mass spectrometry (GC/MS) with both electron impact (EI) and ammonia positive‐ion chemical ionization (PICI). Methyl tetrachlorooctadecanoate was indicated by GC/EIMS. Each chlorinated fatty acid was observed at two retention times, suggesting the presence of isomers. The original fatty acid methyl esters derived from the eel lipids were subjected to GC/MS in the selected‐ion monitoring mode; methyl dichlorooctadecanoate was detected using PICI and methyl tetrachlorooctadecanoate was detected using EI ionization.
Proton‐transfer reactions within ionized methanol clusters: Mass spectrometric and molecular orbital studies
Authors: Lee Sun Young , Shin Dong Nam , Cho Soo Gyeong , Jung Kyung‐Hoon , Jung Kwang Woo
Published: May 2005

Proton‐transfer reactions that proceed within methanol cluster ions were studied using an electron impact time‐of‐flight mass spectrometer. When CH3OH seeded in helium is expanded and ionized by electron impact, the protonated species, (CH3OH)nH+, are the predominant cluster ions in the low‐mass region. In CH3OD clusters, both (CH3OD)nH+ and (CH3OD)nD+ ions are observed. The ion abundance ratios, (CH3OD)nH+/(CH3OD)nD+, show a tendency to decrease as the methanol concentration increases, which is apparently related to the cluster structure and reaction energetics. The results suggest that the effective formation of (CH3OD)nH+ ions at low concentration of CH3OD in the expansion is the result of the relatively facile rotation of methanol molecules within the smaller clusters that tend to form at low CH3OD concentration. Ab initio molecular orbital calculations were carried out to investigate the rearrangement and dissociative pathways of ionized methanol dimer. Ion‐neutral complexes, [CH3OH2+…O(H)CH2] and [CH3OH2+…OCH3], are found to play an important role in the low‐energy pathways for production of CH3OH2+ + CH2OH (and OCH3) from ionized methanol dimer.
Comparison of gas‐phase basicities and ion–molecule reactions of aminobenzoic acids
Authors: Tang Ming , Isbell John , Hodges Bradley , Brodbelt Jennifer
Published: May 2005

Functional group interactions and substituent effects of o‐, m‐ and p‐aminobenzoic acids were examined in a quadrupole ion trap by evaluation of proton‐transfer and methylene substitution reactions. An electron‐withdrawing carboxylic acid group can enhance or reduce the gas‐phase basicity of aniline depending on its location and ability to participate directly in proton bridging. In fact, the gas‐phase basicity of o‐aminobenzoic acid is enhanced by ∼ 7 kcal mol−1 relative to the meta and para isomers in which the substituents do not have cooperative functional group interactions. Collisionally activated dissociation studies of deuterium‐labeled ions provide evidence of proton migration from the amino group to the carboxylic acid group prior to fragmentation. Results of semi‐empirical molecular orbital calculations provided structures for the various protonated aminobenzoic acids. For o‐aminobenzoic acid, the proton bridges between the acid and amine groups.
Fast atom bombardment, frit fast atom bombardment and electrospray ionization mass spectrometric study of organic salts C2+ 2X−: Matrix and anion effects
Authors: Aubagnac Jean‐Louis , Gilles Isabelle , Calas Michèle , Cordina Gérard , Piquet Gilles , Portefaix Philippe , Giral Louis
Published: May 2005

The fast atom bombardment (FAB), frit‐FAB and electrospray ionization mass spectra of bis‐ammonium salts, C2+ 2X−, were compared. The most informative spectra were the FAB mass spectra with m‐nitrobenzyl alcohol as matrix and the Frit‐FAB mass spectra. The nucleophilic character of the iodine anion was established.
Mass and sequence verification of modified oligonucleotides using electrospray tandem mass spectrometry
Authors: Barry John P. , Vouros Paul , Van Schepdael Ann , Law Say‐Jong
Published: May 2005

Electrospray coupled with tandem mass spectrometry is shown to have utility in determining the molecular mass and the sequence of short modified oligonucleotides. The product ion spectrum of a triply deprotonated molecule precursor is dominated by ions formed via two fragmentation pathways: first, fragmentation across the 5′PO phosphate bond, and second, loss of a non‐terminal base with concomitant cleavage of the ribose 3′CO bond. If either of these two pathways is complete with fragmentation occurring at each equivalent position along the phosphodiester backbone, then the oligomer may be sequenced. Alternatively, if both these pathways are only partially complete, their complementarity may be used for more extensive sequencing. The inductive effect of the modification on the nucleobase is shown to influence the latter fragmentation process. The greater the electron affinity of the base modification, the more facile is the loss of that base when the molecule is collisionally activated. In fact, this latter fragmentation dominates the product ion spectrum when a nucleobase contains a substituent that is highly inductively withdrawing. This domination can be such that few other first‐generation fragment ions are present in the product ion spectrum. Sequence information may then require utilization of second‐generation product ions.