Gas-phase ion chemistry and organic chemistry-the story of a hybrid six sector mass spectrometer--the "AutoSpec 6F".

The AutoSpec 6F mass spectrometer is a large, floor standing instrument comprising a pair of commercial EBE geometry (AutoSpec) mass spectrometers coupled in series to provide an hybrid EBE-EBE configuration, (E and B being respectively electrostatic and magnetic sectors.) It was designed in close collaboration between Professor R. Flammang and VG Analytical in Manchester, UK. It was equipped with five collision cells and allowed the recording of high energy CID (collision induced dissociation), MIKES (mass analyzed ion kinetic energy spectrometry) and NRMS (neutralization re-ionization mass spectrometry) data as well as consecutive MSn analyses. The field-free regions between sectors allowed the study of unimolecular decomposition products from long-lived metastable ions. The mass spectrometer became even more versatile when an RF-only quadrupole collision cell was installed between the second and the third electric sector. This allowed the study of associative ion/molecule reactions in the low kinetic energy regime. Bimolecular chemical reactions were performed inside the quadrupole cell when a neutral reagent was introduced and the reaction products were analyzed by high energy CID in the downstream sectors. This paper tells the history and summarizes the capabilities of this versatile instrument.

Aromatic substitution reactions between ionized benzene derivatives and neutral methyl isocyanide.

Aromatic substitution reactions of selected ionized benzenes derivatives (chlorobenzene, nitrobenzene, dimethylphtalates) and phenoxy cation using neutral methyl isocyanide as a nucleophile are shown to efficiently occur in the gas phase. Nitrilium ions are produced in high abundance during these processes. These reactions have been performed in the hexapole collision cell of a large-scale hybrid tandem mass spectrometer. Computed 298 K enthalpy diagrams at the B3LYP/6-31+G(d,p) level of theory confirm the exothermic formation of the N-methylbenzonitrilium ions starting with ionized chloro- and nitrobenzene molecular ions. In this last case, two other exothermic processes are also detected: (i) an oxygen atom transfer yielding ionized nitrosobenzene and neutral methyl isocyanate and (ii) a loss of carbon monoxide from the ion/molecule reaction product generated when metastably generated phenoxy cations (produced in the hexapole collision cell) react with methyl isocyanide. Using extended theoretical calculations, several reaction pathways have been derived. The behavior of the three isomeric dimethyl phthalates has been investigated in the same way.

Reactions of ionized methyl benzoate with methyl isocyanide in the gas phase: nucleophilic aromatic substitutions vs hydrogen migrations.

The chemistry leading to the competitive eliminations of H, CH(3), and OCOCH(3) from adducts of ionized methyl benzoate and neutral methyl isocyanide has been explored using density functional theory molecular orbital calculations. The energies of the various reactants and transition structures were estimated at the B3LYP/6-31+G(d,p) level of theory. Nucleophilic aromatic substitution is proposed to account for the H and OCOCH(3) eliminations. The corresponding sigma-complex intermediates, B(1ipso) and B(1ortho), are stable species lying in deep energy wells situated 70 and 120 kJ/mol, respectively, below the reactants, ionized methyl benzoate and methyl isocyanide. The latter complex, B(1ortho), may be also at the origin of a multistep rearrangement involving hydrogen migrations and methyl elimination from the original methoxy group of the benzoate moiety.

Conversion of natural aldehydes from Eucalyptus citriodora, Cymbopogon citratus, and Lippia multiflora into oximes: GC-MS and FT-IR analysis.

Three carbonyl-containing extracts of essential oils from Eucalyptus citriodora (Myrtaceae), Cymbopogon citratus (Gramineae) and Lippia multiflora (Verbenaceae) were used for the preparation of oximes. The reaction mixtures were analyzed by GC-MS and different compounds were identified on the basis of their retention times and mass spectra. We observed quantitative conversion of aldehydes to their corresponding oximes with a purity of 95 to 99%. E and Z stereoisomers of the oximes were obtained and separated by GC-MS. During GC analysis, the high temperature in the injector was shown to cause partial dehydratation of oximes and the resulting nitriles were readily identified. Based on FT-IR spectroscopy, that revealed the high stability and low volatility of these compounds, the so-obtained oximes could be useful for future biological studies.

Metastable processes investigated on an orthogonal-axis time-of-flight instrument: mass-scale calibration and application.

In this letter, the authors would like to present a rapid method for mass-scale calibration of metastable dissociation in an orthogonalaxis time-of-flight instrument. The calibrating ion is a protonated polyhedral oligomeric silsesquioxane (POSS) generated in electrospray ionization. In addition, dissociation mechanisms for protonated POSS are proposed. Finally, the interest of the method is illustrated in the context of a collision-induced dissociation investigation of sodium-cationized polylactide.

Internal energy effects on the ion/molecule reactions of ionized methyl isocyanide.

Electron ionization of methyl isocyanide in various chemical ionization conditions is reported and, depending on the energy conditions used, different ion/molecule reactions are observed. It is proposed, on the basis of combined quantum chemical (DFT) calculations and tandem mass spectrometric experiments, that a common intermediate could be a cumulenic ionized dimer dissociating in the ion source following two energy depending competitive channels, a loss of a hydrogen atom and a loss of a methyl group. Proposed structures for new cumulenic ions are supported by collision experiments in the high (collisional activation) or/and low (collision- induced dissociations) translational energy regime.

Noncovalent interactions between ([18]crown-6)-tetracarboxylic acid and amino acids: electrospray-ionization mass spectrometry investigation of the chiral-recognition processes.

Chiral recognition of enantiomers by host compounds is one of the most challenging topics in modern host-guest chemistry. Amongst the well-established methods, mass spectrometry (MS) is increasingly used nowadays, due to its low detection limit, short analysis time, and suitability for analyzing mixtures and for studying chiral effects in the gas phase. The development of electrospray-ionization (ESI) techniques provides an invaluable tool to study, in the gas phase, diastereoisomeric complex ions prepared from enantiomer ions and a chiral selector. This paper reports on an ESIMS and ESIMSMS study of the molecular mechanisms that intervene in the chiral-recognition phenomena observed between amino acids and a chiral crown ether. The modified crown ether, namely (+)-([18]crown-6)-2,3,11,12-tetracarboxylic acid, is used as the chiral selector when covalently bound on a stationary phase in liquid chromatography. This study was stimulated by the fact that, except with threonine and proline, consistent elution orders were observed, which indicates that the D enantiomers interact more strongly with the chiral selector than the L enantiomers. For proline, the lack of a primary amino group is likely to be responsible for the nonresolution of the two forms, whereas the second stereogenic center on threonine could explain the reversed elution order. In light of those observations, we performed mass spectrometry experiments to understand more deeply the enantiomeric recognition phenomena, both in solution by the enantiomer-labeled guest method and in the gas phase by gas-phase ligand-exchange ion/molecule reactions. The results have been further supported by quantum chemical calculations. One of the most interesting features of this work is the identification of a nonspecific interaction between proline and the crown ether upon ESIMS analysis.

Gas-phase nitrosation of ethylene and related events in the C2H4NO+ landscape.

The C2H4NO(+) system has been examined by means of quantum chemical calculations using the G2 and G3B3 approaches and tandem mass spectrometry experiments. Theoretical investigation of the C2H4NO(+) potential-energy surface includes 19 stable C2H4NO(+) structures and a large set of their possible interconnections. These computations provide insights for the understanding of the (i) addition of the nitrosonium cation NO(+) to the ethylene molecule, (ii) skeletal rearrangements evidenced in previous experimental studies on comparable systems, and (iii) experimental identification of new C2H4NO(+) structures. It is predicted from computation that gas-phase nitrosation of ethylene may produce C2H4(*)NO(+) adducts, the most stable structure of which is a pi-complex, 1, stabilized by ca. 65 kJ/mol with respect to its separated components. This complex was produced in the gas phase by a transnitrosation process involving as reactant a complex between water and NO(+) (H2O.NO(+)) and the ethylene molecule and fully characterized by collisional experiments. Among the other C 2H 4NO (+) structures predicted by theory to be protected against dissociation or isomerization by significant energy barriers, five were also experimentally identified. These finding include structures CH3CHNO(+) (5), CH 3CNOH (+) ( 8), CH3NHCO(+) (18), CH3NCOH(+) (19), and an ion/neutral complex CH2O...HCNH(+) (12).

Isomeric recognition by ion/molecule reactions: the ionized phenol-cyclohexadienone case.

The isomerization process between ionized phenol and ionized cyclohexadienone is studied by performing ion/molecule reactions with several alkyl nitrites in a hexapole collision cell inserted in a six-sector mass spectrometer. The distinction between both isomeric species is readily achieved on the basis of the completely different reactivity patterns observed for them in subsequent reactions. When reacting with alkyl nitrite, ionized phenol undergoes two competitive reactions corresponding to the formal radical substitution of the hydroxylic hydrogen atom by respectively (i) the nitrosyl radical (m/z 123) and (ii) an alkoxyl radical (m/z 138 if alkyl=ethyl). Both reactions were theoretically demonstrated by density functional theory calculations [B3LYP/6-311++G(d,p)+ZPE] to involve hydrogen-bridged radical cations as key intermediates. The ion/molecule reaction products detected starting from ionized cyclohexadienone as the mass-selected ions arise from *OAlkyl, *OH, and NO2* radical additions. The occurrence of a spontaneous ring-opening of cyclohexadienone radical ion into a distonic species is suggested to account for the observed ion/molecule reaction products. We also demonstrated that ionized cyclohexadienone is partly isomerized during a proton-transfer catalysis process into ionized phenol inside the Hcell with ethyl nitrite as the base. The molecular ions of phenol generated in such conditions consecutively undergo reactions producing m/z 123 and 138 radical cations. The proposed mechanism is supported by results of quantum chemical calculations.

Carboxyketenes from 4-hydroxy-1,3-oxazin-6-ones and Meldrum's acid derivatives.

New 4-hydroxy-1,3-oxazin-6-ones 8 and 16 were prepared from chlorocarbonyl(phenyl)ketene and amides. The flash vacuum thermolysis (FVT) reactions of these compounds and the 4-methoxy derivative 17 were investigated by Ar matrix isolation IR spectroscopy and online mass spectrometry including MS/MS analysis. Carboxy(phenyl)ketene 10 is formed as the major product by thermal fragmentation of 4-hydroxy-1,3-oxazin-6-one 8. This takes place via the unstable 6-hydroxy tautomer 9. Another tautomer, the 5H-isomer 12, leads to the formation of benzoyl isocyanate 13 as a minor product together with phenylketene 14. Carboxy(phenyl)ketene 10 remains detectable at high FVT temperatures but undergoes thermal decarboxylation to phenylketene 14. The same carboxy(phenyl)ketene 10 is also produced in significant amounts by FVT of 5-phenyl-Meldrum's acid 18 via the unstable enol tautomer 19. A small amount of the unsubstituted carboxyketene 20 is observable on FVT of Meldrum's acid 1 itself.

Ion-molecule reactions involving methyl isocyanide and methyl cyanide.

Ion-molecule reactions involving methyl isocyanide and methyl cyanide have been performed in a new rf-only hexapole collision cell inserted in a large-scale tandem mass spectrometer. Beside protonation processes, N-methyl cyanogen ions (CH(3)N(+)CCN) and 1-methyleneiminium-1- ethylenium ions (CH(2)CN(+)CH(2)) have been produced in high yield and fully characterized by high-energy collisional activation. The unimolecular chemistry of the molecular ions of caffeine (1,3,7-trimethyl xanthine) has been revisited on the basis of these new results.

Decarboxylation of metastable methyl benzoate molecular ions.

By using a combination of mass spectrometric methodologies and density functional theory calculations [DFT/B3LYP/6-311 ++ G(d, p)], it is proposed that the decarboxylation of metastable methyl benzoate molecular ions occurs via distonic and ion-neutral complex (INC) intermediates. The same INC involving a complex between the benzyl radical and protonated carbon dioxide is also generated upon decarboxylation of metastable phenylacetic acid molecular ions. Internal proton transfer within the INC produces in fine a mixture of toluene and isotoluene radical cations.

Nitrosation of thiols and thioethers in the gas phase: a combined theoretical and experimental study.

Recent studies have demonstrated the biological importance of the interaction of nitric oxide with proteins such as cytochrome-c or hemoglobin. In particular, the possibility that the nitrosonium cation, NO(+), could reversibly bind to sulfide atom type was proposed. At pH values of biological relevance, nitrosation was proposed to occur through the action of NO(+) carriers such as nitrosothiols or nitrosamines. In this context, the gas phase chemistry of protonated nitrosothiols is studied in the present work by a combination of mass spectrometry and computational methods.

Experimental and theoretical study of the gas-phase interaction between ionized nitrile sulfides and pyridine.

The gas-phase reactivity of ionized nitrile sulfides, R-C[triple bond]N(+)-S*, towards neutral pyridine was studied both experimentally (six sector hybrid mass spectrometer) and theoretically (density functional theory and Møller-Plesset ab initio calculations). An ionized sulfur atom transfer and a cycloaddition process respectively yielding ionized pyridine N-thioxide and a thiazolopyridinium cation were observed. Whereas the very efficient S*+ transfer reaction probably involves the intermediacy of several ion-molecule complexes, the thiazolopyridinium ion formation is likely to be initiated by an electrophilic attack of the R-C[triple bond]N(+)-S* ion on the nitrogen atom of pyridine; the resulting intermediate then undergo an intramolecular substitution of an alpha-hydrogen atom by the sulfur atom.

Cyanoketene and Iminopropadienones.

Cyanoketene (8) is generated in high yields on flash vacuum thermolysis (FVT) of suitably substituted Meldrum's acid derivatives (5-[(alkylamino)(methylthio or alkylamino)methylene]-2,2-dimethyl-1,3-dioxane-4,6-diones) (3e-j), and also on FVT of cyanoacetic acid derivatives 9e,f,g,j,k,m. The major reaction pathway from 3 proceeds via ketenimines 6 and (alkylimino)propadienones 7, the latter undergoing a retro-ene reaction to 8. A minor pathway is via imidoylketenes 4e,h and oxoketenimines 5e,h, which undergo retro-ene reactions to 9. All intermediates were characterized by Ar matrix FTIR and tandem mass spectrometry (collisional activation MS). Trapping of 4, 5, and 8 with nucleophiles is also reported. The preference of 1,3-X shifts over 1,5-H shifts in imidoylketenes 12 (X = SMe or NMe(2)) is corroborated by the calculated activation barriers. Neat cyanoketene is highly reactive, reacting at or below 80 K, and this is attributed to the availability of a low-lying ketene LUMO. The IR spectrum of cyanoketene (Ar, 14 K) is dominated by two absorptions at 2163 (s; C=C=O) and 2239 (w; CN) cm(-)(1) in excellent agreement with density functional (B3-LYP/6-31G) and ab initio (QCISD/6-31G) calculations.