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

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

Substituent effects on the gas‐phase fragmentation reactions of protonated peptides containing benzylamine‐derivatized lysyl residues

Motivated by the need for chemical strategies designed to tune peptide fragmentation to selective cleavage reactions, benzyl ring substituent influence on the relative formation of carbocation elimination (CCE) products from peptides with benzylamine‐derivatized lysyl residues has been examined using collision‐induced dissociation (CID) tandem mass spectrometry. Unsubstituted benzylamine‐derivatized peptides yield a mixture of products derived from amide backbone cleavage and CCE. The latter involves side‐chain cleavage of the derivatized lysyl residue to form a benzylic carbocation [C₇H₇]⁺ and an intact peptide product ion [(MH_n)ⁿ⁺ – (C₇H₇)⁺]^(n‐1)+. The CCE pathway is contingent upon protonation of the secondary ε‐amino group (N_ε) of the derivatized lysyl residue. Using the Hammett methodology to evaluate the electronic contributions of benzyl ring substituents on chemical reactivity, a direct correlation was observed between changes in the CCE product ion intensity ratios (relative to backbone fragmentation) and the Hammett substituent constants, σ, of the corresponding substituents. There was no correlation between the substituent‐influenced gas‐phase proton affinity of N_ε and the relative ratios of CCE product ions. However, a strong correlation was observed between the π orbital interaction energies (ΔE_int) of the eliminated benzylic carbocation and the logarithm of the relative ratios, indicating the predominant factor in the CCE pathway is the substituent effect on the level of hyperconjugation and resonance stability of the eliminated benzylic carbocation. This work effectively demonstrates the applicability of σ (and ΔE_int) as substituent selection parameters for the design of benzyl‐based peptide‐reactive reagents which tune CCE product formation as desired for specific applications. Copyright © 2012 John Wiley & Sons, Ltd.     

Change of the favored routes of EI MS fragmentation when proceeding from N1, N1‐dimethyl‐N2‐arylformamidines to 1,1,3,3‐tetraalkyl‐2‐arylguanidines: substituent effects

Although series of N¹, N¹‐dimethyl‐N²‐arylformamidines and of 1,1,3,3‐tetraalkyl‐2‐arylguanidines are structurally analogous and similar electron‐ionization mass spectral fragmentation may be expected, they display important differences in the favored routes of fragmentation and consequently in substituent effects on ion abundances. In the case of formamidines, the cyclization‐elimination process (initiated by nucleophilic attack of the N‐amino atom on the 2‐position of the phenyl ring) and formation of the cyclic benzimidazolium [M‐H]⁺ ions dominates, whereas the loss of the NR₂ group is more favored for guanidines. In order to gain information on the most probable structures of the principal fragments, quantum‐chemical calculations were performed on a selected set. A good linear relation between log{I[M‐H]⁺I [M]^+?} and σ_R⁺ constants of substituent at para position in the phenyl ring occurs solely for formamidines (r = 0.989). In the case of guanidines, this relation is not significant (r = 0.659). A good linear relation is found between log{I[M‐NMe₂]⁺/I [M]^+?} and σ_p⁺ constants (r = 0.993). Copyright © 2010 John Wiley & Sons, Ltd.     

Fragmentation of deprotonated cyclic dipeptides by electrospray ionization mass spectrometry

The fragmentation pathways of deprotonated cyclic dipeptides have been studied by electrospray ionization multi‐stage mass spectrometry (ESI‐MSⁿ) in negative mode. The results showed that the fragmentation pathways of deprotonated cyclic dipeptides depended significantly on the different substituents, the side chains of amino acid residues at the diketopiperazine ring. In the spectra of deprotonated cyclic dipeptides, the ion [M? H? substituent radical]^? was firstly observed in the ESI mode. The characteristic fragment ions [M? H? substituent radical]^? and [M? H? (substituent? H)]^? could be used as the symbols of particular cyclic dipeptides. The hydrogen/deuterium (H/D) exchange experiment, the high‐resolution mass spectrometry (Q‐TOF) and theoretical calculations were used to rationalize the proposed fragmentation pathways and to verify the differences between the fragmentation pathways. The relative Gibbs free energies (ΔG) of the product ions and possible fragmentation pathways were estimated using the B3LYP/6–31++G(d, p) model. The results have some potential applications in the structural elucidation and interpretation of the mass spectra of homologous compounds and will enrich the gas‐phase ESI‐MS ion chemistry of cyclic dipeptides. Copyright © 2009 John Wiley & Sons, Ltd.     

Evaluation of nitric oxide chemical ionization mass spectra of substituted benzenes

Nitric oxide chemical ionization mass spectra of substituted benzenes obtained with the Townsend discharge technique were studied. There were four kinds of base peaks in the mass spectra, i.e. [M + NO]⁺˙, M⁺˙, [M ? H]⁺ and [M ? OR]⁺ (R = H, CH₃). The formation of the specific ion [M + NO]⁺˙ was highly dependent on the kind of substituent, and it was produced more abundantly in the case of substitutions involving electron-accepting groups. The measure of [M + NO]⁺˙ production was evaluated from the value of the ratio [M + NO]⁺˙/M⁺˙. In mono-substitutions, it was clarified that the ratios of [M + NO]⁺˙/M ⁺˙ were correlated with the Hammett substituent constant s?_p or the electrophilic substituent constant s?_p⁺. Monosubstitutions (C₆H₅R) and toluene substitutions (CH₃C₆H₄R) could be classified into six groups in terms of base peak species, [M + NO]⁺˙/M⁺˙ ratios and substituents. In disubstitutions, the mass spectral patterns were governed by the combination of substituents. Mass spectral distinctions among ortho, meta and para isomers could be made in many cases.     

Ortho‐hydroxyl effect and proton transfer via ion–neutral complex: the fragmentation study of protonated imine resveratrol analogues in mass spectrometry

The fragmentation pathways of protonated imine resveratrol analogues in the gas‐phase were investigated by electrospray ionization–tandem mass spectrometry. Benzyl cations were formed in the imine resveratrol analogues that had an ortho‐hydroxyl group on the benzene ring A. The specific elimination of the quinomethane neutral, CH₂ = C₆H₄ = O, from the two isomeric ions [M1 + H]⁺ and [M3 + H]⁺ via the corresponding ion–neutral complexes was observed. The fragmentation pathway for the related meta‐isomer, ion [M2 + H]⁺ and the other congeners was not observed. Accurate mass measurements and additional experiments carried out with a chlorinated analogue and the trideuterated isotopolog of M1 supported the overall interpretation of the fragmentation phenomena observed. It is very helpful for understanding the intriguing roles of ortho‐hydroxyl effect and ion–neutral complexes in fragmentation reactions and enriching the knowledge of the gas‐phase chemistry of the benzyl cation. Copyright © 2016 John Wiley & Sons, Ltd.     

DFT investigation on the intramolecular and intermolecular proton transfer processes in 2-aminobenzothiazole (ABT) in the gas phase and in different solvents

DFT at the B3LYP/6-311++G(d,p) level of theory was performed to geometrically, thermodynamically, and kinetically investigate the tautomerism process of 2-aminobenzothiazole (ABT) with n water molecules (n = 1–3) and without water in the gas phase and in different solvents with a gradual increase in their dielectric constants. The geometries of the envisaged tautomers were optimized in the gas phase and in solution with the polarized continuum model (PCM). Equilibrium and rate constants for the forward and reverse intra-/intermolecular isolated and water-assisted tautomerism reactions were also calculated. The results suggest that the activation energy of the transition state of direct proton transfer in the isolated reaction is very high and that the rate constant is very slow (~ 10^?24 s), reflecting that the reaction is thermodynamically unfavored, whereas the barrier differences between the transition states of the tautomers decrease gradually as the number of water molecules increases from one to three. Moreover, the rate constants of the proposed reactions are ~ 10²³–10²⁵ faster than those of the isolated reaction, and the water-assisted tautomerism paths can be performed quickly, especially with the assistance of two molecules of water.

     

Tautomer‐Specific Resonant Photoelectron Imaging of Deprotonated Cytosine Anions

Tautomers of the nucleobases play fundamental roles in spontaneous mutations of DNA. Tautomers of neutral cytosine have been studied in the gas phase, but much less is known about charged species. Here, we report the observation and characterization of three tautomers of deprotonated cytosine anions, [trans‐keto‐amino‐N3H‐H8b] (tKAN3H8b^?), [cis‐keto‐amino‐N3H‐H8a] (cKAN3H8a^?) and [keto‐amino‐H] (KAN1^?), produced by electrospray ionization. Excited dipole‐bound states (DBSs) are uncovered for the three anions by photodetachment spectroscopy. Excitations to selected DBS vibrational levels of cKAN3H8a^? and tKAN3H8b^? yield tautomer‐specific resonant photoelectron spectra. The current study provides further insight into tautomerism of cytosine and suggests a new method to study the tautomers of nucleobases using electrospray ionization and anion spectroscopy.     

Fragmentation pathways of 2,3‐dimethyl‐2,3‐dinitrobutane cations in the gas phase

2,3‐Dimethyl‐2,3‐dinitrobutane (DMNB) is an explosive taggant added to plastic explosives during manufacture making them more susceptible to vapour‐phase detection systems. In this study, the formation and detection of gas‐phase [M+H]⁺, [M+Li]⁺, [M+NH₄]⁺ and [M+Na]⁺ adducts of DMNB was achieved using electrospray ionisation on a triple quadrupole mass spectrometer. The [M+H]⁺ ion abundance was found to have a strong dependence on ion source temperature, decreasing markedly at source temperatures above 50°C. In contrast, the [M+Na]⁺ ion demonstrated increasing ion abundance at source temperatures up to 105°C. The relative susceptibility of DMNB adduct ions toward dissociation was investigated by collision‐induced dissociation. Probable structures of product ions and mechanisms for unimolecular dissociation have been inferred based on fragmentation patterns from tandem mass (MS/MS) spectra of source‐formed ions of normal and isotopically labelled DMNB, and quantum chemical calculations. Both thermal and collisional activation studies suggest that the [M+Na]⁺ adduct ions are significantly more stable toward dissociation than their protonated analogues and, as a consequence, the former provide attractive targets for detection by contemporary rapid screening methods such as desorption electrospray ionisation mass spectrometry. Copyright © 2009 Commonwealth of Australia. Published by John Wiley & Sons, Ltd.     

Gas‐phase fragmentation reactions of protonated benzofuran‐ and dihydrobenzofuran‐type neolignans investigated by accurate‐mass electrospray ionization tandem mass spectrometry

We have investigated gas‐phase fragmentation reactions of protonated benzofuran neolignans (BNs) and dihydrobenzofuran neolignans (DBNs) by accurate‐mass electrospray ionization tandem and multiple‐stage (MSⁿ) mass spectrometry combined with thermochemical data estimated by Computational Chemistry. Most of the protonated compounds fragment into product ions B ([M + H–MeOH]⁺), C ([ B –MeOH]⁺), D ([ C –CO]⁺), and E ([ D –CO]⁺) upon collision‐induced dissociation (CID). However, we identified a series of diagnostic ions and associated them with specific structural features. In the case of compounds displaying an acetoxy group at C‐4, product ion C produces diagnostic ions K ([ C –C₂H₂O]⁺), L ([ K –CO]⁺), and P ([ L –CO]⁺). Formation of product ions H ([ D –H₂O]⁺) and M ([ H –CO]⁺) is associated with the hydroxyl group at C‐3 and C‐3′, whereas product ions N ([ D –MeOH]⁺) and O ([ N –MeOH]⁺) indicate a methoxyl group at the same positions. Finally, product ions F ([ A –C₂H₂O]⁺), Q ([ A –C₃H₆O₂]⁺), I ([ A –C₆H₆O]⁺), and J ([ I –MeOH]⁺) for DBNs and product ion G ([ B –C₂H₂O]⁺) for BNs diagnose a saturated bond between C‐7′ and C‐8′. We used these structure‐fragmentation relationships in combination with deuterium exchange experiments, MSⁿ data, and Computational Chemistry to elucidate the gas‐phase fragmentation pathways of these compounds. These results could help to elucidate DBN and BN metabolites in in vivo and in vitro studies on the basis of electrospray ionization ESI‐CID‐MS/MS data only.     

Energy and substituent effects on gaseous ionic decompositions: Electron and charge exchange ionization of benzophenones and benzils

The correlation with substituent constants reported previously for [YØCO]⁺/[ØCO]⁺ ratios in the electron ionization mass spectra of substituted benzophenones and acetophenones has also been observed in the electron ionization spectra of substituted benzils. The [YØCO]⁺/[ØCO]⁺ ratio for the substituted benzils varied with energy of the ionizing electrons according to predictions from a simple kinetic and thermochemical analysis. [YØCO]⁺/[ØCO]⁺ ratios in the charge exchange spectra of benzophenones obtained with Xe, Kr, CO, N₂ and Ar gave good correlations with sub-stituent constants in agreement with the same analysis. Good correlations were also noted for [YØCO]⁺/[ØCO]⁺ ratios with substituent constants for [M]⁺ ions of the benzophenones of the same excess energy (5.5 eV). [YØCO]⁺/[ØCO]⁺ ratios for benzils obtained by charge exchange with [CO]⁺ also showed good correlations with substituent constant. It is suggested that [Ø]⁺ and [YØ]⁺ ions from the benzophenones may be formed primarily by one step decompositions of the molecular ions, but that the [Ø]⁺ and [YØ]⁺ ions from the benzils are formed primarily by decomposition of [ØCO]⁺ and [YØCO]⁺ ions.     

Electron ionization mass spectra and tautomerism of 2-phenacylpyridines

The electron ionization mass spectra of 2-phenacylpyridine (ketimine form) and its 13 derivatives substituted in the benzene ring (1an: a R = H, b 3-Me, c 4-Me, d 4-NH(2), e 3-F, f 4-F, g 4-OMe, h 4-Cl,i 4-N(CH(3))(2),j 4-NO(2), k 4-CF(3), l 4-N(CH(2))(4), m 4- Br, n 3-Br) were recorded at 70 eV to determine the fragmentation routes and to screen the presence of their enolimine tautomers, (Z-)-2-(2-hydroxy-2-phenylvinyl)pyridines in the gas phase. The total ion currents (TIC) of the ions [MH](+), [MHCO](+), 2-PyCH(2)O(+), and RC(6)H(4)CO(+) (= ArCO(+) ) showed a fair or good correlation with the Hammett s constants (R = 0.859, 0.876, 0.912, and 0.926, respectively). The relative abundances (RA) of both the [MCO](+.) and the [MHCO](+) ion increased with the decreasing electron donating ability of the substituents and also correlated relatively well with the Hammett constants (R = 0.834 and 0.907, respectively). These observations, in comparison to the NMR results, show that the relative contribution of the ketimine tautomer also increases in the gas phase with the increasing electron donating ability of the phenyl substituent, i.e. the TIC of the ArCO(+) ion decreases whereas that of [MH](+) ion increases.     

Acid/Base Switching of the Tautomerism and Conformation of a Dioxoporphyrin for Integrated Binary Subtraction

Compared with most of the reported logic devices based on the supramolecular approach, systems based on individual molecules can avoid challenging construction requirements. Herein, a novel dioxoporphyrin DPH₂₂ was synthesized and two of its tautomers were characterized by single‐crystal X‐ray diffraction studies. Compound DPH₂₂ exhibits multichannel controllable stepwise tautomerization, protonation, and deprotonation processes through interactions with H⁺ and F^? ions. By using the addition of H⁺ and F^? ions as inputs and UV/Vis absorption values at λ=412, 510, 562, and 603 nm as outputs, the controlled tautomerism of DPH₂₂ has been successfully used for the construction of an integrated molecular level half‐subtractor and comparator. In addition, this acid/base‐switched tautomerism is reversible, thus endowing the system with ease of reset and recycling; consequently, there is no need to modulate complicated intermolecular interactions and electron‐/charge‐transfer processes.     

Chemical ionization mass spectra of simple 1,3-dioxolanes and their sulphur analogues recorded with methane,isobutane, ammonia and acetone as reagent gas

The mass spectral behaviour of nine 1,3-dioxolanes, seven 1,3-dithiolanes and seven 1,3-oxathiolanes was studied under chemical ionization conditions with ammonia, isobutane, methane, acetone, acetone-d₆ or pentan-3-one as reagent gas. The proton affinity of the first members in each series was not large enough for ammonia to protonate them; instead, the ionization took place through unstable [M + NH₄]⁺ ions. Isobutane, which gave rise to abundant [M + H]⁺ ions in all cases, was the best reagent gas for the determination of the molecular mass. Methane chemical ionization caused extensive fragmentations either through ring cleavage or through the elimination of the largest substituent from ring positions 2 as a neutral hydrocarbon. The ketones used as reagent gas reacted to form adduct ions. In the case of dioxolanes and oxathiolanes, the [M + RCO]⁺ adduct ion decomposed through ring opening and then, as a consequence of intramolecular nucleophilic substitution, through the elimination of a neutral carbonyl compound. Resonance-stabilized dioxolanylium and oxathiolanylium ions were obtained for dioxolanes and oxathiolanes, respectively. This reaction was almost non-existent for the dithiolanes.     

Substituent Effect on the C–NO2 and N–NO2 Bond Dissociation Energies of Nitroaromatic Molecules

Six density function theory methods (B3LYP, B3P86, MPWB1K1, MPWPW91, PBEPBE, TPSS1KCIS3) were used to calculate bond dissociation enthalpies of nitro compounds, where the B3P86 method was found to give the most accurate predictions. Using the B3P86 method meta‐ and para‐substituted nitroaromatics were systematically studied for the first time. The remote substituent effects, Hammett relationships, and the origin of the substituent effects were discussed on the basis of the calculated results. Both meta‐ and para‐substituted nitromethyl‐benzenes showed significant substituent effects and a fair correlation against substituent constants σ_p⁺ The ground state effects were found to play the major role in determining the overall substituent effects. Meanwhile, nitroamino‐ benzenes showed irregular substituent effects and a poorer Hammett correlation, where both ground and radical state effects contributed to the overall substituent effects.     

Substituent effects on ion abundances and energetics in substituted acetophenones

Based on the quasi-equilibrium theory of mass spectra it is shown that the intensity ratio [A]⁺/[M]⁺, where [A]⁺ is a fragment ion and [M]⁺ is the molecular ion, is given by [A]⁺/[M]⁺ = f′ (k₁/k_t) ((1/f) ? 1), where f is the fraction of molecular ions with insufficient energy to fragment, f′ is the fraction of [A]⁺ ions with insufficient energy to fragment, and k₁/k_t is the fraction of fragmenting molecular ions which form [A]⁺. For substituted acetophenones it is shown that f depends on the substituent present and that f′ k₁/k_t is also substituent dependent for formation of both [CH₃CO]⁺ and [YC₆H₄CO]⁺. It is also shown that no direct information concerning the effect of a substituent on the rate of a particular fragmentation reaction can be obtained from intensity studies. The ionization potentials of the parent molecules and the appearance potentials of the [YC₆H₄CO]⁺ fragment ions have been measured for fifteen substituted acetophenones and the correlations with substituent constants are discussed.     

Nitrogen Bridgehead Compounds. Part 81. Synthesis of 9-(benzylidenehydrazono)-6-methyl-4-oxo-6,7,8,9-tetrahydro- and 9-(benzylidenehydrazine)-6-methyl-4-oxo-6,7-dihydro-4H-pyrido[1,2-a]-pyrimidine-3-carboxylates

Reaction of ethyl 9-hydrazono-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carboxylate and benzaldehyde and its derivatives give a tautomeric mixture of 9-arylidenehydrazono-6,7,8,9-tetrahydro- and 9-arylidenehydrazine-6,7-dihydropyrido[1,2-a]pyrimidine derivatives. In the same case the enhydrazine and hydrazone tautomers were separated. The structure of the products were characterised by uv, ir, ¹H and ¹³C nmr. The equilibrium of the tautomers was affected by the substituent of the phenyl ring. A fair linear correlation exists between the logarithms of the equilibrium constants and Hammett σ_m and σ^? constants of the substituents present on the phenyl ring.     

Formation of [M + 15](+) ions from aromatic aldehydes by use of methanol: in-source aldolization reaction in electrospray ionization mass spectrometry

Unexpected [M + 15]⁺ ions were formed during the analysis of aromatic aldehydes by use of methanol in positive‐ion electrospray ionization mass spectrometry. Aromatic aldehydes with electron‐withdrawing groups or electron‐donating groups were all tested to make sure the universality. All the aromatic aldehydes studied with methanol as the solvent could generate [M + 15]⁺ ion, and for most of them, the [M + 15]⁺ ion was more intense than the [M + H]⁺ ion. Deuterium‐labeling experiment, high‐performance liquid chromatography–MS experiment, collision‐induced dissociation experiment, and theoretical calculations were performed to identify the formation of [M + 15]⁺ ion. The proposed reaction mechanism is a gas‐phase aldol reaction between protonated aromatic aldehydes and methanol occurring in electrospray source. Understanding and using this unique gas‐phase ion/molecule reaction can indeed offer a novel and fast approach for the direct identification of aromatic aldehydes. Copyright © 2011 John Wiley & Sons, Ltd.     

Reduction of cationic free-base <Emphasis Type="Italic">meso</Emphasis>-tris-<Emphasis Type="Italic">N</Emphasis>-methylpyridinium-4-yl porphyrins in positive mode electrospray ionization mass spectrometry

Reductions involving more than one electron with formation of the M⁺ and [M+2H]⁺ ions were observed for electrosprayed meso-tris(N-methylpyridinium-4-yl)porphyrin iodides, MI₃. These reductions were studied by using different solvents and flow rates. Formation of the [M+2H]⁺ ions occurred only for protic solvents and to a larger extent at lower flow rates. The type of the fourth substituent does not seem to affect the reduction processes. Formation of the two reduced species, M⁺ and [M+2H]⁺ ions, may occur through the participation of counter ion/solvent clusters. Reduction of multiply charged, non-metallated species with formation of [M+nH]⁺ ions (n>1) was not observed before in positive mode electrospray mass spectrometry.     

DFT and MP2 study of simple and water-assisted tautomerism in amidrazones

DFT and MP2 methods were used to calculate structural parameters, vibrational modes, solvent effect, and energetic properties of amidrazones. Amidrazones can be presented by three tautomeric forms and six isomers. All tautomers and transition states were optimized at the B3LYP/6-311++g** and MP2/6-311++G** levels of theory. The relative stabilities of amidrazone isomers in the gas phase were found to be as 1Z > 1E > 2E > 2Z > 3E > 3Z > TS(1–2) > TS(1–3). The calculated energy differences between E and Z isomers are very low and between different tautomers are nearly low, but the energy barriers for tautomerism interconversions at the gas phase are high. The kinetic and thermodynamic data in solvents (chloroform, tetrahydrofuran, acetone, and water) are nearly similar to those in the gas phase but their rate constants are slightly less than those in the gas phase. Moreover, equilibrium and rate constants of intermolecular tautomerism in presence of 1–3 molecules of water were calculated. Computed energy barriers show that the barrier energy of water-assisted tautomerism is very lower than that in simple tautomerism and also calculated binding energies show that water can stabilize transition states more than tautomers. Therefore, this water-assisted tautomerism can be performed fast, especially with the assistance of two molecules of water.