The abundance of extraterrestrial methanol makes the reaction between methanol molecules in a molecular cluster a possible key step in the search for mechanisms for the formation of more complex molecules under the conditions of the interstellar medium as well as circumstellar and planetary atmospheres. The reaction leading to the formation of the dimethyl ether ion from a methanol molecule interacting with a protonated methanol ion via the elimination of a water molecule is a basic mechanism for the formation of complex organic molecules. Here, we experimentally examine such reactions in the gas phase, analyzing the production and reactivity of protonated cluster ions formed by the ionization of a supersonic jet of methanol. Focusing especially on the post-collisional relaxation of the protonated methanol dimer and trimer ions after high-energy single collisions, the results indicate a strong size selectivity favoring the occurrence of this reaction only in the dimer ion. To elucidate this behavior, the velocity distribution of the eliminated water molecule was measured using an event-by-event coincidence analysis. These results are interpreted using quantum chemical calculations of the dissociation pathways. It turns out that in the dimer case, two transition states are able to contribute to this intracluster reaction. In the trimer case, methanol evaporation appears as the most energetically favorable relaxation pathway.

Here, we present proof of principle studies to demonstrate how the product ions associated with the ion mobility peaks obtained from a High Kinetic Energy-Ion Mobility Spectrometer (HiKE-IMS) measurement of a volatile can be identified using a Proton Transfer Reaction/Selective Reagent Ion-Time-of-Flight-Mass Spectrometer (PTR/SRI-ToF-MS) when operating both instruments at the same reduced electric field value and similar humidities. This identification of product ions improves our understanding of the ion chemistry occurring in the ion source region of a HiKE-IMS. The combination of the two analytical techniques is needed, because in the HiKE-IMS three reagent ions (NO+, H3O+ and O2+•) are present at the same time in high concentrations in the reaction region of the instrument for reduced electric fields of 100 Td and above. This means that even with a mass spectrometer coupled to the HiKE-IMS, the assignment of the product ions to a given reagent ion to a high level of confidence can be challenging. In this paper, we demonstrate an alternative approach using PTR/SRI-ToF-MS that allows separate investigations of the reactions of the reagent ions NO+, H3O+ and O2+•. In this study, we apply this approach to four nitrile containing organic compounds, namely acetonitrile, 2-furonitrile, benzonitrile and acrylonitrile. Both the HiKE-IMS and the PTR/SRI-ToF-MS instruments were operated at a commonly used reduced electric field strength of 120 Td and with gas flows at the same humidities.

Here we explore the potential use of proton transfer reaction/selective reagent ion-time-of-flight-mass spectrometry (PTR/SRI-ToF-MS) to monitor hexafluoroisopropanol (HFIP) in breath. Investigations of the reagent ions H3O+, NO+, and O2+• are reported using dry (relative humidity (rH) ≈ 0%) and humid (rH ≈ 100%)) nitrogen gas containing traces of HFIP, i.e., divorced from the complex chemical environment of exhaled breath. HFIP shows no observable reaction with H3O+ and NO+, but it does react efficiently with O2+• via dissociative charge transfer resulting in CHF2+, CF3+, C2HF2O+, and C2H2F3O+. A minor competing hydride abstraction channel results in C3HF6O+ + HO2• and, following an elimination of HF, C3F5O+. There are two issues associated with the use of the three dominant product ions of HFIP, CHF2+, CF3+, and C2H2F3O+, to monitor it in breath. One is that CHF2+ and CF3+ also result from the reaction of O2+• with the more abundant sevoflurane. The second is the facile reaction of these product ions with water, which reduces analytical sensitivity to detect HFIP in humid breath. To overcome the first issue, C2H2F3O+ is the ion marker for HFIP. The second issue is surmounted by using a Nafion tube to reduce the breath sample's humidity prior to its introduction into drift tube. The success of this approach is illustrated by comparing the product ion signals either in dry or humid nitrogen gas flows and with or without the use of the Nafion tube, and practically from the analysis of a postoperative exhaled breath sample from a patient volunteer.

Halogenated organic compounds represent an important group of chemicals that have found use in a wide array of research, medical and industrial applications. This raises the question as to which analytical techniques are most suitable for detecting and monitoring in real-time these compounds in the environment. To provide underpinning information on the potential use of chemical ionisation mass spectrometric techniques, we present here details of a selective reagent ion-time-of-flight-mass spectrometry (SRI-ToF-MS) fundamental study characterising the reactions of O2+• with six common halogenated organic compounds, namely, 2,2,2-trifluoroethanol (TFE, CF3CH2OH), 1,1,1,-trifluoroacetone (TFA, CH3COCF3), 1,1,2,2-tetrafluoro-3-methoxypropane (TMP, CHF2CF2CH2OCH3), 1,1,1,3,3,3-hexafluoro-2-methoxypropane (isoflurothyl, (CF3)2–CHO–CH3)), 2-chloro-1,1,2-trifluoro-1-methoxyethane (CTME, CH3OCF2CHFCl) and 1-ethoxy-1,1,2,2-tetrafluoroethane (ETE, CH3CH2OCF2CHF2). We investigated the distributions of the product ions as a function of the reduced electric field strength (E/N) between 65 Td and 205 Td. Five of the halogenated organic compounds generated rather simple product ion distributions. Only one, non-halogenated product ion resulted from each of the reactions of O2+• with TFE (CH2OH+), TFA (CH3CO+) and TMP (CH3OCH2+). For the other two out of the first five compounds, isoflurothyl and CTME, three product ions were observed, but only one of these was dominant with a product ion branching percentage of ∼80% throughout the reduced electric field range investigated: C3H4F3O+ resulting from isoflurothyl and C2H3F2O+ from CTME. The sixth compound, ETE, displayed a much richer reaction ion chemistry than the other five compounds. A total of eight product ions were identified, two of which dominated over most of the investigated E/N range, namely C4H5F4O+ and C2H5+. The potential chemical pathways that lead to the formation of the major and minor observed product ions are discussed for all six compounds. We show that SRI-ToF-MS is a useful technique to study the reactions of halogenated organic compounds with O2+•. Its potential use for monitoring TFE, TFA and TMP is limited because the single product ion observed for each of these volatiles is not sufficiently specific and thus characteristic to the originating compound (i.e., reactions of O2+• with non-halogenated organic compounds will also result in the same product ions). However, SRI-ToF-MS could be considered as a potential analytical tool to detect and monitor isoflurothyl, CTME and ETE, as the fluorinated product ions resulting from their reactions with O2+• allow for their detection with a high level of analytical confidence.

As a part of an ongoing study to determine the concentrations of inhalation anaesthetics in the exhaled breath of patients following surgery, separate investigations are being undertaken to determine which soft chemical ionisation mass spectrometric techniques are most suitable for real-time breath measurements. Towards that goal, we present here details of a selective reagent ion-time-of-flight-mass spectrometer study investigating the reactions of O 2 +· with isoflurane, enflurane, desflurane, and sevoflurane. Information on the product ions as a function of reduced electric field and the influence of humidity in the drift (reaction) tube is presented. With increasing humidity in the drift tube, secondary product ion-water reactions lead to significant decreases in the intensities of many of the primary product ions, resulting here in a reduced analytical sensitivity for the four fluranes. However, for breath analysis this is found not to be a major issue owing to the high concentrations of inhalation anaesthetics found in exhaled breath even several days after surgery. This is demonstrated in a clinical measurement involving a patient who had undergone an operational procedure, with sevoflurane being used for maintenance of general anaesthesia. Graphical abstract

The first High Kinetic Energy-Ion Mobility Spectrometry-Mass Spectrometry (HiKE-IMS-MS) studies involving six volatiles (acetone, acetonitrile, methanol, ethanol, 2-propanol, and 1-butanol) and their fully deuterated analogues are reported. The goal is to further our understanding of the ion–molecule chemistry occurring in the HiKE-IMS. This is needed for its full analytical potential to be reached. Product ions are identified as a function of the reduced electric field (30–115 Td) and the influence of sample air humidity in the reaction region on deuterium/hydrogen (D/H) exchange reactions is discussed. Reagent ions include H 3 O + (H 2 O) m ( n = 0, 1, 2 or 3), NO + (H 2 O) n ( m = 0 or 1) and O 2 +· . Reactions with H 3 O + (H 2 O) m lead to protonated monomers (through either proton transfer or ligand switching). Reactions with NO + involve association with acetone and acetonitrile, hydride anion abstraction from ethanol, 2-propanol, and 1-butanol, and hydroxide abstraction from 2-propanol and 1-butanol. With the exception of acetonitrile, O 2 +· predominantly reacts with the volatiles via dissociative charge transfer. A number of sequential secondary ion-volatile processes occur leading to the formation of dimer and trimer-containing ion species, whose intensities depend on a volatile’s concentration and the reduced electric field in the reaction region. Deuterium/hydrogen (D/H) exchange does not occur for product ions from acetone-d 6 and acetonitrile-d 3 , owing to their inert methyl functional groups. For the deuterated alcohols, rapid D/H-exchange reaction at the hydroxy group is observed, the amount of which increased with the increasing humidity of the sample air and/or lowering of the reduced electric field. Graphical abstract

Postirradiation dissociation of molecular clusters has been mainly studied assuming energy redistribution in the entire cluster prior to the dissociation. Here, the evaporation of water molecules from out-of-equilibrium pyridinium-water cluster ions was investigated using the recently developed correlated ion and neutral time-of-flight (COINTOF) mass spectrometry technique in combination with a velocity-map imaging (VMI) device. This special setup enables the measurement of velocity distributions of the evaporated molecules upon high-velocity collisions with an argon atom. The distributions measured for pyridinium-water cluster ions are found to have two distinct components. Besides a low-velocity contribution, which corresponds to the statistical evaporation of water molecules after nearly complete redistribution of the excitation energy within the clusters, a high-velocity contribution is also found in which the molecules are evaporated before the energy redistribution is complete. These two different evaporation modes were previously observed and described for protonated water cluster ions. However, unlike in the case of pure water clusters, the low-velocity part of the distributions for pyridinium-doped water clusters is itself composed of two distinct Maxwell-Boltzmann distributions, indicating that evaporated molecules originate in this case from out-of-equilibrium processes. Statistical molecular dynamics simulations were performed to (i) understand the effects caused in the ensuing evaporation process by the various excitation modes at different initial cluster constituents and to (ii) simulate the distributions resulting from sequential evaporations. The presence of a hydrophobic impurity in water clusters is shown to impact water molecule evaporation due to the energy storage in the internal degrees of freedom of the impurity.

Changes in the headspace volatile profile of tea infusion during brewing were determined by analysing the aliquots taken every 30 s using proton transfer reaction time-of-flight mass spectrometry in conjunction with principal component analysis and hierarchical cluster analysis. The effect of three different brewing temperatures (60, 70 and 80 degrees C), two leaf sizes (broken and full leaves) and two water mineralizations (soft and hard), on the concentration of volatile compounds in the headspace of tea, was studied as a function of infusion time. An increase in brewing temperature resulted in increased volatile content in the headspace, reflecting an increase in extraction efficiency. Such differences on extraction efficiency were more pronounced with increasing brewing times. Leaf size had also a big impact on the extraction of volatile compounds, but mainly during the early phase of brewing. Water mineralization had a low but noticeable impact on the volatile content. Furthermore, clusters of samples prepared with different combinations of brewing parameters but resulting in analogous volatile profiles could be identified using hierarchical clustering analysis.

Dissociative electron attachment to 2-chlorotoluene has been studied experimentally. The formed Cl- fragment appears in the energy range from 0 to 2 eV. Increasing the temperature of the target molecule results in a decrease of the height of the threshold peak (similar to 0 eV) but in a considerable increase of the height of the second peak at 0.78 eV. Such behaviour was observed only rarely and does not occur in similar molecules. We have analysed the out-of-plane vibrations and calculated approximate potential energy curves for the neutral and anionic states. Possible explanations of the observed temperature dependence are discussed.

Atmospheric aerosols are one of the major factors affecting planetary climate, and the addition of anthropogenic molecules into the atmosphere is known to strongly affect cloud formation. The broad variety of compounds present in such dilute media and their specific underlying thermalization processes at the nanoscale make a complete quantitative description of atmospheric aerosol formation certainly challenging. In particular, it requires fundamental knowledge about the role of impurities in water cluster growth, a crucial step in the early stage of aerosol and cloud formation. Here, we show how a hydrophobic pyridinium ion within a water cluster drastically changes the thermalization properties, which will in turn change the corresponding propensity for water cluster growth. The combination of velocity map imaging with a recently developed mass spectrometry technique allows the direct measurement of the velocity distribution of the water molecules evaporated from excited clusters. In contrast to previous results on pure water clusters, the low-velocity part of the distributions for pyridinium-doped water clusters is composed of 2 distinct Maxwell-Boltzmann distributions, indicating out-of-equilibrium evaporation. More generally, the evaporation of water molecules from excited clusters is found to be much slower when the cluster is doped with a pyridinium ion. Therefore, the presence of a contaminant molecule in the nascent cluster changes the energy storage and disposal in the early stages of gas-to-particle conversion, thereby leading to an increased rate of formation of water clusters and consequently facilitating homogeneous nucleation at the early stages of atmospheric aerosol formation.

Nitroimidazoles are important compounds in medicine, biology, and the food industry. The growing need for their structural assignment, as well as the need for the development of the detection and screening methods, provides the motivation to understand their fundamental properties and reactivity. Here, we investigated the decomposition of protonated ronidazole [Roni+H]+ in low-energy and high-energy collision-induced dissociation (CID) experiments. Quantum chemical calculations showed that the main fragmentation channels involve intramolecular proton transfer from nitroimidazole to its side chain followed by a release of NH2CO2H, which can proceed via two pathways involving transfer of H+ from (1) the N3 position via a barrier of TS2 of 0.97 eV, followed by the rupture of the C–O bond with a thermodynamic threshold of 2.40 eV; and (2) the –CH3 group via a higher barrier of 2.77 eV, but with a slightly lower thermodynamic threshold of 2.24 eV. Electrospray ionization of ronidazole using deuterated solvents showed that in low-energy CID, only pathway (1) proceeds, and in high-energy CID, both channels proceed with contributions of 81% and 19%. While both of the pathways are associated with small kinetic energy release of 10–23 meV, further release of the NO• radical has a KER value of 339 meV.

Soft chemical ionization mass spectrometric techniques, such as proton transfer reaction mass spectrometry (PTR-MS), are often used in breath analysis, being particularly powerful for real-time measurements. To ascertain the type and concentration of volatiles in exhaled breath clearly assignable product ions resulting from these volatiles need to be determined. This is difficult for compounds where isomers are common, and one important class of breath volatiles where this occurs are ketones. Here we present a series of extensive measurements on the reactions of H3O+ with a selection of ketones using PTR-MS. Of particular interest is to determine if ketone isomers can be distinguished without the need for pre-separation by manipulating the ion chemistry through changes in the reduced electric field. An additional issue for breath analysis is that the product ion distributions for these breath volatiles are usually determined from direct PTR-MS measurements of the compounds under the normal operating conditions of the instruments. Generally, no account is made for the effects on the ion-molecule reactions by the introduction of humid air samples or increased CO2 concentrations into the drift tubes of these analytical devices resulting from breath. Therefore, another motivation of this study is to determine the effects, if any, on the product ion distributions under the humid conditions associated with breath sampling. However, the ultimate objective for this study is to provide a valuable database of use to other researchers in the field of breath analysis to aid in analysis and quantification of trace amounts of ketones in human breath. Here we present a comprehensive compendium of the product ion distributions as a function of the reduced electric field for the reactions of H3O+. (H2O)n (n = 0 and 1) with nineteen ketones under normal and humid (100% relative humidity for 37 °C) PTR-MS conditions. The ketones selected for inclusion in this compendium are (in order of increasing molecular weight): 2-butanone; 2-pentanone; 3-pentanone; 2-hexanone; 3-hexanone; 2-heptanone; 3-heptanone; 4-heptanone; 3-octanone; 2-nonanone; 3-nonanone; 2-decanone; 3-decanone; cyclohexanone; 3-methyl-2-butanone; 3-methyl-2-pentanone; 2-methyl-3-pentanone; 2-methyl-3-hexanone; and 2-methyl-3-heptanone.

Post-operative isoflurane has been observed to be present in the end-tidal breath of patients who have undergone major surgery, for several weeks after the surgical procedures. A major new non-controlled, non-randomized, and open-label approved study will recruit patients undergoing various surgeries under different inhalation anaesthetics, with two key objectives, namely (1) to record the washout characteristics following surgery, and (2) to investigate the influence of a patient’s health and the duration and type of surgery on elimination. In preparation for this breath study using proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS), it is important to identify first the analytical product ions that need to be monitored and under what operating conditions. In this first paper of this new research programme, we present extensive PTR-TOF-MS studies of three major anaesthetics used worldwide, desflurane (CF3CHFOCHF2), sevoflurane ((CF3)2CHOCH2F), and isoflurane (CF3CHClOCHF2) and a fourth one, which is used less extensively, enflurane (CHF2OCF2CHFCl), but is of interest because it is an isomer of isoflurane. Product ions are identified as a function of reduced electric field (E/N) over the range of approximately 80 Td to 210 Td, and the effects of operating the drift tube under ‘normal’ or ‘humid’ conditions on the intensities of the product ions are presented. To aid in the analyses, density functional theory (DFT) calculations of the proton affinities and the gas-phase basicities of the anaesthetics have been determined. Calculated energies for the ion-molecule reaction pathways leading to key product ions, identified as ideal for monitoring the inhalation anaesthetics in breath with a high sensitivity and selectivity, are also presented.

Product ion distributions resulting from the primary reactions of H3O+ with nine D-labeled volatile organic compounds and the subsequent sequential reactions with H2O have been determined using a Proton Transfer Reaction Time of Flight Mass Spectrometer (PTR-TOF 8000 (IONICON Analytik GmbH)) at various reduced electric field (E/N) values ranging from 80 up to 150 Td and for two different absolute humidity levels of air sample < 0.1% and 5%. The specific D-labeled compounds used in this study are acetone-d(6), toluene-d(8), benzene-d(6), ethanol-d (C2H5OD), ethanol-d(2) (CH3CD2OH), ethanol-d(6), 2-propanol-d(8), 2-propanol-d(3) (CD3CH(OH)CH3), and isoprene-d(5) (CH2CHC(CD2)CD3). With the exception of the two 2-propanol compounds, non-dissociative proton transfer is the dominant primary reaction pathway. For 2-propanol-d(8) and 2-propanol-d(3) the major primary reaction channel involved is dissociative proton transfer. However, unlike their undeuterated counterparts, the primary product ions undergo subsequent deuterium/hydrogen isotope exchange reactions with the ever present water in the drift tube, the extent of which of course depends on the humidity within that tube. This exchange leads to the generation of various isotopologue product ions, the product ion branching percentages of which are also dependent on the humidity in the drift tube. This results in complex mass spectra and the distribution of product ions leads to issues of reduced sensitivity and accuracy. However, the effect of D/H exchange considerably varies between the compounds under study. In the case of acetone-d(6) it is very weak (< 1%), because the exchange process is not facile when the deuterium is in the methyl functional group. In comparison, the H3O+/ benzene-d(6) (C6D6) reaction and sequential reactions with water result in the production of the isotopologue ions C6Dn (H-7(-n))(+ )(where n = 0-6). Changing the value of E/N and/or the humidity in the drift tube considerably affects the amount of the isotope exchange reactions and hence the resulting sequential product ion distributions. An important conclusion of the findings from this work is that care must be taken in the choice of an exogenous deuterated compound for use in breath pharmacokinetic studies using proton transfer reaction mass spectrometry; otherwise the resulting D/H exchange processes impose interpretative problems. (C) 2018 The Authors. Published by Elsevier B.V.

Nitroimidazolic radiosensitizers are used in radiation therapy to selectively sensitize cancer cells deprived of oxygen, and the actual mechanism of radiosensitization is still not understood. Selecting five radiosensitizers (1-methyl-5-nitroimidazole, ronidazole, ornidazole, metronidazole, and nimorazole) with a common 5-nitroimidazolic ring with different substitutions at N1 and C2 positions of the imidazole moiety, we investigate here their binding to nucleobases (A, T, G, and C) and nucleosides (As, Td, Gs, and Cd) via the positive electrospray ionization mass spectrometry experiments. In addition, quantum chemical calculations at the M062x/6-311+G(d,p) level of theory and basis set were used to determine binding energies of the proton bound dimers of a radiosensitizer and a nucleobase. The positive electrospray ionization leads to the formation of proton bound dimers of all radiosensitizers except 1-methyl-5-nitroimidazole in high abundance with C and smaller abundance with G. Ronidazole and metronidazole formed less abundant dimers also with A, while no dimers were observed to be formed at all with T. In contrast to the case of the nucleoside Td, the dimer intensity is as high as that with Cd, while the abundance of the dimer with Gs is smaller than that of the former. The experimental results are consistent with the calculations of binding energies suggesting proton bound dimers with C and G to be the strongest bound ones. Finally, a barrier-free proton transfer is observed when protonated G or C approaches the nitroimidazole ring.

The combination of the Dispositif d'Irradiation d'Agrégats Moléculaire with the correlated ion and neutral time of flight-velocity map imaging technique provides a new way to explore processes occurring subsequent to the excitation of charged nano-systems. The present contribution describes in detail the methods developed for the quantitative measurement of branching ratios and cross sections for collision-induced dissociation processes of water cluster nano-systems. These methods are based on measurements of the detection efficiency of neutral fragments produced in these dissociation reactions. Moreover, measured detection efficiencies are used here to extract the number of neutral fragments produced for a given charged fragment.