Gas-phase Ion-molecule Reactions Research Articles

B-166 Differentiation of Aziridine Functionality from Related Functional Groups in Protonated Analytes by Using Selective Ion-Molecule Reactions

Abstract Background The development of better methods for the rapid and reliable identification of unknown compounds in mixtures is urgently needed in drug development. Aziridines, in particular, are used for drug synthesis but are potentially mutagenic and carcinogenic compounds. However, the detection and identification of these compounds pose challenges for many analytical methods, such as Nuclear Magnetic Resonance (NMR) spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), and X-ray crystallography. These techniques are time-consuming and often require large quantities of highly pure compounds. Methods Therefore, this study demonstrates that selective gas-phase ion-molecule reactions of protonated analytes with neutral tris(dimethylamino)borane (TDMAB), followed by diagnostic collision-activated dissociation (CAD), can be used to differentiate aziridines from structurally related compounds in a modified linear quadrupole ion trap (LQIT) mass spectrometer. The experiments were performed using an atmospheric pressure chemical ionization (APCI) source in positive ion detection mode. TDMAB was purchased from Sigma-Aldrich and used without purification. It was introduced into the ion trap (2 mtorr of helium buffer gas) via an external reagent mixing manifold through a syringe pump at a flow rate of 10 μL h-1 and diluted with helium before entering the ion trap through a variable leak valve. All analytes were prepared at a concentration of 1 mM in methanol. The protonated analytes were transferred into the ion trap, isolated, and allowed to react with TDMAB (MS2 experiments). Results Product ions formed upon reactions of the analyte ions with TDMAB were subjected to a collision-activated dissociation (CAD) experiment (MS3 experiments). CAD on product ions produced diagnostic fragment ions with 25- and 43 m/z-units lower m/z values than the adduct - DMA product ions. Quantum chemical calculations were employed using the Gaussian 16 program calculated at the M06-2X/6-311++G(d,p) level of theory to provide theoretical foundation and to explore the underlying mechanisms of the observed gas-phase reactions. None of the tested structurally related analytes produced a similar fragmentation pattern Conclusions The innovative approach presented in this study offers a promising avenue for enhancing efficiency and accuracy in drug development. The successful differentiation of aziridine is an alternative method in overcoming the limitation of traditional techniques. The findings from the research contributes to the advancement of analytical techniques, addressing critical issues in identifying impurities in drug products. The versatility of the methods extends beyond drug developments, making it applicable in various other fields such as in molecular diagnostics, metabolism and laboratory medicines.

Gas-phase formation of fullerene/9-hydroxyfluorene cluster cations

ABSTRACT In interstellar environment, fullerene species readily react with large molecules (e.g. polycyclic aromatic hydrocarbons, PAHs and their derivatives) in the gas phase, which may be the formation route of carbon dust grains in space. In this work, the gas-phase ion–molecule collision reaction between fullerene cations (${\rm C}_{n}\, ^+$, n = 32, 34,…, 60) and functionalized PAH molecules (9-hydroxyfluorene, C13H10O) are investigated both experimentally and theoretically. The experimental results show that fullerene/9-hydroxyfluorene cluster cations are efficiently formed, leading to a series of large fullerene/9-hydroxyfluorene cluster cations (e.g. [(C13H10O)C60]+, [(C13H10O)3C58]+, and [(C26H18O)(C13H10O)2C48]+). The binding energies and optimized structures of typical fullerene/9-hydroxyfluorene cluster cations were calculated. The bonding ability plays a decisive role in the cluster formation processes. The reaction surfaces, modes, and combination reaction sites can result in different binding energies, which represent the relative chemical reactivity. Therefore, the geometry and composition of fullerene/9-hydroxyfluorene cluster cations are complicated. In addition, there is an enhanced chemical reactivity for smaller fullerene cations, which is mainly attributed to the newly formed deformed carbon rings (e.g. 7 C-ring). As part of the co-evolution network of interstellar fullerene chemistry, our results suggest that ion–molecule collision reactions contribute to the formation of various fullerene/9-hydroxyfluorene cluster cations in the interstellar medium, providing insights into different chemical reactivity caused by oxygenated functional groups (e.g. hydroxyl, OH, or ether, C-O-C) on the cluster formations.

Decarboxylation of fatty acids by ternary zinc cationic complexes studied by mass spectrometry and theoretical calculations

We have shown that fatty acids can be decarboxylated in the gas phase via collision-induced dissociation (CID) of ternary zinc complexes of the general formula [(L)Zn(OOCR)]+, where RC3H7, C6H13, C7H15, C17H35, C17H33, C17H31 and L = 1,10-phenanthroline or 2,2′:6′,2″-terpyridine. These complexes were formed by electrospray ionization of a solution mixture of zinc(II) salt, fatty acid, and the ligand. Two pathways were mapped for the resulting [(L)ZnR]+ organozinc ion: i) a gas-phase ion-molecule reaction with a neutral carboxylic acid R’COOH in the linear quadrupole ion trap resulted in the production of the alkane RH and formation of [(L)Zn(OOCR’)]+; ii) a second CID stage produced an alkene and the ion [(L)ZnH]+ which underwent a subsequent ion-molecule reaction with R’COOH to form [(L)Zn(OOCR’)]+ ion accompanied by the loss of H2. In the case of RR’ = C3H7 (butyric acid), both processes presented formal catalytic cycles with the overall equations C3H7COOHC3H8+ CO2 or C3H7COOHC3H6 + H2+ CO2. Theoretical DFT calculations provided the energetics of reactants/products as well as transition state energies and were in agreement with the experimental data. The work identifies Zn as a potential catalyst for deoxygenation of fatty acid with no fragmentation of the alkyl chain.

Nuclear spin ratios of deuterated ammonia in prestellar cores

Context. Molecules containing two or more hydrogen or deuterium atoms have different nuclear spin states which behave as separate chemical species. The relative abundances of these species can give clues to their origin. Formation on grains is believed to yield statistical spin ratios whereas gas-phase reactions are predicted to result in clear deviations from them. This is also true for ammonia and its deuterated forms NH2D, NHD2, and ND3. Aims. Here we aim to determine the ortho/para ratios of NH2D and NHD2 in dense, starless cores, where their formation is supposed to be dominated by gas-phase reactions. Methods. The Large APEX sub-Millimeter Array (LAsMA) multibeam receiver of the Atacama Pathfinder EXperiment (APEX) telescope was used to observe the prestellar cores H-MM1 and Oph D in Ophiuchus in the ground-state lines of ortho and para NH2D and NHD2. The fractional abundances of these molecules were derived employing three-dimensional radiative transfer modelling, using different assumptions about the abundance profiles as functions of density. We also ran gas-grain chemistry models with different scenarios concerning proton or deuteron exchanges and chemical desorption from grains to find out if one of these models can reproduce the observed spin ratios. Results. The observationally deduced ortho/para ratios of NH2D and NHD2 are in both cores within 10% of their statistical values 3 and 2, respectively, and taking 3 σ limits, deviations from these of about 20% are allowed. Of the chemistry models tested here, the model that assumes proton hop (as opposed to full scrambling) in reactions contributing to ammonia formation, and a constant efficiency of chemical desorption, comes nearest to the observed abundances and spin ratios. Conclusions. The nuclear spin ratios derived here are in contrast with spin-state chemistry models that assume full scrambling in proton donation and hydrogen abstraction reactions leading to deuterated ammonia. The efficiency of chemical desorption strongly influences the predicted abundances of NH3, NH2D, and NHD2, but has a lesser effect on their ortho/para ratios. For these the proton exchange scenario in the gas is decisive. We suggest that this is because of rapid re-processing of ammonia and related cations by gas-phase ion-molecule reactions.

Reactions of gas-phase uranyl formate/acetate anions: reduction of carboxylate ligands to aldehydes by intra-complex hydride attack.

In a previous study, electrospray ionization, collision-induced dissociation (CID), and gas-phase ion-molecule reactions were used to create and characterize ions derived from homogeneous precursors composed of a uranyl cation (UVIO22+) coordinated by either formate or acetate ligands [E. Perez, C. Hanley, S. Koehler, J. Pestok, N. Polonsky and M. Van Stipdonk, Gas phase reactions of ions derived from anionic uranyl formate and uranyl acetate complexes, J. Am. Soc. Mass Spectrom., 2016, 27, 1989-1998]. Here, we describe a follow-up study of anionic complexes that contain a mix of formate and acetate ligands, namely [UO2(O2C-CH3)2(O2C-H)]- and [UO2(O2C-CH3)(O2C-H)2]-. Initial CID of either anion causes decarboxylation of a formate ligand to create carboxylate-coordinated U-hydride product ions. Subsequent CID of the hydride species causes elimination of acetaldehyde or formaldehyde, consistent with reactions that include intra-complex hydride attack upon bound acetate or formate ligands, respectively. Density functional theory (DFT) calculations reproduce the experimental observations, including the favored elimination of formaldehyde over acetaldehyde by hydride attack during CID of [UO2(H)(O2C-CH3)(O2C-H)]-. We also discovered that MSn CID of the acetate-formate complexes leads to generation of the oxyl-methide species, [UO2(O)(CH3)]-, which reacts with H2O to generate [UO2(O)(OH)]-. DFT calculations support the observation that formation of [UO2(O)(OH)]- by elimination of CH4 is favored over H2O addition and rearrangement to create [UO2(OH)2(CH3)]-.

Generation and reactivity of gas-phase phenyloxenium ion

Phenyloxenium ion (POI) is an important intermediate in organic reactions, however, its generation and reactivity have not been extensively investigated. In this study, POI is produced in the gas phase by electrospray ionization tandem mass spectrometry (ESI-MS/MS), isolated for gas phase ion-molecule reactions, and used theoretical calculations to reveal mechanisms to those reactions. It forms adduct ions with H2O, methanol, ethanol, benzene, and toluene, although the structures of the adduct ions are not well-resolved. In contrast, ortho-cyclization with nitriles has been verified by the reaction with acetonitrile and theoretical calculation. Further, Hydride transfer reaction during the reaction with tetrahydrofuran in the gas phase led to experimental values of the hydride affinity and electronic state of POI. Electron transfer studies revealed that the ionization potential of phenoxy radical locates in the range of 8.01–9.19 eV, in line with the calculated value of 8.60 eV for the singlet state POI.

Differentiation of the Aziridine Functionality from Related Functional Groups in Protonated Analytes by Using Selective Ion-Molecule Reactions Followed by Collision-Activated Dissociation in a Linear Quadrupole Ion Trap Mass Spectrometer.

Aziridines are commonly used as reagents for the synthesis of drug substances although they are potentially mutagenic and genotoxic. Therefore, their unambiguous detection is critically important. Unfortunately, tandem mass spectrometry (MS2) based on collision-activated dissociation (CAD), a powerful method used for the identification of many unknown compounds in complex mixtures, does not provide diagnostic fragmentation patterns for ionized aziridines. Therefore, a different mass spectrometry approach based on MS3 experiments is presented here for the identification of the aziridine functionalities. This approach is based on selective gas-phase ion-molecule reactions of protonated analytes with tris(dimethylamino)borane (TDMAB) followed by diagnostic CAD reactions in a modified linear quadrupole ion trap (LQIT) mass spectrometer. TDMAB reacts with protonated aziridines by forming adduct ions that have lost a dimethylamine (DMA) molecule ([M + H + TDMAB - HN(CH3)2]+). CAD on these product ions generated diagnostic fragment ions with m/z-values 25- and 43-units lower than those of the ion-molecule reaction product ions. None of the ion-molecule reaction product ions formed from other, structurally related, protonated analytes produced related fragment ions. Quantum chemical calculations were employed to explore the mechanisms of the observed reactions.

Integrating the potential of ion mobility spectrometry-mass spectrometry in the separation and structural characterisation of lipid isomers.

It is increasingly evident that a more detailed molecular structure analysis of isomeric lipids is critical to better understand their roles in biological processes. The occurrence of isomeric interference complicates conventional tandem mass spectrometry (MS/MS)-based determination, necessitating the development of more specialised methodologies to separate lipid isomers. The present review examines and discusses recent lipidomic studies based on ion mobility spectrometry combined with mass spectrometry (IMS-MS). Selected examples of the separation and elucidation of structural and stereoisomers of lipids are described based on their ion mobility behaviour. These include fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids. Recent approaches for specific applications to improve isomeric lipid structural information using direct infusion, coupling imaging, or liquid chromatographic separation workflows prior to IMS-MS are also discussed, including: 1) strategies to improve ion mobility shifts; 2) advanced tandem MS methods based on activation of lipid ions with electrons or photons, or gas-phase ion-molecule reactions; and 3) the use of chemical derivatisation techniques for lipid characterisation.

A DFT evaluation of molecular reactivity of volatile organic compounds in support of chemical ionization mass spectrometry

Gas-phase molecular properties of volatile organic compounds (VOCs) play an important role in the selection of gas-phase reagent ions for chemical ionization mass spectrometry (CI-MS). Chemical ionization-based mass spectrometry techniques such as proton transfer reaction mass spectrometry (PTR-MS) and selected ion flow-tube mass spectrometry (SIFT-MS) provide real-time, rapid, and online detection and quantification of VOCs using thermodynamics and kinetics of ion-molecule gas-phase reactions. We apply hybrid density functional theory (DFT) to compute proton affinity (PA), ionization energy (IE), and global reactivity parameters for VOCs, which are widely regarded as the primary sources of taints and off-flavors in wine. Atomic polar tensor (APT) charges and total energies at the stationary point for neutral and protonated molecules are also computed. PA and IE values determine the CI-MS mode of reactions, either proton transfer or electron transfer from the reagent gas ions to VOCs. Global reactivity parameters, such as chemical potential (μ), chemical hardness (η), softness (σ), and electrophilic nature (ω) as obtained from frontier molecular orbitals, are considered useful in rationalizing the chemical reactivity patterns of the molecules. A benchmark calculation of indole molecule with MP2, B3LYP, and M06-2X DFT methods at thermodynamically and kinetically stable protonation sites further supports the applied DFT method. Since limited data are available on computed parameters, the reported values would support CI-MS quantification of trace-level VOCs not only in wine but also in various food products.

Different reactivities of H3 O+ (H2 O)n with unsaturated and saturated aldehydes: ligand-switching reactions govern the quantitative analytical sensitivity of SESI-MS.

The detection sensitivity of secondary electrospray ionisation mass spectrometry (SESI-MS) is much lower for saturated aldehydes than for unsaturated aldehydes. This needs to be understood in terms of gas phase ion-molecule reaction kinetics and energetics to make SESI-MS analytically more quantitative. Parallel SESI-MS and selected ion flow tube mass spectrometry (SIFT-MS) analyses were carried out of air containing variable accurately determined concentrations of saturated (C5, pentanal; C7, heptanal; C8 octanal) and unsaturated (C5, 2-pentenal; C7, 2-heptenal; C8, 2-octenal) aldehyde vapours. The influence of the source gas humidity and the ion transfer capillary temperature, 250 and 300°C, in a commercial SESI-MS instrument was explored. Separate experiments were carried out using SIFT to determine the rate coefficients, k73 , for the ligand-switching reactions of the H3 O+ (H2 O)3 ions with the six aldehydes. The relative slopes of the plots of SESI-MS ion signal against SIFT-MS concentration were interpreted as the relative SESI-MS sensitivities for these six compounds. The sensitivities for the unsaturated aldehydes were 20 to 60 times greater than for the corresponding C5, C7 and C8 saturated aldehydes. Additionally, the SIFT experiments revealed that the measured k73 are three or four times greater for the unsaturated than for the saturated aldehydes. The trends in SESI-MS sensitivities are rationally explained by differences in the rates of the ligand-switching reactions, which are justified by theoretically calculated equilibrium rate constants derived from thermochemical density functional theory (DFT) calculations of Gibb's free energy changes. The humidity of SESI gas thus favours the reverse reactions of the saturated aldehyde analyte ions, effectively suppressing their signals in contrast to their unsaturated counterparts.

Modification of a Quadrupole/Orbitrap/Linear Quadrupole Ion Trap Tribrid Mass Spectrometer for Diagnostic Gas-Phase Ion–Molecule Reactions

Tandem mass spectrometry based on diagnostic gas-phase ion-molecule reactions represents a robust method for functional group identification in unknown compounds. To date, most of these reactions have been studied using unit-resolution instruments, such as linear quadrupole ion traps and triple quadrupoles, which cannot be used to obtain elemental composition information for the species of interest. In this study, a high-resolution mass spectrometer, a quadrupole/orbitrap/linear quadrupole ion trap tribrid, was modified by installing a portable reagent inlet system to obtain high-resolution data for ion-molecule reactions. Examination of a previously published test system, the reaction between protonated 1,1'-sulfonyldiimizadole with 2-methoxypropene, demonstrated the ability to perform ion-molecule reactions on the modified tribrid mass spectrometer. High-resolution data were obtained for ion-molecule reactions of three isobaric ions (protonated glycylalanine, protonated glutamine, and protonated lysine) with diethylmethoxyborane. On the basis of these data, the isobaric ions can be differentiated based on both their measured accurate mass as well as the different product ions they generated upon the ion-molecule reactions. In a different experiment, analyte ions were subjected to collision-induced dissociation (CID), and the structures of the resulting fragment ions were examined via diagnostic ion-molecule reactions. This experiment allows for the functional group interrogation of fragment ions and can be used to improve the understanding of the structures of fragment ions generated in the gas phase.

Electronic and Steric Effects on the Reactivity of Seleniranium Ions with Alkenes in the Gas Phase.

Gas phase ion-molecule reactions between seleniranium ions, R-c-SeCH2CH2+, and cis-cyclooctene were used to probe electronic and steric effects of substituents on kinetics and branching ratios. The second-order rate coefficients increased in the order p-OMeC6H4 < C6H5 < p-BrC6H4 < p-CF3C6H4 < m-NO2C6H4, giving a Hammett plot with R2 = 0.98 and ρ = +1.66. The two main pathways include direct transfer of the selenium moiety to the incoming alkene (π-ligand exchange) and the less favored ring-opening by attack at an iranium carbon to give a cis-bicyclic selenonium ion as supported by density functional theory (DFT) calculations. Branching ratios of each pathway indicated that electron-withdrawing groups directed more attack at carbon than selenium in agreement with previous solution-phase results. Increased steric bulk on selenium was investigated by changing the R group from a methyl to t-butyl, which not only shut down π-ligand exchange but also significantly reduced the overall reactivity. Finally, the reactivity of the iranium ion derived from Se-methylselenocysteine was investigated and shown to react faster and favor π-ligand exchange as the leaving group was changed from ethene to acrylic acid.

A SIFT-MS study of positive and negative ion chemistry of the ortho-, meta- and para-isomers of cymene, cresol, and ethylphenol.

Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) is a soft ionisation technique based on gas phase ion-molecule reaction kinetics for the quantification of trace amounts of volatile organic compound vapours. One of its previous limitations is difficulty in resolving isomers, although this can now be overcome using different reactivities of several available reagent cations and anions (H3O+, NO+, O2+˙, O-˙, OH-, O2-˙, NO2-, NO3-). Thus, the ion-molecule reactions of these eight ions with all isomers of the aromatic compounds cymene, cresol and ethylphenol were studied to explore the possibility of their immediate identification and quantification without chromatographic separation. Rate coefficients and product ion branching ratios determined experimentally for the 72 reactions are reported. DFT calculations of their energetics confirmed the feasibility of the suggested reaction pathways. All positive ion reactions proceeded fast but largely did not discriminate between the isomers. The reactivity of the anions was much more varied. In all cases, OH- reacts by proton transfer forming (M-H); NO2- and NO3- were unreactive. The differences observed for product ion branching ratios can be used to identify isomers approximately.

Liberation of carbon monoxide from formic acid mediated by molybdenum oxyanions.

Multistage mass spectrometry experiments, isotope labelling and DFT calculations were used to explore whether selective decarbonylation of formic acid could be mediated by molybdate anions [(MoO3)x(OH)]- (x = 1 and 2) via a formal catalytic cycle involving two steps. In step 1, both molybdate anions undergo gas-phase ion-molecule reactions (IMR) with formic acid to produce the coordinated formates [(MoO3)x(O2CH)]- and H2O. In step 2, both coordinated formates [(MoO3)x(O2CH)]- undergo decarbonylation under collision-induced dissociation (CID) conditions to reform the molybdate anions [(MoO3)x(OH)]- (x = 1 and 2), thus closing a formal catalytic cycle. In the case of [MoO3(O2CH)]- an additional decarboxylation channel also occurs to yield [MoO3(H)]-, which is unreactive towards formic acid. The reaction between [Mo18O3(18OH)]- and formic acid gives rise to [Mo18O3(O2CH)]- highlighting that ligand substitution occurs without 18O/16O exchange between the coordinated 18OH ligand and HC16O2H. The reaction between [(MoO3)x(OD)]- (x = 1 and 2) and DCO2H initially produces [(MoO3)x(OH)]- (x = 1 and 2), indicating that D/H exchange occurs. DFT calculations were carried out to investigate the reaction mechanisms and energetics associated with both steps of the formal catalytic cycle and to better understand the competition between decarbonylation and decarboxylation, which is crucial in developing a selective catalyst. The CO and CO2 loss channels from the monomolybdate anion [MoO3(O2CH)]- have similar barrier heights which is in agreement with experimental results where both fragmentation channels are observed. In contrast, the dimolybdate anion is more selective, since the decarbonylation pathway of [(MoO3)2(O2CH)]- is both kinetically and thermodynamically favoured, which agrees with experimental observations where the CO loss channel is solely observed.

Plausible Sources of Membrane-Forming Fatty Acids on the Early Earth: A Review of the Literature and an Estimation of Amounts.

The first cells were plausibly bounded by membranes assembled from fatty acids with at least 8 carbons. Although the presence of fatty acids on the early Earth is widely assumed within the astrobiology community, there is no consensus regarding their origin and abundance. In this Review, we highlight three possible sources of fatty acids: (1) delivery by carbonaceous meteorites, (2) synthesis on metals delivered by impactors, and (3) electrochemical synthesis by spark discharges. We also discuss fatty acid synthesis by UV or particle irradiation, gas-phase ion-molecule reactions, and aqueous redox reactions. We compare estimates for the total mass of fatty acids supplied to Earth by each source during the Hadean eon after an extremely massive asteroid impact that would have reset Earth's fatty acid inventory. We find that synthesis on iron-rich surfaces derived from the massive impactor in contact with an impact-generated reducing atmosphere could have contributed ∼102times more total mass of fatty acids than subsequent delivery by either carbonaceous meteorites or electrochemical synthesis. Additionally, we estimate that a single carbonaceous meteorite would not deliver a high enough concentration of fatty acids (∼15mM for decanoic acid) into an existing body of water on the Earth's surface to spontaneously form membranes unless the fatty acids were further concentrated by another mechanism, such as subsequent evaporation of the water. Our estimates rely heavily on various assumptions, leading to significant uncertainties; nevertheless, these estimates provide rough order-of-magnitude comparisons of various sources of fatty acids on the early Earth. We also suggest specific experiments to improve future estimates. Our calculations support the view that fatty acids would have been available on the early Earth. Further investigation is needed to assess the mechanisms by which fatty acids could have been concentrated sufficiently to assemble into membranes during the origin of life.

A Diagnostic Nitrosamine Detection Approach for Pharmaceuticals by Using Tandem Mass Spectrometry Based on Diagnostic Gas-Phase Ion-Molecule Reactions.

N-Nitrosamines are strictly regulated in pharmaceutical products due to their carcinogenic nature. Therefore, the ability to rapidly and reliably identify the N-nitroso functionality is urgently needed. Unfortunately, not all ionized N-nitroso compounds produce diagnostic fragment ions and hence tandem mass spectrometry based on collision-activated dissociation (CAD) cannot be used to consistently identify the N-nitroso functionality. Therefore, a more reliable method was developed based on diagnostic functional-group selective ion-molecule reactions in a linear quadrupole ion trap mass spectrometer. 2-Methoxypropene (MOP) was identified as a reagent that reacts with protonated N-nitrosamines in a diagnostic manner by forming an adduct followed by the elimination of 2-propenol (CH3C(OH)═CH2]). From 18 protonated N-nitrosamine model compounds studied, 15 formed the diagnostic product ion. The lack of the diagnostic reaction for three of the N-nitrosamine model compounds was rationalized based on the presence of a pyridine ring that gets preferentially protonated instead of the N-nitroso functionality. These N-nitrosamines can be identified by subjecting a stable adduct formed upon ion-molecule reactions with MOP to CAD. Further, the ability to use ion-molecule reactions followed by CAD to differentiate protonated O-nitroso compounds with a pyridine ring from analogous N-nitrosamines was demonstrated This methodology is considered to be robust for the identification of the N-nitroso functionality in unknown analytes. Lastly, HPLC/MS2 experiments were performed to determine the detection limit for five FDA regulated N-nitrosamines.

Deuterium Isotope Fractionation of Polycyclic Aromatic Hydrocarbons in Meteorites as an Indicator of Interstellar/Protosolar Processing History.

The stable isotope composition of soluble and insoluble organic compounds in carbonaceous chondrites can be used to determine the provenance of organic molecules in space. Deuterium enrichment in meteoritic organics could be a residual signal of synthetic reactions occurring in the cold interstellar medium or an indicator of hydrothermal parent-body reactions. δD values have been measured in grains and bulk samples for a wide range of meteorites; however, these reservoirs are highly variable and may have experienced fractionation during thermal and/or aqueous alteration. Among the plethora of organic compounds in meteorites are polycyclic aromatic hydrocarbons (PAHs), which are stable and abundant in carbonaceous chondrites, and their δD ratio may preserve evidence about their formation environment as well as the influence of parent-body processes. This study tests hypotheses about the potential links between PAHs-deuteration concentrations and their formation conditions by examining the δD ratio of PAHs in three CM carbonaceous chondrites representing an aqueous alteration gradient. We use deuterium enrichments in soluble 2–5-ring PAHs as an indicator of either photon-driven deuteration due to unimolecular photodissociation in warm regions of space, gas-phase ion–molecule reactions in cold interstellar regions of space, or UV photolysis in ices. We also test hypothesized reaction pathways during parent-body processing that differ between partially and fully aromatized PAHs. New methodological approaches were developed to extract small, volatile PAHs without fractionation. Our results suggest that meteoritic PAHs could have formed through reactions in cold regions, with possible overprinting of deuterium enrichment during aqueous parent-body alteration, but the data could not rule out PAH alteration in icy mantles as well.

A Portable Reagent Inlet System Designed to Diminish the Impact of Air and Water to Ion-Molecule Reactions Studied in a Linear Quadrupole Ion Trap.

A portable reagent inlet system for a linear quadrupole ion trap (LQIT) mass spectrometer was designed to diminish the impact of air and water on gas-phase ion-molecule reactions. Compared to the traditional reagent mixing manifolds that has been extensively used for decades, the portable system is much simpler and has fewer junctions and a smaller inner space. These changes reduce the amount of air and water introduced into the mass spectrometer with the reagent. Furthermore, unlike the traditional manifolds, the portable system can be easily attached to or detached from the LQIT mass spectrometer. Finally, the price of the portable system is only 1/10 of that of a traditional manifold as estimated in 2022. Therefore, the portable system has several advantages over the traditional reagent mixing manifolds.

Unmasking the Iron-Oxo Bond of the [(Ligand)Fe-OIAr]2+/+ Complexes.

ArIO (ArI = 2-(tBuSO2)C6H4I) is an oxidant used to oxidize FeII species to their FeIV-oxo state, enabling hydrogen-atom transfer (HAT) and oxygen-atom transfer (OAT) reactions at low energy barriers. ArIO, as a ligand, generates masked Fen=O species of the type Fe(n-2)-OIAr. Herein, we used gas-phase ion–molecule reactions and DFT calculations to explore the properties of masked iron–oxo species and to understand their unmasking mechanisms. The theory shows that the I–O bond cleavage in [(TPA)FeIVO(ArIO)]2+ (12+, TPA = tris(2-pyridylmethyl)amine)) is highly endothermic; therefore, it can be achieved only in collision-induced dissociation of 12+ leading to the unmasked iron(VI) dioxo complex. The reduction of 12+ by HAT leads to [(TPA)FeIIIOH(ArIO)]2+ with a reduced energy demand for the I–O bond cleavage but is, however, still endothermic. The exothermic unmasking of the Fe=O bond is predicted after one-electron reduction of 12+ or after OAT reactivity. The latter leads to the 4e– oxidation of unsaturated hydrocarbons: The initial OAT from [(TPA)FeIVO(ArIO)]2+ leads to the epoxidation of an alkene and triggers the unmasking of the second Fe=O bond still within one collisional complex. The second oxidation step starts with HAT from a C–H bond and follows with the rebound of the C-radical and the OH group. The process starting with the one-electron reduction could be studied with [(TQA)FeIVO(ArIO)]2+ (22+, TQA = tris(2-quinolylmethyl)amine)) because it has a sufficient electron affinity for electron transfer with alkenes. Accordingly, the reaction of 22+ with 2-carene leads to [(TQA)FeIIIO(ArIO)]2+ that exothermically eliminates ArI and unmasks the reactive FeV–dioxo species.

Differentiation of Protonated Sulfonate Esters from Isomeric Sulfite Esters and Sulfones by Gas-Phase Ion-Molecule Reactions Followed by Diagnostic Collision-Activated Dissociation in Tandem Mass Spectrometry Experiments.

Sulfonate esters, a class of potentially mutagenic drug impurities, are strictly regulated in pharmaceuticals. On the other hand, sulfite esters and sulfones, analogs of sulfonate esters, have limited safety concerns. However, previously developed analytical methods for sulfonate ester identification cannot be used to differentiate sulfonate esters from the isomeric sulfite esters and sulfones. A tandem mass spectrometric method is introduced here for the differentiation of these compounds. Diisopropoxymethylborane (DIMB) reacts with protonated sulfonate esters, sulfite esters, and sulfones (and many other compounds) in the gas phase to form the product ion [M + H + DIMB - CH3CH(OH)CH3]+. Upon collision-activated dissociation (CAD), these product ions generate diagnostic fragment ions that enable the differentiation of sulfonate esters, sulfite esters, and sulfones from each other. For example, SO2 elimination enabled the unambiguous identification of sulfite esters. On the other hand, elimination of CH3B═O followed by elimination of (CH3)2C═O was only observed for sulfonate esters. Neither type of diagnostic fragment ions was detected for the products of sulfones. However, the product ions formed for sulfones with an additional hydroxyl substituent underwent the elimination of another CH3CH(OH)CH3 molecule, which enabled their identification. Finally, ion-molecule reactions of DIMB with various other functionalities were also examined. Some of them yielded the product ions [M + H + DIMB - CH3CH(OH)CH3]+ but none of these product ions underwent the diagnostic CAD reactions discussed above. Quantum chemical calculations were employed to explore the mechanisms of the reactions. The limits of detection for the diagnostic ion-molecule reaction product ions in high-performance liquid chromatography (HPLC)/mass spectrometry (MS2) experiments were found to range from 0.075 to 1.25 nmol.